title: 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.
  
  
  OBJECTIVE
  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.
authors.forename: J
authors.initials: J
authors.lastname: Ampuero
authors.forename: M
authors.initials: M
authors.lastname: Romero-Gómez
authors.forename: K R
authors.initials: KR
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D021983:Cyclophilins / Q000037:antagonists & inhibitors; D016572:Cyclosporine / Q000627:therapeutic use; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D021983:Cyclophilins; D016572:Cyclosporine; D007372:Interferons; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C499715:alisporivir