Clinical and Molecular Hepatology

"Surveillance"

Review Article

Hepatocellular Carcinoma Surveillance: A Health Economic Evaluation: Qi-Feng Chen, Xiong-Ying Jiang, Song Chen, Jiongliang Wang, Ming Zhao; Received September 19, 2025 Accepted January 1, 2026 Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1060 [Accepted]

Abstract
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Hepatocellular carcinoma (HCC) imposes a major health and economic burden worldwide, with disproportionate effects in low- and middle-income countries (LMICs). Surveillance in high-risk populations, typically using semiannual ultrasound and alpha-fetoprotein (AFP) testing, has been shown to be cost-effective by enabling earlier detection and improving survival. Yet, its overall value is reduced by poor adherence and the limited sensitivity of ultrasound, particularly in patients with metabolic-associated steatotic liver disease. Emerging approaches—including abbreviated MRI, multi-biomarker models (e.g., GALAD), and liquid biopsy assays such as methylated DNA markers—demonstrate greater diagnostic accuracy and potential economic advantages compared with conventional methods. Integration of artificial intelligence (AI) into imaging may further enhance efficiency and reduce downstream costs. Moving toward precision surveillance, guided by individualized risk stratification that incorporates etiology, fibrosis stage, and molecular profiles, can optimize allocation of resources and maximize cost-effectiveness at the population level. Interventions to improve adherence, including mailed outreach and behavioral economic incentives, have shown both clinical benefit and cost savings, underscoring the role of implementation science. Because socioeconomic disparities influence both access and outcomes, economic models must explicitly address equity to achieve sustainable impact. Future research should prioritize prospective trials that evaluate not only clinical performance but also the real-world cost-effectiveness of novel technologies and stratified surveillance strategies. For LMICs, adapting proven models into affordable, context-appropriate programs is essential. By combining prevention, precision risk assessment, innovative technologies, and equitable implementation, HCC surveillance can deliver both clinical and economic value, reducing the global burden of disease.

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Letter to the Editor

Comment on “High Steatosis-Associated Fibrosis Estimator Scores Predict Hepatocellular Carcinoma in Viral and Non-Viral Hepatitis and Metabolic Dysfunction-Associated Steatotic Liver Disease”: Prajnasini Satapathy, Rachana Mehta, Ranjana Sah; Received August 2, 2025 Accepted August 6, 2025 Published online August 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0875 [Accepted]

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Editorial

HCC Surveillance After Curative Treatment: A New Frontier for Abbreviated MRI Editorial on: “Non-contrast MRI for Detection of Late Recurrent Hepatocellular Carcinoma After Curative Treatment: Comparison to CT”: Hyungjin Rhee, Jin-Young Choi; Received July 16, 2025 Accepted July 24, 2025 Published online July 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0786 [Accepted]

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Correspondences

HCC predictors in routine practice for patients with chronic liver diseases: Correspondence to editorial on “High SAFE scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction associated steatotic liver disease”: Tung-Hung Su, Jia-Horng Kao; Clin Mol Hepatol 2026;32(1):e52-e54.
Published online February 26, 2025; DOI: https://doi.org/10.3350/cmh.2025.0187

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Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to letter to the editor on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”: Hee Yeon Kim, Miyoung Choi, Dae Won Jun; Clin Mol Hepatol 2025;31(1):e105-e107.
Published online November 4, 2024; DOI: https://doi.org/10.3350/cmh.2024.0937

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Letter to the Editor

Hepatic neoplasm

Urgent need for education on hepatocellular carcinoma surveillance among high-risk population in China: Lei Cai, Chao Li, Li-Yang Sun, Yong-Kang Diao, Ming-Da Wang, Tian Yang; Clin Mol Hepatol 2025;31(1):e39-e43.
Published online October 23, 2024; DOI: https://doi.org/10.3350/cmh.2024.0813

Citations

Citations to this article as recorded by

Persisting challenges in the early detection of hepatocellular carcinoma
Ashwini Arvind, Kennedy Redmon, Amit G Singal
Expert Review of Anticancer Therapy.2025; 25(3): 229. CrossRef

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Crossref

Correspondence

Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to editorial on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”: Hee Yeon Kim, Miyoung Choi, Dae Won Jun; Clin Mol Hepatol 2025;31(1):e48-e51.
Published online September 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0777

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Original Article

Liver fibrosis, cirrhosis, and portal hypertension

Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis: Hee Yeon Kim, Jung Hwan Yu, Young Eun Chon, Seung Up Kim, Mi Na Kim, Ji Won Han, Han Ah Lee, Young-Joo Jin, Jihyun An, Miyoung Choi, Dae Won Jun; Clin Mol Hepatol 2024;30(Suppl):S199-S213.
Published online July 30, 2024; DOI: https://doi.org/10.3350/cmh.2024.0351

