Optimizing triple therapy and IFN/RBV-free regimens for hepatitis C virus infection

Abstract

Treatment of chronic hepatitis C virus infection has substantially improved following the advent of direct acting antiviral (DAA) agents. Although the first generation protease inhibitors telaprevir and boceprevir improved sustained viral response (SVR) rates, adverse events remain severe and immature termination of the therapy is frequent; however, intensive dose modification has improved completion and SVR rates. Interferon-free DAA combination therapies, such as asunaprevir and daclatasvir dual therapy are under development and promise higher SVR rates with fewer adverse events. Resistance monitoring and modification of DAA therapy based on pre-existing or de novo resistance variants should be considered. Future therapies are expected to have pan-genotypic activity with shorter duration and improved tolerability, even among cirrhotic and liver transplant patients.

Keywords:

• direct-acting antiviral agents
• NS5A inhibitor
• polymerase inhibitor
• protease inhibitor
• sustained viral response

Acknowledgements

The authors thank the doctors of Hiroshima Liver Study Group for their efforts to complete the survey. They also thank Asumi Nakasaki for clerical assistance.

Financial & competing interests disclosure

This work is partially supported by Grants-in-Aid for scientific research and development from the Ministry of Health, Labor and Welfare and the Ministry of Education, Culture, Sports, Science and Technology, Japan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Almost 200 million people are chronically infected with hepatitis C virus.

• Failure to clear the virus greatly increases the risk of cirrhosis and hepatocellular carcinoma.

• Until recently, 48 weeks of combination therapy with pegylated interferon and ribavirin was the standard of care for the common but difficult-to-treat genotype 1.

• However, fewer than half of patients achieved a sustained viral response with this therapy, and many patients experienced severe side effects.

• Direct-acting antiviral (DAA) agents, beginning with telaprevir and boceprevir, were recently approved for treatment of genotype 1 as part of a triple therapy with peg-interferon and ribavirin.

• Triple therapy increased the sustained viral response rate to >70%, but many patients are ineligible for the treatment, and side effects are more severe, including rash, pruritus and anemia.

• However, many new DAAs are currently under development or pending approval, including second-wave and second-generation protease inhibitors, NS5A inhibitors and polymerase inhibitors.

• The eventual goal of these new DAAs is to provide all-oral, interferon-free DAA combination therapies that are effective against multiple hepatitis C virus genotypes and are safe and well-tolerated even among cirrhotic patients and liver transplant recipients.

• Nonetheless, high costs and rapid emergence of antiviral resistance may complicate the short-term implementation of DAA therapies.

Notes