Hepatitis C virus: Is it time to say goodbye yet? Perspectives and challenges for the next decade

Abstract

The majority of individuals exposed to hepatitis C virus (HCV) establish a persistent infection, which is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. Major progress has been made during the past twenty-five years in understanding the HCV life cycle and immune responses against HCV infection. Increasing evidence indicates that host genetic factors can significantly influence the outcome of HCV infection and the response to interferon alpha-based antiviral therapy. The arrival of highly effective and convenient treatment regimens for patients chronically infected with HCV has improved prospects for the eradication of HCV worldwide. Clinical trials are evaluating the best anti-viral drug combination, treatment doses and duration. The new treatments are better-tolerated and have shown success rates of more than 95%. However, the recent breakthrough in HCV treatment raises new questions and challenges, including the identification of HCV-infected patients and to link them to appropriate health care, the high pricing of HCV drugs, the emergence of drug resistance or naturally occurring polymorphism in HCV sequences which can compromise HCV treatment response. Finally, we still do not have a vaccine against HCV. In this concise review, we will highlight the progress made in understanding HCV infection and therapy. We will focus on the most significant unsolved problems and the key future challenges in the management of HCV infection.

Keywords: Direct-acting antivirals; Drug resistance; Hepatitis C virus; Host genetics; Pathogenesis; Vaccine.

Figure 1

Milestones in hepatitis C virus basic research and treatment. HCV: Hepatitis C virus; DAA: Direct-acting antiviral; IFN: Interferons; IL28B: Interleukin-28B; RBV: Ribavirin; pegIFNα: Pegylated interferon-alpha.