PREAMBLE
Since its initial publication in 2004, the clinical practice guidelines of the Korean Association for the Study of the Liver (KASL) for management of hepatitis C have been updated in 2013 [
1], 2015 [
2], and 2017 [
3], incorporating emerging scientific evidence and clinical experience. Following the 2017 revision, the hepatitis C treatment landscape underwent a paradigm shift with the introduction of pan-genotypic direct-acting antivirals (DAAs), which are associated with shorter treatment durations, improved tolerability, and sustained virological response (SVR) rates exceeding 95%, regardless of genotype. These therapeutic advances have significantly simplified treatment and expanded access to curative care.
In parallel with these developments, the World Health Organization (WHO) has outlined a global strategy targeting the elimination of hepatitis C virus (HCV) by 2030, encouraging countries to enhance efforts in early diagnosis and treatment accessibility. In alignment with this global objective, Korea has undertaken policy initiatives aimed at reducing the national burden of hepatitis C through proactive case identification and treatment. Accordingly, KASL has revised its guidelines to reflect recent scientific advances and to support evidence-based decision-making in the local clinical context.
The 2025 revision presents a comprehensive update based on the latest domestic and international research, endorsing simplified treatment algorithms that primarily recommend pan-genotypic DAAs, irrespective of genotype classification. Additionally, the update provides detailed guidance for patients with treatment failure, cirrhosis, comorbidities, chronic kidney disease (CKD), or post-transplant status.
The revised guidelines also emphasize the importance of early screening and treatment to facilitate timely diagnosis and care. They introduce a screening-integrated treatment strategy that aligns with recent updates in national health policy and insurance coverage, aiming to enhance implementation feasibility in real-world clinical practice.
Developed based on current clinical evidence, these guidelines are intended to offer practical and authoritative support for healthcare professionals. KASL remains committed to ongoing updates and research initiatives in pursuit of the global goal of hepatitis C elimination.
Target population and intended users
The target groups for these guidelines are patients with HCV, including those newly or previously diagnosed, individuals with chronic hepatitis C or cirrhosis, patients with CKD, and those co-infected with human immunodeficiency virus (HIV) or hepatitis B virus (HBV).
The intended users include physicians, healthcare providers involved in the diagnosis and treatment of HCV, as well as resident physicians, clinical practitioners, and medical educators.
Development, funding, and revision process
The Clinical Practice Guidelines Committee for the Management of Hepatitis C, consisting of 11 hepatologists, was established with the approval of the KASL Board of Executives (
Supplementary Table 1). The revision process was funded by KASL. Each committee member was responsible for collecting and analyzing relevant source data within their area of expertise. The final manuscript was developed through a collaborative authorship process.
The recommendations are graded according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system (
Table 1) [
4-
6]. Randomized controlled trials are considered to provide a high level of evidence, whereas observational studies are considered to provide a low level of evidence. These levels may be adjusted based on factors that influence the quality of the studies. The levels of evidence are categorized as follows: A, high-quality evidence with minimal likelihood of a change in the conclusion; B, moderate-quality evidence with a possibility of change; and C, low-quality evidence with a significant likelihood of change. The strength of each recommendation is also determined according to the GRADE system and is classified as either strong (1) or weak (2) based on the quality of evidence, the balance between benefits and harms, and relevant socioeconomic factors such as cost and availability. A strong recommendation indicates that the intervention is appropriate for most patients, supported by high-quality evidence and aligned with patient values, preferences, cost-effectiveness, and adherence. A weak recommendation implies less certainty, but the intervention may still be considered appropriate for many patients depending on clinical judgment, resource availability, and individual circumstances.
The revision committee identified the following key clinical questions as essential elements to be addressed in the 2025 guidelines.
Epidemiology
What are the current prevalence and incidence rates of hepatitis C in Korea?
Risk factors
Which populations are at increased risk of hepatitis C infection?
What are the recommended strategies for hepatitis C screening?
Diagnosis
How should acute and chronic hepatitis C be diagnosed? What is the appropriate evaluation strategy for individuals with accidental exposure to HCV?
Treatment
What baseline assessments are required prior to initiating antiviral therapy?
Which patients should receive a simplified treatment approach?
What are the recommended initial treatment regimens?
What on-treatment monitoring is required?
How should sustained virologic response be assessed?
Which patients require long-term surveillance for hepatocellular carcinoma (HCC)?
Is post-treatment monitoring for reinfection necessary?
What are the recommended retreatment strategies for patients with prior treatment failure?
Treatment in special populations
Which patients with decompensated cirrhosis are eligible for DAA therapy?
What are the recommended DAA regimens for patients with decompensated cirrhosis?
Which DAA regimens are suitable for patients with CKD?
What treatment considerations apply to patients who are co-infected with HIV or HBV?
Does antiviral therapy affect the occurrence or recurrence of HCC?
What are the recommended treatment strategies for patients with concurrent HCC?
How should HCV infection be managed during pregnancy?
What are the treatment recommendations for the pediatric and adolescent population with hepatitis C?
How should recurrent HCV infection be managed in post-liver transplant recipients?
What treatment considerations apply to HCV infection following non-hepatic organ transplantation?
Should potential drug–drug interactions between immunosuppressive agents and DAAs be assessed?
Review of the manuscript and approval process
Each manuscript was authored by designated members of the revision committee and subsequently reviewed, discussed, and approved during a series of formal committee meetings. The quality of the manuscript was evaluated according to the standards outlined in the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, with additional consideration of the academic integrity of the content.
The guidelines underwent external review and revision informed by expert consultation with an infectious disease specialist and a pediatrician. A seven-member external advisory panel appointed by KASL conducted a formal peer review and discussion of the manuscript (
Supplementary Table 1 and
2). Additional feedback was obtained through a public hearing and a dedicated symposium open to all KASL members. The final version was formally approved by the KASL Board of Executives.
The Korean version of the 2025 KASL Clinical Practice Guidelines for the Management of Hepatitis C was released in May 2025 during the Liver Week 2025 and published on the official KASL website (
http://www.kasl.org). Future revisions will be considered as new evidence emerges, particularly when updates are warranted to optimize the management of hepatitis C and support public health efforts in Korea.
EPIDEMIOLOGY
HCV is one of the major causes of acute and chronic hepatitis, liver cirrhosis, and HCC in Korea [
7]. HCV infection has been classified as a Group 3 notifiable infectious disease in Korea, and has been under nationwide mandatory case-based surveillance since 2017. Although a vaccine has not yet been developed, the advent of DAAs has made possible effective treatment for HCV infection. Accordingly, understanding the epidemiology of HCV infection in Korea and establishing strategies tailored to the domestic context are crucial for public health.
According to estimates from 2022, approximately 50 million people worldwide were infected with HCV, accounting for about 0.7% of the global population [
8]. Prevalence is higher in the Eastern Mediterranean (1.8%), Europe (0.9%), and Africa (0.7%), although there is substantial variation both between and within countries [
8]. The Western Pacific region, including Korea, also carries a significant burden of HCV infection, with a prevalence of approximately 0.4% and an estimated 7.1 million people living with HCV [
8].
Anti-HCV positivity rate
Testing for antibody to hepatitis C (anti-HCV) has been included in the Korea National Health and Nutrition Examination Survey (KNHANES) since 2012. From 2013 to 2023, the average anti-HCV positivity rate was approximately 0.7% [
9]. Between 2019 and 2023, the positivity rate was 0.6% among individuals aged ≥10 years (0.6% in both men and women) and 0.7% among those aged ≥19 years, with rates increasing with age (
Fig. 1) [
9]. Studies conducted since the 2000s targeting health screening participants at the regional or national level reported anti-HCV positivity rates ranging from 0.6% to 0.8% [
10,
11]. A multicenter study in 2015 involving adults aged ≥20 years reported an anti-HCV positivity rate of 0.60%, reflecting a 30% decrease compared to 2009 [
11]. This study also found significant regional differences, with higher rates observed in Jeju, Gyeongbuk, Gyeongnam, Busan, and Jeonnam [
11]. In a pilot project conducted in 2020 by the KASL under the supervision of the Korea Disease Control and Prevention Agency (KDCA), the anti-HCV positivity rate among 104,918 individuals born in 1964 (age 56) was 0.75% (0.75% in men, 0.76% in women), with higher rates observed in Busan (1.44%) and Ulsan (1.05%) [
12].
HCV ribonucleic acid (RNA) positivity rate
HCV RNA positivity indicates current HCV infection. However, the reported positivity rates vary across the limited number of studies conducted in Korea. The KNHANES conducted HCV RNA testing from 2012 to 2015, during which 33.5% (63 of 188) of anti-HCV positive individuals were HCV RNA positive [
13]. In a research project supported by KDCA, which analyzed anti-HCV-positive blood samples between 2016 and 2020, the HCV RNA positivity rate was 15.7%, corresponding to an estimated 52,000 active infections nationwide [
14]. As of 2024, the KNHANES has resumed HCV RNA testing among individuals with positive anti-HCV results.
A single-center study analyzing 1 million individuals between 2001 and 2020 reported an anti-HCV positivity rate of 1.8%, among whom 65.7% were positive for HCV RNA [
15]. In a 2015 multicenter study of health screening participants, HCV RNA testing was performed in 60% of those who tested positive for anti-HCV, yielding an HCV RNA positivity rate of 25.4% [
11]. Another single-center retrospective study of 80,000 surgical patients from 2019 and 2021 reported an anti-HCV positivity rate of 0.69%, with 37.3% testing positive for HCV RNA [
16]. In the 2020 KDCA-KASL pilot project, 0.18% of participants were HCV RNA positive, accounting for 24% of individuals with positive anti-HCV results [
12].
Prevalence in high-risk groups
The risk groups for HCV infection have included people who inject drugs (PWID), individuals with hemophilia or Hansen’s disease, those undergoing dialysis for CKD, and specific migrant populations. Blood transfusion was once the most common route of HCV transmission in Korea, but it has become negligible since the implementation of anti-HCV screening in 1991 and the nucleic acid amplification test in 2005 [
17].
PWID represent a risk group of HCV infection in Korea. Studies reported a 57% HCV RNA positivity rate among 107 PWID between 2005 and 2006, and a 48.4% anti-HCV positivity rate with a 98.1% HCV RNA positivity rate among 318 PWID between 2007 and 2010 [
18]. A retrospective review of medical records from three healthcare institutions treating PWID between 2012 and 2022 showed an anti-HCV positivity rate of 39.7% (148 of 373 patients) [
19].
Patients with hemophilia or Hansen’s disease are also at increased risk. A 2002 study reported a 42.3% anti-HCV positivity rate, associated with older age and more advanced disease [
20]. More recent data from 2019 reported an anti-HCV positivity rate of 23.9% for hemophilia A and 15.7% for hemophilia B, with HCV RNA positivity observed in a small proportion (2.2% and 0.7%, respectively) [
21]. Patients with Hansen’s disease showed a significantly higher anti-HCV positivity rate (28.5%) compared to the general population of non-Hansen’s residents (6.5%) between 2009 and 2017 [
22].
Hemodialysis has been identified as a significant risk factor for HCV infection. According to the Korean Society of Nephrology, the anti-HCV positivity rate was 3% in 2011 and 4% in 2016 [
23]. In 2013, the rate was 3.4% among patients undergoing hemodialysis and 2.5% among those receiving peritoneal dialysis [
23].
Although data are limited, higher HCV prevalence has been noted among foreign workers and North Korean defectors. Screening conducted by the KASL from 2008 to 2015 reported a 1.8–2.6% anti-HCV positivity rate among foreign workers, especially those from China and Mongolia. Among North Korean defectors, a 2020–2021 study found an anti-HCV positivity rate of 1.9% [
24].
The global burden of HCV has declined, with an estimated 1 million new infections reported in 2022, a reduction from 1.5 million infections and 290,000 deaths in 2019, likely attributable to expanded prevention efforts and the widespread use of effective DAA therapies [
8,
25,
26]. In Korea, the number of newly reported cases of HCV infection was 10,811 in 2018; 9,810 in 2019; 11,850 in 2020; 10,116 in 2021; 8,308 in 2022; and 7,249 in 2023 [
27]. After excluding duplicate case reports and previously treated patients, the incidence rates per 100,000 population were 12.7 in 2018, 12.0 in 2019, and 11.0 in 2020, with an average of 11.9 [
28]. In 2019, the overall incidence rate was 17.2 per 100,000, showing a marked age-related increase: 1.4 per 100,000 in individuals aged 20–29 years, 29.1 per 100,000 in those aged 50–59 years, and 43.1 per 100,000 in those aged 70–79 years. No significant gender-based differences were observed in age-specific HCV incidence rates [
29].
Globally, HCV genotype 1 is the most prevalent, accounting for approximately 44–50% of cases, with about one-third of these cases occurring in East Asia. The second most common is genotype 3, representing approximately 17–30% of cases worldwide, and is frequently observed in South Asia, Eastern Europe, and Australia. Genotypes 2, 4, and 6 account for the remaining cases, while genotype 5 is rare (<1%). Genotypes 1 and 3 are predominant across most countries regardless of economic status, whereas genotypes 4 and 5 are primarily prevalent in lower-income regions [
30-
32].
In Korea, the most common HCV genotypes are 1b (45–58%) and 2a (32–51%), with other genotypes such as 1a, 2b, 3, 4, and 6 also identified [
33-
35]. According to a 2022 KDCA-supported study analyzing the serologic characteristics of viral hepatitis in Korea, genotype 2 (50.0%) and 1b (46.2%) were the most prevalent, followed by genotypes 3 (2.3%), 1a (1.1%), 6 (0.2%), and 4 (0.1%) [
36].
RISK FACTORS
Transmission routes
HCV transmission occurs primarily through parenteral exposure. Major transmission routes include transfusion of HCV-contaminated blood or blood products, organ transplants from HCV-positive donors, injection drug use, unsafe injection or medical procedures, needlestick injuries with contaminated needles, sexual contact with HCV-infected individuals, and vertical transmission from mothers to children.
Before 1991, blood transfusion was a major route for HCV transmission. This risk has markedly decreased since the introduction of blood donor screening [
37-
39]. In high-income countries with low HCV prevalence, such as the United States and Europe, injection drug use is currently the predominant route of transmission [
40]. In contrast, in low- and middle-income countries with moderate to high HCV prevalence, unsafe injection practices including the reuse of syringes, needles, or injection fluids, as well as unsterilized surgical procedures, endoscopy, and dental procedures remain major routes of transmission [
41]. Nevertheless, sporadic cases of HCV infections caused by unsafe medical procedures continue to be reported even in high-income countries [
42]. A study from Italy linked acute hepatitis C to various medical procedures, including neurosurgery, otolaryngological surgery, vascular surgery, ophthalmologic surgery, biopsies, and endoscopic procedures [
43]. Similarly, a 2015 outbreak in Korea was traced back to the reuse of syringes and contaminated injection fluids at a medical facility [
44]. Therefore, it is essential to adhere to standard precautions to prevent exposure to blood and bodily fluids during all invasive medical procedures.
Additional risk factors include improperly sterilized body piercings, acupuncture, and tattoos, as identified in several meta-analyses [
45-
47]. The risk of occupational HCV transmission from exposure to infected blood (e.g., via needlestick injuries) ranges from 0.9% to 2.2% [
48,
49]. The possibility of sexual transmission of HCV remains controversial. Monogamous heterosexual intercourse is generally associated with minimal risk. In contrast, elevated risk has been consistently reported in individuals with multiple sexual partners, those engaging in anal intercourse, sexual activities likely to cause mucosal trauma, sex with a partner co-infected with HIV or other sexually transmitted infection, and men who have sex with men [
50,
51]. Vertical transmission occurs in approximately 5.8% of cases when both the anti-HCV and HCV RNA are positive in the mother, increasing to 10.8% in case of maternal HIV co-infection [
52]. The risk of HCV transmission through breastfeeding is extremely low, and breastfeeding is considered safe unless nipple injury or bleeding is present [
53].
A prospective cohort study conducted from 2007 to 2011 at five university hospitals in Korea involving 1,173 HCV patients and 534 controls identified several independent risk factors for HCV infection: older age, injection drug use, needlestick injuries, history of transfusions before 1995, and presence of tattoos [
54]. In a case-control study from hospitals located in high-prevalence regions (Busan, Gyeongnam, and Jeonnam), sharing razors, having multiple sexual partners, employment as dock workers, tattooing, transfusions, surgeries involving bleeding, acupuncture, and body piercing were significantly associated with HCV infection [
55].
A global review of publications since 2008 reported that more than half of PWID in most regions are infected with HCV [
56]. In Korea, the anti-HCV positivity rate among PWID in the late 2000s was 48%, with 98% of them showing detectable HCV RNA [
18]. While 51% of hepatitis C cases in the United States are associated with PWID [
57], the corresponding proportion in Korea is only 7% [
58].
Korean cohort studies have demonstrated that PWID have significantly higher rates of multiple sexual partners, incarceration history, accidental needlestick injuries, tattoos, piercings, and exposure to commercial shaving compared to individuals who do not inject drugs [
58]. A prospective registry study (2022–2024) conducted at four major drug treatment institutions in Korea found that 89% of drug users reported injection drug use, and the anti-HCV positivity rate among them was 33.7%, HCV RNA was detected in 10.2% of participants, and only 50% of those with detectable HCV RNA were linked to treatment [
59].
Patients undergoing hemodialysis are at increased risk for HCV infection due to potential exposure to blood. A meta-analysis reported a global HCV prevalence of 20.7% among hemodialysis patients, with regional variations: Africa (28.0%), Asia (22.3%), North America (16.5%), Europe (20.1%), and Australasia/New Zealand (3.6%) [
60]. In Korea, the anti-HCV prevalence among hemodialysis patients declined markedly from 27.3% in 1989 to 3.4% in 2023 [
23]. Despite this progress, sporadic outbreaks continue to occur in dialysis units even in developed countries, likely due to non-transfusion-related sources of contamination. Identified risk factors include reuse of priming receptacles without proper disinfection, handling blood specimens near medications and clean supplies, use of mobile carts for injectable medications, patient HCV prevalence ≥10%, a patient-to-staff ratio ≥7:1, and treatment duration ≥2 years [
61]. Although some studies have reported a lower incidence of HCV infection among patients treated with dedicated dialysis machines, the difference was not significant [
62]. Both Korean and international guidelines on hemodialysis emphasize thorough disinfection of surfaces between sessions and strict adherence to infection control protocols. However, routine use of dedicated dialysis machines or rooms for patients with HCV infection is not recommended [
63,
64].
Given the absence of an effective vaccine, adherence to standard hygiene and infection control practices is essential. Individuals infected with HCV should avoid sharing personal items such as toothbrushes, razors, and nail clippers. PWID should be strongly advised to cease injection practices and must avoid reuse or improper disposal of injection equipment. Although the risk of sexual transmission is low among monogamous couples, condom use is recommended for individuals with multiple sexual partners. Routine prenatal HCV screening is not universally recommended unless the pregnant woman has identifiable risk factors. HCV infection status alone does not necessitate changes in delivery methods or breastfeeding practices, unless there is visible nipple injury or bleeding. Healthcare facilities must strictly adhere to standard precautions during procedures involving potential blood exposure. In community settings, procedures such as tattooing, piercing, and acupuncture should only be performed with single-use or appropriately sterilized equipment.
Screening
Screening for hepatitis C is generally recommended for individuals at high risk, including those who received blood transfusions or organ transplants prior to 1992, PWID, patients undergoing hemodialysis, individuals living with HIV, patients with hemophilia or Hansen’s disease, children born to HCV-infected mothers, and healthcare workers with occupational exposure to HCV-positive blood or mucous membranes (
Table 2) [
65].
Due to challenges in identifying high-risk individuals in routine clinical settings, the United States expanded its recommendations in 2012 to include one-time HCV antibody testing for all adults born between 1945 and 1965, based on evidence of cost-effectiveness [
66]. With the rising incidence of HCV infection among younger populations, primarily due to the increase in injection drug use, the United States Preventive Services Task Force updated its guidelines in 2020 to recommend one-time screening for all adults aged 18 to 79 years [
67]. In Egypt, where the anti-HCV prevalence reached as high as 4.6%, a nationwide mass screening program that covered 80% of the population effectively reduced the prevalence by linking screening efforts with DAA treatment [
68]. Therefore, appropriate HCV screening strategies should be established based on each country’s epidemiological characteristics and the availability of healthcare resources.
In Korea, a multicenter cohort study conducted from 2007 to 2017 revealed that 89% of 2,758 patients with detectable HCV RNA were asymptomatic, and 50% had normal alanine aminotransferase (ALT) levels (<40 U/L). The mean age was 57 years, with 91.5% of patients older than 40 years, and only 5.6% reported a history of injection drug use [
69]. These findings suggest that, given the epidemiological characteristics of the Korean HCV patient population, symptom-based detection or routine health checkups are unlikely to be effective in identifying HCV-infected individuals, and risk factor–based screening may have limited effectiveness.
Based on the 2012–2016 KNHANES, the highest anti-HCV prevalence in Korea was observed among adults aged 40 to 65 years, with a mean age of 57–58 years. These findings led to the implementation of a national pilot screening program during 2020–2021, targeting individuals aged 56 years as part of routine health checkups. Among those screened, the anti-HCV and HCV RNA positivity rates were 0.75% and 0.18%, respectively. A cost-effectiveness analysis using data from this pilot program projected substantial health benefits from universal screening at age 56 compared to no screening: a 50% reduction in compensated cirrhosis, 48% in decompensated cirrhosis, 49% in hepatocellular carcinoma, 43% in need for liver transplantation, and 49% in liver-related mortality. The incremental cost-effectiveness ratio was estimated at 8,164,704 KRW per quality-adjusted life year (QALY), which is well below the per capita gross domestic product (35,821,274 KRW/QALY), indicating that universal screening is cost-effective [
12].
As a result, beginning in 2025, anti-HCV testing has been incorporated into the national health checkup for all citizens at the age of 56. While population-wide screening of all adults would ultimately be desirable to achieve HCV elimination, nationwide screening has commenced in a stepwise manner. This birth cohort–based screening strategy is expected to facilitate early detection and treatment of hepatitis C. Ultimately, nationwide, population-based screening is essential for effective elimination of hepatitis C.
[Recommendation]
1. Nationwide large-scale screening is recommended for elimination of hepatitis C. (A1)
DIAGNOSIS
To confirm HCV infection, biochemical tests, HCV serologic tests, and RNA assays should be performed, accompanied by a comprehensive history collection and physical examination to identify possible transmission routes and prevent further spread. HCV genotype and subgenotype testing may assist in the selection of antiviral therapy. Imaging studies, liver biopsy, or non-invasive assessments of liver fibrosis are useful for evaluating disease severity. The interpretation of serologic and virologic test results is summarized in
Table 3.
The anti-HCV test, which is relatively inexpensive and rapid, serves as a primary screening modality for high-risk groups and is utilized in the diagnosis of both acute and chronic hepatitis C [
70]. Enzyme immunoassays (EIA) or enhanced chemiluminescent immunoassays, which detect antibodies directed against HCV core and non-structural proteins (NS3, NS4, NS5), are predominantly used [
71,
72].
Anti-HCV typically becomes detectable approximately 8 to 9 weeks after an initial infection, with greater than 97% seropositivity achieved within 6 months. However, because anti-HCV is not a neutralizing antibody and may persist even after recovery, it cannot distinguish between current and past infections and cannot detect reinfection (
Fig. 2) [
65,
73]. Negative anti-HCV results may be observed during the early phase of acute infection or in immunocompromised individuals (e.g., HIV-infected persons, transplant recipients), necessitating confirmatory HCV RNA testing (
Fig. 3) [
74,
75]. Conversely, false-positive results may occur due to autoimmune diseases or nonspecific cross-reactivity, particularly in populations with a low HCV prevalence (<1%) [
76-
78].
HCV RNA tests
Detection of HCV RNA, through either qualitative or quantitative assays performed on plasma or serum, confirms the presence of acute or chronic infections, with a recommended quantification threshold ≥15 IU/mL [
79,
80].
HCV RNA typically becomes detectable approximately two weeks after infection, rapidly reaching a plateau. Following the peak in ALT levels, HCV RNA levels begin to decrease in parallel with ALT [
81,
82]. In chronic infections, HCV RNA levels generally remain stable over time [
82,
83]. HCV RNA levels do not correlate significantly with hepatic inflammation or fibrosis and tend to be relatively constant in the absence of antiviral therapy (
Fig. 2) [
84,
85].
Given the potential for fluctuations in HCV RNA levels, individuals with suspected recent infection but undetectable HCV RNA should undergo HCV RNA retesting after 3 to 6 months [
79,
86,
87]. In high-risk populations, reinfection may occur after either spontaneous clearance or SVR. The presence of reinfection can be confirmed through HCV RNA assays, particularly when it is clinically suspected or in individuals at ongoing risk (
Fig. 3) [
79].
HCV genotyping/subgenotyping tests
HCV is characterized by high genetic diversity, with eight distinct genotypes and more than 100 subgenotypes currently identified [
88]. HCV genotyping is typically performed by analyzing critical regions such as the 5’ untranslated region, core, or NS5B coding regions using reverse hybridization or next-generation sequencing (NGS)-based deep sequencing [
89-
91].
