Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial (original) (raw)

Combination treatment with pegylated-interferon-α and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-α pathway may affect anti-viral responses, we analyzed the relationship between variants in these genes and SVR among participants in the HALT-C trial. Patients had advanced chronic hepatitis C and had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-α2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered non-responders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-α pathway. This analysis compares genotypes for participants with an SVR to non-responders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n=131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio [aOR], 0.57; p=0.02); IFNAR2 Ex2-33C (aOR, 2.09; p=0.02); JAK1 IVS22+112T (aOR, 1.66; p=0.04); and ADAR Ex9+14A (aOR, 1.67; p=0.03). For the TYK2 -2256A promoter region variant a borderline association was present among European American participants (OR, 1.51; p=0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2-2256 carried the A variant compared to 68/120 (57%) non-responders (p=0.006). In conclusion, genetic polymorphisms in the interferon-α pathway may affect responses to antiviral therapy of chronic hepatitis C. Welzel et al.

Sign up for access to the world's latest research.

checkGet notified about relevant papers

checkSave papers to use in your research

checkJoin the discussion with peers

checkTrack your impact