“Hep C, where art thou”: What are the remaining (fundable) questions in hepatitis C virus research?

Abstract

Hepatitis C virus (HCV) has dominated the field of hepatology for the past 25 years, and its cure in the majority of treated patients is one of the greatest achievements in all of medicine. However, the latter has led to the belief by some that HCV research should be shelved for other, more pressing areas. The mission for HCV eradication is far from accomplished. As a historical reference, we should consider that disease elimination has required vaccination with all previously controlled infections including smallpox and polio and that simple, effective treatment is not sufficient in most infections to lead to substantial control. Syphilis is the best example, for which a single dose of penicillin (which literally costs pennies and that we have had since 1945) is curative in early stages. Not only have we not eradicated syphilis, rates of infection have increased in many places within the United States in recent years. Most HCV-infected subjects are unaware of their infection, remaining at risk for transmission to others and disease progression, including cirrhosis and hepatocellular carcinoma. In the era of highly effective direct-acting antivirals (DAAs), many questions pertaining to HCV remain, but they are more complex and difficult to answer. Here, I provide my perspective on some of these salient issues: the residual risk for disease progression after sustained virologic response, the optimal approach to current DAA failures, the impact of targeting people who inject drugs with DAAs, vaccine prospects, and application of neutralizing HCV glycoprotein antibodies. (HEPATOLOGY 2017;65:341-349).

Hepatitis C Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination

“…4 It is debated that elimination without the availability of a vaccine has never been attained for any infectious disease. 23 Elimination of viral hepatitis will require a shifting emphasis from a focus on individual patients to a focus on a coordinated public health approach to interruption of transmission and infection through prevention and treatment. 1 In the presence of highly effective and safe DAA, the goal should be to reduce the disease burden in every country that requires enhanced rates of diagnosis and treatment, as well as strategies to prevent new infections.…”

Hepatitis C Virus Manipulates Humans as its Favorite Host for a Long‐Term Relationship

“…Predominant CD4 + T‐cell epitopes in HCV nonstructural proteins are immunogenic in the context of class II molecules. Replication‐defective adenoviral constructs, chimpanzee adenoviral vector, and modified vaccinia Ankara vector are in use as vehicles for vaccine development using HCV nonstructural regions in prime‐boost regimens of human trial . Sustained and balanced memory and effector T‐cell responses were noted using a prime and boost vaccination strategy.…”

“…Replication-defective adenoviral constructs, chimpanzee adenoviral vector, and modified vaccinia Ankara vector are in use as vehicles for vaccine development using HCV nonstructural regions in prime-boost regimens of human trial. (74,75) Sustained and balanced memory and effector T-cell responses were noted using a prime and boost vaccination strategy. A human efficacy study is underway in a large cohort of high-risk individuals.…”

A trivalent HCV vaccine elicits broad and synergistic polyclonal antibody response in mice and rhesus monkey

“…Although recently approved direct-acting antiviral agents (DAAs) can cure HCV infection, problems remain including therapy accessibility and potential drug resistance 2. In addition, although DAAs could cure HCV infection, some patients may still develop into progressive liver failure 3. Historically, it has been difficult to eliminate viral infectious diseases by therapeutics alone.…”