In high-income regions, including South Korea, North America, and Europe, the predominant subgenotypes are 1a, 1b, 2a, 2b, 2c, 3a, 4a, 5a, and 6a. Currently, pan-genotypic DAAs, such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, are approved and widely used for HCV treatment without the need for genotyping or subgenotyping [
88,
92]. Nonetheless, relatively lower SVR rates have been reported in patients with rare genotypes after DAA therapy. Therefore, in populations such as migrants from low- or middle-income countries, such as those from Africa or South Asia, or in patients with prior DAA treatment failure, genotyping/subgenotyping assays may be helpful before initiating antiviral therapy. Moreover, in populations with high risk of reinfection, such as PWID or men who have sex with men, genotyping/subgenotyping may be considered prior to treatment, based on the clinician’s judgment [
93-
97].
HCV exhibits rapid replication and an inherently high error rate of its viral polymerase, leading to the development of viral quasispecies [
98]. This genetic diversity contributes to the emergence of resistance-associated substitutions (RAS) [
99].
Detection of HCV RAS can be performed using population or deep sequencing methods, although no standardized testing protocol has been universally established [
100]. Currently, the efficacy of pan-genotypic DAAs is not substantially compromised by the presence of baseline RAS [
79]. Therefore, routine pre-treatment resistance testing is not recommended when pan-genotypic DAAs are used. Nevertheless, in patients with genotype 3 infection, the presence of NS5A RAS Y93H prior to sofosbuvir/velpatasvir treatment or of A30K prior to glecaprevir/pibrentasvir treatment may be associated with reduced treatment efficacy [
101,
102]. In addition, routine monitoring of RAS during treatment is not currently recommended.
There has been growing demand for simple, rapid, and cost-effective diagnostic tools to support HCV elimination efforts, leading to the development of various point-of-care testing (POCT) methods [
103]. These range from simple lateral flow assays, which detect anti-HCV in saliva within 20 minutes without the need for specialized equipment, to more advanced cartridge-based systems that detect HCV RNA from fingerstick blood samples within two hours [
104-
107]. A meta-analysis demonstrated that the OraQuick
® HCV Rapid Antibody Test, a saliva-based lateral flow assay, exhibits high sensitivity (98%, 95% confidence interval [CI] 97–98%) and specificity (100%, 95% CI 100–100%) compared to the EIA reference standard [
105]. The Xpert
® HCV Viral Load test, recently approved by the U.S. Food and Drug Administration (FDA) as the first POCT for HCV RNA detection, demonstrated high sensitivity (95.5–100%) and specificity (98.1–100%) using fingerstick blood, with near-perfect diagnostic accuracy [
106,
107].
The average incidence of anti-HCV seroconversion in healthcare workers following accidental percutaneous exposure to HCV-infected blood is 1.8% (range 0–7%) in various countries [
108-
114] and 0.92% in South Korea [
48]. When an individual is exposed to an HCV-positive source, baseline testing for anti-HCV and serum ALT levels should be performed. If anti-HCV is negative, an HCV RNA assay should be performed 4 to 6 weeks after exposure to enable early detection. Even when all baseline tests are negative, follow-up testing for anti-HCV and ALT levels is recommended 4 to 6 months post-exposure [
111,
115]. If anti-HCV is positive, confirmatory testing such as HCV RNA should be performed.
[Recommendation]
1. Anti-HCV testing is recommended for individuals with suspected acute or chronic HCV infection. (A1)
2. HCV RNA testing should be performed to confirm active infection in individuals with a positive anti-HCV test. (A1)
3. HCV RNA testing is required even when anti-HCV is negative if acute HCV infection is suspected or if un explained liver disease is present in immunocompromised patients. (A1)
4. Immediately following exposure to HCV-infected blood or body fluids, anti-HCV and serum ALT levels should be tested. If anti-HCV is negative, HCV RNA testing should be performed 4 to 6 weeks after exposure for early detection. If all baseline tests are negative, follow-up testing for anti-HCV and serum ALT level should be conducted 4 to 6 months after exposure (B2).
TREATMENT
Goals of hepatitis C therapy
The primary aim of hepatitis C therapy is to prevent complications associated with chronic HCV infection, including liver cirrhosis, HCC, and extrahepatic manifestations, and to reduce liver-related and all-cause mortality through viral eradication. In addition, successful treatment can reduce stigma and the prevalence of infection, limiting transmission of the virus [
79,
116]. As long-term clinical outcomes are not readily measurable, the practical therapeutic goal is SVR, defined as undetectable serum HCV RNA for at least 12 weeks post-treatment.
SVR is considered a definitive indicator of HCV eradication, as more than 99% of patients who achieve SVR do not experience recurrence of detectable HCV RNA [
117,
118]. SVR is associated with histologic improvement in liver fibrosis in more than 90% of patients [
119-
121], as well as with a significantly reduced risk of cirrhosis-related complications [
122], a lower incidence of hepatocellular carcinoma [
123-
125], and improved overall survival [
124,
126] compared to patients who do not achieve SVR. Furthermore, SVR contributes to resolution or improvement of HCV-related extrahepatic manifestations, including mixed cryoglobulinemia and glomerulonephritis [
127,
128].
[Recommendation]
1. The primary objective of treatment for chronic hepatitis C is eradication of HCV infection, preventing complications such as liver cirrhosis, HCC, extrahepatic manifestations, and HCV-related mortality. Treatment also contributes to reducing stigma and preventing further transmission. (A1)
2. The short-term therapeutic goal is to achieve SVR, defined as undetectable serum HCV RNA for at least 12 weeks post-treatment. (A1)
Indications for treatment
Currently available oral antiviral therapies for hepatitis C are well tolerated and associated with minimal adverse effects and few contraindications. Therefore, all patients with acute or chronic hepatitis C who do not have explicit contraindications should be considered candidates for treatment [
79,
116]. As approximately half of patients with chronic HCV infection present with normal or near-normal ALT levels [
69], antiviral therapy is recommended for all individuals with detectable serum HCV RNA, regardless of ALT level. Treatment should be prioritized in patients with advanced liver fibrosis (≥F2) or established cirrhosis to reduce the risk of hepatic decompensation and hepatocellular carcinoma [
129]. Immediate treatment is also indicated in patients awaiting liver transplantation; those with severe HCV-related extrahepatic manifestations (e.g., mixed cryoglobulinemia, glomerulonephritis); and individuals at high risk of transmission, including PWID, incarcerated individuals, women of reproductive age planning pregnancy, and patients receiving hemodialysis [
79,
116].
Antiviral therapy with oral agents can effectively result in SVR in cases of acute hepatitis C [
130-
134]. In particular, early initiation of treatment among high-risk populations, such as individuals with HIV infection, has been shown to significantly reduce subsequent cases of acute hepatitis C [
135]. Therefore, immediate initiation of antiviral therapy upon detection of HCV RNA is recommended, rather than awaiting spontaneous viral clearance [
79,
116].
With the advent of oral antiviral regimens that exclude protease inhibitors, treatment is now feasible for patients with decompensated cirrhosis, who were previously ineligible. However, antiviral therapy is not recommended for patients with a limited life expectancy due to non–liver-related comorbidities or for those who are not candidates for liver transplantation and are unlikely to benefit from viral eradication [
79,
116].
[Recommendation]
1. Antiviral therapy should be offered to all patients with acute or chronic hepatitis C who do not have contraindications to treatment. (A1)
2. Treatment should be prioritized for patients with advanced liver disease (fibrosis stage ≥F2 or cirrhosis), those with severe HCV-related extrahepatic manifestations, individuals awaiting or having undergone liver transplantation, and populations at high risk of transmission. (A1)
3. Antiviral therapy is not recommended for patients with limited life expectancy due to non–liver-related comorbidities or those who are not candidates for liver transplantation and are unlikely to benefit from viral eradication. (B1)
Treatment strategy
Prompt initiation of treatment following hepatitis C diagnosis is critical to successful management and eradication of HCV infection. Given the high efficacy, pan-genotypic coverage, and favorable safety profiles of currently available oral antiviral regimens, a simplified treatment strategy is recommended for patients who 1) have never received treatment and 2) have neither cirrhosis nor compensated cirrhosis (Child–Pugh Class A), as shown in
Table 4 [
116,
136,
137]. This approach allows immediate initiation of pan-genotypic therapy for the recommended duration without the need for genotype testing or on-treatment monitoring. Assessment of SVR at least 12 weeks post-treatment is sufficient [
92,
138]. Nonetheless, additional follow-up during treatment may be necessary to evaluate potential drug–drug interactions and ensure treatment adherence [
139,
140], particularly in highly accessible healthcare settings such as those in South Korea.
A simplified treatment strategy using pan-genotypic drugs may also be appropriate for patients with genotypes 3 or 6. However, pre-treatment genotyping or RAS testing may be beneficial in genotype 3-infected individuals with cirrhosis or in those in regions with high genotype 3 prevalence [
30].
However, a simplified strategy is not suitable for all patients. A comprehensive pre-treatment evaluation, including HCV genotyping and RAS testing when appropriate, is recommended for individuals with factors that may reduce treatment efficacy, comorbid conditions requiring on-treatment monitoring, or a risk of major drug-drug interactions. Patients who should not be treated with simplified strategies include those with 1) prior HCV treatment, 2) HBV coinfection, 3) compensated cirrhosis with end-stage renal disease (ESRD) (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m²), 4) current or past decompensated liver disease (Child–Pugh score ≥7), 5) pregnancy, 6) suspected or confirmed hepatocellular carcinoma, and 7) a history of liver transplantation, among others [
116,
136,
137].
[Recommendation]
1. A simplified treatment strategy using pan-genotypic oral antiviral agents with SVR assessment only after treatment completion is recommended for treatment-naïve patients without cirrhosis or with compensated cirrhosis. (A1)
2. The simplified treatment strategy is not recommended for patients with prior HCV treatment experience, HBV co-infection, compensated cirrhosis with ESRD (eGFR <30 mL/min/1.73 m²), decompensated cirrhosis (Child–Pugh score ≥7), pregnancy, suspected or confirmed hepatocellular carcinoma, or a history of liver transplantation. (A1)
Pre-treatment assessments
Before initiating treatment, a comprehensive assessment of factors that may influence the treatment process or outcomes is essential for patients diagnosed with hepatitis C. This includes a review of current medications to identify potential drug interactions with DAAs. The presence of HCC or pregnancy should also be evaluated. Additionally, patients should be assessed for reinfection risk factors such as intravenous drug use, hemodialysis, unsafe medical procedures, and HIV coinfection. Comorbid liver conditions, overall disease severity, and severity of hepatic fibrosis also must be carefully evaluated.
The prevalence of HBV and HCV coinfection varies across regions and is difficult to accurately estimate due to the lack of large-scale epidemiological studies [
141]. A Korean multicenter prospective HCV cohort study reported a 3.0% HBV coinfection rate among 1,173 patients, and another prospective Korean study showed a 2.4% rate in 758 patients [
54,
142]. In the United States, one prospective and one retrospective study reported HBV coinfection rates of 5.8% and 1.4%, respectively [
143,
144]. Because HBV/HCV coinfection is associated with poorer clinical outcomes than monoinfection [
145], all HCV-infected patients should be screened for hepatitis B surface antigen (HBsAg), anti-HBc, and anti-HBs to assess current or prior HBV infection. Practical management of HBsAg-positive or anti-HBc-positive patients during and after DAA therapy follows the KASL clinical practice guideline for management of chronic hepatitis B 2022 coinfection section [
146].
While recent data on the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among Korean HCV patients are limited, recent studies suggest a steady increase in prevalence in Korea. According to the KNHANES data, MASLD prevalence increased from 18.6% (1998–2001) to 21.5% (2016–2017) [
147], and another study analyzing 2009 national health check-up data reported a prevalence of 27.5% [
148]. In a Korean prospective HCV cohort study, 30.1% of patients were obese (body mass index [BMI] ≥25 kg/m
2) [
54]. A Taiwanese study involving 5,840 HCV patients found a MASLD prevalence of 34.0% [
149], with no significant change observed after HCV cure (34.0% vs. 34.8%,
P=0.17). The only factor significantly associated with MASLD improvement was BMI reduction (odds ratio [OR] 0.89; 95% CI 0.85–0.92;
P<0.001). In a study by Liu et al. [
150] involving 1,598 HCV patients, MASLD was identified as a significant risk factor for HCC even after HCV cure (hazard ratio [HR] 2.07; 95% CI 1.36–3.16;
P<0.001). Given the increasing prevalence and its impact on outcomes, MASLD should be systematically assessed before and monitored after HCV treatment.
According to a Korean prospective HCV cohort study, 53.4% of patients reported current or past alcohol consumption [
54]. Alcohol use is a well-known risk factor for liver cirrhosis progression, decompensated cirrhosis, HCC development, and mortality in HCV patients [
151-
153]. In a prospective study of 192 cirrhotic HCV patients, Vandenbulcke et al. [
154] reported that alcohol users had a significantly higher risk of HCC (HR 3.43; 95% CI 1.49–7.92;
P=0.004). Therefore, alcohol use should be systematically assessed in all patients with hepatitis C.
Albeit less prevalent than HBV, ALD, and MASLD, chronic hepatitis C can present with autoimmune features or coexist with autoimmune hepatitis AIH. We recommend selective evaluation for AIH when autoimmunity is suggested by clinical or laboratory findings, such as elevated immunoglobulin G or positivity for anti-nuclear antibody or smooth muscle antibody. When AIH is suspected, liver biopsy may be considered for definitive differentiation. Universal screening for AIH in all patients with chronic hepatitis C is not routinely recommended.
The prognosis of patients with HCV infection varies according to the severity of liver disease [
155,
156], affecting the risks of HCC, liver-related complications, and mortality and guiding surveillance strategies. Accordingly, liver fibrosis stage should be evaluated prior to treatment to identify patients who require ongoing HCC surveillance following SVR.
Liver disease severity can be assessed using either non-invasive tests or liver biopsy. While biopsy remains the reference standard based on scoring systems like METAVIR and Ishak [
1,
157,
158], it is now rarely performed due to the high efficacy of DAAs, as well as the limitations of biopsy such as invasiveness, sampling variability, and inter-observer inconsistency [
79,
116]. Biopsy may still be considered in select cases when differentiating from other liver diseases such as MASLD, alcoholic liver disease, or autoimmune hepatitis.
Non-invasive tests, on the other hand, provide a safer and more convenient method for assessing liver fibrosis. These include serum biomarker-based tests and transient elastography. Liver fibrosis evaluation in patients with hepatitis C should follow the 2024 KASL Clinical Practice Guidelines for Noninvasive Tests to Assess Liver Fibrosis in Chronic Liver Disease [
159].
Although fibrosis stage does not affect SVR rates due to the high efficacy of pan-genotypic DAAs [
160-
162], patients with genotype 3 and cirrhosis have demonstrated lower SVR rates than non-cirrhotic patients, as shown in a phase 3 trial involving 277 patients and a retrospective study of 153 patients [
163,
164]. In cases of decompensated cirrhosis, the prognosis and treatment strategy depend on residual liver function; thus, referral to a specialist or liver transplant center is recommended. Decompensated cirrhosis is defined as the presence of one or more complications of portal hypertension, such as ascites, variceal bleeding, hepatic encephalopathy, or jaundice [
165,
166]. Details of treatment are provided in the ‘Decompensated Cirrhosis’ section of this guideline.
[Recommendation]
1. Patients with HCV infection should undergo a comprehensive pre-treatment evaluation for comorbid liver diseases, including HBV infection, MASLD, alcohol-related liver disease, and others. (A1)
2. Assessment of liver fibrosis using either liver biopsy or non-invasive tests should be performed to estimate prognosis in patients with HCV infection. (A1)
On-treatment monitoring
Pan-genotypic DAA therapy is generally well tolerated, with a very low incidence of serious adverse events leading to treatment discontinuation. In a phase 3 trial of 12-week sofosbuvir/velpatasvir therapy, the discontinuation rate due to adverse events was less than 1%, with fatigue and headache the most commonly reported symptoms, showing no significant difference compared to placebo [
160,
163]. In a Korean phase 3 study involving 54 HCV patients, no serious treatment-related adverse events were reported, although one patient (1.8%) discontinued treatment due to elevated AST or ALT levels [
167]. In a large-scale observational study from Taiwan including 3,480 patients, the treatment discontinuation rate was 0.3%, and the incidence of serious adverse events was 0.03% [
168]. In a phase 3 study of 8- or 12-week glecaprevir/pibrentasvir therapy, the treatment discontinuation rate was less than 0.5%, with fatigue and headache the most commonly reported symptoms [
161,
169]. A pooled analysis of phase 2 and 3 trials conducted in Korea found no serious drug-related adverse events [
170].
Nevertheless, caution is warranted when treating patients with decompensated cirrhosis or those who have undergone liver transplantation, as clinical data in these populations remain limited. A meta-analysis of 60 studies by An et al. [
171] reported a treatment discontinuation rate of 6.0% in patients with decompensated cirrhosis. In a Japanese multicenter prospective study of 72 such patients, 2.8% discontinued treatment due to adverse events [
172].
Routine HCV RNA monitoring during DAA therapy is generally not required due to the high efficacy and tolerability of these agents. However, in cases of suboptimal adherence, HCV RNA testing may be considered at the discretion of the treating physician [
116]. Among patients without cirrhosis, HCV RNA typically becomes undetectable by week 4 of DAA therapy [
173]. Notably, among 1,253 patients with detectable HCV RNA at the end of therapy, 89.3% achieved SVR [
174].
[Recommendation]
1. Evaluation of drug-related adverse events and treatment adherence is necessary during DAA therapy for hepatitis C. (B1)
2. Routine HCV RNA monitoring during DAA therapy is not recommended in patients with good adherence. (B1)
Antiviral agents
The treatment of chronic hepatitis C has progressed remarkably over the past three decades since the introduction of interferon alpha in 1991. DAAs, first introduced in 2011, exert their antiviral effects by targeting various stages of the HCV life cycle. Based on their mechanism of action, DAAs are categorized into three classes: NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors.
NS3/4A protease inhibitors were the first class of DAAs developed and functioned by inhibiting the cleavage of the HCV polyprotein, a crucial step in viral replication. First-generation agents such as boceprevir and telaprevir were later followed by simeprevir, asunaprevir, paritaprevir, grazoprevir, voxilaprevir, and glecaprevir. NS5A inhibitors suppress HCV replication and assembly and demonstrate synergistic antiviral effects when used in combination with other agents. This class includes daclatasvir, ledipasvir, ombitasvir, elbasvir, velpatasvir, and pibrentasvir. NS5B polymerase inhibitors include sofosbuvir and dasabuvir [
3].
Since 2020, pan-genotypic regimens achieving SVR rates ≥95% across all HCV genotypes have become the standard of care. Consequently, interferon-based therapies and many earlier-generation oral DAAs are no longer recommended and have been withdrawn from approval and the market.
As of 2025 in Korea, the currently approved and marketed DAAs include sofosbuvir/velpatasvir (EPCLUSA
®), glecaprevir/pibrentasvir (MAVIRET
®), and sofosbuvir/velpatasvir/voxilaprevir (VOSEVI
®), as shown in
Table 5. These regimens are highly effective, well-tolerated, associated with a low risk of resistance, convenient to administer, and require short treatment durations. For treatment-naïve patients without cirrhosis or with compensated cirrhosis, the first-line options are sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks.
Sofosbuvir/velpatasvir is a fixed-dose combination tablet containing the NS5B polymerase inhibitor sofosbuvir (400 mg) and the NS5A inhibitor velpatasvir (100 mg). It is administered orally once daily, irrespective of food intake.
It is recommended as a 12-week regimen for genotypes 1 through 6, regardless of prior treatment history or the presence of cirrhosis. In patients with decompensated cirrhosis, treatment extension or coadministration with ribavirin may be required (see “Decompensated cirrhosis” section).
Pharmacokinetics
Sofosbuvir is metabolized in the liver via cathepsin A, carboxylesterase 1, histidine triad nucleotide-binding protein 1, and the pyrimidine nucleotide biosynthesis pathway to form GS-331007, its primary circulating metabolite. Approximately 80% of GS-331007 is excreted in the urine and 15% in the feces. Velpatasvir is primarily metabolized by cytochrome P450 enzymes CYP2B6, CYP2C8, and CYP3A4 and is excreted mainly via the biliary route.
The plasma exposure (area under the curve, AUC) of both sofosbuvir and velpatasvir in patients with moderate or severe hepatic impairment is comparable to that in patients with normal liver function; therefore, no dose adjustment is required in patients with hepatic dysfunction, including those with decompensated cirrhosis.
Although the AUC of sofosbuvir increases in patients with renal impairment, and the drug was initially not recommended for those with an eGFR <30 mL/min/1.73 m², subsequent clinical studies in patients with renal dysfunction, including those on dialysis, demonstrated its safety and efficacy [
175]. Accordingly, no dose adjustment is currently needed in patients with CKD, regardless of severity.
Drug interactions
Sofosbuvir and velpatasvir should not be used with drugs that strongly induce P-glycoprotein (P-gp) or cytochromes (CYP) P2B6, CYP2C8, or CYP3A4, which reduce their effectiveness. Contraindicated medications include carbamazepine, phenytoin, phenobarbital, rifampin, rifapentine, rifabutin, St. John’s wort, efavirenz, modafinil, and bosentan.
Agents that increase gastric pH, such as antacids, histamine H2 receptor antagonists, and proton pump inhibitors, may impair velpatasvir solubility and reduce its absorption. When coadministered, careful attention is required to maintain therapeutic effectiveness.
Velpatasvir inhibits several drug transporters (P-gp, breast cancer resistance protein [BCRP], organic anion transporting polypeptide [OATP] 1B1/1B3, OATP2B1), which may increase levels of other medications such as topotecan (contraindicated), tenofovir, statins, and digoxin—monitoring or dose adjustment may be needed. Increased exposure to tenofovir-based antiretroviral regimens, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors such as atorvastatin and rosuvastatin, or digoxin may necessitate dose adjustment and clinical monitoring.
Coadministration with amiodarone can cause life-threatening bradycardia or cardiac arrest and is contraindicated. If unavoidable, inpatient monitoring for at least 48 hours is required, followed by continued outpatient cardiac monitoring for two weeks.
Efficacy
Multiple clinical trials [
160,
163] and real-world studies [
168,
176-
180] have demonstrated that a 12-week sofosbuvir/velpatasvir regimen without ribavirin achieves an SVR rate of approximately 99% (range: 97–100%) across genotypes 1, 2, 4, 5, and 6, irrespective of baseline NS5A RASs.
In the ASTRAL-1 trial [
160], which enrolled 740 treatment-naïve and treatment-experienced patients with genotypes 1, 2, 4, 5, or 6 and with or without compensated cirrhosis, the SVR rate was 99%, significantly higher than with placebo, and consistent across all subgroups. The ASTRAL-2 trial [
163] compared 12 weeks of sofosbuvir/velpatasvir with sofosbuvir plus ribavirin in genotype 2 patients and showed significantly higher efficacy with the former (99% vs. 94%,
P<0.05). A Korean phase 3 study involving 53 patients with genotype 1 or 2 reported an SVR rate of 98.1%. The only non-responder had discontinued treatment early due to elevated AST and ALT [
167].
In the ASTRAL-3 study of 552 genotype 3 patients [
163], the SVR rate following 12 weeks of sofosbuvir/velpatasvir exceeded 95% (95% CI 92–98%), which was significantly higher than the 80% (95% CI 75–85%) achieved with 24 weeks of sofosbuvir plus ribavirin. Among those with cirrhosis or prior treatment experience, SVR rates remained high (91% and 90%, respectively), outperforming the 24-week regimen (66% and 63%, respectively). NS5A RASs were detected in 40% of patients who experienced virologic relapses.
A real-world cohort study of 293 genotype 3 patients, including 11.2% with baseline NS5A RASs, demonstrated an SVR rate of 95.9%, with no significant impact of RAS on treatment response [
181]. Another large-scale study comparing sofosbuvir/velpatasvir with sofosbuvir/daclatasvir in 2,824 genotype 3 patients reported similar SVR rates (92% vs. 90.8%), though sofosbuvir/velpatasvir was more effective in patients with cirrhosis (86.5% vs. 84.8%) [
182].
A pooled real-world analysis of 12 cohorts across multiple genotypes reported an overall SVR rate of 98.9% with sofosbuvir/velpatasvir, including 98.3% in genotype 3 and 97.9% in patients with compensated cirrhosis [
176]. The primary reasons for treatment failure were early discontinuation (26.5%) or loss to follow-up (67%).
Adverse events and safety
Headache and fatigue are the most common side effects of sofosbuvir/velpatasvir. Among patients with cirrhosis, mild headache and fatigue occurred in approximately 10%, a frequency comparable to that observed with placebo. In patients with decompensated cirrhosis receiving ribavirin in combination, anemia was reported in about 10%.
Glecaprevir/pibrentasvir
Glecaprevir (300 mg), an NS3/4A protease inhibitor, and pibrentasvir (120 mg), an NS5A inhibitor, are co-formulated into a fixed-dose combination tablet. The recommended dosage is three tablets orally once daily with food. This regimen is indicated for patients with HCV genotypes 1 through 6 without cirrhosis or with compensated cirrhosis and is administered for 8 weeks. It is contraindicated in patients with decompensated cirrhosis due to its NS3/4A protease inhibitor component. For genotype 1 or 3 patients with prior treatment experience, treatment duration varies depending on the previously used agents and typically requires 12 to 16 weeks (see “Retreatment” section).
Pharmacokinetics
Glecaprevir/pibrentasvir is primarily metabolized by CYP3A and is excreted predominantly via the biliary route, with less than 1% eliminated in the urine. In patients with moderate hepatic impairment (Child–Pugh B), the AUC of glecaprevir increases approximately two-fold. In those with severe hepatic impairment (Child–Pugh C), the AUCs of glecaprevir and pibrentasvir increase by approximately 11-fold and 2-fold, respectively. Consequently, this regimen is contraindicated in patients with decompensated cirrhosis (Child–Pugh B or C). No dose adjustment is required in patients with CKD, including those receiving dialysis.