Background/Aims
Although important, clinically significant liver fibrosis is often overlooked in the general population. We aimed to examine the prevalence of clinically significant liver fibrosis using noninvasive tests (NITs) in the general population.
Methods
We collected data from four databases (MEDLINE, Embase, Cochrane Library, and KoreaMed) from inception to June 13, 2023. Original articles reporting the prevalence of clinically significant liver fibrosis in the general population were included. The Stata metaprop function was used to obtain the pooled prevalence of liver fibrosis with NITs in the general population.
Results
We screened 6,429 articles and included 45 eligible studies that reported the prevalence of clinically significant liver fibrosis in the general population. The prevalence of advanced liver fibrosis, using the high probability cutoff of the fibrosis-4 (FIB-4) index, was 2.3% (95% confidence interval [CI], 1.2–3.7%). The prevalence of significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis, assessed using vibration-controlled transient elastography (VCTE) among the general population, was 7.3% (95% CI, 5.9–8.8%), 3.5% (95% CI, 2.7–4.5), and 1.2% (95% CI, 0.8–1.8%), respectively. Region-based subgroup analysis revealed that the highest prevalence of advanced fibrosis using the high probability cutoff of the FIB-4 index was observed in the American region. Furthermore, the American region exhibited the highest prevalence of significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis, using VCTE.
Conclusions
Previously undiagnosed clinically significant liver fibrosis is found in the general population through NITs. Future research is necessary to stratify the risk in the general population.

Citations

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Modified FIB-4 Index in Type 2 Diabetes Mellitus with Steatosis: A Non-Linear Predictive Model for Advanced Hepatic Fibrosis
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Review

Viral hepatitis

Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication: Chung-Feng Huang, Manar Hijaze Awad, Meital Gal-Tanamy, Ming-Lung Yu; Clin Mol Hepatol 2024;30(3):326-344.
Published online April 26, 2024; DOI: https://doi.org/10.3350/cmh.2024.0155

Abstract
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Hepatitis C virus (HCV) infection is one of the major etiologies of hepatocellular carcinoma (HCC) with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in chronic hepatitis C (CHC) patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the direct-acting antiviral (DAA) era and might be due to preexisting inflammatory and fibrotic liver backgrounds, immune dysregulation between host and virus interactions, as well as host epigenetic scars, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors, and HCC surveillance strategy for HCC development after HCV eradication in CHC patients.

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Editorials

Hepatic neoplasm

Clinical practice guidelines and real-world practice for hepatocellular carcinoma in Taiwan: Bridging the gap: Shen-Yung Wang; Clin Mol Hepatol 2023;29(2):349-351.
Published online March 20, 2023; DOI: https://doi.org/10.3350/cmh.2023.0082

7,723 View
84 Download

Hepatic neoplasm

What should be done to reduce the discrepancy between guidelines and real-life practice for hepatocellular carcinoma in Korea?: Min Kyung Park, Yoon Jun Kim; Clin Mol Hepatol 2023;29(2):332-334.
Published online March 16, 2023; DOI: https://doi.org/10.3350/cmh.2023.0080

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Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma
Ye Rim Kim, Sung Won Chung, Min-Ju Kim, Won-Mook Choi, Jonggi Choi, Danbi Lee, Han Chu Lee, Ju Hyun Shim
Journal of Hepatocellular Carcinoma.2024; Volume 11: 1235. CrossRef

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Hepatic neoplasm

Hepatocellular carcinoma surveillance in non-alcoholic fatty liver disease – who and how?: Margaret LP Teng, Darren Jun Hao Tan, Cheng Han Ng, Daniel Q. Huang; Clin Mol Hepatol 2023;29(2):404-407.
Published online March 14, 2023; DOI: https://doi.org/10.3350/cmh.2023.0069

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Viral hepatitis

The imitator of immune-tolerant chronic hepatitis B: A killer in disguise: Moon Haeng Hur, Jeong-Hoon Lee; Clin Mol Hepatol 2023;29(2):363-366.
Published online March 9, 2023; DOI: https://doi.org/10.3350/cmh.2023.0079

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Reviews

Hepatic neoplasm

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Taiwan perspective: Tung-Hung Su, Chih-Horng Wu, Tsung-Hao Liu, Cheng-Maw Ho, Chun-Jen Liu; Clin Mol Hepatol 2023;29(2):230-241.
Published online January 30, 2023; DOI: https://doi.org/10.3350/cmh.2022.0421

Abstract
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Hepatocellular carcinoma (HCC) is the fourth most common cancer and the second leading cause of cancer-related death in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan developed and updated the guidelines for HCC management in 2020. In clinical practice, we follow these guidelines and the reimbursement policy of the government. In Taiwan, abdominal ultrasonography, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) tests are performed for HCC surveillance every 6 months or every 3 months for high-risk patients. Dynamic computed tomography, magnetic resonance imaging, and contrast-enhanced ultrasound have been recommended for HCC surveillance in extremely high-risk patients or those with poor ultrasonographic visualization results. HCC is usually diagnosed through dynamic imaging, and pathological diagnosis is recommended. Staging of HCC is based on a modified version of the Barcelona Clinic Liver Cancer (BCLC) system, and the HCC management guidelines in Taiwan actively promote curative treatments including surgery and locoregional therapy for BCLC stage B or C patients. Transarterial chemoembolization (TACE), drug-eluting bead TACE, transarterial radioembolization, and hepatic artery infusion chemotherapy may be administered for patients with BCLC stage B or C HCC. Sorafenib and lenvatinib are reimbursed as systemic therapies, and regorafenib and ramucirumab may be reimbursed in cases of sorafenib failure. First-line atezolizumab with bevacizumab is not yet reimbursed but may be administered in clinical practice. Systemic therapy and external beam radiation therapy may be used in specific patients. Early switching to systemic therapy in TACE-refractory patients is a recent paradigm shift in HCC management.

