Suppressor of cytokine signal 3 and IL28 genetic variation predict the viral response to peginterferon and ribavirin

Abstract

The aim of this study was to investigate the relationship among the expression of suppressor of cytokine signaling 3 (SOCS 3) in the liver, the SNPs in the IL28B locus, and the outcome of interferon therapy. Prior to interferon treatment, we immunostained 67 liver specimens from chronic hepatitis C (CHC) patients who were receiving peginterferon alpha-2b/ribavirin therapy for suppressor of cytokine signaling 3 (SOCS3), and compared the expression of SOCS3, IL28 polymorphisms and other clinical factors between the patients and compared their eventual outcomes. Significant differences between the low SOCS3 group and high SOCS3 group were found in age, as well as in the platelet, transaminase, gamma-glutamyl transpeptidase levels. The incidence of high SOCS3 was not significantly different between subjects with the TT genotype and the TG genotype (TT : TG = 71%:29%, P = 0.250). In a multivariate analysis, age (≥65 years old) (odds ratio 0.221 [0.120-0.966], P = 0.045), IL28B gene (genotype TT) (odds ratio 5.422 [1.254-23.617], P = 0.024) and SOCS3 (high) (odds ratio 0.308 [0.104-0.948], P = 0.040) were significant predictors of the interferon response. In patients with the TT genotype, those with low SOCS3 immunostaining showed a high sustained virological response (69%), while the sustained virological rate was low (27%) in the patients with high SOCS3 immunostaining. Using a combination of the SOCS3 immunostained area in the liver and the expression of IL28B single nucleotide polymorphisms might be a useful predictor of hepatitis C virus clearance by interferon therapy.