Drug interactions
Glecaprevir and pibrentasvir are substrates of P-gp and BCRP and are weak inhibitors of CYP3A, CYP1A2, and UDP-glucuronosyltransferase 1A1. Glecaprevir is also a substrate of OATP1B1/3. Co-administration with moderate to strong inducers of P-gp or CYP enzymes can significantly reduce drug concentrations and compromise therapeutic efficacy. These agents include anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin), antituberculosis medications (rifampin, rifapentine, rifabutin), herbal supplements (St. John’s wort), HIV antiretrovirals (efavirenz), and endothelin receptor antagonists (bosentan) and are contraindicated.
HIV protease inhibitors such as atazanavir, darunavir, lopinavir, and ritonavir may increase the exposure of glecaprevir/pibrentasvir and are contraindicated. The regimen should not be used in patients receiving cyclosporine at doses exceeding 100 mg per day.
As inhibitors of P-gp, BCRP, and OATP1B1/3, glecaprevir/pibrentasvir may elevate plasma concentrations of substrates of these transporters. Concomitant use with aliskiren, dabigatran, or certain statins (atorvastatin, lovastatin, simvastatin) is contraindicated. For other statins, dose adjustment is recommended to reduce the risk of myopathy and rhabdomyolysis. The dose of pravastatin should be reduced by 50%, and that of rosuvastatin should not exceed 5 mg per day. When co-administered with digoxin, the digoxin dose should be halved.
Immunosuppressants such as everolimus, sirolimus, or tacrolimus may require close monitoring and dose adjustment when coadministered with glecaprevir/pibrentasvir, particularly if cyclosporine dose exceeds 100 mg per day. Ethinyl estradiol-containing contraceptives are not recommended due to the potential risk of ALT elevation.
Efficacy
In treatment-naïve patients, an 8-week regimen of glecaprevir/pibrentasvir achieves high SVR rates irrespective of HCV genotype or presence of cirrhosis. Multiple clinical trials [
94,
161,
170,
183] and real-world studies [
162,
184-
186] have reported SVR rates of approximately 98–99% for genotypes 1, 2, and 4–6 and 95–98% for genotype 3. Head-to-head comparisons between 8-week and 12-week regimens demonstrated no additional benefit from extended therapy [
169,
187,
188], supporting the recommendation of an 8-week course for most patients.
A pooled analysis of 1,248 patients previously treated with interferon, peginterferon, ribavirin, or sofosbuvir (excluding those with decompensated cirrhosis) showed an overall SVR rate of 97.6% (95% CI 96.6–98.3%), with no significant difference based on cirrhosis status. Treatment failures were mainly observed in genotypes 3 and 5 [
183].
In a phase 3 trial conducted in 47 Asian countries (VOYAGE-1 and VOYAGE-2), SVR rates were 97.2% (95% CI 95.5–98.9%) with 8-week therapy in non-cirrhotic patients and 99.4% (95% CI 98.2–100%) in cirrhotic patients treated for 12 or 16 weeks [
94]. A pooled analysis of five Korean studies reported an SVR rate of 98.8% (95% CI 96.7–99.6%), including 32.5% of patients with prior treatment experience. Among cirrhotic patients, the SVR rate was 98.7% (95% CI 96.2–99.6%) [
170]. Initially, 12-week treatment was preferred in patients with compensated cirrhosis; however, the EXPEDITION-8 trial demonstrated that 8-week therapy yielded an SVR rate of 97.7% (95% CI 96.1–99.3%) in such a population [
161]. Accordingly, 8-week treatment is now recommended for all genotypes regardless of cirrhosis status.
In genotype 3 treatment-naïve, non-cirrhotic patients, SVR with 8-week treatment is approximately 95% (95% CI 92–98%) [
189]. In contrast, treatment-experienced genotype 3 patients achieve an SVR of 91% (95% CI 72–97%) with 12-week therapy, indicating that a 16-week regimen may be preferred irrespective of cirrhosis to achieve optimal outcomes (95–96%) (See the “Retreatment” section) [
190].
This regimen is contraindicated in decompensated cirrhosis due to its protease inhibitor component.
Adverse events and safety
The most frequently reported adverse events are headache and fatigue, which are typically mild and self-limiting.
Sofosbuvir/velpatasvir/voxilaprevir
Sofosbuvir (400 mg; NS5B polymerase inhibitor), velpatasvir (100 mg; NS5A inhibitor), and voxilaprevir (100 mg; NS3/4A protease inhibitor) are co-formulated into a single tablet, administered once daily orally with or without food. This regimen is not recommended as a first-line pan-genotypic treatment. It is indicated for patients with prior failure of NS5A inhibitor-containing regimens, genotype 3 infection with compensated cirrhosis, or detectable NS5A RASs. The recommended treatment duration is 12 weeks.
Pharmacokinetics
Voxilaprevir is primarily metabolized by CYP3A4 and eliminated via the biliary route. Compared to individuals with normal hepatic function, its AUC is increased by 1.7-fold in Child–Pugh A, 3-fold in Child–Pugh B, and 5-fold in Child–Pugh C. Therefore, this regimen is contraindicated in patients with decompensated cirrhosis (Child–Pugh B or C). No dose adjustment is required in patients with renal impairment, including those on dialysis.
Drug interactions
Sofosbuvir, velpatasvir, and voxilaprevir are substrates of P-gp and BCRP. Voxilaprevir is additionally a substrate of OATP1B1/1B3. Strong or moderate inducers of P-gp or CYP enzymes (e.g., carbamazepine, phenytoin, rifampin, efavirenz, St. John’s wort) reduce drug exposure and are contraindicated. OATP inhibitors such as atazanavir, lopinavir, and cyclosporine markedly increase voxilaprevir levels and are also contraindicated.
Medications that increase gastric pH, such as antacids, H2 receptor antagonists, and proton pump inhibitors, may reduce velpatasvir and voxilaprevir absorption and should be used with caution.
Velpatasvir and voxilaprevir inhibit P-gp, BCRP, and OATP1B1/1B3; velpatasvir also inhibits OATP2B1. Co-administration with substrates of these transporters may elevate their plasma levels. Contraindicated drugs include statins (e.g., atorvastatin, rosuvastatin, simvastatin), anticancer agents (e.g., topotecan, irinotecan), and dabigatran.
Amiodarone coadministration is contraindicated due to the risk of life-threatening bradycardia. If unavoidable, close monitoring is warranted. When used with digoxin, serum levels should be monitored. Tenofovir-containing regimens and lipid-lowering agents (e.g., ezetimibe, pravastatin) may require dose adjustment and monitoring. Ethinyl estradiol-containing oral contraceptives are contraindicated due to an increased risk of ALT elevation.
Efficacy
Studies have evaluated whether an 8-week course of sofosbuvir/velpatasvir/voxilaprevir could serve as an alternative to the standard 12-week sofosbuvir/velpatasvir regimen in treatment-naïve patients. Nevertheless, the shorter regimen demonstrated slightly lower efficacy. In the POLARIS-2 and POLARIS-3 trials [
191], which compared 8 weeks of sofosbuvir/velpatasvir/voxilaprevir to 12 weeks of sofosbuvir/velpatasvir according to cirrhosis status, SVR rates with the 8-week regimen were 95% (95% CI 93–97%) in non-cirrhotic patients and 96% (95% CI 91–99%) in those with cirrhosis. Although efficacy was high, the 8-week regimen did not demonstrate non-inferiority to the 12-week sofosbuvir/velpatasvir regimen, which achieved SVR rates of 98% in non-cirrhotic and 96% in cirrhotic patients. In particular, among genotype 1a patients, the SVR rate with the 8-week regimen was 92%, compared to 99% with 12 weeks of sofosbuvir/velpatasvir, further supporting the preference for the 12-week regimen as first-line therapy.
Therefore, sofosbuvir/velpatasvir/voxilaprevir is mainly reserved for patients with limited treatment options, such as those with genotype 3 infection with compensated cirrhosis and baseline Y93H RAS to velpatasvir, prior treatment failure with cirrhosis, and those who failed NS5A inhibitor-containing regimens.
Adverse events and safety
Common adverse events include headache, fatigue, diarrhea, and nausea, with incidence rates similar to those observed with placebo.
Commonly used medications in Korea and their potential drug-drug interactions with DAAs are summarized in
Table 6. For the most current information on drug interactions, clinicians should refer to www.hep-druginteractions. org or the official prescribing information.
[Recommendation]
1. In treatment-naïve patients without cirrhosis or with compensated cirrhosis, a simplified treatment strategy using either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks is recommended, regardless of genotype. (A1)
2. Before initiating DAAs, potential drug-drug interactions should be carefully assessed to ensure safety and efficacy. (A1)
Post-treatment assessment and monitoring
Even after achieving SVR, patients with pre-treatment cirrhosis or advanced liver fibrosis remain at risk for HCC. A meta-analysis evaluating patients who achieved SVR following DAA therapy reported an HCC incidence of 0.47 per 100 person-years in individuals without cirrhosis, compared to a significantly higher rate of 2.99 per 100 person-years in those with cirrhosis [
192]. Similarly, a multicenter Korean study found that cirrhosis was significantly associated with an increased risk of HCC development [
124,
193], as well as increased rates of liver transplantation and mortality [
124]. In a retrospective European multicenter study of patients with compensated advanced chronic liver disease who achieved SVR, 3.6% developed hepatic decompensation and 7.8% developed HCC during a median follow-up of six years [
194]. Accordingly, patients with cirrhosis or advanced fibrosis should undergo continued surveillance for HCC and monitoring for cirrhosis-related complications, even after achieving SVR. In contrast, patients without advanced fibrosis have a low incidence of HCC, and routine surveillance s not recommended due to its limited cost-effectiveness.
Recent meta-analyses have evaluated the utility of non-invasive tests in predicting the risk of HCC following SVR. A pre-treatment liver stiffness measurement (LSM) >12.6 kPa and a fibrosis-4 (FIB-4) index >3.25 demonstrated AUC values of 0.79 and 0.73, respectively. Post-treatment LSM values >11.2 kPa and FIB-4 values >3.25 yielded AUCs of 0.77 and 0.70, respectively [
195]. These results support the use of non-invasive assessments, both prior to and following antiviral therapy, to identify patients who may benefit from HCC surveillance. Additionally, despite achieving SVR, patients with continued excessive alcohol intake or coexisting MASLD remain at risk for disease progression and require continued management of these risk factors [
150,
196,
197]. In contrast, patients who fail to achieve SVR are at significantly higher risk for liver disease progression and HCC development compared to those who achieve SVR [
198].
Reinfection with HCV may occur following re-exposure, particularly among PWID [
199-
201] and those with HIV and HCV coinfection [
202]. Rossi et al. [
201] reported that PWID within three years prior to SVR experienced an 8.1-fold higher reinfection rate than non-PWID. Similarly, Johannesson et al. [
200] reported that recent use of injected drug within the past six months was significantly associated with an increased risk of reinfection (HR 2.84; 95% CI 1.32–6.13;
P=0.008). Huang et al. [
203] demonstrated a reinfection rate of 23.25 per 1,000 person-years (95% CI 4.24–53.39) in patients with HIV and HCV coinfection, which was substantially higher than that observed in the HCV monoinfected population (0.89 per 1,000 person-years; 95% CI 0.16–2.03). Accordingly, patients at high risk for reinfection should undergo regular HCV RNA monitoring after achieving SVR.
[Recommendation]
1. Patients with pre-treatment cirrhosis (A1) or advanced fibrosis (B1) should continue HCC surveillance and monitoring for cirrhosis-related complications, even after achieving SVR.
2. Patients with ongoing excessive alcohol consumption or coexisting MASLD require continued management of these factors following SVR. (B1)
3. Patients who fail to achieve SVR should receive the same management as those with chronic hepatitis or cirrhosis. (B1)
4. Patients at high risk of reinfection should undergo regular HCV RNA monitoring after achieving SVR. (B1)
Retreatment of DAA failures
Although the SVR rates following DAA therapy currently exceed 95% [
204], a subset of patients may experience virologic failure (i.e., failure to achieve an SVR) and require retreatment. During the interferon era, treatment failure occurred more frequently due to various reasons, including early discontinuation caused by adverse effects, non-response, partial response, virological breakthrough during treatment, or relapse after treatment. In contrast, DAA regimens are well tolerated, and early discontinuation is rare. The incidence of non-response or on-treatment failure is extremely low, at approximately 0.3% [
176]. Excluding cases of poor adherence or loss to follow-up, failure rates following treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir were approximately 1.0–1.2%, with relapse the predominant form of treatment failure [
162,
176].
Distinguishing between relapse and reinfection
In patients with renewed detection of HCV RNA after previously achieving an undetectable level following DAA therapy, recurrent HCV infection may result from either relapse, defined as reactivation of the original virus after treatment cessation [
115], or reinfection, which refers to new viral acquisition after achieving SVR [
205]. Although reinfection typically allows reapplication of the standard first-line regimen and requires reassessment of preventive strategies, relapse often requires a more robust salvage regimen. Therefore, distinguishing between relapse and reinfection is clinically critical [
136].
Clinically, relapses usually occur within 4 to 12 weeks after treatment completion, as the residual virus replicates rapidly, resulting in SVR failure. In contrast, reinfection can occur at any time after achieving an SVR and is commonly associated with ongoing high-risk behaviors such as intravenous drug use or exposure to non-sterile procedures, including tattooing, acupuncture, or body piercing [
205]. In the absence of known risk factors for reinfection, relapse is more likely; however, continued exposure to risk factors increases the likelihood of reinfection [
79]. Notably, early reinfection (shortly after DAA-induced SVR) or late relapse (more than one year post-SVR), particularly in immunocompromised patients such as those with HIV coinfection, may occur [
206]. Consequently, distinguishing between relapse and reinfection based solely on clinical information can be challenging.
In such cases, comparing HCV genotypes before and after recurrence is helpful. A different genotype after therapy indicates reinfection [
79,
116]. If the genotype remains the same, NGS and phylogenetic analysis may be employed to differentiate relapse from reinfection [
118,
207]. However, these methods are not feasible in routine clinical practice due to limitations in cost, time, and availability. Furthermore, simplified treatment strategies often omit baseline genotyping, preventing post-treatment genotype comparison.
When relapse and reinfection cannot be definitively distinguished, it is advisable to assume relapse and initiate retreatment with a salvage regimen that has a high barrier to resistance. This conservative approach minimizes the risk of treatment failure in true relapse cases, while the use of a salvage regimen in reinfection does not compromise efficacy. Therefore, when the distinction is unclear, managing retreatment as relapse is a reasonable and effective strategy [
136].
Considerations before retreatment
When planning retreatment for a patient who failed previous therapy, it is necessary to comprehensively evaluate contributing factors, which include patient-, viral-, and drug-related factors. Patient-related factors include poor adherence, drug–drug interactions, presence of cirrhosis or impaired liver function, and comorbidities. Viral factors include HCV genotype (particularly genotype 3) and RAS [
79,
208]. In addition, inadequate treatment duration and use of regimens with a low genetic barrier to resistance are also potential contributors to failure. Therefore, retreatment regimen should be based on a careful review of prior treatment history and of potential failure mechanisms.
RAS has historically been considered a major cause of DAA treatment failure. If pre-treatment resistance testing is available, it may assist in the selection of an optimal regimen [
79]. However, current standard salvage regimens possess a high barrier to resistance, and the presence of RAS has not been shown to significantly affect retreatment success rates [
116,
209]. For example, in the POLARIS-1 study, which included 146 patients with genotype 1 infection who had previously failed an NS5A-containing regimen, most exhibited NS3/4A or NS5A RAS, but retreatment with sofosbuvir/velpatasvir/voxilaprevir achieved high SVR rates of 96–100%, and the presence of RAS was not a significant predictor of treatment response [
210]. In the context of current retreatment regimens, the clinical value of RAS testing is limited. Moreover, RAS testing is not standardized and may not be widely available; therefore, retreatment regimens often are chosen without routine resistance testing [
116].
Retreatment regimens
Treatment failure with sofosbuvir-based regimens
In patients who fail sofosbuvir-based therapy, the triple combination of sofosbuvir/velpatasvir/voxilaprevir has demonstrated high treatment success rates. In the POLARIS-1 trial, which enrolled 263 patients who had failed prior DAA regimens including an NS5A inhibitor, the SVR rate following 12 weeks of sofosbuvir/velpatasvir/voxilaprevir was 96% (253/263) [
210]. Patients without evidence of cirrhosis achieved an SVR rate of 99%, compared with 93% among those with cirrhosis. Neither HCV genotype nor the baseline RAS profile significantly influenced treatment outcomes. In the deferred treatment arm of the same study (POLARIS-1), which included patients initially randomized to placebo, the overall SVR rate was 97% (143/147), and 96% (73/76) had experienced prior failure of sofosbuvir/NS5A inhibitor-containing regimens [
211]. In the POLARIS-4 trial, which included patients who had failed DAA regimens not containing an NS5A inhibitor, the SVR rate for 12 weeks of sofosbuvir/velpatasvir/voxilaprevir was 98% (178/182), with no significant difference according to the presence of NS3 or NS5A RAS [
210]. A meta-analysis including 2,887 patients across nine clinical trials and 15 real-world studies reported an overall SVR rate of 95% with sofosbuvir/velpatasvir/voxilaprevir. However, lower SVR rates were observed in specific subgroups, including patients with genotype 3 (86.1%), those with cirrhosis (88.8%), those with prior treatment with sofosbuvir/velpatasvir (84.1%), and patients with HCC (71.1%) [
212]. The presence of baseline RAS did not correlate with treatment outcomes. Accordingly, a 12-week regimen of sofosbuvir/velpatasvir/voxilaprevir is the preferred retreatment regimen in patients who have failed a sofosbuvir-based regimen with an NS5A inhibitor. However, in patients infected with genotype 3 and compensated cirrhosis, who show higher treatment failure rates [
213,
214], the addition of ribavirin to the regimen for 12 weeks is recommended. If ribavirin is contraindicated, extending the treatment duration to 24 weeks may be considered [
116].
In patients who failed a sofosbuvir-based regimen without prior exposure to an NS3/4A protease inhibitor, glecaprevir/pibrentasvir for 16 weeks may be considered as an alternative retreatment option [
116]. However, this regimen is not appropriate for those previously treated with an NS3/4A protease inhibitor due to potential resistance. A phase 2 study of 42 patients with genotype 1 (79% subtype 1a, 24% with cirrhosis), who had failed NS5A- or NS3/4A-containing regimens, achieved an SVR rate of 94% (16/17) following a 16-week treatment with glecaprevir/pibrentasvir [
215,
216]. In a phase 3b trial of genotype 1 patients who failed sofosbuvir/NS5A-based therapy, a 16-week treatment with glecaprevir/pibrentasvir (with ribavirin added for those with cirrhosis) resulted in SVR rates of 94% in non-cirrhotic and 97% in cirrhotic patients [
217]. The outcomes were superior to those in the 12-week treatment group, which showed SVR rates of 90% and 86%, respectively. However, no benefit was noted with ribavirin addition. These data suggest glecaprevir/pibrentasvir for 16 weeks as an effective retreatment option for patients who failed sofosbuvir/NS5A-based regimens, particularly in those with genotype 1. This regimen is not recommended for genotype 3 patients due to insufficient evidence [
116].
There is limited evidence regarding retreatment in patients with decompensated cirrhosis who previously failed sofosbuvir-based therapy. In a small study evaluating a 24-week course of sofosbuvir/velpatasvir with ribavirin, the SVR rate in cirrhotic patients was 78% (14/18), suggesting that DAA-based retreatment may be effective in this population [
218].
Treatment failure with glecaprevir/pibrentasvir
For patients who have failed prior treatment with glecaprevir/pibrentasvir, a 12-week regimen of sofosbuvir/velpatasvir/voxilaprevir has demonstrated efficacy as a retreatment strategy. In a prospective observational study involving 31 patients who had failed glecaprevir/pibrentasvir, the SVR rate following a 12-week sofosbuvir/velpatasvir/voxilaprevir regimen was 94% (29/31), with only two patients experiencing relapses four weeks after treatment completion [
219]. In a multinational retrospective study involving 52 patients who had failed glecaprevir/pibrentasvir (9 of whom received ribavirin), the SVR rate following 12 to 24 weeks of sofosbuvir/velpatasvir/voxilaprevir treatment was 97.8% [
220]. Another multicenter retrospective study reported a 90.2% (37/41) SVR rate after 12 weeks of sofosbuvir/velpatasvir/voxilaprevir [
221]. Although these studies did not systematically evaluate the benefit of ribavirin or treatment extension, patients with genotype 3 infection and cirrhosis were associated with lower treatment success rates [
220]. In contrast, no treatment failures were reported among patients who received ribavirin-containing regimens [
221]. Thus, in patients with genotype 3 or cirrhosis, treatment with sofosbuvir/velpatasvir/voxilaprevir plus ribavirin for 12 weeks is recommended [
116]. If ribavirin cannot be used, the treatment duration may be extended to 24 weeks.
Additionally, the combination of sofosbuvir, glecaprevir/pibrentasvir, and ribavirin may be considered as a retreatment option in patients who have failed prior glecaprevir/pibrentasvir therapy. In the phase 3b MAGELLAN-3 trial, patients with genotypes 1, 2, 4, 5, or 6 who had no history of NS3 protease or NS5A inhibitor exposure and no cirrhosis received a 12-week course of sofosbuvir, glecaprevir/pibrentasvir, and ribavirin [
222]. Patients with genotype 3 infection, cirrhosis, or prior exposure to a protease/NS5A inhibitor (e.g., glecaprevir/pibrentasvir) received 16 weeks of treatment. The overall SVR rate was 96% (22/23), with a single relapse observed in a patient with genotype 1a infection, cirrhosis, and a complex RAS profile. Thus, 16 weeks of sofosbuvir, glecaprevir/pibrentasvir, and ribavirin may be considered for the retreatment of patients who have failed glecaprevir/pibrentasvir.
Treatment failure with multiple DAA regimens
Evidence regarding retreatment options for patients who fail multiple DAA regimens, including combinations such as sofosbuvir/velpatasvir/voxilaprevir and sofosbuvir plus glecaprevir/pibrentasvir, is currently limited. As mentioned above, the MAGELLAN-3 study reported a 96% (22/23) SVR rate following 12 to 16 weeks of the sofosbuvir, glecaprevir/pibrentasvir, and ribavirin combination in patients with various prior DAA exposure [
222]. Notably, the study did not include patients who had failed treatment with sofosbuvir/velpatasvir/voxilaprevir. In a multinational retrospective study of patients who had failed sofosbuvir/velpatasvir/voxilaprevir, various rescue regimens were applied, including sofosbuvir/velpatasvir/voxilaprevir with or without ribavirin (4 patients); glecaprevir/pibrentasvir (2 patients); sofosbuvir plus glecaprevir/pibrentasvir with or without ribavirin (15 patients); and sofosbuvir/velpatasvir plus ribavirin (1 patient) [
223]. Treatment durations ranged from 12 to 24 weeks, with an overall SVR rate of 81%.
Additional case reports have demonstrated that extended treatment durations may be beneficial in select refractory cases. One case report demonstrated successful SVR following 24 weeks of sofosbuvir, glecaprevir/pibrentasvir, and ribavirin [
224], while another described that 52 weeks of sequential DAA regimens were required to achieve an SVR [
225]. These findings suggest that prolonged treatment durations (>24 weeks) may be necessary in some difficult-to-treat cases, although robust supporting data are limited. Future recommendations may evolve as new clinical trial results become available.
In summary, retreatment following DAA failure should be individualized based on prior treatment history, HCV genotype, and the severity of the underlying liver disease. For most patients, sofosbuvir/velpatasvir/voxilaprevir is the recommended regimen, with the addition of ribavirin or treatment extension in those with cirrhosis. For patients who fail multiple DAA regimens, treatment should be guided by expert consultation due to limited evidence.