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Hepatic neoplasm

Clinical practice guideline and real-life practice in hepatocellular carcinoma: A Korean perspective: Myung Ji Goh, Dong Hyun Sinn, Jong Man Kim, Min Woo Lee, Dong Ho Hyun, Jeong Il Yu, Jung Yong Hong, Moon Seok Choi; Clin Mol Hepatol 2023;29(2):197-205.
Published online January 5, 2023; DOI: https://doi.org/10.3350/cmh.2022.0404

Abstract
PDF

Hepatocellular carcinoma (HCC) is a major cause of death in many countries, including South Korea. To provide useful and sensible advice for clinical management of patients with HCC, the Korean Liver Cancer Association and National Cancer Center Korea Practice Guideline Revision Committee have recently revised the practice guidelines for HCC management. However, there are some differences between practice guidelines and real-life clinical practice. In this review, we describe some key recommendations of the 2022 version of practice guidelines and the real-life clinical situation in South Korea, together with discussion about efforts needed to reduce the difference between guidelines and real-life clinical practice.

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Hepatic neoplasm

Preventive strategy for nonalcoholic fatty liver disease-related hepatocellular carcinoma: Yuri Cho, Bo Hyun Kim, Joong-Won Park; Clin Mol Hepatol 2023;29(Suppl):S220-S227.
Published online November 10, 2022; DOI: https://doi.org/10.3350/cmh.2022.0360

Abstract
PDF

The incidence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, including Asia. Most patients with NAFLD-related HCC are at a much-advanced stage and older age at the time of diagnosis than those with virus-related HCC because they have not undergone HCC surveillance. This review provides an overview of the mechanism of hepatocarcinogenesis in NAFLD, preventive strategies for NAFLDrelated HCC, and strategies for the surveillance of patients with NAFLD.

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Hepatic neoplasm

Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease: Karim Seif El Dahan, Darine Daher, Amit G. Singal; Clin Mol Hepatol 2023;29(Suppl):S207-S219.
Published online September 14, 2022; DOI: https://doi.org/10.3350/cmh.2022.0247

Abstract
PDF

Non-alcoholic fatty liver disease (NAFLD) may progress to cirrhotic or non-cirrhotic hepatocellular carcinoma (HCC), and is currently recognized as the fastest growing cause of HCC worldwide. Accordingly, professional society guidelines recommend HCC surveillance in patients with cirrhosis from any etiology, and some may consider it beneficial in subgroups with non-cirrhotic NAFLD at higher risk for HCC. Notably, patients with NAFLD-related HCC are more likely to have HCC diagnosed at more advanced stages and have poorer outcomes when compared to other etiologies, and suboptimal effectiveness of HCC surveillance programs is a major culprit. In this review, we summarize the current guidelines for HCC surveillance and discuss its benefits versus potential harms for NAFLD patients. We also address the unique challenges of HCC surveillance in NAFLD, including higher proportion of NAFLD-related HCC without cirrhosis, poor recognition of at-risk patients, lack of consensus regarding the value of surveillance in non-cirrhotic NAFLD, subpar effectiveness of surveillance tools related to NAFLD phenotype, and preponderant surveillance underuse among NAFLD patients. Finally, we examine the effectiveness of currently used surveillance tools (i.e., ultrasound and alpha fetoprotein) and outline future perspectives including emerging risk stratification tools, imaging surveillance strategies (e.g., abbreviated magnetic resonance imaging protocols), blood-based biomarkers (e.g., GALAD and circulating tumor DNA panels), and interventions to improve surveillance adherence.

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Editorial

Surveillance for hepatocellular carcinoma: It is time to move forward: Bo Hyun Kim, Yuri Cho, Joong-Won Park; Clin Mol Hepatol 2022;28(4):810-813.
Published online September 6, 2022; DOI: https://doi.org/10.3350/cmh.2022.0257

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Original Articles

Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease: Won Sohn, Danbee Kang, Minwoong Kang, Eliseo Guallar, Juhee Cho, Yong-Han Paik; Clin Mol Hepatol 2022;28(4):851-863.
Published online June 3, 2022; DOI: https://doi.org/10.3350/cmh.2022.0037

