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.
Professor Reddy and colleagues from Pennsylvania, USA provided a comprehensive summary of the literature evaluating the unique characteristics and evolving therapies in genotype 3.
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.
The research team found that HCV genotype 3 is more prevalent in Asia and among intra-venous drug users.
|NS5A inhibitors have performed more poorly in genotype 3|
|Alimentary Pharmacology & Therapeutics|
The team noted that 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).
The team observed that 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.
Professor Reddy and colleagues conclude, "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."