Review article: HCV genotype 3 – the new treatment challenge

Abstract

Background: Over the past several years, hepatitis C therapy has been pegylated interferon and ribavirin based. Although protease inhibitor-based therapy has enhanced response rates in genotype 1, the recent advances in therapy have demonstrated a challenge in genotype 3, a highly prevalent infection globally.

Aim: To provide a comprehensive summary of the literature evaluating the unique characteristics and evolving therapies in genotype 3.

Methods: A structured search in PubMed, the Cochrane Library and EMBASE was performed using defined key words, including only full text papers and abstracts in English.

Results: HCV genotype 3 is more prevalent in Asia and among intra-venous drug users. Furthermore, it interferes with lipid and glucose metabolism, and the natural history involves a more rapid progression of liver disease and a higher incidence of hepatocellular carcinoma (HCC). New therapies with protease inhibitors have focused on genotype 1 largely and have demonstrated enhanced responses, but have limited activity against genotype 3. Thus far, in clinical trials, NS5B and NS5A inhibitors have performed more poorly in genotype 3, while a cyclophilin inhibitor, alisporivir, has shown promise.

Conclusions: As treatments for HCV have evolved, genotype 3 has become the most difficult to treat. Furthermore, genotype 3 has special characteristics, such as insulin resistance and alterations in lipid metabolism, which may partly explain the lower treatment responses. A great deal of emphasis on advancing therapy is needed in this population that appears to have a more rapid progression of liver disease and a higher incidence of HCC.