Background/Aims
This study aimed to investigate the effect of hepatocellular carcinoma (HCC) surveillance using the Korea National Liver Cancer Screening Program on the receipt of curative treatment for HCC and mortality in patients with chronic liver disease.
Methods
This population-based cohort study from the Korean National Health Insurance Service included 2003 to 2015 claims data collected from 1,209,825 patients aged ≥40 years with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Patients were divided according to HCC surveillance using ultrasonography and serum alpha-fetoprotein every 6–12 months. The study outcomes were the receipt of curative treatment (surgical resection, radiofrequency ablation, or liver transplantation) and all-cause mortality.
Results
The study population consisted of 1,209,825 patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (median age, 52.0 years; interquartile range, 46–55 years; 683,902 men [56.5%]). The proportion of participants who underwent HCC surveillance was 52.7% (n=657,889). During 10,522,940 person-years of follow-up, 74,433 HCC cases developed, including 36,006 patients who underwent curative treatment. The surveillance group had a significantly higher proportion of curative treatment for HCC than the non-surveillance group after adjusting for confounding factors (adjusted hazard ratio [HR], 5.64; 95% confidence interval [CI], 5.48–5.81). The surveillance group had a significantly lower mortality rate than the non-surveillance group (adjusted HR, 0.56; 95% CI, 0.55–0.56).
Conclusions
HCC surveillance using the national screening program in patients with chronic viral hepatitis or liver cirrhosis provides better opportunity for curative treatment for HCC and improves overall survival.

Citations

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IEEE Sensors Journal.2024; 24(11): 18288. CrossRef
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Yuri Cho, Bo Hyun Kim, Young-Suk Lim
Digestive Disease Interventions.2024; 08(03): 169. CrossRef
Association of physical activity, including amount and maintenance, with the risk of HCC among patients with type 2 diabetes
Wonkyung Han, Kyungdo Han, Seong Gyu Hwang, Sang Hoon Ahn, Mi Na Kim
JHEP Reports.2024; 6(10): 101166. CrossRef
Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma
Jiwon Hong, Jung Woo Eun, Geum Ok Baek, Jae Youn Cheong, Seryoung Park, Soon Sun Kim, Hyo Jung Cho, Su Bin Lim
Clinical and Molecular Hepatology.2024; 30(3): 360. CrossRef
Evolving trends in treatment patterns for hepatocellular carcinoma in Korea from 2008 to 2022: a nationwide population-based study
Ji Won Han, Won Sohn, Gwang Hyeon Choi, Jeong Won Jang, Gi Hyeon Seo, Bo Hyun Kim, Jong Young Choi
Journal of Liver Cancer.2024; 24(2): 274. CrossRef
Correspondence on Editorial regarding “Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease”
Won Sohn, Yong-Han Paik
Clinical and Molecular Hepatology.2023; 29(1): 182. CrossRef
Cost-effectiveness of expanded antiviral treatment for chronic hepatitis B virus infection in China: an economic evaluation
Sihui Zhang, Chao Wang, Bei Liu, Qing-Bin Lu, Jia Shang, Yihua Zhou, Jidong Jia, Xiaoyuan Xu, Huiying Rao, Bingfeng Han, Tianshuo Zhao, Linyi Chen, Mingzhu Xie, Jiahao Cui, Juan Du, Jing zeng, Ninghua huang, Yaqiong Liu, Lei Zhang, Hui Zhuang, Fuqiang Cui
The Lancet Regional Health - Western Pacific.2023; 35: 100738. CrossRef
A new model predicts hepatocellular carcinoma in patients with HBV-related decompensated liver cirrhosis and long-term antiviral therapy: a prospective study
Hao-dan Mao, Shu-qin Zheng, Su-hua Yang, Ze-yu Huang, Yuan Xue, Min Zhou
PeerJ.2023; 11: e15014. CrossRef
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Shen-Yung Wang
Clinical and Molecular Hepatology.2023; 29(2): 349. CrossRef
The clinical management of hepatocellular carcinoma in China: Progress and challenges
Shan Shan, Jidong Jia
Clinical and Molecular Hepatology.2023; 29(2): 339. CrossRef
The prime time for management of hepatocellular carcinoma in Hong Kong
Landon L. Chan, Stephen L. Chan
Clinical and Molecular Hepatology.2023; 29(2): 345. CrossRef
What should be done to reduce the discrepancy between guidelines and real-life practice for hepatocellular carcinoma in Korea?
Min Kyung Park, Yoon Jun Kim
Clinical and Molecular Hepatology.2023; 29(2): 332. CrossRef
Clinical practice guideline and real-life practice in hepatocellular carcinoma: A Korean perspective
Myung Ji Goh, Dong Hyun Sinn, Jong Man Kim, Min Woo Lee, Dong Ho Hyun, Jeong Il Yu, Jung Yong Hong, Moon Seok Choi
Clinical and Molecular Hepatology.2023; 29(2): 197. CrossRef
Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Taiwan perspective
Tung-Hung Su, Chih-Horng Wu, Tsung-Hao Liu, Cheng-Maw Ho, Chun-Jen Liu
Clinical and Molecular Hepatology.2023; 29(2): 230. CrossRef
Establishment and application of a survival rate graph model based on biomarkers and imaging indexes after primary hepatocellular carcinoma resection
Yue Xu, Xiaoqin Yao, Jinmei Li, Guoyuan Zhang, Guangcheng Luo, Qiang Wang
Cancer Medicine.2023; 12(12): 13329. CrossRef
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Beom Kyung Kim, Sang Hoon Ahn
Journal of the Formosan Medical Association.2023; 122(12): 1238. CrossRef
A machine learning model for predicting hepatocellular carcinoma risk in patients with chronic hepatitis B
Hye Won Lee, Hwiyoung Kim, Taeyun Park, Soo Young Park, Young Eun Chon, Yeon Seok Seo, Jae Seung Lee, Jun Yong park, Do Young Kim, Sang Hoon Ahn, Beom Kyung Kim, Seung Up Kim
Liver International.2023; 43(8): 1813. CrossRef
Risk factors associated with late hepatocellular carcinoma detection in patients undergoing regular surveillance
Sangmi Jang, Young-Joo Jin, Jin-Woo Lee, Dam Kwon, Jung Hwan Yu
Medicine.2023; 102(32): e34637. CrossRef
Surveillance for hepatocellular carcinoma: It is time to move forward
Bo Hyun Kim, Yuri Cho, Joong-Won Park
Clinical and Molecular Hepatology.2022; 28(4): 810. CrossRef
Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis
Jae Lee, Tae Lim, Hye Lee, Seung Kim, Jun Park, Do Kim, Sang Ahn, Hyun Lee, Jung Lee, Ja Kim, In Min, Beom Kim
Diagnostics.2022; 13(1): 3. CrossRef

