Liver Interleukin-8 Messenger RNA Expression and Interferon Sensitivity-Determining Region Mutations Relate to Treatment Response in Hepatitis C 1B

Abstract

Background

In vitro study has shown that mechanisms for inhibiting interferon (IFN)-α antiviral action by non-structural 5A protein include interaction with IFN-induced RNA-dependent protein kinase and induction of interleukin (IL)-8 expression. Mutations in the non-structural 5A IFN sensitivity-determining region (ISDR) were reported to correlate with sustained virological response (SVR). IL-8 is associated with the inhibition of IFN-α action. We investigated whether pretreatment ISDR mutations and hepatic IL-8 messenger RNA (mRNA) expression had an effect on the SVR rate under combination therapy.

Methods

A total of 53 HCV-1b patients who completed 24 weeks of pegylated-IFN-α2b plus ribavirin, a 24-week follow-up and had enough tissue specimens were enrolled. Liver biopsy was performed within 6 months before antiviral therapy. Hepatic IL-8 mRNA expression was measured by real-time reverse transcriptase PCR.

Results

Of 53 patients, 30 exhibited SVR. Multivariate analysis revealed that hepatic IL-8 mRNA expression <1.5x10-⁴ (OR 6.66, 95% CI 1.77-25.05) and ISDR mutations ≥4 (OR 12.20, 95% CI 1.23-125.00) were independent predictors of SVR. Fibrosis scores and alanine aminotransferase levels were predictive of hepatic IL-8 mRNA expression by multiple linear regression analysis (r²=0.204).

Conclusions

SVR to combination therapy in hepatitis C 1b patients was associated with down-regulated hepatic IL-8 mRNA expression and ISDR mutations. Fibrosis scores and alanine aminotransferase levels were predictive of hepatic IL-8 mRNA expression.