Antiviral treatment of hepatitis C virus infection and factors affecting efficacy

Abstract

Hepatitis C virus (HCV) infection is the leading cause of chronic liver-related diseases, including cirrhosis, liver failure, and hepatocellular carcinoma. Currently, no effective vaccine is available for HCV infection. Polyethylene glycol interferon-α (PegIFN-α) in combination with ribavirin (RBV) is the standard of care (SOC) for chronic hepatitis C. However, the efficacy of PegIFN-α and RBV combination therapy is less than 50% for genotype 1 HCV, which is the dominant virus in humans. In addition, IFN and RBV have several severe side effects. Therefore, strategies to improve sustained virological response (SVR) rates have been an important focus for clinical physicians. The serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in 2011. The addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV infection. Several direct-acting antiviral drugs currently in late-stage clinical trials, both with and without peg-IFN and RBV, have several advantages over the previous SOC, including higher specificity and efficacy, fewer side effects, and the ability to be administered orally, and might be optimal regimens in the future. Factors affecting the efficacy of anti-HCV treatments based on IFN-α include the HCV genotype, baseline viral load, virological response during treatment, host IL28B gene polymorphisms and hepatic steatosis. However, determining the effect of the above factors on DAA therapy is necessary. In this review, we summarize the development of anti-HCV agents and assess the main factors affecting the efficacy of antiviral treatments.

Keywords: Hepatitis C virus, Treatment, Interferon, Protease inhibitors, IL28B protein, Polymorphisms, Viral load, Genotype, Hepatic steatosis

Core tip: Understanding the effectiveness and affecting factors of antiviral regimens are critical for making informed treatment decisions for hepatitis C virus (HCV) infection. In this review, we have summarized the history of anti-HCV agents from interferon to the direct-acting antiviral drugs (DAAs) without polyethylene glycol interferon-α therapies and the affecting factors of antiviral treatment, focusing on investigating the optimal combination of antiviral therapies to achieve higher efficacy and better medication compliance. Although the efficacy of DAAs is significantly improved, many unmet needs and questions remain, such as avoidance of cross-resistance, the remaining high incidence of side effects, the role of IL28B status as well as the management of patients who do not respond to therapy.