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Hepatic neoplasm

Serum fibrosis index-based risk score predicts hepatocellular carcinoma in untreated patients with chronic hepatitis B: Lilian Yan Liang, Hye Won Lee, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip, Yee-Kit Tse, Vicki Wing-Ki Hui, Grace Chung-Yan Lui, Henry Lik-Yuen Chan, Grace Lai-Hung Wong; Clin Mol Hepatol 2021;27(3):499-509.
Published online February 26, 2021; DOI: https://doi.org/10.3350/cmh.2020.0333

Background/Aims
Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients.
Methods
Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort.
Results
180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted.
Conclusion
A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.

Citations

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Liver elastography-based risk score for predicting hepatocellular carcinoma risk
Chan Tian, Chunyan Ye, Haiyan Guo, Kun Lu, Juan Yang, Xiao Wang, Xinyuan Ge, Chengxiao Yu, Jing Lu, Longfeng Jiang, Qun Zhang, Ci Song
JNCI: Journal of the National Cancer Institute.2025; 117(4): 761. CrossRef
Development and Validation of a Machine Learning-Based Model Used for Predicting Hepatocellular Carcinoma Risk in Patients with Hepatitis B-Related Cirrhosis: A Retrospective Study
Yixin Hou, Jianguo Yan, Ke Shi, Xiaoli Liu, Fangyuan Gao, Tong Wu, Peipei Meng, Min Zhang, Yuyong Jiang, Xianbo Wang
OncoTargets and Therapy.2024; Volume 17: 215. CrossRef
Comparison of models to predict incident chronic liver disease: a systematic review and external validation in Chinese adults
Xue Cong, Shuyao Song, Yingtao Li, Kaiyang Song, Cameron MacLeod, Yujie Cheng, Jun Lv, Canqing Yu, Dianjianyi Sun, Pei Pei, Ling Yang, Yiping Chen, Iona Millwood, Shukuan Wu, Xiaoming Yang, Rebecca Stevens, Junshi Chen, Zhengming Chen, Liming Li, Christia
BMC Medicine.2024;[Epub] CrossRef
Post-operative recurrence of liver cancer according to antiviral therapy for detectable hepatitis B viremia: A nationwide study
Byungyoon Yun, Sang Hoon Ahn, Juyeon Oh, Jin-Ha Yoon, Beom Kyung Kim
European Journal of Internal Medicine.2023; 107: 66. CrossRef
Comparable Mortality Between Asian Patients with Chronic Hepatitis B Under Long-Term Antiviral Therapy vs Matched Control: A Population-Based Study
Byungyoon Yun, Juyeon Oh, Sang Hoon Ahn, Jin-Ha Yoon, Beom Kyung Kim
American Journal of Gastroenterology.2023; 118(6): 1001. CrossRef
Statin use is associated with better post‐operative prognosis among patients with hepatitis B virus‐related hepatocellular carcinoma
Byungyoon Yun, Sang Hoon Ahn, Juyeon Oh, Jin‐Ha Yoon, Beom Kyung Kim
European Journal of Clinical Investigation.2023;[Epub] CrossRef
Comparable outcomes between immune-tolerant and active phases in noncirrhotic chronic hepatitis B: a meta-analysis
Han Ah Lee, Seung Up Kim, Yeon Seok Seo, Sang Hoon Ahn, Chai Hong Rim
Hepatology Communications.2023; 7(2): e0011. CrossRef
Outcome of untreated low-level viremia versus antiviral therapy-induced or spontaneous undetectable HBV-DNA in compensated cirrhosis
Daniel Q. Huang, Nobuharu Tamaki, Hyung Woong Lee, Soo Young Park, Yu Rim Lee, Hye Won Lee, Seng Gee Lim, Tae Seop Lim, Masayuki Kurosaki, Hiroyuki Marusawa, Toshie Mashiba, Masahiko Kondo, Yasushi Uchida, Haruhiko Kobashi, Koichiro Furuta, Namiki Izumi,
Hepatology.2023; 77(5): 1746. CrossRef
Prognostic Significance of Hemoglobin, Albumin, Lymphocyte and Platelet (HALP) Score in Hepatocellular Carcinoma
Jing Zhou, Daofeng Yang
Journal of Hepatocellular Carcinoma.2023; Volume 10: 821. CrossRef
Prediction model of hepatitis B virus-related hepatocellular carcinoma in patients receiving antiviral therapy
Beom Kyung Kim, Sang Hoon Ahn
Journal of the Formosan Medical Association.2023; 122(12): 1238. CrossRef
A machine learning model for predicting hepatocellular carcinoma risk in patients with chronic hepatitis B
