Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients

Background and Aim: 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: A total of 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 24weeks. IR was defined as Homeostasis Model for Assessment of IR (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: Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [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%) patients had HOMA-IR>2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [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.