[Recommendation]
General recommendations
1. When retreating patients after treatment failure, the selection of the retreatment regimen should consider previously administered agents, the HCV genotype, the presence of cirrhosis, and liver function. The selected retreatment regimen should rely on currently available agents with proven efficacy. (A1)
2. For patients in whom it is clinically difficult to distinguish whether virologic failure is due to relapse or reinfection, retreatment can be guided by the assumption of relapse. (C2)
Retreatment following sofosbuvir-based treatment failure
1. Patients with HCV genotypes 1, 2, 4, 5, or 6 without cirrhosis or with compensated cirrhosis
(1) Patients should be treated with sofosbuvir/velpatasvir/voxilaprevir for 12 weeks. (A1)
(2) In patients without prior exposure to NS5A inhibitors or NS3/4A protease inhibitors, treatment with glecaprevir/pibrentasvir for 16 weeks should be considered. (A1)
2. Patients with HCV genotype 3 with or without compensated cirrhosis
(1) Patients without cirrhosis should be treated with sofosbuvir/velpatasvir/voxilaprevir for 12 weeks. (A1)
(2) Patients with cirrhosis should be treated with sofosbuvir/velpatasvir/voxilaprevir plus weight-based ribavirin for 12 weeks. (A1) Patients with contraindications to the use of ribavirin or who experience poor tolerance may be treated with sofosbuvir/velpatasvir/voxilaprevir alone for 24 weeks. (C2)
3. Patients with HCV genotypes 1–6 infection who have decompensated cirrhosis may be treated with sofosbuvir/velpatasvir plus weight-based ribavirin for 24 weeks. (C2)
Retreatment following glecaprevir/pibrentasvir treatment failure
1. Patients with HCV genotypes 1–6, with or without compensated cirrhosis
(1) Patients without cirrhosis can be treated with sofosbuvir/velpatasvir/voxilaprevir for 12 weeks. (B1) Patients with HCV genotype 3 infection or with evidence of cirrhosis may be treated with sofosbuvir/velpatasvir/voxilaprevir plus weight-based ribavirin for 12 weeks or with sofosbuvir/velpatasvir/voxilaprevir alone for 24 weeks if ribavirin is contraindicated or poorly tolerated. (C2)
(2) Patients can be treated with sofosbuvir, glecaprevir/pibrentasvir plus weight-based ribavirin for 16 weeks. (B1)
Retreatment following failure of multiple DAA regimens
1. Patients with HCV genotypes 1–6 with or without compensated cirrhosis
(1) Patients can be treated with sofosbuvir/velpatasvir/voxilaprevir plus weight-based ribavirin for 24 weeks. (B1)
(2) Patients can be treated with glecaprevir/pibrentasvir plus sofosbuvir and weight-based ribavirin for 16 weeks. (B1) Extending treatment to 24 weeks is recommended for patients with cirrhosis and HCV genotype 3 infection or those with prior failure with the combination of glecaprevir/pibrentasvir plus sofosbuvir. (B1)
TREATMENT IN SPECIAL POPULATIONS
Decompensated cirrhosis
Liver transplantation is the only definitive treatment for patients with decompensated cirrhosis. Prognosis in this population varies significantly depending on the recurrence of complications related to portal hypertension and fluctuations in the model for end-stage liver disease (MELD) score [
226]. Anticipated waiting time for liver transplantation also may differ depending on institutional policy or individual clinical circumstances. Therefore, in patients with decompensated cirrhosis and concurrent HCV infection, the timing of antiviral therapy should be determined based on the indication for liver transplantation, donor availability, the feasibility of transplantation, and residual liver function.
Supporting evidence from an international study includes a cohort of 149 patients with Child–Pugh class B or C who were treated with DAAs, reporting an overall SVR rate of 81%. For genotypes 1 and 2, which are the most prevalent in Korea, the SVR rates were 84.8% and 87.5%, respectively. Achievement of SVR and a reduction in the MELD score by ≥2 points were identified as the key factors associated with improved outcomes, including hepatic decompensation, HCC, liver transplantation, and mortality [
227]. In another study involving patients with advanced liver disease or decompensated cirrhosis, defined as MELD score ≥10 or complications due to portal hypertension, an SVR rate of 90.5% was achieved. Among these patients, 24% exhibited a ≥3-point improvement in MELD score within six months, and 29% showed sustained improvement lasting more than four years. Ultimately, 25% of patients achieved a MELD score ≤10 [
228]. A Japanese study of 65 patients with genotype 1 or 2 and Child–Pugh class B or C treated with sofosbuvir/velpatasvir reported an SVR rate of 92.2%. Among those who achieved SVR, 22.7% showed a ≥3-point improvement in MELD score. Additionally, there were significant improvements in Child–Pugh and albumin-bilirubin grades following antiviral therapy [
229].
Collectively, these studies suggest that treatment with DAAs in patients with decompensated cirrhosis, including those with Child–Pugh class C, leads to improvement in clinical status and biochemical markers in most cases [
230-
232]. Despite these benefits, patients with more advanced baseline liver disease may experience liver-related mortality or require transplantation even after achieving SVR [
233]. Although available predictive data are limited, patients with MELD scores >20 or severe complications from portal hypertension may be better suited for liver transplantation as a first-line approach rather than antiviral therapy [
234,
235]. Furthermore, for patients expected to undergo liver transplantation within three months, it is recommended to prioritize liver transplantation and consider antiviral therapy after transplantation based on the presence of HCV recurrence [
235].
Protease inhibitors can increase drug plasma concentrations and lead to toxicity in patients with advanced liver disease [
236]. For this reason, they are contraindicated in patients with a history of decompensated complications or with Child–Pugh class B or C cirrhosis. In general, patients with either a history of decompensated events or current decompensated cirrhosis (Child–Pugh class B or C) should be treated with a combination of sofosbuvir and an NS5A inhibitor, such as velpatasvir [
3]. The addition of ribavirin can further enhance the efficacy of DAA therapy in this population. When ribavirin is contraindicated or poorly tolerated, the duration of DAA treatment should be extended [
237]. In patients with decompensated cirrhosis, ribavirin is started at a dose of 600 mg per day and may be gradually titrated. A recent study from Japan reported that a 12-week regimen of sofosbuvir/velpatasvir without ribavirin in patients with decompensated cirrhosis achieved an SVR rate of 92.3% in those with genotypes 1 or 2, suggesting that this regimen may be effective even in the absence of ribavirin [
229].
In a study involving 276 patients with decompensated cirrhosis (Child–Pugh class B or C; 159 with genotype 1a, 48 with genotype 1b, 12 with genotype 2, 39 with genotype 3, and 8 with genotype 4), participants were randomly assigned to receive sofosbuvir/velpatasvir for 12 weeks, sofosbuvir/velpatasvir with ribavirin for 12 weeks, or sofosbuvir/velpatasvir for 24 weeks. The SVR rates were as follows: 88%, 94%, and 93% for genotype 1a; 89%, 100%, and 88% for genotype 1b; 100%, 100%, and 75% for genotype 2; 50%, 85%, and 50% for genotype 3; and 100%, 100%, and 100% for genotype 4, respectively. In another study with 102 patients with decompensated cirrhosis (80 with genotype 1, 21 with genotype 2, and 1 with genotype 3), patients were randomized to receive sofosbuvir/velpatasvir for 12 weeks or sofosbuvir/velpatasvir with ribavirin for 12 weeks. The SVR rates achieved were 98% and 87.5% for genotype 1 and 89% and 100% for genotype 2, while the single patient with genotype 3 who received sofosbuvir/velpatasvir and ribavirin therapy failed to achieve SVR [
238].
Currently, there is no real-world clinical data available for patients with decompensated cirrhosis in Korea. A retrospective real-world clinical study conducted in Taiwan included 107 patients with decompensated cirrhosis (47 with genotype 1, 37 with genotype 2, 10 with genotype 3, and 6 with genotype 6). Those patients were treated with sofosbuvir/velpatasvir and ribavirin for 12 weeks, achieving SVR rates of 91.5%, 88.1%, 90%, and 83.3%, respectively [
239]. In a Japanese real-world study involving 82 patients with decompensated cirrhosis (55 with genotype 1, 24 with genotype 2, 1 with genotype 3, 1 with genotype 1+2, and 1 unknown), treatment with sofosbuvir/velpatasvir for 12 weeks resulted in a 90% SVR rate [
240]. Another Japanese real-world study involving 72 patients with decompensated cirrhosis (50 with genotype 1 and 22 with genotype 2) reported an SVR rate of 95.8% following the same treatment regimen [
172].
[Recommendation]
1. All patients with decompensated cirrhosis (Child–Pugh class B or C) who are HCV RNA positive should be referred to a hepatology specialist or a liver transplantation center. (C1)
2. In cases of severe hepatic dysfunction, liver transplantation should be prioritized. If transplantation is not feasible due to limited availability or accessibility, treatment with a DAA regimen may be considered in patients with potential for hepatic function improvement. (B2)
3. In patients awaiting liver transplantation or those with advanced hepatic impairment, DAA therapy should be administered with close monitoring for adverse drug reactions and treatment-related toxicity. (B1)
4. Protease inhibitors should be avoided in patients with decompensated cirrhosis due to the increased risk of adverse events. (A1)
5. Patients with decompensated cirrhosis should be treated with a combination regimen of sofosbuvir/velpatasvir and ribavirin. Ribavirin should be initiated at 600 mg and titrated up to 1,200 mg in patients weighing ≥75 kg or to 1,000 mg in those weighing <75 kg. The total treatment duration should be 12 weeks. (A1) If ribavirin is contraindicated or not tolerated, a 24-week course of sofosbuvir/velpatasvir monotherapy is recommended. (A1)
6. In patients with genotype 1 or 2 and decompensated cirrhosis who are unable to receive ribavirin, a 12-week course of sofosbuvir/velpatasvir monotherapy may be considered as an alternative treatment option. (B2)
Chronic kidney disease
Patients with CKD and concurrent HCV infection exhibit a higher rate of progression to ESRD compared to uninfected individuals. Among patients undergoing hemodialysis, HCV infection is also associated with increased mortality [
241,
242]. Antiviral therapy for HCV has been shown to reduce the risk of dialysis and should be strongly considered in patients with CKD and HCV infection [
243]. For patients awaiting kidney transplantation, screening for anti-HCV is essential, as post-transplant immunosuppression may accelerate HCV-related liver injury. In patients with confirmed HCV infection, antiviral therapy should be considered because infected recipients demonstrate lower post-transplant survival rates and increased risks for complications such as post-transplant diabetes mellitus and glomerulonephritis compared to those who are uninfected [
244-
246].
The decision to initiate hepatitis C treatment in patients with CKD should be based on the severity of liver disease and the potential for treatment-related adverse effects, similar to patients with normal renal function. Given that patients with CKD are frequently prescribed multiple medications, potential drug-drug interactions should be carefully reviewed before starting antiviral therapy. Colchicine, which is commonly used for gout, has been reported to interact with glecaprevir/pibrentasvir and may induce rhabdomyolysis even with a 50% dose reduction [
247]. Therefore, in patients receiving colchicine, particularly those with impaired renal function, muscle-related adverse events should be closely monitored, and discontinuation of colchicine may be considered during DAA therapy [
247].
Sofosbuvir is primarily eliminated through renal excretion. As a result, the use of sofosbuvir-based regimens in patients with severe renal impairment (eGFR <30 mL/min/1.73 m
2) initially raised concerns regarding safety. In a phase 2 trial of 59 patients with ESRD on dialysis who received sofosbuvir/velpatasvir therapy for 12 weeks, plasma concentrations of the sofosbuvir metabolite GS-331007 increased by more than 20-fold. However, no increase in adverse events or mortality was observed in ESRD patients, similar to patients with preserved renal function [
175]. A large insurance claims-based study in the United States demonstrated that treatment with a sofosbuvir-based regimen did not increase the risk of dialysis compared to non-sofosbuvir-based regimens in patients with moderate to severe renal impairment [
248]. In another study conducted in India, 31 patients on dialysis achieved an SVR rate of 96.8% following treatment with sofosbuvir/velpatasvir. Dyspnea was the most commonly reported adverse event, but no serious drug-related toxicity was observed [
249]. A meta-analysis of 21 studies involving 717 patients with eGFR <30 mL/min/1.73 m
2 (58.4% on dialysis) reported an SVR rate of 97.1%, with a 4.8% rate of serious adverse events [
250]. In a Korean real-world retrospective study of 82 CKD patients treated with DAAs for 12 weeks, including 62 patients with eGFR 30–60 mL/min/1.73 m
2, 25 with eGFR <30 mL/min/1.73 m
2, and 22 on dialysis, the SVR rates were 91.9%, 91.6%, and 90.9%, respectively. No treatment-related serious adverse events or deterioration in renal function were reported [
251]. These findings support the use of a sofosbuvir-containing regimen across all stages of CKD without the need for dose adjustment [
252,
253].
[Recommendation]
1. In patients with CKD and concurrent HCV infection, treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir is recommended. The treatment duration should follow that used for patients with normal renal function. (A1)
2. In patients with a history of decompensated complications or decompensated cirrhosis (Child–Pugh class B or C) and severe renal impairment (eGFR <30 mL/min/1.73 m2), a 12-week course of sofosbuvir/velpatasvir with low-dose ribavirin (200 mg/day) is recommended. If ribavirin is contraindicated or not tolerated, a 24-week course of sofosbuvir/velpatasvir monotherapy may be considered. (B1)
Hepatocellular carcinoma
Before the introduction of DAAs, interferon-based therapies were associated with a reduced risk of recurrence in patients with HCV-associated HCC who achieved SVR following curative treatment. With the advent of DAAs, SVR rates have markedly improved. Early reports from small-scale studies, however, raised concerns that DAA therapy administered after curative treatment for HCC might be associated with an increased risk of tumor recurrence and more aggressive tumor behavior [
254]. Subsequent studies investigating the impact of DAAs on HCC recurrence have reported inconsistent results. Many of these studies were limited by small sample sizes and significant heterogeneity in patient characteristics, making it difficult to draw definitive conclusions. Nevertheless, a landmark analysis from a large North American cohort found no significant difference in recurrence rates between DAA-treated and untreated patients, with improved overall survival observed in the DAA-treated group [
255,
256]. In addition, a nationwide study using data from the Korean Health Insurance Review and Assessment Service showed that, among patients undergoing curative treatments such as hepatic resection or radiofrequency ablation, those who received DAAs exhibited a lower recurrence rate than untreated patients [
257]. Based on these findings, the timely initiation of DAA therapy in patients with cured HCV-related HCC is considered appropriate to prevent further liver disease progression and to improve survival outcomes.
Since most pivotal clinical trials evaluating the efficacy of DAAs excluded patients with HCC, data on treatment outcomes in this population remain limited. In a study by Prenner et al. [
258], treatment failure occurred more frequently in patients with HCV-related cirrhosis and HCC than in those without HCC (21% vs. 12%), with the highest rate (43%) observed in patients who had active HCC at the time of DAA therapy. The presence of active tumors was independently associated with treatment failure. Similarly, a study by Beste et al. [
259] reported SVR rates of 91% in patients without HCC, 74% in those with HCC, and 94% in those with a history of HCC who had undergone liver transplantation, suggesting that the presence of active HCC at the time of treatment may compromise efficacy. In contrast, a retrospective study from Taiwan found no significant difference in SVR between patients with cured and residual HCC (97.3% vs. 92.1%) [
260]. These findings suggest that patients with a complete response to HCC therapy may achieve favorable outcomes with DAAs, whereas the presence of residual tumors yields inconsistent results, precluding definitive interpretation.
According to the 2019 expert consensus by the American Gastroenterological Association, patients with HCC who are eligible for curative treatments such as hepatic resection or local ablative therapy should begin DAA therapy after achieving a confirmed complete response. A delay of 4 to 6 months following cancer treatment is considered acceptable to ensure tumor control [
261]. For patients not eligible for transplantation, hepatic resection, or local ablation but without vascular invasion or distant metastasis, transarterial chemoembolization (TACE) may be considered. Several studies have evaluated the efficacy of DAAs in this subgroup. In the study by Beste et al. [
259], among 244 patients undergoing TACE, the SVR rate with subsequent DAA therapy was 70%, although tumor response status was not reported. In contrast, a North American multicenter study reported an SVR rate of 89% (112/126) in patients who achieved a complete response to TACE prior to DAA therapy [
256]. In a Taiwanese cohort, all 46 patients without residual tumors post-TACE achieved SVR, as did 92% (22/24) of those with residual tumors [
262]. These findings support the use of DAA therapy in patients demonstrating a favorable tumor response following TACE, because it may preserve liver function and enable continued cancer treatment.
Data on DAA therapy in patients with advanced HCC involving vascular invasion or distant metastasis are sparse. An earlier study reported an SVR rate of 59% in patients treated with sorafenib [
259]. However, a more recent nationwide cohort study from Taiwan demonstrated a very high SVR rate of 94.9% in patients with advanced HCC classified as stage C according to the Barcelona Clinic Liver Cancer (BCLC) system. Importantly, achieving SVR was independently associated with improved overall survival, and this benefit was observed not only in early-stage HCC but also in BCLC stage B and C diseases [
263,
264]. These findings suggest that, although ongoing tumor progression may still compromise treatment efficacy [
265], patients with controlled or treatable disease may benefit from DAA therapy by preserving hepatic function and enabling continuation of anti-cancer treatment. Further prospective studies are warranted to clarify the survival benefit of DAA therapy in patients with advanced HCC.
[Recommendation]
1. In cured HCV-related HCC, DAA therapy is recommended to improve survival. (A1)
2. In patients eligible for hepatic resection or percutaneous local ablation for HCC, DAA therapy can be initiated after confirmation of a complete response to cancer treatment. (B1)
3. In patients who have undergone TACE and achieved complete or partial response with expected long-term survival, DAA therapy may be considered. (C1)
COINFECTIONS
Human immunodeficiency virus coinfection
HIV and HCV share similar transmission routes, and it is estimated that approximately 2.3 million people worldwide are coinfected with the two viruses. Among individuals living with HIV, the global prevalence of HCV coinfection is estimated to be around 6.2%, while that in South Korea ranges from 1.7% to 5.2% [
266-
268]. The prevalence of HCV coinfection in people with HIV varies by route of transmission, with a rate less than 10% among those infected through sexual contact and of approximately 80% among PWID [
266].
Compared to HCV monoinfection, patients coinfected with HIV and HCV typically exhibit higher HCV RNA levels and a lower rate of spontaneous viral clearance, with more than 90% progressing to chronic HCV infection [
269,
270]. Furthermore, liver fibrosis progresses more rapidly in this population, resulting in a higher risk of cirrhosis or HCC [
271]. The rate of liver disease progression becomes comparable to that observed in individuals with HCV monoinfection following the initiation of antiretroviral therapy [
272,
273].
Given the relatively high prevalence of coinfection, routine HCV screening is recommended for all HIV-infected individuals. Initial screening should be performed using anti-HCV testing [
274]. In patients with low CD4 cell counts, antibody production may be impaired; therefore, HCV RNA testing should be conducted in those with unexplained liver disease despite a negative anti-HCV result [
275]. For individuals at high risk, such as those engaging in high-risk sexual behaviors (e.g., multiple partners, anal intercourse, or sexual practices involving mucosal trauma) or those who inject drugs, annual HCV screening is recommended.
HCV treatment in coinfected patients follows the same principles as in HCV monoinfection. Pan-genotypic DAA regimens, such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, have demonstrated SVR rates exceeding 95% in treatment-naïve coinfected individuals [
276,
277]. For salvage therapy using sofosbuvir/velpatasvir/voxilaprevir, an SVR rate of 82.4% has been reported [
278]. In Korea, small retrospective studies have shown SVR rates ranging from 90.9% to 100% in coinfected patients receiving DAA therapy [
279,
280]. When treating HIV/HCV-coinfected patients, potential drug–drug interactions should be carefully reviewed (
Table 7), and co-management with an HIV specialist is recommended.
[Recommendation]
1. All individuals with HIV infection should be screened for anti-HCV. (A1)
2. HCV RNA testing should be performed in HIV-infected patients with unexplained liver disease, regardless of anti-HCV serostatus. (B1)
3. Patients with HIV/HCV coinfection should be treated with DAA therapy according to the same protocols used for HCV monoinfection. (A1)
4. When treating HCV in HIV/HCV-coinfected patients, potential drug–drug interactions must be carefully reviewed, and co-management with an HIV specialist is recommended. (A1)
Hepatitis B virus coinfection
In Korea, the prevalence of HBV coinfection among patients with chronic HCV infection is estimated to be approximately 2.4% to 3.0% [
54,
142]. Compared to monoinfection, patients with HBV/HCV coinfection tend to exhibit more severe hepatic inflammation, necrosis, and fibrosis. The risks of progression to cirrhosis, decompensated liver disease, and HCC are also significantly higher [
145,
281-
284]. Before initiating treatment in patients with HBV/HCV coinfection, quantitative testing for HBV DNA and HCV RNA should be performed. If HCV RNA is detectable, antiviral therapy for HCV should be initiated using pan-genotypic DAA regimens, following the same approach as in HCV monoinfection. If HBV DNA is detectable, antiviral therapy for HBV should be considered based on hepatitis B e antigen status, HBV DNA and ALT levels, and the degree of liver fibrosis. Treatment should follow the same principles as for HBV monoinfection, regardless of HCV RNA detectability.
The use of DAAs for treating HCV infection in HBV/HCV-coinfected patients may lead to HBV reactivation [
285-
287]. A meta-analysis reported that 14.1% of patients experienced either newly detectable HBV DNA or an increase from baseline within 4 to 12 weeks after initiating DAA therapy, and 12.2% experienced concurrent ALT elevation [
285]. In another meta-analysis, HBV reactivation (defined as a ≥2 log
10 IU/mL increase in HBV DNA from baseline) occurred in 24% of patients with chronic HBV infection. Among those with resolved HBV infection (HBsAg-negative and anti-HBc-positive), HBsAg seroreversion or detectable HBV DNA (≥20 IU/mL) was observed in 1.4% [
286]. Cases of liver failure and liver transplantation following HBV reactivation during or after DAA therapy have also been reported. Therefore, careful monitoring is recommended when administering DAAs to patients with HBV/HCV coinfection, and prophylactic antiviral therapy may be considered, particularly in those with detectable HBV DNA [
287]. For treatment of HBV in this population, entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) is recommended. When TDF is coadministered with sofosbuvir/velpatasvir, an increase in TDF plasma levels has been reported; thus, potential adverse effects such as renal function impairment should be closely monitored during therapy [
276].
[Recommendation]
1. In patients with HBV/HCV coinfection, each virus should be treated independently or concurrently according to the treatment principles applied to monoinfection. (A1)
2. The risk for HBV reactivation during or after DAA therapy should be monitored closely. If reactivation occurs, prompt initiation of anti-HBV therapy is recommended. (A1)
TRANSPLANTATION
Pre-transplant treatment
In nearly all patients with detectable HCV RNA at the time of liver transplantation, reinfection occurs within hours after the transplantation [
288]. Compared to those without HCV, patients with active HCV infection at the time of transplantation experience significantly higher rates of graft loss (HR 1.30; 95% CI 1.21–1.39) and mortality (HR 1.23; 95% CI 1.12–1.35) [
289]. If untreated, HCV can cause progressive injury of the transplanted liver, with cirrhosis developing in 2 to 30% of patients within one year. Complications of decompensated cirrhosis occur in 40% of patients within one year and in 70% within three years, contributing to poor outcomes [
290,
291]. Fibrosing cholestatic hepatitis develops in 5–10% of patients and may result in graft loss and mortality if not properly managed [
292]. Therefore, eradicating HCV before transplantation is crucial for improving graft survival and overall prognosis.
Beyond preventing post-transplant recurrence, pre-transplant DAA therapy can improve liver function and potentially reduce the need for liver transplantation or delay the timing of transplantation [
293]. In patients awaiting deceased donor transplantation, the timing of transplantation is unpredictable. If transplantation occurs during DAA therapy, the treatment duration may be incomplete. In Korea, where deceased donor liver transplantation is predominant, this unpredictability complicates decisions on timing of antiviral therapy. Among patients with decompensated cirrhosis receiving DAA therapy while awaiting transplantation, the overall SVR rate was reported to be 90.5%. Notably, 97% of those with a MELD score ≥21 and available virologic outcomes achieved SVR. However, when deaths occurring before SVR assessment were considered as treatment failures, the overall SVR rate decreased to 78.6% [
228].
Following antiviral therapy, improvement in biochemical parameters such as MELD and Child–Pugh scores may reflect improvement in liver function. A reduction in MELD score, however, may lower the patient’s priority on the transplant waiting list. Recent studies have demonstrated favorable outcomes with post-transplant DAA therapy. For patients with significantly impaired liver function, it may be preferable to proceed with transplantation before initiating antiviral treatment. In those with concomitant HCC eligible for transplantation, post-transplant DAA therapy has also been reported to be cost-effective [
294].
Patients with HCV infection after liver transplantation should undergo antiviral therapy. If fibrosing cholestatic hepatitis, advanced fibrosis, or portal hypertension develops, early initiation of antiviral therapy is strongly recommended, as these conditions are associated with rapid disease progression and a high risk of graft loss [
295,
296].
Due to the high prevalence of HCV in Western countries, transplantation from HCV RNA-positive donors has become increasingly common. Previously, organs from HCV RNA-positive donors were contraindicated for HCV-negative recipients. However, with the advent of DAAs, post-transplant DAA therapy has been shown to be both safe and effective. Recent studies indicate that the use of organs from HCV-positive donors is associated with shorter wait times for transplantation [
297,
298] and reduced disease-related mortality among recipients [
299-
301].
In a study of 43 patients with recurrent HCV infection after transplantation, sofosbuvir/velpatasvir achieved an SVR in 97.7% of patients [
302]. Among 79 recipients of liver grafts from HCV-positive donors, post-transplant antiviral therapy initiated at a median of 7.5 days (95% CI 0.3–23.9 days) resulted in an SVR rate of 96% [
303]. Similarly, glecaprevir/pibrentasvir achieved a 96% SVR rate in 25 patients with recurrent HCV infection after transplantation, with therapy initiated at a mean of 35 days (95% CI 1–179 days) after transplantation. Among these, 24% (6 patients) had prior experience with DAA therapy [
304]. Comparable results were reported in the MAGELLAN-2 study, which included 80 liver or kidney transplant recipients and demonstrated an SVR rate of 98% [
305].
Prospective studies evaluating the efficacy of sofosbuvir/velpatasvir/voxilaprevir after transplantation are currently insufficient. In one study, six patients, including those previously exposed to NS5A inhibitors, were treated with sofosbuvir/velpatasvir/voxilaprevir, and all achieved SVR [
302]. Further prospective studies involving larger cohorts are warranted to better define treatment efficacy.
A systematic review assessing DAA therapy after liver transplantation reported an SVR rate of 99.6% among 253 patients, suggesting that post-transplant antiviral therapy is highly effective and relatively safe [
306]. However, the optimal timing of treatment initiation has not yet been well-established. Only one study has investigated preemptive DAA therapy prior to HCV RNA detection in HCV RNA-negative recipients of HCV-positive donor livers, providing limited evidence [
306].