Hye Won Lee, Hwiyoung Kim, Taeyun Park, Soo Young Park, Young Eun Chon, Yeon Seok Seo, Jae Seung Lee, Jun Yong park, Do Young Kim, Sang Hoon Ahn, Beom Kyung Kim, Seung Up Kim
Liver International.2023; 43(8): 1813. CrossRef
HBV seroprevalence and liver fibrosis status among population born before national immunization in Southern Thailand: Findings from a health check-up program
Supinya Sono, Jirayu Sae-Chan, Apichat Kaewdech, Naichaya Chamroonkul, Pimsiri Sripongpun, Jason T. Blackard
PLOS ONE.2022; 17(6): e0270458. CrossRef
The Age, Gamma-Glutamyl Transpeptidase and Platelet Index: A Novel Noninvasive Model for Predicting Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Related Liver Cirrhosis
Kai Liu, Zeyu Huang, Suhua Yang, Lin Lin, Shuqin Zheng, Xiujun Zhang, Yuan Xue, Weibin Xie
Journal of Hepatocellular Carcinoma.2022; Volume 9: 1057. CrossRef
Surveillance for hepatocellular carcinoma: It is time to move forward
Bo Hyun Kim, Yuri Cho, Joong-Won Park
Clinical and Molecular Hepatology.2022; 28(4): 810. CrossRef
Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis
Jae Lee, Tae Lim, Hye Lee, Seung Kim, Jun Park, Do Kim, Sang Ahn, Hyun Lee, Jung Lee, Ja Kim, In Min, Beom Kim
Diagnostics.2022; 13(1): 3. CrossRef
Risk of hepatocellular carcinoma in untreated patients with chronic hepatitis B: Independent of HBeAg status?
Ho Soo Chun, Minjong Lee
Clinical and Molecular Hepatology.2021; 27(3): 448. CrossRef

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Persistence of intrahepatic hepatitis B virus DNA integration in patients developing hepatocellular carcinoma after hepatitis B surface antigen seroclearance: Jeong Won Jang, Jin Seoub Kim, Hye Seon Kim, Kwon Yong Tak, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Lewis R. Roberts; Clin Mol Hepatol 2021;27(1):207-218.
Published online December 3, 2020; DOI: https://doi.org/10.3350/cmh.2020.0115

Background/Aims
The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.

Methods
Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.

Results
HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.

Conclusions
The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

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275 Download
36 Web of Science
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Letter to the Editor

Hepatic neoplasm

How long should physicians follow up with patients after curative treatment for hepatocellular carcinoma?: Bo Hyun Kim; Clin Mol Hepatol 2020;26(4):579-581.
Published online September 23, 2020; DOI: https://doi.org/10.3350/cmh.2020.0200

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Cause of death and cause-specific mortality for primary liver cancer in South Korea: A nationwide population-based study in hepatitis B virus-endemic area
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Editorial

Hepatic neoplasm

Should you advocate for hepatocellular carcinoma surveillance in patients with alcohol-related liver disease or non-alcoholic fatty liver disease?: Ju Hyun Shim; Clin Mol Hepatol 2020;26(2):183-184.
Published online March 12, 2020; DOI: https://doi.org/10.3350/cmh.2020.0042

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Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1
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Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease
Yoshio Sumida, Masashi Yoneda, Yuya Seko, Hiroshi Ishiba, Tasuku Hara, Hidenori Toyoda, Satoshi Yasuda, Takashi Kumada, Hideki Hayashi, Takashi Kobayashi, Kento Imajo, Masato Yoneda, Toshifumi Tada, Takumi Kawaguchi, Yuichiro Eguchi, Satoshi Oeda, Hirokaz
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Cancers.2020; 12(11): 3347. CrossRef

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Review

Hepatic neoplasm

Hepatocellular carcinoma surveillance in the 21st century: Saving lives or causing harm?: Ibrahim A. Hanouneh, Naim Alkhouri, Amit G. Singal; Clin Mol Hepatol 2019;25(3):264-269.
Published online March 4, 2019; DOI: https://doi.org/10.3350/cmh.2019.1001

