The role of steatosis in the progression of liver damage in chronic hepatitis C (CHC) was studied. Enrolled were 180 consecutive liver biopsy-proven CHC patients and 41 additional subjects with a known duration of infection. We evaluated the histological activity index (HAI), grade of fibrosis and steatosis, body mass index (BMI; kg/m 2 ), distribution of body fat, HCV genotype, and levels of HCV RNA. Eighty six (48%) patients showed steatosis, and a higher prevalence was observed in genotype 3a infection (P < .01). A correlation between the grade of steatosis and fibrosis was observed (P < .001). Fibrosis was also associated with age (P < .001). After adjusting for age, the association between steatosis and fibrosis remained significant. The grade of steatosis also correlated with the HAI (P < .007) with a significant increase in periportal necrosis. No relation was found between steatosis and age, gender, iron storage, or levels of HCV RNA. Patients with a high grade of steatosis (>30%) showed higher serum levels of ␥-GT and ALT (P < .001). Overall, steatosis was not significantly associated to BMI. Analysis by single genotype showed a significant association between the grade of steatosis and BMI in type 1 infection r ؍ .689; P < .001) and with levels of HCV RNA in type 3a infection r ؍ .786; P < .001). Visceral fat distribution rather than BMI proved to be associated with steatosis (P < .001). Data obtained from patients with a known date of infection confirmed that steatosis grades 3-4 were associated with a higher annual rate of fibrosis progression, and showed that alcohol and steatosis act together in increasing fibrosis (P < .05). Our data indicate that steatosis is an important cofactor in increasing liver necroinflammatory activity and in accelerating fibrosis in CHC. Visceral obesity and genotype 3a play a role in the development of steatosis. (HEPATOLOGY 2001;33: 1358-1364