Because DAAs may interact with immunosuppressive agents, particularly protease inhibitors such as glecaprevir, careful monitoring and adjustment of immunosuppressant doses may be required. Early initiation of DAA therapy has been associated with acute kidney injury and treatment failure in some cases [
306,
307]. Therefore, it is generally considered safer to begin antiviral therapy after immunosuppressant dosing has stabilized. Both the American and European guidelines recommend close monitoring of immunosuppressant levels when using glecaprevir-based regimens following liver transplant [
79,
116].
In kidney transplant recipients with HCV infection, the progression of liver fibrosis and liver-related mortality are increased. HCV treatment was previously recommended prior to kidney transplantation [
308]. However, following the introduction of DAA therapy, accumulating evidence has demonstrated that post-transplant antiviral treatment is both safe and cost-effective. Even in recipients of kidneys from HCV RNA-positive donors, a 12-week course of DAA therapy has yielded excellent SVR rates [
288,
309,
310]. A meta-analysis of 16 studies including 557 recipients of kidneys from HCV-positive donors reported an overall SVR rate of 97.7%, and the one-year graft survival rate was 97.6%, indicating that DAA therapy does not adversely affect transplant outcomes [
307].
In heart transplantation, a systematic review of 195 patients reported that 97% developed HCV infection after receiving a heart from an HCV-positive donor, but 100% achieved SVR following DAA therapy [
310]. Successful HCV treatment has also been documented after lung, pancreas, small intestine, and corneal transplants [
311]. Therefore, DAA therapy may be considered relatively safe in non-liver transplant recipients once immunosuppressant dosing has stabilized.
[Recommendation]
1. In patients with chronic HCV infection awaiting liver transplantation, treatment with DAAs is recommended to improve liver function and prevent post-transplant recurrence. (B1)
2. Patients with confirmed recurrent hepatitis C following liver transplantation should be prioritized for antiviral therapy. (A1)
3. In cases of recurrent hepatitis C after liver transplantation, a 12-week course of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir is recommended. (A1)
4. In patients with confirmed hepatitis C following non-liver organ transplantation, a 12-week course of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir is recommended. (A1)
5. In transplant recipients, DAA therapy should be initiated after stabilization of the immunosuppressive regimen, if clinically feasible. (C2)
PREGNANCY, BREASTFEEDING, AND PEDIATRIC PATIENTS
Preconception and perinatal transmission
In pregnant women with HCV infection, pregnancy-related complications such as preterm birth, low birth weight, congenital anomalies, and intrahepatic cholestasis of pregnancy (ICP) may occur [
312]. If HCV is not treated before or during pregnancy, maternal and fetal outcomes may be adversely affected. If ICP develops, immediate referral to a specialist is recommended [
313]. In cases of cirrhosis, the risk of preeclampsia, bleeding complications, preterm delivery, low birth weight, and fetal death increases significantly [
314]. Therefore, pregnant women with cirrhosis should undergo multidisciplinary counseling to assess pregnancy-related risks.
Infants born to mothers with HCV infection are at risk of exposure and vertical transmission (mother-to-child transmission, MTCT). Between 2011 and 2014, it is estimated that approximately 29,000 women with HCV infection gave birth worldwide [
116]. With the global rise in HCV prevalence, the incidence of vertical transmission is expected to increase. The seroprevalence of anti-HCV in pregnant women has been reported to range from 0.49% to 1.7% [
315,
316]. In Korea, two studies involving more than 20,000 and 5,000 pregnant women, respectively, reported anti-HCV positivity rates of 0.42% and 0.44%. Among those who tested positive, 57–60% had detectable HCV RNA [
317,
318].
In Western studies, among 2,514 pregnant women, 2.1% (54 women) were positive for HCV RNA. Among the 49 infants born to these mothers, 7 tested positive for HCV, corresponding to an MTCT rate of 14% [
319]. Previous studies estimated the perinatal transmission rate at 1–6.2% [
320,
321], but more recent data have reported rates as high as 5 to 15% [
319,
322]. The risk of transmission increases in a mother with HIV coinfection or an HCV RNA level ≥6 log
10 IU/mL [
52,
322,
323].
There is no clear evidence that cesarean section reduces the risk of MTCT of HCV [
324]. Although HCV RNA can be detected in breast milk, transmission via breastfeeding has not been documented; thus, breastfeeding is not contraindicated [
325]. However, breastfeeding is not recommended when there is direct exposure to maternal blood or body fluids, such as in cases of nipple injury or bleeding, or in mothers coinfected with HIV [
116].
As maternal anti-HCV can be passively transferred to the infant, anti-HCV testing is recommended after 18 months of age [
324,
326]. For earlier diagnosis, HCV RNA may be performed; however, its sensitivity is low (approximately 22%) within the first 1–2 months of life. Testing after 6 months of age is preferred, as sensitivity increases to greater than 85% [
326,
327].
In 2023, the American College of Obstetricians and Gynecologists (ACOG) recommended including HCV screening as part of routine prenatal evaluation [
328]. The AASLD also recommends that women with HCV receive antiviral therapy before pregnancy to reduce the risk of MTCT. In Korea, given the increasing adoption of universal HCV screening, screening may be considered during prenatal care for pregnant women with identifiable risk factors.
Current evidence is insufficient to support recommendations for the use of DAAs during pregnancy, due to limited clinical experience and a short history of use. A recent small prospective study investigated the use of sofosbuvir/ledipasvir in pregnant women with HCV. In that study, 26 women were treated during the second or third trimester, all achieved SVR, and no treatment-related adverse fetal outcomes were reported. Although HCV RNA was initially detected in four infants at four weeks of age, all tested negative by 12 weeks [
329]. A retrospective meta-analysis including 109 pregnant women treated with DAAs, including sofosbuvir/ledipasvir (n=37), sofosbuvir/velpatasvir (n=27), or glecaprevir/pibrentasvir (n=3), reported an overall SVR rate of 98.4%, with no fetal-related adverse events [
330]. Several prospective clinical trials, including the HIP-2 Study, STORC, and IMPAACT2041, are currently ongoing to evaluate the safety and efficacy of sofosbuvir/ledipasvir or glecaprevir/pibrentasvir during pregnancy.
The American and European liver societies suggest that antiviral therapy be considered during pregnancy only when clearly indicated. The ACOG and the Society for Maternal-Fetal Medicine currently recommend the use of DAA during pregnancy only within the context of clinical trials due to concerns regarding fetal safety. Considering the ongoing clinical trials and the low prevalence of hepatitis C among women of childbearing age in South Korea, routine use of DAA therapy during pregnancy is not currently recommended. Postpartum initiation of antiviral treatment is preferable when clinically appropriate.
Pediatric patients
Although the prevalence of chronic hepatitis C in children is relatively low, an estimated 3.5 to 5 million children are infected with HCV worldwide [
331,
332]. In the United States, the seroprevalence of anti-HCV has been reported as 0.2% among children aged 6–11 years (approximately 31,000 children) and 0.4% among adolescents aged 12–19 years (approximately 101,000 individuals) [
333].
In Korea, data on HCV infection among children and adolescents are still scarce. A 1995 study reported seroprevalence rates of 0.8% in children aged 6–11 years and 0.4% in those aged 16–24 years [
334]. According to the 2023 KNHANES, the anti-HCV positivity rate among individuals aged 10–19 years was 0.3% [
9]. Given the increasing prevalence of injection drug use and HCV infection in younger populations in Western countries, longitudinal studies are warranted to monitor trends in HCV prevalence among Korean children and adolescents.
Follow-up testing for HCV infection is recommended in infants born to HCV-infected mothers. To confirm infection, HCV RNA testing is recommended after 18 months of age [
335,
336]. Spontaneous viral clearance occurs in approximately 2–50% of infected infants by four years of age [
332,
337,
338]. Accordingly, the diagnosis of chronic hepatitis C in children is usually confirmed after the age of four. The diagnostic evaluation and testing protocols are consistent with those used in adults.
The natural history of HCV infection in children differs from that in adults. Children are more likely to achieve spontaneous viral clearance, maintain normal ALT levels [
339], exhibit slower progression of fibrosis, and experience a lower incidence of severe liver injury [
332,
340,
341]. Nevertheless, given their long life expectancy and potential risk of transmission to others, timely initiation of antiviral therapy is recommended in pediatric patients with HCV infection. The safety and efficacy of pediatric HCV treatment have been well established with the widespread use of DAAs. The cost-effectiveness of DAA treatment in children aged ≥6 years has also been demonstrated in Western countries [
342]. Based on these findings, the FDA approved the use of DAAs in children aged 3 to <18 years in 2019.
Although ribavirin is approved for use in pediatric patients, DAAs such as sofosbuvir/velpatasvir or glecaprevir/pibrentasvir are generally preferred due to their favorable efficacy and safety profiles. In a real-world study involving adolescents aged 12–18 years treated with sofosbuvir/ledipasvir (400/90 mg for 12 weeks), SVR was achieved in 98.7% of cases [
343]. In a cohort of 216 children aged 3–17 years, treatment with sofosbuvir/velpatasvir achieved an SVR rate of 92% [
344]. The most commonly reported adverse events included headache, fatigue, and nausea in adolescents (12–17 years); vomiting, cough, and headache in children aged 6–11 years; and vomiting in those aged 3–5 years. Similarly, in the DORA study involving 80 children aged 3–12 years, an 8-week course of glecaprevir/pibrentasvir achieved an SVR rate of 98%, with no serious adverse events reported, irrespective of HCV genotype [
345].
Weight-based dosing of DAAs is used in pediatric patients. Because there are potential concerns regarding the effects of DAA therapy on growth in adolescents, treatment duration is limited to 12 weeks for sofosbuvir/velpatasvir and 8 weeks for glecaprevir/pibrentasvir. Recommended dosing regimens are summarized in
Table 8 [
116].
[Recommendation]
1. Antiviral therapy during pregnancy may be considered on an individual basis, with careful assessment of maternal and fetal safety. Decisions should be made in consultation with a specialist. (B2)
2. To confirm HCV infection in infants, anti-HCV testing should be performed after 18 months of age due to the potential persistence of maternally derived antibodies. (B2)
3. Suspected HCV infection in pediatric patients should be diagnosed and evaluated according to the same protocols used in adults. (B1)
4. In pediatric patients aged ≥3 years with chronic hepatitis C, antiviral therapy is recommended using sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks, with weight-based dosing. (A1)
FOOTNOTES
-
Authors’ contributions
List of author contributions is available at the official website of Clinical and Molecular Hepatology (Supplementary Table 1, https://doi.org/10.3350/cmh.2025.0045).
-
Conflicts of Interest
A conflict of interest statement is available at the official website of Clinical and Molecular Hepatology (Supplementary Table 3, https://doi.org/10.3350/cmh.2025.0045).
SUPPLEMENTARY MATERIAL
Supplementary material is available at Clinical and Molecular Hepatology website (
http://www.e-cmh.org).
Figure 1.Age- and gender-specific anti-HCV positivity rates in South Korea, from 2019 to 2023.9 anti-HCV, antibody to hepatitis C virus. HCV, hepatitis C virus.
Figure 2.
Figure 3.Diagnostic algorithm for hepatitis C virus infection. HCV, hepatitis C virus; RNA, ribonucleic acid; SVR, sustained virological response. *Assessment should be based on objective sources such as medical records. In addition, repeat HCV RNA testing may be considered at the judgment of the physician. **If an alternative etiology of acute liver injury has been identified, deferral of repeat HCV RNA testing may be considered.
Table 1.Grading of Recommendations, Assessment, Development and Evaluation (adapted from the GRADE system) [
4-
6]
Table 1.
|
Quality of evidence |
Criteria |
|
High (A) |
Further research is very unlikely to change our confidence in the estimate of effect. |
|
Moderate (B) |
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. |
|
Low (C) |
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Any change of estimate is uncertain. |
|
Strength of recommendation
|
Criteria
|
|
Strong (1) |
Factors influencing the strength of the recommendation included the quality of the evidence, presumed patient-important outcomes, and cost. |
|
Weak (2) |
Variability in preference and values, or higher uncertainty. |
|
Recommendation is made with less certainty, higher cost or resource consumption. |
Table 2.Target populations for HCV infection screening [
65]
Table 2.
|
1) Individuals suspected of having acute or chronic HCV infection |
|
2) Individuals who have received blood/blood product transfusions or organ transplants prior to implementation of HCV screening |
|
3) Individuals with a history of injection drug use |
|
4) Individuals who have ever undergone hemodialysis |
|
5) Individuals with HIV infection |
|
6) Individuals with hemophilia |
|
7) Individuals with a sexual partner infected with HCV*
|
|
8) Children born to mothers infected with HCV |
|
9) Healthcare worker exposed to HCV-positive blood through needlestick injury or mucosal contact |
Table 3.Interpretation of HCV assays results [
65]
Table 3.
|
Anti-HCV |
HCV RNA |
Interpretation |
Recommendation |
|
Positive |
Positive |
Acute hepatitis C |
|
|
Chronic hepatitis C |
|
|
Positive |
Negative |
Resolved HCV infection |
Repeat anti-HCV and HCV RNA testing in 3-6 months |
|
Acute HCV infection during low-level viremia |
|
during low-level viremia |
|
False-positive anti-HCV test |
|
False-negative HCV RNA test |
|
Negative |
Positive |
Early acute HCV infection |
Repeat anti-HCV and HCV RNA testing in 3–6 months |
|
Chronic HCV infection in immunocompromised host |
|
False-positive HCV RNA test |
Table 4.Simplified HCV treatment strategies
Table 4.
|
Subjects for simplified HCV treatment |
Exclusion*
|
|
Indication |
Adults with HCV infection (any genotype) who meet both of the following: |
1) Prior HCV treatment |
|
1) No prior HCV treatment |
2) Hepatitis B virus coinfection |
|
2) No cirrhosis or compensated cirrhosis (Child–Pugh class A) |
3) Compensated cirrhosis with end-stage renal disease (eGFR<30 mL/min/1.73 m2) |
|
4) Current or prior decompensated cirrhosis (Child–Pugh score ≥7) |
|
5) Pregnancy |
|
6) Hepatocellular carcinoma |
|
7) Liver transplantation recipient |
|
Drugs |
Sofosbuvir/velpatasvir 1 tablet once daily for 12 weeks or glecaprevir/pibrentasvir 3 tablets once daily for 8 weeks |
|
Table 5.Direct acting antivirals for the HCV treatment
Table 5.
|
Product |
Brand name |
Presentation |
Posology |
|
Sofosbuvir/velpatasvir |
EPCLUSA®
|
Sofosbuvir 400 mg/velpatasvir 100 mg (1 tablet) |
1 tablet once daily, with or without food |
|
Glecaprevir/pibrentasvir |
MAVYRET®
|
Glecaprevir 100 mg/pibrentasvir 40 mg (1 tablet) |
3 tablets once daily, with food |
|
Sofosbuvir/velpatasvir/voxilaprevir |
VOSEVI®
|
Sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg (1 tablet) |
1 tablet once daily, with food |
|
Ribavirin |
VIRAMID®, RIBAVIRIN®
|
Ribavirin 200 mg (1 capsule) |
Body weight |
|
<75 kg; 1,000 mg/day (divided twice daily) |
|
≥75 kg; 1,200 mg/day (divided twice daily) |
Table 6.Drug-drug interaction of direct-acting antivirals
Table 6.
|
SOF |
SOF/VEL |
SOF/VEL/VOX |
GLE/PIB |
|
Lipid lowering agents |
|
|
|
|
|
Atorvastatin |
◆ |
■ |
■ |
X |
|
Pitavastatin |
◆ |
■ |
X |
■ |
|
Pravastatin |
◆ |
◆ |
■ |
■ |
|
Rosuvastatin |
◆ |
■ |
X |
■ |
|
Simvastatin |
◆ |
■ |
X |
X |
|
Fluvastatin |
◆ |
■ |
X |
■ |
|
Lovastatin |
◆ |
■ |
X |
X |
|
Ezetimibe |
◆ |
◆ |
■ |
■ |
|
Fenofibrate |
◆ |
◆ |
◆ |
◆ |
|
Bezafibrate |
◆ |
◆ |
◆ |
◆ |
|
Alirocumab |
◆ |
◆ |
◆ |
◆ |
|
Evolocumab |
◆ |
◆ |
◆ |
◆ |
|
Gemfibrozil |
◆ |
◆ |
◆ |
■ |
|
Antiarrhythmics |
|
|
|
|
|
Amiodarone |
X |
X |
X |
■ |
|
Digoxin |
◆ |
■ |
■ |
■ |
|
Flecainide |
◆ |
◆ |
◆ |
◆ |
|
Lidocaine (Lignocaine) |
◆ |
◆ |
◆ |
◆ |
|
Propafenone |
◆ |
◆ |
◆ |
◆ |
|
Quinidine |
◆ |
■ |
■ |
■ |
|
Vernakalant |
◆ |
◆ |
◆ |
◆ |
|
Beta blockers |
|
|
|
|
|
Atenolol |
◆ |
◆ |
◆ |
◆ |
|
Bisoprolol |
◆ |
◆ |
◆ |
◆ |
|
Carvedilol |
◆ |
■ |
■ |
■ |
|
Propranolol |
◆ |
◆ |
◆ |
◆ |
|
Calcium channel blockers |
|
|
|
|
|
Amlodipine |
◆ |
◆ |
◆ |
◆ |
|
Diltiazem |
◆ |
■ |
■ |
■ |
|
Nifedipine |
◆ |
◆ |
◆ |
◆ |
|
Verapamil |
◆ |
◆ |
■ |
■ |
|
Hypertension/heart failure agents |
|
|
|
|
|
Candesartan |
◆ |
◆ |
▲ |
▲ |
|
Irbesartan |
◆ |
◆ |
▲ |
■ |
|
Losartan |
◆ |
◆ |
◆ |
◆ |
|
Olmesartan |
◆ |
◆ |
■ |
■ |
|
Telmisartan |
◆ |
◆ |
■ |
■ |
|
Valsartan |
◆ |
◆ |
■ |
◆ |
|
Doxazosin |
◆ |
◆ |
◆ |
◆ |
|
Enalapril |
◆ |
◆ |
■ |
■ |
|
Amiloride |
◆ |
◆ |
◆ |
◆ |
|
Furosemide |
◆ |
◆ |
◆ |
◆ |
|
Spironolactone |
◆ |
◆ |
◆ |
◆ |
|
Torasemide |
◆ |
◆ |
◆ |
◆ |
|
Hydralazine |
◆ |
◆ |
◆ |
◆ |
|
Hydrochlorothiazide |
◆ |
◆ |
◆ |
◆ |
|
Bosentan |
◆ |
X |
X |
X |
|
Sildenafil |
◆ |
◆ |
◆ |
◆ |
|
Immunosuppressants |
|
|
|
|
|
Azathioprine |
◆ |
◆ |
◆ |
◆ |
|
Cyclosporine |
▲ |
▲ |
X |
■ |
|
Etanercept |
◆ |
◆ |
◆ |
◆ |
|
Infliximab |
◆ |
◆ |
◆ |
◆ |
|
Mycophenolate |
◆ |
◆ |
◆ |
◆ |
|
Sirolimus |
◆ |
◆ |
■ |
■ |
|
Tacrolimus |
▲ |
▲ |
▲ |
■ |
|
Anticoagulant, anti-platelet and fibrinolytic |
|
|
|
|
|
Apixaban |
◆ |
▲ |
▲ |
▲ |
|
Clopidogrel |
◆ |
◆ |
◆ |
◆ |
|
Dabigatran |
◆ |
■ |
X |
X |
|
Dalteparin |
◆ |
◆ |
◆ |
◆ |
|
Edoxaban |
◆ |
■ |
X |
■ |
|
Enoxaparin |
◆ |
◆ |
◆ |
◆ |
|
Heparin |
◆ |
◆ |
◆ |
◆ |
|
Rivaroxaban |
◆ |
■ |
■ |
■ |
|
Ticagrelor |
◆ |
■ |
■ |
■ |
|
Warfarin |
■ |
■ |
■ |
■ |
|
Anticonvulsants |
|
|
|
|
|
Carbamazepine |
■ |
■ |
X |
■ |
|
Clonazepam |
◆ |
◆ |
◆ |
◆ |
|
Eslicarbazepine |
◆ |
■ |
X |
■ |
|
Gabapentin |
◆ |
◆ |
◆ |
◆ |
|
Lamotrigine |
◆ |
◆ |
◆ |
◆ |
|
Levetiracetam |
◆ |
◆ |
◆ |
◆ |
|
Oxcarbazepine |
■ |
■ |
X |
■ |
|
Phenobarbital |
■ |
■ |
X |
■ |
|
Phenytoin |
■ |
■ |
X |
■ |
|
Pregabalin |
◆ |
◆ |
◆ |
◆ |
|
Primidone |
■ |
■ |
X |
■ |
|
Topiramate |
◆ |
◆ |
◆ |
◆ |
|
Valproic acid |
◆ |
◆ |
◆ |
◆ |
|
Zonisamide |
◆ |
◆ |
◆ |
◆ |
|
Antidiabetics |
|
|
|
|
|
Acarbose |
◆ |
◆ |
◆ |
◆ |
|
Dapagliflozin |
◆ |
◆ |
◆ |
◆ |
|
Dulaglutide |
◆ |
◆ |
◆ |
◆ |
|
Empagliflozin |
◆ |
■ |
■ |
◆ |
|
Gliclazide |
◆ |
◆ |
◆ |
◆ |
|
Glimepiride |
◆ |
◆ |
◆ |
◆ |
|
Glipizide |
◆ |
◆ |
◆ |
◆ |
|
Insulin |
◆ |
◆ |
◆ |
◆ |
|
Linagliptin |
◆ |
◆ |
◆ |
◆ |
|
Liraglutide |
◆ |
◆ |
◆ |
◆ |
|
Metformin |
◆ |
◆ |
◆ |
◆ |
|
Pioglitazone |
◆ |
◆ |
◆ |
◆ |
|
Rosiglitazone |
◆ |
◆ |
◆ |
◆ |
|
Saxagliptin |
◆ |
◆ |
◆ |
◆ |
|
Semaglutide |
◆ |
◆ |
◆ |
◆ |
|
Sitagliptin |
◆ |
◆ |
◆ |
◆ |
|
Tirzepatide |
◆ |
◆ |
◆ |
◆ |
|
Vildagliptin |
◆ |
◆ |
■ |
▲ |
|
Hepatitis nucleoside/tide analogues |
|
|
|
|
|
Entecavir |
◆ |
◆ |
◆ |
◆ |
|
Lamivudine |
◆ |
◆ |
◆ |
◆ |
|
Ribavirin |
◆ |
◆ |
■ |
◆ |
|
Tenofovir alafenamide |
◆ |
◆ |
◆ |
◆ |
|
Tenofovir disoproxil fumarate |
◆ |
■ |
■ |
◆ |
|
Antidepressants |
|
|
|
|
|
Amitriptyline |
◆ |
◆ |
◆ |
◆ |
|
Bupropion |
◆ |
◆ |
◆ |
◆ |
|
Duloxetine |
◆ |
◆ |
◆ |
◆ |
|
Escitalopram |
◆ |
◆ |
◆ |
◆ |
|
Fluoxetine |
◆ |
◆ |
◆ |
◆ |
|
Lithium |
◆ |
◆ |
◆ |
◆ |
|
Mirtazapine |
◆ |
◆ |
◆ |
◆ |
|
Nortriptyline |
◆ |
◆ |
◆ |
◆ |
|
Paroxetine |
◆ |
◆ |
◆ |
◆ |
|
Sertraline |
◆ |
◆ |
◆ |
◆ |
|
Trazodone |
◆ |
◆ |
◆ |
◆ |
|
Venlafaxine |
◆ |
◆ |
◆ |
◆ |
|
Antipsychotics/neuroleptics |
|
|
|
|
|
Amisulpride |
◆ |
◆ |
◆ |
◆ |
|
Aripiprazole |
◆ |
◆ |
◆ |
■ |
|
Chlorpromazine |
◆ |
◆ |
◆ |
◆ |
|
Clozapine |
◆ |
◆ |
◆ |
■ |
|
Haloperidol |
◆ |
◆ |
◆ |
◆ |
|
Olanzapine |
◆ |
◆ |
◆ |
◆ |
|
Paliperidone |
◆ |
■ |
■ |
■ |
|
Pimozide |
◆ |
◆ |
◆ |
X |
|
Promazine |
◆ |
◆ |
◆ |
◆ |
|
Quetiapine |
◆ |
◆ |
◆ |
■ |
|
Risperidone |
◆ |
▲ |
▲ |
▲ |
|
Sulpiride |
◆ |
◆ |
◆ |
◆ |
|
Zuclopentixol |
◆ |
◆ |
◆ |
◆ |
Table 7.Concomitant Use of HIV and HCV antiviral agents
Table 7.
|
HIV drugs |
HCV drugs |
|
SOF |
SOF/VEL |
SOF/VEL/VOX |
GLE/PIB |
|
NRTIs (nucleoside analogue reverse transcriptase inhibitor) |
|
|
|
ABC |
◆ |
◆ |
◆ |
◆ |
|
FTC |
◆ |
◆ |
◆ |
◆ |
|
TDF |
◆ |
■ |
■ |
◆ |
|
TAF |
◆ |
◆ |
◆ |
◆ |
|
PIs (protease inhibitor) |
|
|
|
|
|
ATV/r or ATV/c |
◆ |
◆ |
X |
X |
|
DRV/r |
◆ |
◆ |
■ |
X |
|
DRV/c |
◆ |
◆ |
◆ |
X |
|
LPV/r |
◆ |
◆ |
X |
X |
|
NNRTIs (non-nucleoside analogue reverse transcriptase inhibitor) |
|
|
|
DOR |
◆ |
◆ |
◆ |
◆ |
|
EFV |
◆ |
X |
X |
X |
|
ETR |
◆ |
X |
X |
X |
|
NVP |
◆ |
X |
X |
X |
|
RPV |
◆ |
◆ |
◆ |
◆ |
|
Entry/integrase inhibitors |
|
|
|
|
|
DTG |
◆ |
◆ |
◆ |
◆ |
|
CAB |
◆ |
◆ |
◆ |
◆ |
|
EVG/c/FTC/TDF |
◆ |
■ |
■ |
◆ |
|
EVG/c/FTC/TAF |
◆ |
◆ |
◆ |
◆ |
|
BIC/FTC/TAF |
◆ |
◆ |
◆ |
■ |
|
RAL |
◆ |
◆ |
◆ |
◆ |
|
MVC |
◆ |
◆ |
◆ |
◆ |
Table 8.Recommended doses of direct-acting antivirals for hepatitis C in pediatrics based on body weight
Table 8.
|
Body weight (kg) |
Sofosbuvir/velpatasvir (once daily, 12 weeks) |
|
<17 |
150 mg/37.5 mg |
|
17–30 |
200 mg/50 mg |
|
>30 |
400 mg/100 mg |
|
Glecaprevir/pibrentasvir (once daily, 8 weeks)
|
|
<20 |
150 mg/60 mg |
|
20–30 |
200 mg/80 mg |
|
30–45 |
250 mg/100 mg |
|
>45 and >12 years* |
300 mg/120 mg |
Abbreviations
American College of Obstetricians and Gynecologists
Appraisal of Guidelines for Research and Evaluation II
breast cancer resistance protein
chemiluminescent immunoassays
estimated glomerular filtration rate
Grading of Recommendations
human immunodeficiency virus
incremental cost-effectiveness ratio
intrahepatic cholestasis of pregnancy
Korean Association for the Study of the Liver
Korea Disease Control and Prevention Agency
Korea National Health and Nutrition Examination Survey
liver stiffness measurement
metabolic dysfunction-associated steatotic liver disease
model for end-stage liver disease
mother-to-child transmission
nucleic acid amplification test
next-generation sequencing
organic anion transporting polypeptide
quality-adjusted life year
resistance-associated substitutions
sustained virological response
transarterial chemoembolization
tenofovir disoproxil fumarate
UDP-glucuronosyltransferase
World Health Organization
REFERENCES
- 1. Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2014;20:89-136.
