Early viral and peripheral blood mononuclear cell responses to pegylated interferon and ribavirin treatment: the first 24 h.

Objectives: This study explored gene expression differences in predicting response to pegylated interferon (IFN-PEG) and ribavirin (RBV) in hepatitis C infection. Current treatment for hepatitis C virus (HCV) with IFN-PEG alpha-2a/b and RBV is an expensive regimen with frequent significant side-effects where less than 60% of patients ultimately achieve a sustained virological response. Responders and nonresponders may not be identified for up to 6 months post-treatment. This dichotomy may be because of differences in the molecular genetic response.

Methods: Peripheral blood mononuclear cell samples were obtained from a cohort of 31 infected individuals within the first 24 h of treatment and the extracted RNA was hybridized to genome expression microarrays. Hepatitis C viral kinetics was also examined in these patients. The ability of differentially regulated genes to predict response to therapy was assessed with treatment outcome.

Results: Distinct patterns of gene expression distinguished responders from nonresponders to HCV treatment. The ultimate response to treatment with IFN-PEG and RBV was observed within the first 24 h of treatment by a greater drop in viral load (mean HCV RNA decline of 1.92+/-1.26 log10 IU/ml) in responders compared with nonresponders (P<0.007). Induced genes achieved maximal response within 12 h of therapy which coincided with a rapid decline in HCV RNA between 12 and 24 h. This study revealed that peripheral blood mononuclear cell metallothionein 2A, CCRL2, tumour necrosis factor-alpha-induced protein 6 (TNFAIP6) and IFN-induced protein with tetratricopeptide repeats 2 expression predicted viral treatment response to therapy verified by quantitative real time polymerase chain reaction.

Conclusion: This study has identified a noninvasive gene microarray pattern and a set of verified genes to be predictive of hepatitis C patient response to IFN-PEG and RBV treatment within the first 24 h. The potential of this noninvasive diagnostic approach and identified genes as biomarkers of response to treatment warrants further investigation.