Critical challenges and emerging opportunities in hepatitis C virus research in an era of potent antiviral therapy: Considerations for scientists and funding agencies

Abstract

The development and clinical implementation of direct-acting antivirals (DAAs) has revolutionized the treatment of chronic hepatitis C. Infection with any hepatitis C virus (HCV) genotype can now be eliminated in more than 95% of patients with short courses of all-oral, well-tolerated drugs, even in those with advanced liver disease and liver transplant recipients. DAAs have proven so successful that some now consider HCV amenable to eradication, and continued research on the virus of little remaining medical relevance. However, given 400,000 HCV-related deaths annually important challenges remain, including identifying those who are infected, providing access to treatment and reducing its costs. Moreover, HCV infection rarely induces sterilizing immunity, and those who have been cured with DAAs remain at risk for reinfection. Thus, it is very unlikely that global eradication and elimination of the cancer risk associated with HCV infection can be achieved without a vaccine, yet research in that direction receives little attention. Further, over the past two decades HCV research has spearheaded numerous fundamental discoveries in the fields of molecular and cell biology, immunology and microbiology. It will continue to do so, given the unique opportunities afforded by the reagents and knowledge base that have been generated in the development and clinical application of DAAs. Considering these critical challenges and new opportunities, we conclude that funding for HCV research must be sustained.

Hepatitis C virus infection is inhibited by a non-canonical antiviral signaling pathway targeted by NS3-NS4A

“…Notably, although the current direct-acting antivirals treat HCV-induced disease, they do not always prevent re-infection in cured individuals. Therefore, there is an urgent need for future studies into the development of a vaccine to reduce the global burden of HCV infection (3).…”

Hypervariable region 1 and N-linked glycans of hepatitis C regulate virion neutralization by modulating envelope conformations

“…Chronic infection dramatically increases the risk of developing liver cirrhosis and hepatocellular carcinoma (2,3). Effective direct-acting antivirals are available, but due to a high number of occult infections and the high cost of treatment, the need for a prophylactic vaccine remains high (4). Other licensed human vaccines rely mainly on inducing neutralizing antibodies (NAbs) (5), and NAbs protect against HCV infection in vivo (6,7).…”

The interplay between viruses and TRIM family proteins

“…22,50 The most successful current treatment against HCV is direct acting antivirals (DAA) which have shown to eliminate HCV infection with any genotype in 95% of the cases. 23 But emerging evidence is showing the high relapse rate of DAA treatment even after successful eradication of virus. 51,52 In another study, performed in our molecular virology lab, we have reported high relapse rates of DAA against HCV patients for the first time 53 implying the need of new strategic therapies; therefore, this study is aimed to find potent antiviral genes for the eradication of different viral infection.…”

“…HCV infection is the cause of about half a million deaths annually and has been identified as 25 th major cause of death . The most successful current treatment against HCV is direct acting antivirals (DAA) which have shown to eliminate HCV infection with any genotype in 95% of the cases . But emerging evidence is showing the high relapse rate of DAA treatment even after successful eradication of virus .…”