IL28B rs12979860 CC Genotype, Metabolic Profile and SVR in Patients with Genotype 1 Chronic Hepatitis C.

Background and Aims: Patients with genotype 1 chronic hepatitis C (G1-CHC) frequently display steatosis and insulin resistance (IR), due to both metabolic and viral factors. Clinically, this translates to accelerated liver disease progression and a reduced response to therapy. Sustained virological response (SVR) in G1-CHC is also strongly associated with polymorphisms near the IL28B gene, but the interaction between IL28B genotype and insulin resistance and their combine effects of SVR has not been defined. We tested the association between the IL28B rs12979860 genotype and metabolic features, including IR, and evaluated their relative impact on SVR. Methods: Four hundreds and thirty-four G1-CHC consecutively biopsied patients in three tertiary centers were genotyped for the IL28B rs12979860 SNP. Their metabolic profile included assessment of lipid levels and insulin resistance (IR) by the homeostasis model assessment (HOMA-IR). Results: IL28B CC patients had higher levels of total and LDL cholesterol, lower triglycerides, and a lower prevalence of both IR and moderate severe steatosis (p<0.05). By multiple logistic regression analysis, BMI (OR 1.223, p<0.001), triglycerides (OR 1.007, p=0.006), IL28B CC (OR 0.378, p=0.001) and HCVRNA >850000UI (OR 1.803, p=0.01) were independently associated with IR. IL28B CC (OR 8.350, p<0.001) and IR (OR 0.432, p=0.005), but not steatosis (OR 0.582, p=0.25), were independently associated with SVR. See later re strengthening this if we can show an interaction Conclusions: In G1-CHC patients the IL28B rs12979860 CC genotype is associated with reduced insulin resistance independent of the classical risk factors. Both IL28B rs12979860 genotype and HOMA-IR additively and nteractively strongly influence the outcome of antiviral therapy.