Future landscape of hepatitis C research – Basic, translational and clinical perspectives

Abstract

With the latest all-oral interferon- and ribavirin-free regimens based on direct acting antivirals against the hepatitis C virus (HCV), sustained virological response rates of >90% are achieved, which is equivalent to cure. This has become possible for all genotypes and all subgroups of patients, including many of the most difficult-to-treat populations so far. Since a prophylactic HCV vaccine is not yet available, control of HCV infection will for the time being have to rely on the use of effective and safe antiviral treatments as well as their accessibility and affordability. Different approaches may apply to different parts of the world, eradication of HCV representing a major long-term goal. Whether hepatitis C becomes the first chronic viral infection to be eradicated without a prophylactic vaccine remains to be shown. Here, we briefly summarize advances in the molecular virology of hepatitis C, highlight lessons of biological relevance that were learned through the study of HCV, and its translational and clinical implications. We have also listed selected unsolved challenges, emphasizing that HCV is a unique model and that advances in this direction may yield knowledge of broad biological significance, novel technologies and insights into related important human pathogens.

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus‐coinfected individuals in EuroSIDA

“…Nonetheless, we have already seen a rapid increase in DAA uptake in 2014 and 2015 for all EuroSIDA regions except Eastern Europe . As DAAs are highly effective for all genotypes , we expect to see SVR rates improving in the DAA era.…”

A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

“…As HCV is an RNA virus and RNA has a limited life-span, blocking replication for a finite time is sufficient to eliminate the virus. This is indeed achieved by recently introduced direct acting antivirals, and chronic hepatitis C can now be cured in most patients [4,5]. …”

Hepatitis C virus infection in children and adolescents

“…However, no virus to date has been globally eradicated without the development of a prophylactic vaccine. A preventative vaccine is needed to stop HCV transmission to uninfected individuals and to those who are cured with DAA but remain at risk for re‐exposure and persistence of infection 5. Major obstacles to HCV vaccine development are the diversity of the virus, the ability of the virus to evade the immune response in infected individuals with high rates of mutation, and development of “quasispecies,” which are distinct but closely related HCV variants that can be present in a single individual 5, 137, 142.…”

“…A preventative vaccine is needed to stop HCV transmission to uninfected individuals and to those who are cured with DAA but remain at risk for re‐exposure and persistence of infection 5. Major obstacles to HCV vaccine development are the diversity of the virus, the ability of the virus to evade the immune response in infected individuals with high rates of mutation, and development of “quasispecies,” which are distinct but closely related HCV variants that can be present in a single individual 5, 137, 142. Additional immune‐evading strategies that have been identified include antibody avoidance, cytotoxic T lymphocyte escape, and a failure to initiate an appropriate T cell response during the beginning of infection, among others 143, 144, 145, 146, 147, 148.…”

“…HCV infection across the pediatric age spectrum differs from infection acquired later in life in a variety of ways, including modes of transmission, rates of spontaneous clearance or progression of fibrosis, the potential duration of chronic infection when acquired at birth, and significantly, available treatment options 4. While several reviews have recently been published regarding aspects of HCV infection in adults,3, 5, 6 our goal is to present a practical overview of the epidemiology, diagnosis, clinical features, natural history, and management of HCV infection in children and adolescents.…”