Contribution of obesity to hepatitis C-related fibrosis progression.

Hepatitis C virus (HCV) disease progression is variable. Identification of factors predictive of rapid progression is an important goal for improving patient management. The aim of this study was to evaluate the predictive role of several variables, including some that are etiologically related to the nonalcoholic steatohepatitis (NASH) syndrome such us obesity, in fibrosis progression in both patients with elevated and normal transaminase levels. A total of 114 chronic HCV-infected (HCV-RNA positive) patients were recruited prospectively between 2000 and 2001. All patients had at least one liver biopsy. The annual change in fibrosis stage (fibrosis progression rate) was assessed from the time of presumed infection (fibrosis = 0) among those who had only one biopsy (n = 97) or between two biopsies if these were available (n = 17). Based on published data, we arbitrarily defined a patient as a rapid progressor when the fibrosis progression rate was > 0.2 U/yr. Potential predictors of rapid progression were: age at infection and biopsy, sex, significant alcohol intake (> 50 g/day), risk factor of HCV acquisition (based on answers to a questionnaire), obesity (based on body mass index [BMI]), autoantibodies, iron overload (ferritin, transferrin saturation), diabetes, hyperlipidemia, anti-HBcore IgG, genotype, and viral load. The median fibrosis progression rate was 0.05 U/yr (range 0-1.58 yr). In all, 22 patients (19%) were rapid progressors. Variables associated with progression by multivariate analysis included: advanced age at infection (p = 0.0001), BMI > or = 25 (p = 0.01), and ALT > 1.5 times upper limit of normal (p = 0.01). Among patients with ALT > 1.5 times upper limit of normal, these variables were advanced age at infection, BMI > or = 25, diabetes and transferrin saturation > 45. Among those with normal ALT levels, only BMI > or = 30 was predictive of progression. Obesity, advanced age at infection, and elevated ALT levels predict rapid disease progression, suggesting that measures aimed at weight reduction may play a significant role in hepatitis C management. The natural history of hepatitis C is independent of the presence of autoimmunity markers.