Abstract
PDF

Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide. Prognosis and treatment options largely depend on tumor stage at diagnosis, with curative treatments only available if detected at an early stage. However, two thirds of patients with HCC are diagnosed at a late stage and not eligible for cure. Therefore several liver professional societies recommend HCC surveillance using abdominal ultrasound with or without alpha fetoprotein in at-risk populations, including patients with cirrhosis and subsets of those with chronic hepatitis B. Available data suggest HCC surveillance can significantly improve early tumor detection, curative treatment eligibility, and overall survival. However, the potential benefits of HCC surveillance must be considered in light a shifting HCC demographic from a viral-mediated cancer to an increasing proportion of patients having non-alcoholic steatohepatitis, which has been shown to limit ultrasound sensitivity and may mitigate observed benefits. Further, benefits of HCC surveillance must be weighed against potential physical, financial and psychological harms. Continued data for both benefits and harms of HCC surveillance in contemporary populations are necessary. In the interim, providers should continue to strive for high quality HCC surveillance in at-risk patients.

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Editorial

Hepatic neoplasm

Surveillance of hepatocellular carcinoma: is only ultrasound enough?: Woo Kyoung Jeong; Clin Mol Hepatol 2017;23(3):222-223.
Published online September 19, 2017; DOI: https://doi.org/10.3350/cmh.2017.0046

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Original Articles

Hepatic neoplasm

Pitfalls in surveillance for hepatocellular carcinoma: How successful is it in the real world?: Linda L. Wong, Ruel J. Reyes, Sandi A. Kwee, Brenda Y. Hernandez, Sumodh C. Kalathil, Naoky C. Tsai; Clin Mol Hepatol 2017;23(3):239-248.
Published online July 14, 2017; DOI: https://doi.org/10.3350/cmh.2017.0008

Abstract
PDF

Background/Aims
Surveillance for hepatocellular carcinoma (HCC) with ultrasound in high-risk populations is generally believed to improve opportunities for treatment. However, tumors are still missed due to various factors. This study explores success versus failure of HCC surveillance. Methods: This is a retrospective study of 1,125 HCC cases. Categories considered for successful detection were largest tumor ≤3.0 cm, single tumors ≤3.0 cm and ≤2.0 cm, and adherence to Milan criteria. Examined factors were age <60 years, gender, rural residence, body-mass index (BMI), hepatitis infection, smoking, diabetes, hyperlipidemia, cirrhosis, ascites, and Model for End-Stage Liver Disease <10. Results: HCC was found on surveillance in 257 patients with a mean tumor size of 3.17 cm; multiple tumors were seen in 28% of cases, bilateral tumors in 7.4%, and vascular invasion in 3.7%. Surveillance was successful in 61.5% of cases involving a largest tumor ≤3.0 cm, with BMI ≥35 negatively affecting detection (odds ratio [OR] 0.28, P=0.014) and cirrhosis positively affecting detection (OR 2.31, P=0.036). Ultrasound detected 19.1% of single tumors ≤2.0 cm with ascites improving the detection rate (OR 3.89, P=0.001). Finally, adherence to Milan criteria occurred in 75.1% of cases, revealing negative associations with diabetes (OR 0.48, P=0.044 and male gender (OR 0.49, P=0.08). Conclusions: Although surveillance is recommended for HCC, not all surveillance ultrasound are ideal. Tumor detection can depend on gender, BMI, diabetes, cirrhosis, and ascites and is achieved in 19.1–75% of cases depending on the definition of success. Closer follow-up or additional imaging might be necessary for some patient subgroups.

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Hepatic neoplasm

A lexicon for hepatocellular carcinoma surveillance ultrasonography: benign versus malignant lesions: Chansik An, Gulbahor Rakhmonova, Kyunghwa Han, Nieun Seo, Jin Young Lee, Myeong-Jin Kim, Mi-Suk Park; Clin Mol Hepatol 2017;23(1):57-65.
Published online March 24, 2017; DOI: https://doi.org/10.3350/cmh.2016.0041

Abstract
PDF

Background/Aims
To suggest a lexicon for liver ultrasonography and to identify radiologic features indicative of benign or malignant lesions on surveillance ultrasonography.
Methods
This retrospective study included 188 nodules (benign, 101; malignant, 87) from 175 at-risk patients identified during surveillance ultrasonography for hepatocellular carcinoma. We created a lexicon for liver ultrasonography by reviewing relevant literature regarding the ultrasonographic features of hepatic lesions. Using this lexicon, two abdominal radiologists determined the presence or absence of each ultrasonographic feature for the included hepatic lesions. Independent factors associated with malignancy and interobserver agreement were determined by logistic regression analysis and kappa statistics, respectively.
Results
Larger tumor size (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.183; P<0.001), multinodular confluent morphology (OR, 7.712; 95% CI, 1.053-56.465; P=0.044), thick hypoechoic rim (OR, 5.878; 95% CI, 2.681-12.888; P<0.001), and posterior acoustic enhancement (OR, 3.077; 95% CI, 1.237-7.655; P=0.016) were independently associated with malignant lesions. In a subgroup analysis of lesions <2 cm, none of the ultrasonographic features were significantly associated with malignancy or benignity. Interobserver agreement for morphology was fair (κ=0.36), while those for rim (κ=0.427), echogenicity (κ=0.549), and posterior acoustic enhancement (κ=0.543) were moderate.
Conclusions
For hepatic lesions larger than 2 cm, some ultrasonography (US) features might be suggestive of malignancy. We propose a lexicon that may be useful for surveillance US.

