Insulin resistance and diabetes increase fibrosis in the liver of patients with HCV genotype 1 infection

Objectives: Metabolic factors may affect the course of chronic hepatitis C (CHC). Insulin resistance (IR) determines steatosis, but its direct role in affecting progression of hepatic fibrosis is less clear. We aimed to assess whether increasing degrees of IR, up to overt diabetes, are linked to steatosis and to higher stages of fibrosis in patients with CHC due to genotype 1-HCV (G1-HCV). Methods: Two hundred and one consecutive patients with G1-HCV infection were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, by the homeostasis model assessment (HOMA). Non-diabetic patients were defined insulin resistant if HOMA-IR was >2.7. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis. Results: Ninety-six patients were non-insulin resistant (Group 1), 76 were insulin resistant without diabetes (Group 2), and 29 were diabetic (Group 3). At multivariate analysis, fibrosis ≥3 was independently associated with high necroinflammatory activity (OR 2.994; 95%CI 1.422-6.098), low platelets (OR 0.994 95%CI 0.981-0.999), low cholesterol (OR 0.987; 95%CI 0.976-0.998), high ferritin (OR 1.002; 95%CI 1.001-1.004), and a high prevalence of IR (OR 2.692; 95%CI 1.463-4.954). Diabetic patients were twice more likely to have severe fibrosis (60%) than those with IR but no diabetes (30%) (p=0.006). The degree of steatosis and that of fibrosis were weakly associated with each other (p=0.42) Conclusions: In subjects with CHC due to G1-HCV, IR and overt diabetes are major determinants of advanced fibrosis regardless of the degree of steatosis, mainly in the presence of severe necroinflammation.