IL28B genetic variation and ratio of y-GT/ALT as predictors for virological response in chronic hepatitis C virus genotype 1 infected patients

Introduction: Chronic hepatitis C virus (HCV) genotype 1 infection is currently treated with pegylated interferon-α and ribavirin (PEG-IFN-α/RBV). This therapy leads to successful virus eradication in about half of the patients. With regard to the upcoming directly acting antiviral drugs, predictive factors are demanded more than before to help in the decision on a standard combination or a triple therapy.

Methods: This retrospective study analysed the therapy outcomes of 264 patients with chronic genotype 1 hepatitis C with regard to IL28B rs12979860 and rs8099917 genotypes and pretreatment ratio of serum γ-GT and ALT activity. Conventional prognostic features were also assessed.

Results: IL28B rs12979860 and rs8099917 genotypes and pretreatment serum γ-GT/ALT-ratios were significantly related to treatment outcome. With a cut-off value of 0.70, the pretreatment serum γ-GT/ALT ratio performed even better than IL28B genotypes in terms of sensitivity, specificity and positive and negative predictive values (PPV and NPV). A logistic regression analysis revealed an Odds ratio of 26.7 (Confidence interval: 10–71.1) when a low pretreatment serum γ-GT/ALT-ratio plus IL28B rs12979860 C homozygosity was compared to low pretreatment serum γ-GT/ALT ratio and IL28B rs12979860 heterozygosity and T homozygosity. Additional predictive factors associated with SVR could be confirmed as age under 50 years (p<0.01), rapid virological response (RVR, p<0.01) and histological absence of steatosis (p<0.01). Laparoscopic evidence of absence of cirrhosis (p=0.02) was also found to be related to therapy response.

Conclusion: IL28B genotypes help to identify patients who most likely will benefit from an IFN-α based combination therapy in a non-triaged, ordinary cohort. Considering the pretreatment serum γ-GT/ALT ratio enhances its predictability significantly.