- 2. Korean Association for the Study of the Liver. KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2016;22:76-139.
- 3. Korean Association for the Study of the Liver (KASL). 2017 KASL clinical practice guidelines management of hepatitis C: Treatment of chronic hepatitis C. Clin Mol Hepatol 2018;24:169-229.
- 4. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011;64:383-394.
- 5. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011;64:401-406.
- 6. Andrews J, Guyatt G, Oxman AD, Alderson P, Dahm P, Falck-Ytter Y, et al. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol 2013;66:719-725.
- 7. Suh DJ, Jeong SH. Current status of hepatitis C virus infection in Korea. Intervirology 2006;49:70-75.
- 8. World Health Organization (WHO). Global hepatitis report 2024: action for access in low- and middle-income countries. WHO web site, <https://www.who.int/publications/i/item/9789240091672>. Accessed 9 Apr 2025.
- 9. Korea Disease Control and Prevention Agency. Korea Disease Control and Prevention Agency. National Health Statistics 2023: Korea National Health and Nutrition Examination Survey (KNHANES Ⅸ-2). Korea Disease Control and Prevention Agency web site, <https://knhanes.kdca.go.kr/knhanes/archive/wsiStatsClct.do> Accessed 12 Sep 2025.
- 10. Kim DY, Kim IH, Jeong SH, Cho YK, Lee JH, Jin YJ, et al. A nationwide seroepidemiology of hepatitis C virus infection in South Korea. Liver Int 2013;33:586-594.
- 11. Jang ES, Ki M, Choi HY, Kim KA, Jeong SH. The change in the nationwide seroprevalence of hepatitis C virus and the status of linkage to care in South Korea from 2009 to 2015. Hepatol Int 2019;13:599-608.
- 12. Jang JY, Kim DY, Chang Y. Efficacy of national screening program for hepatitis C virus. Korea Disease Control and Prevention Agency web site, <https://library.nih.go.kr/ncmiklib/synap/skin/doc.html?fn=e7f32d3c80cfe71310e5ae4dffa8d2c8a73fbbacb6fcf33194fa52a9664ff181&rs=/roms/ncmik/st1/synap/202512&fileKey=164282&pn=1> Accessed 9 Apr 2025.
- 13. Kim KA, Lee JS. Prevalence, awareness, and treatment of hepatitis C virus infection in South Korea: Evidence from the Korea National Health and Nutrition Examination Survey. Gut Liver 2020;14:644-651.
- 14. Kim IH, Ki M, Jeong SH, Kim KA, An J, Choi GH, et al. A study on improving performance indicators and surveillance systems in the basic plan for viral hepatitis (B·C) management. Korea Disease Control and Prevention Agency web site, <https://library.nih.go.kr/ncmiklib/synap/synapPreview.do?FILE_GROUP=202758&PK_FILE_SEQ=206616&PN=1> Accessed 9 Apr 2025.
- 15. Choi J, Park J, Lee D, Shim JH, Kim KM, Lim YS, et al. The Korean hepatitis C virus care cascade in a tertiary institution: current status and changes in testing, link to care, and treatment. Gut Liver 2022;16:964-975.
- 16. Lee JS, Lee HW, Kim MN, Kim BK, Park JY, Kim DY, et al. Hepatitis C virus infection in patients undergoing surgery in a single tertiary academic center. J Gastroenterol Hepatol 2024;39:1155-1163.
- 17. Shin HR. Epidemiology of hepatitis C virus in Korea. Intervirology 2006;49:18-22.
- 18. Min JA, Yoon Y, Lee HJ, Choi J, Kwon M, Kim K, et al. Prevalence and associated clinical characteristics of hepatitis B, C, and HIV infections among injecting drug users in Korea. J Med Virol 2013;85:575-582.
- 19. Kim J, Choi GH, Jang OJ, Chon Y, Cho SN, Kwon D, et al. Hepatitis C virus seroprevalence in persons who inject drugs in Korea, 2012-2022: a multicenter, retrospective study. J Korean Med Sci 2023;38:e357.
- 20. Kim SY, Kook JH, Choi IS, Kim SJ, Kook H, Hwang TJ. Viral hepatitis and change of lymphocyte subpopulation in hemophiliacs in Chonnam KwangJu area. Korean J Blood Transfus 2002;13:43-51.
- 21. Korea Hemophilia Association. 2019 Korean hemophilia annual report. Korea Hemophilia Association web site, <http://www.kohem.org/load.asp?sub_p=board/board&b_code=8&page=1&f_cate=&idx=2789&board_md=view>. Accessed 9 Apr 2025.
- 22. Kim JP, Kang KH, Park JM. Seropositivity of hepatitis C virus among persons affected leprosy in Korea. Korean Lepr Bull 2018;51:13-21.
- 23. Korean Society of Nephrology. Trends in epidemiologic characteristics of end-stage kidney disease from 2023 KORDS (Korean Renal Data System). Korean Society of Nephrology web site, <https://www.ksn.or.kr/bbs/?code=report_eng>. Accessed 9 Apr 2025.
- 24. Hong YM, Yoon KT, Park YJ, Woo HY, Heo J. Seroprevalence of hepatitis C virus infection in North Korean defectors residing in Korea. J Korean Med Sci 2023;38:e270.
- 25. Cui F, Blach S, Manzengo Mingiedi C, Gonzalez MA, Sabry Alaama A, Mozalevskis A, et al. Global reporting of progress towards elimination of hepatitis B and hepatitis C. Lancet Gastroenterol Hepatol 2023;8:332-342.
- 26. World Health Organization (WHO). Guidance for country validation of viral hepatitis elimination and path to elimination. World Health Organization web site, <https://www.who.int/publications/i/item/9789240078635>. Accessed 18 Feb 2025.
- 27. Korea Disease Control and Prevention Agency. Infectious Disease Portal - Hepatitis C Statistics. Korea Disease Control and Prevention Agency web site, <https://dportal.kdca.go.kr/pot/is/st/hcv.do>. Accessed 18 Feb 2025.
- 28. Lee CH, Choi GH, Choi HY, Han S, Jang ES, Chon YE, et al. Core indicators related to the elimination of hepatitis B and C virus infection in South Korea: A nationwide study. Clin Mol Hepatol 2023;29:779-793.
- 29. Chon YE, Jo A, Yoon EL, Lee J, Shin HG, Ko MJ, et al. The incidence and care cascade of the hepatitis C virus in Korea. Gut Liver 2023;17:926-932.
- 30. Petruzziello A, Marigliano S, Loquercio G, Cozzolino A, Cacciapuoti C. Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes. World J Gastroenterol 2016;22:7824-7840.
- 31. Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol 2017;2:161-176.
- 32. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015;61:77-87.
- 33. Seong MH, Kil H, Kim JY, Lee SS, Jang ES, Kim JW, et al. Clinical and epidemiological characteristics of Korean patients with hepatitis C virus genotype 6. Clin Mol Hepatol 2013;19:45-50.
- 34. Han CJ, Lee HS, Kim HS, Choe JH, Kim CY. Hepatitis C virus genotypes in Korea and their relationship to clinical outcome in type C chronic liver diseases. Korean J Intern Med 1997;12:21-27.
- 35. Cho EJ, Jeong SH, Han BH, Lee SU, Yun BC, Park ET. Hepatitis C virus (HCV) genotypes and the influence of HCV subtype 1b on the progression of chronic hepatitis C in Korea: a single center experience. Clin Mol Hepatol 2012;18:219-224.
- 36. Korea Disease Control and Prevention Agency. 2025 viral hep- atitis control guidelines (hepatitis A, B, C, and E). Osong: Korea Disease Control and Prevention Agency; 2025.
- 37. Busch MP, Glynn SA, Stramer SL, Strong DM, Caglioti S, Wright DJ, et al. A new strategy for estimating risks of transfusion-transmitted viral infections based on rates of detection of recently infected donors. Transfusion 2005;45:254-264.
- 38. Shan H, Ren FR, Zhao HY, Zhang YZ, Wen GX, Yao FZ, et al. A multi-Chinese blood center study testing serologic-negative donor samples for hepatitis C virus and human immunodeficiency virus with nucleic acid testing. Transfusion 2007;47:2011-2016.
- 39. Vermeulen M, Lelie N, Sykes W, Crookes R, Swanevelder J, Gaggia L, et al. Impact of individual-donation nucleic acid testing on risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission by blood transfusion in South Africa. Transfusion 2009;49:1115-1125.
- 40. Papatheodoridis G, Hatzakis A. Public health issues of hepatitis C virus infection. Best Pract Res Clin Gastroenterol 2012;26:371-380.
- 41. Kermode M. Unsafe injections in low-income country health settings: need for injection safety promotion to prevent the spread of blood-borne viruses. Health Promot Int 2004;19:95-103.
- 42. Gutelius B, Perz JF, Parker MM, Hallack R, Stricof R, Clement EJ, et al. Multiple clusters of hepatitis virus infections associated with anesthesia for outpatient endoscopy procedures. Gastroenterology 2010;139:163-170.
- 43. Caminada S, Mele A, Ferrigno L, Alfonsi V, Crateri S, Iantosca G, et al. Risk of parenterally transmitted hepatitis following exposure to invasive procedures in Italy: SEIEVA surveillance 2000-2021. J Hepatol 2023;79:61-68.
- 44. Chung YS, Choi JY, Han MG, Park KR, Park SJ, Lee H, et al. A large healthcare-associated outbreak of hepatitis C virus genotype 1a in a clinic in Korea. J Clin Virol 2018;106:53-57.
- 45. Hayes MO, Harkness GA. Body piercing as a risk factor for viral hepatitis: an integrative research review. Am J Infect Control 2001;29:271-274.
- 46. Hyun MH, Kim JH, Jang JW, Song JE, Song DS, Lee HW, et al. Risk of hepatitis C virus transmission through acupuncture: a systematic review and meta-analysis. Korean J Gastroenterol 2023;82:127-136.
- 47. Jafari S, Copes R, Baharlou S, Etminan M, Buxton J. Tattooing and the risk of transmission of hepatitis C: a systematic review and meta-analysis. Int J Infect Dis 2010;14:e928-940.
- 48. Ryoo SM, Kim WY, Kim W, Lim KS, Lee CC, Woo JH. Transmission of hepatitis C virus by occupational percutaneous injuries in South Korea. J Formos Med Assoc 2012;111:113-117.
- 49. Tomkins SE, Elford J, Nichols T, Aston J, Cliffe SJ, Roy K, et al. Occupational transmission of hepatitis C in healthcare workers and factors associated with seroconversion: UK surveillance data. J Viral Hepat 2012;19:199-204.
- 50. Tohme RA, Holmberg SD. Is sexual contact a major mode of hepatitis C virus transmission? Hepatology 2010;52:1497-1505.
- 51. Yaphe S, Bozinoff N, Kyle R, Shivkumar S, Pai NP, Klein M. Incidence of acute hepatitis C virus infection among men who have sex with men with and without HIV infection: a systematic review. Sex Transm Infect 2012;88:558-564.
- 52. Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis 2014;59:765-773.
- 53. European Paediatric Hepatitis C Virus Network. Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. BJOG 2001;108:371-377.
- 54. Seong MH, Kil H, Kim YS, Bae SH, Lee YJ, Lee HC, et al. Clinical and epidemiological features of hepatitis C virus infection in South Korea: a prospective, multicenter cohort study. J Med Virol 2013;85:1724-1733.
- 55. Sohn HS, Kim JR, Ryu SY, Lee YJ, Lee MJ, Min HJ, et al. Risk factors for hepatitis C virus (HCV) infection in areas with a high prevalence of HCV in the Republic of Korea in 2013. Gut Liver 2016;10:126-132.
- 56. Degenhardt L, Peacock A, Colledge S, Leung J, Grebely J, Vickerman P, et al. Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review. Lancet Glob Health 2017;5:e1192-e1207.
- 57. Murphy EL, Bryzman SM, Glynn SA, Ameti DI, Thomson RA, Williams AE, et al. Risk factors for hepatitis C virus infection in United States blood donors. NHLBI Retrovirus Epidemiology Donor Study (REDS). Hepatology 2000;31:756-762.
- 58. Kim KA, Choi GH, Jang ES, Kim YS, Lee YJ, Kim IH, et al. Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID. Epidemiol Health 2021;43:e2021077.
- 59. Jeong SH. Strategy on prevention and management of hepatitis C for people who inject drugs in South Korea. Korea Disease Control and Prevention Agency web site, <https://library.nih.go.kr/ncmiklib/synap/skin/doc.html?fn=4a3c23df26f49b3b3e2a5155dc1c8a152c4ca15f8ac6960bb831a3bc7583fb76&rs=/roms/ncmik/st1/synap/202512&fileKey=247348&pn=1> Accessed 21 Sep 2025.
- 60. Greeviroj P, Lertussavavivat T, Thongsricome T, Takkavatakarn K, Phannajit J, Avihingsanon Y, et al. The world prevalence, associated risk factors and mortality of hepatitis C virus infection in hemodialysis patients: a meta-analysis. J Nephrol 2022;35:2269-2282.
- 61. Shimokura G, Chai F, Weber DJ, Samsa GP, Xia GL, Nainan OV, et al. Patient-care practices associated with an increased prevalence of hepatitis C virus infection among chronic hemodialysis patients. Infect Control Hosp Epidemiol 2011;32:415-424.
- 62. Bravo Zuñiga JI, Loza Munárriz C, López-Alcalde J. Isolation as a strategy for controlling the transmission of hepatitis C virus (HCV) infection in haemodialysis units. Cochrane Database Syst Rev 2016;2016:CD006420.
- 63. Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl (2011) 2018;8:91-165.
- 64. Korea Disease Control and Prevention Agency. Guidelines for Infection Management in Dialysis Units, 2023. Korea Disease Control and Prevention Agency web site, <https://www.kdca.go.kr/kdca/2861/subview.do?enc=Zm5jdDF8QEB8JTJGYmJzJTJGa2RjYSUyRjU1JTJGMjI4MTQ2JTJGYXJ0Y2xWaWV3LmRvJTNG> Accessed 21 Sep 2025.
- 65. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009;49:1335-1374.
- 66. Moyer VA. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2013;159:349-357.
- 67. Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, et al. Screening for hepatitis C Virus infection in adolescents and adults: US preventive services task force recommendation statement. JAMA 2020;323:970-975.
- 68. Waked I, Esmat G, Elsharkawy A, El-Serafy M, Abdel-Razek W, Ghalab R, et al. Screening and treatment program to eliminate hepatitis C in Egypt. N Engl J Med 2020;382:1166-1174.
- 69. Nam JY, Jang ES, Kim YS, Lee YJ, Kim IH, Cho SB, et al. Epidemiological and clinical characteristics of hepatitis C virus infection in South Korea from 2007 to 2017: a prospective multicenter cohort study. Gut Liver 2020;14:207-217.
- 70. Pawlotsky JM. Molecular diagnosis of viral hepatitis. Gastroenterology 2002;122:1554-1568.
- 71. Pawlotsky JM. Use and interpretation of virological tests for hepatitis C. Hepatology 2002;36:S65-73.
- 72. Kim S, Kim JH, Yoon S, Park YH, Kim HS. Clinical performance evaluation of four automated chemiluminescence immunoassays for hepatitis C virus antibody detection. J Clin Microbiol 2008;46:3919-3923.
- 73. Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, et al. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med 1992;327:1899-1905.
- 74. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med 2001;345:41-52.
- 75. Thio CL, Nolt KR, Astemborski J, Vlahov D, Nelson KE, Thomas DL. Screening for hepatitis C virus in human immunodeficiency virus-infected individuals. J Clin Microbiol 2000;38:575-577.
- 76. Meyer zum Büschenfelde KH, Gerken G, Manns M. Hepatitis C virus (HCV) and autoimmune liver diseases. Arch Virol Suppl 1992;4:201-204.
- 77. Heinrichs A, Antoine M, Steensels D, Montesinos I, Delforge ML. HCV false positive immunoassays in patients with LVAD: A potential trap! J Clin Virol 2016;78:44-46.
- 78. Moorman AC, Drobenuic J, Kamili S. Prevalence of false-positive hepatitis C antibody results, National Health and Nutrition Examination Study (NHANES) 2007-2012. J Clin Virol 2017;89:1-4.
- 79. European Association for the Study of the Liver. EASL rec- ommendations on treatment of hepatitis C: Final update of the series. J Hepatol 2020;73:1170-1218.
- 80. de Leuw P, Sarrazin C, Zeuzem S. How to use virological tools for the optimal management of chronic hepatitis C. Liver Int 2011;31 Suppl 1:3-12.
- 81. Alter HJ, Seeff LB. Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective on long-term outcome. Semin Liver Dis 2000;20:17-35.
- 82. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005;5:215-229.
- 83. Wieland SF, Chisari FV. Stealth and cunning: hepatitis B and hepatitis C viruses. J Virol 2005;79:9369-9380.
- 84. Nguyen TT, Sedghi-Vaziri A, Wilkes LB, Mondala T, Pockros PJ, Lindsay KL, et al. Fluctuations in viral load (HCV RNA) are relatively insignificant in untreated patients with chronic HCV infection. J Viral Hepat 1996;3:75-78.
- 85. Ferreira-Gonzalez A, Shiffman ML. Use of diagnostic testing for managing hepatitis C virus infection. Semin Liver Dis 2004;24 Suppl 2:9-18.
- 86. Arase Y, Ikeda K, Chayama K, Murashima N, Tsubota A, Suzuki Y, et al. Fluctuation patterns of HCV-RNA serum level in patients with chronic hepatitis C. J Gastroenterol 2000;35:221-225.
- 87. Hajarizadeh B, Grady B, Page K, Kim AY, McGovern BH, Cox AL, et al. Patterns of hepatitis C virus RNA levels during acute infection: the InC3 study. PLoS One 2015;10:e0122232.
- 88. Vo-Quang E, Pawlotsky JM. ‘Unusual’ HCV genotype subtypes: origin, distribution, sensitivity to direct-acting antiviral drugs and behaviour on antiviral treatment and retreatment. Gut 2024;73:1570-1582.
- 89. Chevaliez S, Bouvier-Alias M, Brillet R, Pawlotsky JM. Hepatitis C virus (HCV) genotype 1 subtype identification in new HCV drug development and future clinical practice. PLoS One 2009;4:e8209.
- 90. Yang R, Wei L. Profile of the VERSANT HCV genotype 2.0 assay. Expert Rev Mol Diagn 2018;18:995-1004.
- 91. Dirani G, Paesini E, Mascetra E, Farabegoli P, Dalmo B, Bartolini B, et al. A novel next generation sequencing assay as an alternative to currently available methods for hepatitis C virus genotyping. J Virol Methods 2018;251:88-91.
- 92. Solomon SS, Wagner-Cardoso S, Smeaton L, Sowah LA, Wimbish C, Robbins G, et al. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial. Lancet Gastroenterol Hepatol 2022;7:307-317.
- 93. Childs K, Davis C, Cannon M, Montague S, Filipe A, Tong L, et al. Suboptimal SVR rates in African patients with atypical genotype 1 subtypes: Implications for global elimination of hepatitis C. J Hepatol 2019;71:1099-1105.
- 94. Wei L, Wang G, Alami NN, Xie W, Heo J, Xie Q, et al. Glecaprevir-pibrentasvir to treat chronic hepatitis C virus infection in Asia: two multicentre, phase 3 studies- a randomised, double-blind study (VOYAGE-1) and an open-label, single-arm study (VOYAGE-2). Lancet Gastroenterol Hepatol 2020;5:839-849.
- 95. Wei L, Lim SG, Xie Q, Văn KN, Piratvisuth T, Huang Y, et al. Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial. Lancet Gastroenterol Hepatol 2019;4:127-134.
- 96. Midgard H, Weir A, Palmateer N, Lo Re V, Pineda JA, Macías J, et al. HCV epidemiology in high-risk groups and the risk of reinfection. J Hepatol 2016;65:S33-S45.
- 97. Martinello M, Carson JM, Van Der Valk M, Rockstroh JK, Ingiliz P, Hellard M, et al. Reinfection incidence and risk among people treated for recent hepatitis C virus infection. AIDS 2023;37:1883-1890.
- 98. Coppola N, Minichini C, Starace M, Sagnelli C, Sagnelli E. Clinical impact of the hepatitis C virus mutations in the era of directly acting antivirals. J Med Virol 2016;88:1659-1671.
- 99. Pawlotsky JM. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology 2016;151:70-86.
- 100. Fourati S, Pawlotsky JM. Virologic tools for HCV drug resistance testing. Viruses 2015;7:6346-6359.
- 101. Hezode C, Reau N, Svarovskaia ES, Doehle BP, Shanmugam R, Dvory-Sobol H, et al. Resistance analysis in patients with genotype 1-6 HCV infection treated with sofosbuvir/velpatasvir in the phase III studies. J Hepatol 2018;68:895-903.
- 102. Krishnan P, Pilot-Matias T, Schnell G, Tripathi R, Ng TI, Reisch T, et al. Pooled resistance analysis in patients with hepatitis C virus genotype 1 to 6 infection treated with glecaprevir-pibrentasvir in phase 2 and 3 clinical trials. Antimicrob Agents Chemother 2018;62:e01249-18.
- 103. Pauly MD, Ganova-Raeva L. Point-of-care testing for hepatitis viruses: a growing need. Life (Basel) 2023;13:2271.
- 104. Gao F, Talbot EA, Loring CH, Power JJ, Dionne-Odom J, Alroy-Preis S, et al. Performance of the OraQuick HCV rapid antibody test for screening exposed patients in a hepatitis C outbreak investigation. J Clin Microbiol 2014;52:2650-2652.
- 105. Tang W, Chen W, Amini A, Boeras D, Falconer J, Kelly H, et al. Diagnostic accuracy of tests to detect hepatitis C antibody: a meta-analysis and review of the literature. BMC Infect Dis 2017;17:695.
- 106. Lamoury FMJ, Bajis S, Hajarizadeh B, Marshall AD, Martinello M, Ivanova E, et al. Evaluation of the Xpert HCV Viral Load finger-stick point-of-care assay. J Infect Dis 2018;217:1889-1896.
- 107. Grebely J, Lamoury FMJ, Hajarizadeh B, Mowat Y, Marshall AD, Bajis S, et al. Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study. Lancet Gastroenterol Hepatol 2017;2:514-520.
- 108. Puro V, Petrosillo N, Ippolito G. Risk of hepatitis C seroconversion after occupational exposures in health care workers. Italian Study Group on Occupational Risk of HIV and Other Bloodborne Infections. Am J Infect Control 1995;23:273-277.
- 109. Cannon CG, DeRonde MM, Pendy L, Kerley LM. Hepatitis C virus infection in healthcare workers: risk of exposure and infection. Infect Control Hosp Epidemiol 1994;15:745-750.
- 110. Alter MJ. The epidemiology of acute and chronic hepatitis C. Clin Liver Dis 1997;1:559-568.
- 111. U.S. Public Health Service. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2001;50:1-52.
- 112. Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Teo CG, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep 2012;61:1-32.
