Review article: <scp>HCV</scp> genotype 3 – the new treatment challenge

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>To provide a comprehensive summary of the literature evaluating the unique characteristics and evolving therapies in genotype 3.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A structured search in PubMed, the Cochrane Library and <jats:styled-content style="fixed-case">EMBASE</jats:styled-content> was performed using defined key words, including only full text papers and abstracts in English.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:styled-content style="fixed-case">HCV</jats:styled-content> 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, <jats:styled-content style="fixed-case">NS</jats:styled-content>5B and <jats:styled-content style="fixed-case">NS</jats:styled-content>5A inhibitors have performed more poorly in genotype 3, while a cyclophilin inhibitor, alisporivir, has shown promise.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>As treatments for <jats:styled-content style="fixed-case">HCV</jats:styled-content> 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.</jats:p></jats:sec>