Effects of IL28B rs12979860 CC Genotype on Metabolic Profile and Sustained Viral Response in Patients with Genotype 1 Chronic Hepatitis C

BACKGROUND & AIMS: Patients with genotype 1 chronic hepatitis C (G1-CHC) frequently develop steatosis and insulin resistance (IR), caused by metabolic and viral factors. These accelerate progression of liver disease progression and reduce the response to therapy. A sustained virologic response (SVR) to therapy in patients with G1-CHC is strongly associated with polymorphisms near the IL28B gene, but the interaction between IL28B genotype and IR, and their combined effects on SVR, have not been defined. We tested the association between the IL28B rs12979860 single nucleotide polymorphism (SNP) and metabolic features, including IR, and evaluated their effects on SVR. METHODS: We performed genotype analysis of IL28B rs12979860 for 434 Caucasian G1-CHC patients who underwent consecutive biopsy analysis at 3 tertiary centers. Metabolic profile analyses included assessments of lipid levels and IR by the homeostasis model assessment (HOMA-IR). RESULTS: Patients with the CC polymorphism in IL28B had higher levels of total and low-density lipoprotein cholesterol, lower levels of triglycerides, and lower prevalences of IR and moderate-severe steatosis (P<.05) than patients without this genotype. By multiple logistic regression analysis, body mass index (odds ratio [OR], 1.223; P<.001), level of triglyceride (OR, 1.007; P=.006), the CC polymorphism in IL28B (OR, 0.378; P=.001) and levels of HCV RNA>850,000 IU/ml (OR, 1.803; P=.01) were associated with IR. The CC polymorphism in IL28B (OR, 8.350; P<.001) and IR (OR, 0.432; P=.005), but not steatosis (OR, 0.582; P=0.25), were associated with an SVR. CONCLUSIONS: In Caucasian patients with G1-CHC, the IL28B rs12979860 CC genotype is associated with reduced IR. IL28B rs12979860 genotype and HOMA-IR strongly affect the outcome of antiviral therapy.