- 113. Mitsui T, Iwano K, Masuko K, Yamazaki C, Okamoto H, Tsuda F, et al. Hepatitis C virus infection in medical personnel after needlestick accident. Hepatology 1992;16:1109-1114.
- 114. Kubitschke A, Bahr MJ, Aslan N, Bader C, Tillmann HL, Sarrazin C, et al. Induction of hepatitis C virus (HCV)-specific T cells by needle stick injury in the absence of HCV-viraemia. Eur J Clin Invest 2007;37:54-64.
- 115. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011;55:245-264.
- 116. Bhattacharya D, Aronsohn A, Price J, Lo Re V. Hepatitis C guidance 2023 Update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis 2023;ciad319.
- 117. Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology 2010;139:1593-1601.
- 118. Sarrazin C, Isakov V, Svarovskaia ES, Hedskog C, Martin R, Chodavarapu K, et al. Late relapse versus hepatitis C virus reinfection in patients with sustained virologic response after sofosbuvir-based therapies. Clin Infect Dis 2017;64:44-52.
- 119. Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000;132:517-524.
- 120. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002;122:1303-1313.
- 121. Rockey DC, Friedman SL. Fibrosis regression after eradication of hepatitis C virus: from bench to bedside. Gastroenterology 2021;160:1502-1520.
- 122. Pradat P, Tillmann HL, Sauleda S, Braconier JH, Saracco G, Thursz M, et al. Long-term follow-up of the hepatitis C HENCORE cohort: response to therapy and occurrence of liver-related complications. J Viral Hepat 2007;14:556-563.
- 123. Tanaka Y, Ogawa E, Huang CF, Toyoda H, Jun DW, Tseng CH, et al. HCC risk post-SVR with DAAs in East Asians: findings from the REAL-C cohort. Hepatol Int 2020;14:1023-1033.
- 124. Choi GH, Jang ES, Kim YS, Lee YJ, Kim IH, Cho SB, et al. Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study. World J Gastroenterol 2022;28:4182-4200.
- 125. Lv GJ, Ji D, Yu L, Chen HY, Chen J, He M, et al. Risk of hepatocellular carcinoma occurrence after antiviral therapy for patients with chronic hepatitis C Infection: a systematic review and meta-analysis. Hepatol Int 2024;18:1459-1471.
- 126. Ogawa E, Kawano A, Kohjima M, Koyanagi T, Dohmen K, Ooho A, et al. Long-term liver morbidity and mortality after hepatitis C virus elimination by direct-acting antivirals. J Gastroenterol Hepatol 2025;40:971-978.
- 127. Comarmond C, Garrido M, Pol S, Desbois AC, Costopoulos M, Le Garff-Tavernier M, et al. Direct-acting antiviral therapy restores immune tolerance to patients with hepatitis C virus-induced cryoglobulinemia vasculitis. Gastroenterology 2017;152:2052-2062.
- 128. Cacoub P, Si Ahmed SN, Ferfar Y, Pol S, Thabut D, Hezode C, et al. Long-term efficacy of interferon-free antiviral treatment regimens in patients with hepatitis C virus-associated cryoglobulinemia vasculitis. Clin Gastroenterol Hepatol 2019;17:518-526.
- 129. Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, et al. The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients. Hepatology 2006;43:1303-1310.
- 130. Deterding K, Spinner CD, Schott E, Welzel TM, Gerken G, Klinker H, et al. Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study. Lancet Infect Dis 2017;17:215-222.
- 131. Naggie S, Fierer DS, Hughes MD, Kim AY, Luetkemeyer A, Vu V, et al. Ledipasvir/sofosbuvir for 8 weeks to treat acute hepatitis C virus infections in men with human immunodeficiency virus infections: sofosbuvir-containing regimens without interferon for treatment of acute HCV in HIV-1 infected individuals. Clin Infect Dis 2019;69:514-522.
- 132. Martinello M, Orkin C, Cooke G, Bhagani S, Gane E, Kulasegaram R, et al. Short-duration pan-genotypic therapy with glecaprevir/pibrentasvir for 6 weeks among people with recent hepatitis C viral infection. Hepatology 2020;72:7-18.
- 133. Matthews GV, Bhagani S, Van der Valk M, Rockstroh J, Feld JJ, Rauch A, et al. Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection. J Hepatol 2021;75:829-839.
- 134. Maasoumy B, Ingiliz P, Spinner CD, Cordes C, Stellbrink HJ, Schulze Zur Wiesch J, et al. Sofosbuvir plus velpatasvir for 8 weeks in patients with acute hepatitis C: the HepNet acute HCV-V study. JHEP Rep 2023;5:100650.
- 135. Boerekamps A, van den Berk GE, Lauw FN, Leyten EM, van Kasteren ME, van Eeden A, et al. Declining hepatitis C virus (HCV) incidence in dutch human immunodeficiency virus-positive men who have sex with men after unrestricted access to HCV therapy. Clin Infect Dis 2018;66:1360-1365.
- 136. Ghany MG, Morgan TR. Hepatitis C guidance 2019 update: American association for the study of liver diseases-infectious diseases society of America recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology 2020;71:686-721.
- 137. Yu ML, Tai CM, Mo LR, Kuo HT, Huang CF, Tseng KC, et al. An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan. Hepatol Int 2024;18:461-475.
- 138. Dore GJ, Feld JJ, Thompson A, Martinello M, Muir AJ, Agarwal K, et al. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial. J Hepatol 2020;72:431-440.
- 139. Heo M, Norton BL, Pericot-Valverde I, Mehta SH, Tsui JI, Taylor LE, et al. Optimal hepatitis C treatment adherence patterns and sustained virologic response among people who inject drugs: The HERO study. J Hepatol 2024;80:702-713.
- 140. Flamm SL, Mangia A. Adherence in hepatitis C virus treatment: what we know. Semin Liver Dis 2024;44:258-271.
- 141. Konstantinou D, Deutsch M. The spectrum of HBV/HCV coinfection: epidemiology, clinical characteristics, viralinteractions and management. Ann Gastroenterol 2015;28:221-228.
- 142. Kim YJ, Lee JW, Kim YS, Jeong SH, Kim YS, Yim HJ, et al. Clinical features and treatment efficacy of peginterferon alfa plus ribavirin in chronic hepatitis C patients coinfected with hepatitis B virus. Korean J Hepatol 2011;17:199-205.
- 143. Tyson GL, Kramer JR, Duan Z, Davila JA, Richardson PA, El-Serag HB. Prevalence and predictors of hepatitis B virus coinfection in a United States cohort of hepatitis C virus-infected patients. Hepatology 2013;58:538-545.
- 144. Bini EJ, Perumalswami PV. Hepatitis B virus infection among American patients with chronic hepatitis C virus infection: prevalence, racial/ethnic differences, and viral interactions. Hepatology 2010;51:759-766.
- 145. Pol S, Haour G, Fontaine H, Dorival C, Petrov-Sanchez V, Bourliere M, et al. The negative impact of HBV/HCV coinfection on cirrhosis and its consequences. Aliment Pharmacol Ther 2017;46:1054-1060.
- 146. Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2022;28:276-331.
- 147. Park SH, Plank LD, Suk KT, Park YE, Lee J, Choi JH, et al. Trends in the prevalence of chronic liver disease in the Korean adult population, 1998-2017. Clin Mol Hepatol 2020;26:209-215.
- 148. Lee HH, Lee HA, Kim EJ, Kim HY, Kim HC, Ahn SH, et al. Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease. Gut 2024;73:533-540.
- 149. Huang CF, Dai CY, Lin YH, Wang CW, Jang TY, Liang PC, et al. Dynamic change of metabolic dysfunction-associated steatotic liver disease in chronic hepatitis C patients after viral eradication: A nationwide registry study in Taiwan. Clin Mol Hepatol 2024;30:883-894.
- 150. Liu CH, Cheng PN, Fang YJ, Chen CY, Kao WY, Lin CL, et al. Risk of de novo HCC in patients with MASLD following direct-acting antiviral-induced cure of HCV infection. J Hepatol 2025;82:582-593.
- 151. Bedogni G, Miglioli L, Masutti F, Ferri S, Castiglione A, Lenzi M, et al. Natural course of chronic HCV and HBV infection and role of alcohol in the general population: the Dionysos Study. Am J Gastroenterol 2008;103:2248-2253.
- 152. Deuffic-Burban S, Deltenre P, Buti M, Stroffolini T, Parkes J, Mühlberger N, et al. Predicted effects of treatment for HCV infection vary among European countries. Gastroenterology 2012;143:974-985.
- 153. Deuffic-Burban S, Deltenre P, Louvet A, Canva V, Dharancy S, Hollebecque A, et al. Impact of viral eradication on mortality related to hepatitis C: a modeling approach in France. J Hepatol 2008;49:175-183.
- 154. Vandenbulcke H, Moreno C, Colle I, Knebel JF, Francque S, Sersté T, et al. Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study. J Hepatol 2016;65:543-551.
- 155. Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 2016;65:727-733.
- 156. Chun HS, Kim BK, Park JY, Kim DY, Ahn SH, Han KH, et al. Design and validation of risk prediction model for hepatocellular carcinoma development after sustained virological response in patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 2020;32:378-385.
- 157. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996;24:289-293.
- 158. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22:696-699.
- 159. Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, et al. KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024;30:S5-S105.
- 160. Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373:2599-2607.
- 161. Brown RS Jr, Buti M, Rodrigues L, Chulanov V, Chuang WL, Aguilar H, et al. Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: the EXPEDITION-8 trial. J Hepatol 2020;72:441-449.
- 162. Lampertico P, Carrión JA, Curry M, Turnes J, Cornberg M, Negro F, et al. Real-world effectiveness and safety of glecaprevir/pibrentasvir for the treatment of patients with chronic HCV infection: a meta-analysis. J Hepatol 2020;72:1112-1121.
- 163. Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, Pianko S, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med 2015;373:2608-2617.
- 164. Asselah T, Bourgeois S, Pianko S, Zeuzem S, Sulkowski M, Foster GR, et al. Sofosbuvir/velpatasvir in patients with hepatitis C virus genotypes 1-6 and compensated cirrhosis or advanced fibrosis. Liver Int 2018;38:443-450.
- 165. de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C. Baveno VII - Renewing consensus in portal hypertension. J Hepatol 2022;76:959-974.
- 166. D’Amico G, Bernardi M, Angeli P. Towards a new definition of decompensated cirrhosis. J Hepatol 2022;76:202-207.
- 167. Heo J, Kim YJ, Lee SW, Lee YJ, Yoon KT, Byun KS, et al. Efficacy and safety of sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir for hepatitis C in Korea: a Phase 3b study. Korean J Intern Med 2023;38:504-513.
- 168. Cheng PN, Mo LR, Chen CT, Chen CY, Huang CF, Kuo HT, et al. Sofosbuvir/velpatasvir for hepatitis C virus infection: real-world effectiveness and safety from a nationwide registry in Taiwan. Infect Dis Ther 2022;11:485-500.
- 169. Zeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med 2018;378:354-369.
- 170. Heo J, Kim YJ, Lee JW, Kim JH, Lim YS, Han KH, et al. Efficacy and safety of Glecaprevir/pibrentasvir in Korean patients with chronic hepatitis C: a pooled analysis of five phase II/III trials. Gut Liver 2021;15:895-903.
- 171. An J, Park DA, Ko MJ, Ahn SB, Yoo JJ, Jun DW, et al. Direct-acting antivirals for HCV treatment in decompensated liver cirrhosis patients: a systematic review and meta-analysis. J Pers Med 2022;12:1517.
- 172. Takaoka Y, Miura K, Morimoto N, Ikegami T, Kakizaki S, Sato K, et al. Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection. Hepatol Res 2021;51:51-61.
- 173. Sidharthan S, Kohli A, Sims Z, Nelson A, Osinusi A, Masur H, et al. Utility of hepatitis C viral load monitoring on direct-acting antiviral therapy. Clin Infect Dis 2015;60:1743-1751.
- 174. Zarębska-Michaluk D, Flisiak R, Janczewska E, Berak H, Mazur W, Janocha-Litwin J, et al. Does a detectable HCV RNA at the end of DAA therapy herald treatment failure? Antiviral Res 2023;220:105742.
- 175. Borgia SM, Dearden J, Yoshida EM, Shafran SD, Brown A, Ben-Ari Z, et al. Sofosbuvir/velpatasvir for 12 weeks in hepatitis C virus-infected patients with end-stage renal disease undergoing dialysis. J Hepatol 2019;71:660-665.
- 176. Mangia A, Milligan S, Khalili M, Fagiuoli S, Shafran SD, Carrat F, et al. Global real-world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: analysis of 5552 patients from 12 cohorts. Liver Int 2020;40:1841-1852.
- 177. Wilton J, Wong S, Yu A, Ramji A, Cook D, Butt ZA, et al. Real-world effectiveness of sofosbuvir/velpatasvir for treatment of chronic hepatitis C in British Columbia, Canada: a population-based cohort study. Open Forum Infect Dis 2020;7:ofaa055.
- 178. Mangia A, Piazzolla V, Giannelli A, Visaggi E, Minerva N, Palmieri V, et al. SVR12 rates higher than 99% after sofosbuvir/velpatasvir combination in HCV infected patients with F0-F1 fibrosis stage: a real world experience. PLoS One 2019;14:e0215783.
- 179. Liu CH, Chen PY, Chen JJ, Lo CC, Su WW, Tseng KC, et al. Sofosbuvir/velpatasvir for patients with chronic hepatitis C virus infection and compensated liver disease: real-world data in Taiwan. Hepatol Int 2021;15:338-349.
- 180. Huang YT, Hsieh YY, Chen WM, Tung SY, Wei KL, Shen CH, et al. Sofosbuvir/velpatasvir is an effective treatment for patients with hepatitis C and advanced fibrosis or cirrhosis in a real-world setting in Taiwan. BMC Gastroenterol 2021;21:259.
- 181. von Felden J, Vermehren J, Ingiliz P, Mauss S, Lutz T, Simon KG, et al. High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance-associated substitutions in hepatitis C genotype 3 infection. Aliment Pharmacol Ther 2018;47:1288-1295.
- 182. Belperio PS, Shahoumian TA, Loomis TP, Mole LA, Backus LI. Real-world effectiveness of daclatasvir plus sofosbuvir and velpatasvir/sofosbuvir in hepatitis C genotype 2 and 3. J Hepatol 2019;70:15-23.
- 183. Zuckerman E, Gutierrez JA, Dylla DE, de Ledinghen V, Muir AJ, Gschwantler M, et al. Eight weeks of treatment with glecaprevir/pibrentasvir is safe and efficacious in an integrated analysis of treatment-naïve patients with hepatitis C virus infection. Clin Gastroenterol Hepatol 2020;18:2544-2553.
- 184. Park YJ, Woo HY, Heo J, Park SG, Hong YM, Yoon KT, et al. Real-life effectiveness and safety of glecaprevir/pibrentasvir for Korean patients with chronic hepatitis C at a single institution. Gut Liver 2021;15:440-450.
- 185. Lu M, Rupp LB, Melkonian C, Trudeau S, Daida YG, Schmidt MA, et al. Real-world safety and effectiveness of an 8-week regimen of glecaprevir/pibrentasvir in patients with hepatitis C and cirrhosis. Adv Ther 2024;41:744-758.
- 186. Trifan A, Stanciu C, Streinu-Cercel A, Culinescu A, Baroiu L, Dumitru E, et al. Effectiveness of 8-week treatment with glecaprevir/pibrentasvir in treatment-naïve or -experienced HCV patients: results from an observational retrospective study in real-life settings (ODYSSEY). J Gastrointestin Liver Dis 2024;33:503-509.
- 187. Asselah T, Kowdley KV, Zadeikis N, Wang S, Hassanein T, Horsmans Y, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with hepatitis C virus genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol 2018;16:417-426.
- 188. Kwo PY, Poordad F, Asatryan A, Wang S, Wyles DL, Hassanein T, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67:263-271.
- 189. Flamm S, Mutimer D, Asatryan A, Wang S, Rockstroh J, Horsmans Y, et al. Glecaprevir/pibrentasvir in patients with chronic HCV genotype 3 infection: An integrated phase 2/3 analysis. J Viral Hepat 2019;26:337-349.
- 190. Wyles D, Poordad F, Wang S, Alric L, Felizarta F, Kwo PY, et al. Glecaprevir/pibrentasvir for hepatitis C virus genotype 3 patients with cirrhosis and/or prior treatment experience: a partially randomized phase 3 clinical trial. Hepatology 2018;67:514-523.
- 191. Jacobson IM, Lawitz E, Gane EJ, Willems BE, Ruane PJ, Nahass RG, et al. Efficacy of 8 weeks of sofosbuvir, velpatasvir, and voxilaprevir in patients with chronic HCV infection: 2 phase 3 randomized trials. Gastroenterology 2017;153:113-122.
- 192. Kim NJ, Vutien P, Cleveland E, Cravero A, Ioannou GN. Fibrosis stage-specific incidence of hepatocellular cancer after hepatitis C cure with direct-acting antivirals: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2023;21:1723-1738.
- 193. Park Y, Na SK, Yoon JH, Kim SE, Park JW, Kim GA, et al. Prognosis following sustained virologic response in korean chronic hepatitis C patients treated with sofosbuvir-based treatment: data from a multicenter prospective observational study up to 7 years. Medicina (Kaunas) 2024;60:1132.
- 194. Semmler G, Alonso López S, Pons M, Lens S, Dajti E, Griemsmann M, et al. Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure. Hepatology 2025;81:609-624.
- 195. Lee HA, Kim MN, Lee HA, Choi M, Yu JH, Jin YJ, et al. Noninvasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus: a systematic review and meta-analysis. Clin Mol Hepatol 2024;30:S172-S185.
- 196. Minami T, Tateishi R, Fujiwara N, Nakagomi R, Nakatsuka T, Sato M, et al. Impact of obesity and heavy alcohol consumption on hepatocellular carcinoma development after HCV eradication with antivirals. Liver Cancer 2021;10:309-319.
- 197. Kim NJ, Pearson M, Vutien P, Su F, Moon AM, Berry K, et al. Alcohol use and long-term outcomes among U.S. veterans who received direct-acting antivirals for hepatitis C treatment. Hepatol Commun 2020;4:314-324.
- 198. Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol 2018;68:25-32.
- 199. Hajarizadeh B, Cunningham EB, Valerio H, Martinello M, Law M, Janjua NZ, et al. Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: a meta-analysis. J Hepatol 2020;72:643-657.
- 200. Johannesson JM, Fridriksdottir RH, Löve TJ, Runarsdottir V, Hansdóttir I, Löve A, et al. High rate of hepatitis C virus reinfection among recently injecting drug users: results from the TraP Hep C program-a prospective nationwide, population-based study. Clin Infect Dis 2022;75:1732-1739.
- 201. Rossi C, Butt ZA, Wong S, Buxton JA, Islam N, Yu A, et al. Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort. J Hepatol 2018;69:1007-1014.
- 202. Reiberger T, Lens S, Cabibbo G, Nahon P, Zignego AL, Deterding K, et al. EASL position paper on clinical follow-up after HCV cure. J Hepatol 2024;81:326-344.
- 203. Huang P, Wang Y, Yue M, Ge Z, Xia X, Jeyarajan AJ, et al. The risk of hepatitis C virus recurrence in hepatitis C virus-infected patients treated with direct-acting antivirals after achieving a sustained virological response: a comprehensive analysis. Liver Int 2021;41:2341-2357.
- 204. Fierer DS, Wyles DL. Re-treatment of hepatitis C infection after multiple failures of direct-acting antiviral therapy. Open Forum Infect Dis 2020;7:ofaa095.
- 205. Minosse C, Gruber CEM, Rueca M, Taibi C, Zaccarelli M, Grilli E, et al. Late relapse and reinfection in HCV patients treated with direct-acting antiviral (DAA) drugs. Viruses 2021;13:1151.
- 206. Guardigni V, Cento V, Ianniruberto S, Badia L, Aragri M, Conti M, et al. HCV very late relapse following an atypical viral kinetics in a HIV patient treated for hepatitis C with direct-acting antivirals. Infection 2018;46:717-720.
- 207. Cuypers L, Pérez AB, Chueca N, Aldamiz-Echevarría T, Alados JC, Martínez-Sapiña AM, et al. Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: unravelled by phylogenetic analysis. PLoS One 2018;13:e0201268.
- 208. Pawlotsky JM. Retreatment of hepatitis C virus-infected patients with direct-acting antiviral failures. Semin Liver Dis 2019;39:354-368.
- 209. Ridruejo E, Pereson MJ, Flichman DM, Di Lello FA. Hepatitis C virus treatment failure: clinical utility for testing resistance-associated substitutions. World J Hepatol 2021;13:1069-1078.
- 210. Bourlière M, Gordon SC, Flamm SL, Cooper CL, Ramji A, Tong M, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med 2017;376:2134-2146.
- 211. Bourlière M, Gordon SC, Schiff ER, Tran TT, Ravendhran N, Landis CS, et al. Deferred treatment with sofosbuvir-velpatasvir-voxilaprevir for patients with chronic hepatitis C virus who were previously treated with an NS5A inhibitor: an open-label substudy of POLARIS-1. Lancet Gastroenterol Hepatol 2018;3:559-565.
- 212. Devan P, Tiong KLA, Neo JE, Mohan BP, Wijarnpreecha K, Tam YCS, et al. Treatment outcomes of sofosbuvir/velpatasvir/voxilaprevir in direct-acting antiviral-experienced hepatitis C virus patients: a systematic review and meta-analysis. Viruses 2023;15:1489.
- 213. Papaluca T, Roberts SK, Strasser SI, Stuart KA, Farrell G, MacQuillan G, et al. Efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir for hepatitis C virus (HCV) NS5A-inhibitor experienced patients with difficult to cure characteristics. Clin Infect Dis 2021;73:e3288-e3295.
- 214. Llaneras J, Riveiro-Barciela M, Lens S, Diago M, Cachero A, García-Samaniego J, et al. Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs. J Hepatol 2019;71:666-672.
- 215. Poordad F, Felizarta F, Asatryan A, Sulkowski MS, Reindollar RW, Landis CS, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology 2017;66:389-397.
- 216. Poordad F, Pol S, Asatryan A, Buti M, Shaw D, Hézode C, et al. Glecaprevir/pibrentasvir in patients with hepatitis C virus genotype 1 or 4 and past direct-acting antiviral treatment failure. Hepatology 2018;67:1253-1260.
- 217. Lok AS, Sulkowski MS, Kort JJ, Willner I, Reddy KR, Shiffman ML, et al. Efficacy of glecaprevir and pibrentasvir in patients with genotype 1 hepatitis C virus infection with treatment failure after NS5A inhibitor plus sofosbuvir therapy. Gastroenterology 2019;157:1506-1517.
- 218. Gane EJ, Shiffman ML, Etzkorn K, Morelli G, Stedman CAM, Davis MN, et al. Sofosbuvir-velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients previously treated with a direct-acting antiviral regimen. Hepatology 2017;66:1083-1089.
- 219. Pearlman B, Perrys M, Hinds A. Sofosbuvir/velpatasvir/voxilaprevir for previous treatment failures with glecaprevir/pibrentasvir in chronic hepatitis C infection. Am J Gastroenterol 2019;114:1550-1552.
- 220. de Salazar A, Dietz J, di Maio VC, Vermehren J, Paolucci S, Müllhaupt B, et al. Prevalence of resistance-associated substitutions and retreatment of patients failing a glecaprevir/pibrentasvir regimen. J Antimicrob Chemother 2020;75:3349-3358.
- 221. Ruiz-Cobo JC, Llaneras J, Forns X, Gallego Moya A, Conde Amiel I, Arencibia A, et al. Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir. Aliment Pharmacol Ther 2024;60:201-211.
- 222. Wyles D, Weiland O, Yao B, Weilert F, Dufour JF, Gordon SC, et al. Retreatment of patients who failed glecaprevir/pibrentasvir treatment for hepatitis C virus infection. J Hepatol 2019;70:1019-1023.
- 223. Dietz J, Di Maio VC, de Salazar A, Merino D, Vermehren J, Paolucci S, et al. Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy. J Hepatol 2021;74:801-810.
- 224. Bernhard B, Stickel F. Successful fourth line treatment of a relapse patient with chronic hepatitis C virus infection genotype 3a using sofosbuvir, glecaprevir/pibrentasvir, and ribavirin: a case report. Z Gastroenterol 2020;58:451-455.
- 225. Trudeau S, Mendiratta V, Dababneh Y, Hollingsworth J, Gordon SC. Letter to the editor: successful treatment of multidrug resistant hepatitis C after >12 months of continuous therapy with direct-acting antivirals. Hepatology 2023;77:E9-E10.
- 226. Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, et al. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology. J Hepatol 2020;73:842-854.
- 227. Krassenburg LAP, Maan R, Ramji A, Manns MP, Cornberg M, Wedemeyer H, et al. Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity. J Hepatol 2021;74:1053-1063.
- 228. Verna EC, Morelli G, Terrault NA, Lok AS, Lim JK, Di Bisceglie AM, et al. DAA therapy and long-term hepatic function in advanced/decompensated cirrhosis: Real-world experience from HCV-TARGET cohort. J Hepatol 2020;73:540-548.
- 229. Tada T, Kurosaki M, Nakamura S, Hasebe C, Kojima Y, Furuta K, et al. Real-world clinical outcomes of sofosbuvir and velpatasvir treatment in HCV genotype 1- and 2-infected patients with decompensated cirrhosis: A nationwide multicenter study by the Japanese Red Cross Liver Study Group. J Med Virol 2021;93:6247-6256.
