Host-targeting therapies for hepatitis C virus infection: current developments and future applications

Area of Science:

• Hepatology
• Virology
• Drug Discovery

Background:

• Chronic hepatitis C virus (HCV) infection is a major global cause of liver disease and hepatocellular carcinoma (HCC).
• Direct-acting antivirals (DAAs) have transformed HCV therapy, offering interferon-free treatment with high sustained virologic response rates.
• Despite DAA success, challenges persist, including treatment access, failure in some patients, and ongoing HCC risk in those with advanced fibrosis.

Purpose of the Study:

• To review host-targeting agents (HTAs) for HCV therapy.
• To discuss the potential of HTAs as pan-genotypic antiviral approaches with a high barrier to resistance.
• To explore the role of HTAs in combination therapy with DAAs for challenging HCV cases.

Main Methods:

• Review of preclinical and clinical data on HTAs for HCV.
• Analysis of HTAs targeting conserved host proteins essential for the HCV life cycle.
• Evaluation of HTAs' complementary mechanisms of action when combined with DAAs.

Main Results:

• HTAs target conserved host factors, offering potential pan-genotypic activity and a high resistance barrier.
• HTAs can act via mechanisms complementary to DAAs.
• HTAs show promise for improving management of difficult-to-treat HCV populations.

Conclusions:

• HTAs represent a promising therapeutic avenue for hepatitis C virus infection.
• Combining HTAs with DAAs may enhance treatment efficacy and overcome existing limitations.
• Further development of HTAs is crucial for advancing HCV cure strategies and reducing HCC risk.