Citations

Citations to this article as recorded by

Focal Hyperechoic Hepatic Lesions in Northern Region of Saudi Arabia: Prevalence, Radiologic Features, and Clinical Relevance
Fatimah M. Alonzi, Mohammed J. Alsaadi, Khaled Said Karam, Essa M. Alanzi, Noura K. Alhathal, Maram F. Alreshidi, Abdulrahman M. Alfuraih
Journal of Clinical Medicine.2025; 14(19): 6987. CrossRef
Sonographic appearance of focal liver lesions and likelihood of hepatocellular carcinoma in adult Thais with chronic hepatitis B virus infection
Sarana Suttivanich, Kamonwan Soonklang, Pantajaree Hiranrat, Surachate Siripongsakun
Journal of Clinical Ultrasound.2024; 52(4): 377. CrossRef
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Shang-Chin Huang, Ja-Der Liang, Shih-Jer Hsu, Tzu-Chan Hong, Hung-Chih Yang, Jia-Horng Kao
Clinical and Molecular Hepatology.2021; 27(2): 305. CrossRef

19,496 View
212 Download
3 Web of Science
Crossref

Hepatic neoplasm

Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease: Chansik An, Youn Ah Choi, Dongil Choi, Yong Han Paik, Sang Hoon Ahn, Myeong-Jin Kim, Seung Woon Paik, Kwang-Hyub Han, Mi-Suk Park; Clin Mol Hepatol 2015;21(3):279-286.
Published online September 30, 2015; DOI: https://doi.org/10.3350/cmh.2015.21.3.279

Abstract
PDF

Background/Aims

The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate.

Methods

Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients.

Results

The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234).

Conclusions

The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC.

Citations

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Could patients who underwent hepatic resection due to hepatocellular carcinoma with high alpha-fetoprotein be monitored for recurrence by alpha-fetoprotein Level?: Woo Young Shin, M.D., Kyung-Suk Suh, M.D.1, Taehoon Kim, M.D.1, Young Min Jeon, M.D.1, Nam-Joon Yi, M.D.1, Kuhn Uk Lee, M.D.1; Korean J Hepatol 2010;16(2):168-175.
Published online June 25, 2010; DOI: https://doi.org/10.3350/kjhep.2010.16.2.168

Abstract
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Background/Aims
The follow-up strategy after hepatectomy for hepatocellular carcinoma (HCC) usually depends on the experience of physician, resulting in frequent imaging studies, which leads to increased cost. Hence, we investigated the role of monitoring alpha-fetoprotein (AFP) levels after hepatectomy in patients with preoperative high AFP. Methods: From January 2000 to December 2004, 66 patients who underwent curative hepatectomy due to HCC with preoperative AFP level >400 ng/ml were reviewed. Changes in AFP level after the operation were investigated. The recurrence was suspected in case of two consecutive increase of AFP over cut-off value. Cut-off value was determined by ROC curve. All patients were divided into 2 groups: patients who met the definition (Group S) and those who didn`t (Group D). Results: AFP level of 20ng/ml was proposed as the cut-off value for diagnosis of recurrence by ROC curve. Thirty two patients who didn`t have the AFP level decreased below 20 ng/ml after the resection had HCC recurred, whereas 16 out of 34 patients who had AFP decreased had tumor recurrence. The AFP level of patients without recurrence was kept below 20 ng/ml during the follow-up. The AFP level of 44 out of 48 recurred patients increased over 20ng/ml upon recurrence. By definition, group D were 5 patients. In 4 patients of group D, the AFP level didn`t increase above 20 ng/ml upon recurrence. These patients had HCC and they recurred 1 year after the surgery. Conclusions: In patients with preoperative AFP level >400 ng/ml, the AFP level tended to increase above 20ng/ml at recurrence mostly within 1 year. Hence, we proposed that these patients could be monitored by only AFP until 1 year after surgery.

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Hazem M. Zakaria, Anwar Mohamed, Hazem Omar, Nahla K. Gaballa
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Serum alpha-fetoprotein level per total tumor volume as a predictor of recurrence of hepatocellular carcinoma after resection
Yeshika Sharma, Michael J. Weaver, Daniel R. Ludwig, Kathryn Fowler, Neeta Vachharajani, William C. Chapman, Jeffrey S. Crippin
Surgery.2018; 163(5): 1002. CrossRef
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Korean Journal of Medicine.2012; 82(5): 603. CrossRef

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