Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha. Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides and small-interfering RNAs are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.
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Background/Aims Interferon-based treatment is not appropriate for a large number of patients with chronic hepatitis C for various medical and social reasons. Newly developed directly acting antivirals (DAAs) have been used to treat chronic hepatitis C without severe adverse effects and have achieved a sustained viral response (SVR) rate of 80-90% with short treatment duration. We were interested to determine whether all patients who failed to respond to or were ineligible for interferon-based therapy could be treated with DAAs.
Methods Medical records of patients with positive serum anti-hepatitis C virus (HCV) or HCV RNA between January 2009 and December 2013 were reviewed. Demographic, clinical, and treatment data were collected for analysis.
Result s: A total of 876 patients were positive for both anti-HCV and HCV RNA. Of these, 244 patients were eligible for interferon, although this was associated with relapse in 39 (16%) of patients. In total, 130 patients stopped interferon therapy (67% adverse effects, 28% non-adherent, 4% malignancy, 1% alcohol abuse) and 502 patients were ineligible (66% medical contraindications, 25% non-adherent, 5% socioeconomic problems). Among 671 patients who were ineligible for or failed to respond to interferon therapy, more than 186 (27.7%) could not be treated with DAA due to financial, social, or cancer-related conditions.
Conclusions Newly developed DAAs are a promising treatment for patients with chronic hepatitis C who are ineligible for or failed to respond to interferon-based therapy. Nevertheless, not all chronic hepatitis C patients can be treated with DAAs due to various reasons.
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Chul Hyun Kim , Byung Do Park , Jin Woo Lee , Young Soo Kim , Seok Jeong , Don Haeng Lee , Hyung Gil Kim , Yong Woon Shin , Key Sook Kwon , Jung Il Lee
Korean J Hepatol 2009;15(1):70-79. Published online March 31, 2009
Backgrounds/Aims The ultimate goal of antiviral therapy using interferon/pegylated interferon combined with ribavirin in chronic C-viral hepatitis is to achieve a sustained virologic response (SVR). Several studies have shown that the reappearance rate of hepatitis C virus (HCV) RNA in serum after the achievement of an SVR is less than 1%; the durability of an SVR in Korean patients is not known. The aim of this study was to determine the durability of the virologic response in chronic hepatitis C patients with an SVR to antiviral therapy. Methods: A total of 156 patients who were treated successfully with interferon/peginterferon and ribavirin were evaluated retrospectively. Patients received either subcutaneous conventional interferon alpha 3×10(6) units three times a week or subcutaneous pegylated interferon (α-2a: 180 μg, α-2b: 80-100 μg) once a week in combination with ribavirin at 600-1,200 mg daily (depending on body weight). Patients with HCV genotype 1 were treated for 48 weeks, whereas those with non-genotype 1 were treated for 24 weeks. Results: Eighty-two patients underwent treatment with conventional interferon and ribavirin, whereas 74 patients were treated with pegylated interferon and ribavirin. An SVR was achieved in 73 patients (73/156, 46.8%). HCV RNA reappeared in eight patients (8/73, 11.0%, detected by qualitative PCR), including one patient with persistent viremia (1/73, 1.4%). Conclusions: Reappearance of HCV RNA after earlier achievement of an SVR might appear more frequently than previously reported. Close follow-up of these patients is recommended and the implication of temporary viremia should be determined in the future. (Korean J Hepatol 2008;15:70-79)
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