- 230. Manns M, Samuel D, Gane EJ, Mutimer D, McCaughan G, Buti M, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis 2016;16:685-697.
- 231. Welzel TM, Petersen J, Herzer K, Ferenci P, Gschwantler M, Wedemeyer H, et al. Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort. Gut 2016;65:1861-1870.
- 232. Curry MP, O’Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 2015;373:2618-2628.
- 233. Belli LS, Berenguer M, Cortesi PA, Strazzabosco M, Rockenschaub SR, Martini S, et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: a European study. J Hepatol 2016;65:524-531.
- 234. El-Sherif O, Jiang ZG, Tapper EB, Huang KC, Zhong A, Osinusi A, et al. Baseline factors associated with improvements in decompensated cirrhosis after direct-acting antiviral therapy for hepatitis C virus infection. Gastroenterology 2018;154:2111-2121.
- 235. Terrault NA, McCaughan GW, Curry MP, Gane E, Fagiuoli S, Fung JYY, et al. International liver transplantation society consensus statement on hepatitis C management in liver transplant candidates. Transplantation 2017;101:945-955.
- 236. Mak LY, Seto WK, Lai CL, Yuen MF. An update on the toxicological considerations for protease inhibitors used for hepatitis C infection. Expert Opin Drug Metab Toxicol 2018;14:483-491.
- 237. Lu M, Wu KH, Li J, Moorman AC, Spradling PR, Teshale EH, et al. Adjuvant ribavirin and longer direct-acting antiviral treatment duration improve sustained virological response among hepatitis C patients at risk of treatment failure. J Viral Hepat 2019;26:1210-1217.
- 238. Takehara T, Sakamoto N, Nishiguchi S, Ikeda F, Tatsumi T, Ueno Y, et al. Efficacy and safety of sofosbuvir-velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 3 trial. J Gastroenterol 2019;54:87-95.
- 239. Liu CH, Chen CY, Su WW, Liu CJ, Lo CC, Huang KJ, et al. Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis. Clin Mol Hepatol 2021;27:575-588.
- 240. Tahata Y, Hikita H, Mochida S, Kawada N, Enomoto N, Ido A, et al. Sofosbuvir plus velpatasvir treatment for hepatitis C virus in patients with decompensated cirrhosis: a Japanese real-world multicenter study. J Gastroenterol 2021;56:67-77.
- 241. Lee JJ, Lin MY, Chang JS, Hung CC, Chang JM, Chen HC, et al. Hepatitis C virus infection increases risk of developing end-stage renal disease using competing risk analysis. PLoS One 2014;9:e100790.
- 242. Fabrizi F, Dixit V, Messa P. Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality? J Viral Hepat 2012;19:601-607.
- 243. Liu CH, Lin JW, Liu CJ, Su TH, Wu JH, Tseng TC, et al. Long-term evolution of estimated glomerular filtration rate in patients with antiviral treatment for hepatitis C virus infection. Clin Gastroenterol Hepatol 2023;21:424-434.
- 244. Aroldi A, Lampertico P, Montagnino G, Passerini P, Villa M, Campise MR, et al. Natural history of hepatitis B and C in renal allograft recipients. Transplantation 2005;79:1132-1136.
- 245. Bruchfeld A, Wilczek H, Elinder CG. Hepatitis C infection, time in renal-replacement therapy, and outcome after kidney transplantation. Transplantation 2004;78:745-750.
- 246. Choy BY, Chan TM, Lai KN. Recurrent glomerulonephritis after kidney transplantation. Am J Transplant 2006;6:2535-2542.
- 247. Harrison DS, Giang J, Darling JM. An interaction between glecaprevir, pibrentasvir, and colchicine causing rhabdomyolysis in a patient with chronic renal disease. Clin Liver Dis (Hoboken) 2020;15:17-20.
- 248. Sulkowski M, Telep LE, Colombo M, Durand F, Reddy KR, Lawitz E, et al. Sofosbuvir and risk of estimated glomerular filtration rate decline or end-stage renal disease in patients with renal impairment. Aliment Pharmacol Ther 2022;55:1169-1178.
- 249. Gaur N, Malhotra V, Agrawal D, Singh SK, Beniwal P, Sharma S, et al. Sofosbuvir-velpatasvir fixed drug combination for the treatment of chronic hepatitis C infection in patients with end-stage renal disease and kidney transplantation. J Clin Exp Hepatol 2020;10:189-193.
- 250. Li M, Chen J, Fang Z, Li Y, Lin Q. Sofosbuvir-based regimen is safe and effective for hepatitis C infected patients with stage 4-5 chronic kidney disease: a systematic review and meta-analysis. Virol J 2019;16:34.
- 251. Ryu JE, Song MJ, Kim SH, Kwon JH, Yoo SH, Nam SW, et al. Safety and effectiveness of direct-acting antivirals in patients with chronic hepatitis C and chronic kidney disease. Korean J Intern Med 2022;37:958-968.
- 252. Lawitz E, Flisiak R, Abunimeh M, Sise ME, Park JY, Kaskas M, et al. Efficacy and safety of glecaprevir/pibrentasvir in renally impaired patients with chronic HCV infection. Liver Int 2020;40:1032-1041.
- 253. Huang CF, Tseng KC, Cheng PN, Hung CH, Lo CC, Peng CY, et al. Impact of sofosbuvir-based direct-acting antivirals on renal function in chronic hepatitis C patients with impaired renal function: a large cohort study from the nationwide HCV registry program (TACR). Clin Gastroenterol Hepatol 2022;20:1151-1162.
- 254. Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, Lens S, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016;65:719-726.
- 255. Singal AG, Rich NE, Mehta N, Branch A, Pillai A, Hoteit M, et al. Direct-acting antiviral therapy not associated with recurrence of hepatocellular carcinoma in a multicenter North American cohort study. Gastroenterology 2019;156:1683-1692.
- 256. Singal AG, Rich NE, Mehta N, Branch AD, Pillai A, Hoteit M, et al. Direct-acting antiviral therapy for hepatitis C virus infection is associated with increased survival in patients with a history of hepatocellular carcinoma. Gastroenterology 2019;157:1253-1263.
- 257. Ahn YH, Lee H, Han JE, Cho HJ, Cheong JY, Park B, et al. Effect of direct-acting antivirals for hepatitis C virus-related hepatocellular carcinoma recurrence and death after curative treatment. J Liver Cancer 2022;22:125-135.
- 258. Prenner SB, VanWagner LB, Flamm SL, Salem R, Lewandowski RJ, Kulik L. Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals. J Hepatol 2017;66:1173-1181.
- 259. Beste LA, Green PK, Berry K, Kogut MJ, Allison SK, Ioannou GN. Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma. J Hepatol 2017;67:32-39.
- 260. Huang CF, Yeh ML, Huang CI, Liang PC, Lin YH, Hsieh MY, et al. Equal treatment efficacy of direct-acting antivirals in patients with chronic hepatitis C and hepatocellular carcinoma? A prospective cohort study. BMJ Open 2019;9:e026703.
- 261. Singal AG, Lim JK, Kanwal F. AGA clinical practice update on interaction between oral direct-acting antivirals for chronic hepatitis C infection and hepatocellular carcinoma: expert review. Gastroenterology 2019;156:2149-2157.
- 262. Chi CT, Chen CY, Su CW, Chen PY, Chu CJ, Lan KH, et al. Direct-acting antivirals for patients with chronic hepatitis C and hepatocellular carcinoma in Taiwan. J Microbiol Immunol Infect 2021;54:385-395.
- 263. Lee TY, Tsai PC, Lee SW, Yu ML. Emerging evidence supports direct-acting antiviral therapy for HCC patients beyond the early stage. Clin Mol Hepatol 2025 Mar 4;doi: 10.3350/cmh.2025.0235.
- 264. Lee SW, Yang SS, Tsai PC, Huang CF, Chen CY, Hung CH, et al. Direct-acting antiviral therapy for patients with hepatitis C virus-related hepatocellular carcinoma: A nationwide cohort study. Clin Mol Hepatol 2025;31:899-913.
- 265. Lee SW, Chen LS, Yang SS, Huang YH, Lee TY. Direct-acting antiviral therapy for hepatitis C virus in patients with BCLC stage B/C hepatocellular carcinoma. Viruses 2022;14:2316.
- 266. Platt L, Easterbrook P, Gower E, McDonald B, Sabin K, Mc-Gowan C, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis 2016;16:797-808.
- 267. Lee S, Lee SH, Lee SJ, Kim KH, Lee JE, Cho H, et al. Incidence and risk factors of hepatitis C virus infection among human immunodeficiency virus (HIV) patients in a large HIV clinic in South Korea. Korean J Intern Med 2016;31:772-778.
- 268. Kim YC, Ahn JY, Kim JM, Kim YJ, Park DW, Yoon YK, et al. Human immunodeficiency virus (HIV) and hepatitis virus coinfection among HIV-infected Korean patients: the Korea HIV/AIDS cohort study. Infect Chemother 2017;49:268-274.
- 269. Thomas DL, Astemborski J, Vlahov D, Strathdee SA, Ray SC, Nelson KE, et al. Determinants of the quantity of hepatitis C virus RNA. J Infect Dis 2000;181:844-851.
- 270. Hernandez MD, Sherman KE. HIV/hepatitis C coinfection natural history and disease progression. Curr Opin HIV AIDS 2011;6:478-482.
- 271. Graham CS, Baden LR, Yu E, Mrus JM, Carnie J, Heeren T, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis 2001;33:562-569.
- 272. Bräu N, Salvatore M, Ríos-Bedoya CF, Fernández-Carbia A, Paronetto F, Rodríguez-Orengo JF, et al. Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy. J Hepatol 2006;44:47-55.
- 273. Sterling RK, Wegelin JA, Smith PG, Stravitz RT, Luketic VA, Fuchs M, et al. Similar progression of fibrosis between HIV/HCV-infected and HCV-infected patients: analysis of paired liver biopsy samples. Clin Gastroenterol Hepatol 2010;8:1070-1076.
- 274. Panneer N, Lontok E, Branson BM, Teo CG, Dan C, Parker M, et al. HIV and hepatitis C virus infection in the United States: whom and how to test. Clin Infect Dis 2014;59:875-882.
- 275. Bonacini M, Puoti M. Hepatitis C in patients with human immunodeficiency virus infection: diagnosis, natural history, meta-analysis of sexual and vertical transmission, and therapeutic issues. Arch Intern Med 2000;160:3365-3373.
- 276. Wyles D, Bräu N, Kottilil S, Daar ES, Ruane P, Workowski K, et al. Sofosbuvir and velpatasvir for the treatment of hepatitis C virus in patients coinfected with human immunodeficiency virus type 1: an open-label, phase 3 study. Clin Infect Dis 2017;65:6-12.
- 277. Rockstroh JK, Lacombe K, Viani RM, Orkin C, Wyles D, Luetkemeyer AF, et al. Efficacy and safety of glecaprevir/pibrentasvir in patients coinfected with hepatitis C virus and human immunodeficiency virus type 1: The EXPEDITION-2 study. Clin Infect Dis 2018;67:1010-1017.
- 278. Wilson E, Covert E, Hoffmann J, Comstock E, Emmanuel B, Tang L, et al. A pilot study of safety and efficacy of HCV retreatment with sofosbuvir/velpatasvir/voxilaprevir in patients with or without HIV (RESOLVE STUDY). J Hepatol 2019;71:498-504.
- 279. Lim DH, Jeong JY, Nam S, Choi J, Kwon HC, Yoon YB, et al. Clinical characteristics and treatment outcomes of patients with hepatitis C virus and human immunodeficiency virus coinfection: experience at a single center in Korea. J Korean Med Sci 2021;36:e308.
- 280. Lee S, Lee JE, Lee SO, Lee SH. Treatment outcomes of HCV infection in people living with HIV: a case series from a single center in Korea. Infect Chemother 2024;56:386-394.
- 281. Sagnelli E, Pasquale G, Coppola N, Scarano F, Marrocco C, Scolastico C, et al. Influence of chronic coinfection with hepatitis B and C virus on liver histology. Infection 2004;32:144-148.
- 282. Crockett SD, Keeffe EB. Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection. Ann Clin Microbiol Antimicrob 2005;4:13.
- 283. Lee LP, Dai CY, Chuang WL, Chang WY, Hou NJ, Hsieh MY, et al. Comparison of liver histopathology between chronic hepatitis C patients and chronic hepatitis B and C-coinfected patients. J Gastroenterol Hepatol 2007;22:515-517.
- 284. Crespo J, Lozano JL, de la Cruz F, Rodrigo L, Rodríguez M, San Miguel G, et al. Prevalence and significance of hepatitis C viremia in chronic active hepatitis B. Am J Gastroenterol 1994;89:1147-1151.
- 285. Chen G, Wang C, Chen J, Ji D, Wang Y, Wu V, et al. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: A systematic review and meta-analysis. Hepatology 2017;66:13-26.
- 286. Mücke MM, Backus LI, Mücke VT, Coppola N, Preda CM, Yeh ML, et al. Hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2018;3:172-180.
- 287. Oh JH, Park DA, Ko MJ, Yoo JJ, Yim SY, Ahn JH, et al. Direct-acting antivirals and the risk of hepatitis B reactivation in hepatitis B and C co-infected patients: a systematic review and meta-analysis. J Pers Med 2022;12:1957.
- 288. Garcia-Retortillo M, Forns X, Feliu A, Moitinho E, Costa J, Navasa M, et al. Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology 2002;35:680-687.
- 289. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 2002;122:889-896.
- 290. Berenguer M, López-Labrador FX, Wright TL. Hepatitis C and liver transplantation. J Hepatol 2001;35:666-678.
- 291. Wiesner RH, Sorrell M, Villamil F. Report of the first International Liver Transplantation Society expert panel consensus conference on liver transplantation and hepatitis C. Liver Transpl 2003;9:S1-9.
- 292. Gane E. The natural history and outcome of liver transplantation in hepatitis C virus-infected recipients. Liver Transpl 2003;9:S28-34.
- 293. Bunchorntavakul C, Reddy KR. Treat chronic hepatitis C virus infection in decompensated cirrhosis - pre- or post-liver transplantation? the ironic conundrum in the era of effective and well-tolerated therapy. J Viral Hepat 2016;23:408-418.
- 294. Tapper EB, Hughes MS, Buti M, Dufour JF, Flamm S, Firdoos S, et al. The optimal timing of hepatitis C therapy in transplant eligible patients with child B and C cirrhosis: a cost-effectiveness analysis. Transplantation 2017;101:987-995.
- 295. Blasco A, Forns X, Carrión JA, García-Pagán JC, Gilabert R, Rimola A, et al. Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation. Hepatology 2006;43:492-499.
- 296. Neumann UP, Berg T, Bahra M, Seehofer D, Langrehr JM, Neuhaus R, et al. Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. J Hepatol 2004;41:830-836.
- 297. Bhamidimarri KR, Ladino M, Pedraza F, Guerra G, Mattiazzi A, Chen L, et al. Transplantation of kidneys from hepatitis C-positive donors into hepatitis C virus-infected recipients followed by early initiation of direct acting antiviral therapy: a single-center retrospective study. Transpl Int 2017;30:865-873.
- 298. Scalea JR, Barth RN, Munivenkatappa R, Philosophe B, Cooper M, Whitlow V, et al. Shorter waitlist times and improved graft survivals are observed in patients who accept hepatitis C virus+ renal allografts. Transplantation 2015;99:1192-1196.
- 299. Sawinski D, Forde KA, Lo Re V, Goldberg DS, Cohen JB, Locke JE, et al. Mortality and kidney transplantation outcomes among hepatitis C virus-seropositive maintenance dialysis patients: a retrospective cohort study. Am J Kidney Dis 2019;73:815-826.
- 300. Altshuler PJ, Helmers MR, Schiazza AR, Hu R, Han JJ, Herbst DA, et al. HCV-positive allograft use in heart transplantation is associated with increased access to overdose donors and reduced waitlist mortality without compromising outcomes. J Card Fail 2022;28:32-41.
- 301. Shelton BA, Sawinski D, Mehta S, Reed RD, MacLennan PA, Locke JE. Kidney transplantation and waitlist mortality rates among candidates registered as willing to accept a hepatitis C infected kidney. Transpl Infect Dis 2018;20:e12829.
- 302. Saracco M, Tandoi F, Maletta F, Balagna R, Romagnoli R, Martini S. Early post-liver transplant use of direct-acting antivirals in naive and NS5A inhibitor-experienced HCV patients. J Viral Hepat 2023;30:201-208.
- 303. Agarwal K, Castells L, Müllhaupt B, Rosenberg WMC, McNabb B, Arterburn S, et al. Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. J Hepatol 2018;69:603-607.
- 304. Ueda Y, Kobayashi T, Ikegami T, Miuma S, Mizuno S, Akamatsu N, et al. Efficacy and safety of glecaprevir and pibrentasvir treatment for 8 or 12 weeks in patients with recurrent hepatitis C after liver transplantation: a Japanese multicenter experience. J Gastroenterol 2019;54:660-666.
- 305. Agarwal K, Angus P, et al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis C virus infection. Hepatology 2018;68:1298-1307.
- 306. Snyder HS, Wiegel JJ, Khalil K, Summers BB, Tan T, Jonchhe S, et al. A systematic review of direct acting antiviral therapies in hepatitis C virus-negative liver transplant recipients of hepatitis C-viremic donors. Pharmacotherapy 2022;42:905-920.
- 307. Gordon CE, Adam GP, Jadoul M, Martin P, Balk EM. Kidney transplantation from hepatitis C virus-infected donors to uninfected recipients: a systematic review for the KDIGO 2022 hepatitis C clinical practice guideline update. Am J Kidney Dis 2023;82:410-418.
- 308. Martin P, Fabrizi F. Hepatitis C virus and kidney disease. J Hepatol 2008;49:613-624.
- 309. Coilly A, Samuel D. Pros and Cons: usage of organs from donors infected with hepatitis C virus - revision in the directacting antiviral era. J Hepatol 2016;64:226-231.
- 310. Villegas-Galaviz J, Anderson E, Guglin M. Clinical outcomes of heart transplantation using hepatitis c-viremic donors: a systematic review with meta-analysis. J Heart Lung Transplant 2022;41:538-549.
- 311. Edmonds C, Carver A, DeClercq J, Choi L, Peter M, Schlendorf K, et al. Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting. Am J Surg 2022;223:975-982.
- 312. Connell LE, Salihu HM, Salemi JL, August EM, Weldeselasse H, Mbah AK. Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes. Liver Int 2011;31:1163-1170.
- 313. Wijarnpreecha K, Thongprayoon C, Sanguankeo A, Upala S, Ungprasert P, Cheungpasitporn W. Hepatitis C infection and intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2017;41:39-45.
- 314. Puljic A, Salati J, Doss A, Caughey AB. Outcomes of pregnancies complicated by liver cirrhosis, portal hypertension, or esophageal varices. J Matern Fetal Neonatal Med 2016;29:506-509.
- 315. Okamoto M, Nagata I, Murakami J, Kaji S, Iitsuka T, Hoshika T, et al. Prospective reevaluation of risk factors in mother-to-child transmission of hepatitis C virus: high virus load, vaginal delivery, and negative anti-NS4 antibody. J Infect Dis 2000;182:1511-1514.
- 316. Claret G, Noguera A, Esteva C, Muñoz-Almagro C, Sánchez E, Fortuny C. Mother-to-child transmission of hepatitis C virus infection in Barcelona, Spain: a prospective study. Eur J Pediatr 2007;166:1297-1299.
- 317. Kang MJ, Kim HJ, Park KJ, Kang KH, Ahn HS. Prevalence of HCV infection in pregnant women and vertical transmission. Korean J Obstet Gynecol 2004;2045-2050.
- 318. Kim YW, Lee JM, Kim GJ, Lee HM, Kim SY, Lee JS, et al. Hepatitis C virus infection in pregnancy. Korean J Obstet Gynecol 2000;597-603.
- 319. Jhaveri R, Hashem M, El-Kamary SS, Saleh DA, Sharaf SA, El-Mougy F, et al. Hepatitis C virus (HCV) vertical transmission in 12-month-old infants born to HCV-infected women and assessment of maternal risk factors. Open Forum Infect Dis 2015;2:ofv089.
- 320. European Paediatric Hepatitis C Virus Network. A significant sex--but not elective cesarean section--effect on mother-to-child transmission of hepatitis C virus infection. J Infect Dis 2005;192:1872-1879.
- 321. Pembrey L, Newell ML, Tovo PA. The management of HCV infected pregnant women and their children European paediatric HCV network. J Hepatol 2005;43:515-525.
- 322. Shebl FM, El-Kamary SS, Saleh DA, Abdel-Hamid M, Mikhail N, Allam A, et al. Prospective cohort study of mother-to-infant infection and clearance of hepatitis C in rural Egyptian villages. J Med Virol 2009;81:1024-1031.
- 323. Cottrell EB, Chou R, Wasson N, Rahman B, Guise JM. Reducing risk for mother-to-infant transmission of hepatitis C virus: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2013;158:109-113.
- 324. American Academy of Pediatrics. Committee on Infectious Diseases. Hepatitis C virus infection. Pediatrics 1998;101:481-485.
- 325. US Department of Health and Human Services. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998;47:1-39.
- 326. Mast EE, Hwang LY, Seto DS, Nolte FS, Nainan OV, Wurtzel H, et al. Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J Infect Dis 2005;192:1880-1889.
- 327. Polywka S, Pembrey L, Tovo PA, Newell ML. Accuracy of HCV-RNA PCR tests for diagnosis or exclusion of vertically acquired HCV infection. J Med Virol 2006;78:305-310.
- 328. VN Chilaka, JC Konje. Viral hepatitis in pregnancy: ACOG Clinical Practice Guideline No. 6. Obstet Gynecol 2023;142:745-759.
- 329. Yattoo GN, Shafi SM, Dar GA, Sodhi JS, Gorka S, Dhar N, et al. Safety and efficacy of treatment for chronic hepatitis C during pregnancy: a prospective observational study in Srinagar, India. Clin Liver Dis (Hoboken) 2023;22:134-139.
- 330. Quek JWE, Loo JH, Lim EQ, Chung AH, Othman ABB, Tan JJ, et al. Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis. EClinicalMedicine 2024;74:102727.
- 331. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014;61:S45-57.
- 332. Indolfi G, Easterbrook P, Dusheiko G, El-Sayed MH, Jonas MM, Thorne C, et al. Hepatitis C virus infection in children and adolescents. Lancet Gastroenterol Hepatol 2019;4:477-487.
- 333. Alter MJ, Kruszon-Moran D, Nainan OV, McQuillan GM, Gao F, Moyer LA, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999;341:556-562.
- 334. Kwon JH, Bae SH. [Current status and clinical course of hepatitis C virus in Korea]. Korean J Gastroenterol 2008;51:360-367.
- 335. Aniszewska M, Kowalik-Mikołajewska B, Pokorska-Spiewak M, Marczyńska M. [Anti-HCV testing as a basic standard of monitoring HCV mother-to-child infection: advantages and disadvantages of the method]. Przegl Epidemiol 2012;66:341-345.
- 336. England K, Pembrey L, Tovo PA, Newell ML. Excluding hepatitis C virus (HCV) infection by serology in young infants of HCV-infected mothers. Acta Paediatr 2005;94:444-450.
- 337. Garazzino S, Calitri C, Versace A, Alfarano A, Scolfaro C, Bertaina C, et al. Natural history of vertically acquired HCV infection and associated autoimmune phenomena. Eur J Pediatr 2014;173:1025-1031.
- 338. Farmand S, Wirth S, Löffler H, Woltering T, Kenzel S, Lainka E, et al. Spontaneous clearance of hepatitis C virus in vertically infected children. Eur J Pediatr 2012;171:253-258.
- 339. Guido M, Rugge M, Jara P, Hierro L, Giacchino R, Larrauri J, et al. Chronic hepatitis C in children: the pathological and clinical spectrum. Gastroenterology 1998;115:1525-1529.
- 340. Mizuochi T, Takano T, Yanagi T, Ushijima K, Suzuki M, Miyoshi Y, et al. Epidemiologic features of 348 children with hepatitis C virus infection over a 30-year period: a nationwide survey in Japan. J Gastroenterol 2018;53:419-426.
- 341. Bortolotti F, Verucchi G, Cammà C, Cabibbo G, Zancan L, Indolfi G, et al. Long-term course of chronic hepatitis C in children: from viral clearance to end-stage liver disease. Gastroenterology 2008;134:1900-1907.
- 342. Curtis MR, Epstein RL, Pei P, Linas BP, Ciaranello AL. Cost-effectiveness of strategies for treatment timing for perinatally acquired hepatitis C virus. JAMA Pediatr 2024;178:489-496.
- 343. Serranti D, Nebbia G, Cananzi M, Nicastro E, Di Dato F, Nuti F, et al. Efficacy of sofosbuvir/ledipasvir in adolescents with chronic hepatitis C genotypes 1, 3, and 4: a real-world study. J Pediatr Gastroenterol Nutr 2021;72:95-100.
- 344. Jonas MM, Romero R, Rosenthal P, Lin CH, Verucchi G, Wen J, et al. Sofosbuvir-velpatasvir in children 3-17 years old with hepatitis C virus infection. J Pediatr Gastroenterol Nutr 2024;78:1342-1354.
- 345. Jonas MM, Rhee S, Kelly DA, Del Valle-Segarra A, Feiterna-Sperling C, Gilmour S, et al. Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in children with chronic HCV: part 2 of the DORA study. Hepatology 2021;74:19-27.
, on behalf of the Korean Association for the Study of the Liver (KASL)
