Background: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients.
Methods: 303 treatment-naïve Asian-region patients with CHC Genotype 2/3 were enrolled in a multicenter phase 3, study of albinterferon alfa-2b plus ribavirin for 24 weeks. IR was defined as HOMA-IR > 2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4)
Results: IR was available in 263 non-diabetic Asian-region patients (HCV-2 = 171, HCV-3 = 92), and 433 non-Asian region patients (407 "Caucasian"); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis) = 201(77%) and F2-F4 (significant fibrosis) = 59 (23%), and steatosis prevalence of grade 0 = 169 (65%), grade 1 = 64 (25%), grade 2/3 = 27 (10%). Median HOMA-IR was 1.8 (Interquartile range: 1.2 - 2.7); 100 (38%) of patients had HOMA-IR > 2. Factors independently associated with significant fibrosis included HOMA-IR (OR = 8.42), necro-inflammatory grade (OR = 3.17), age (OR = 1.07) and serum total cholesterol levels (OR = 0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort.
Conclusions: In this subgroup study of Asian-region HCV Genotype-2 or -3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis.