Hepatic steatosis is common in chronic hepatitis C and has been linked to concurrent obesity, insulin resistance, diabetes, disease severity, and poor response to therapy. Racial differences in rates of obesity and diabetes may contribute to racial differences in hepatic steatosis and treatment response. The aim of the present study was to compare hepatic steatosis and its associations between African American (AA) and Caucasian American (CA) patients with chronic hepatitis C, genotype 1, participating in a prospective study of peginterferon and ribavirin therapy. Liver biopsy results were available from 194 AA patients and 205 CA patients. The 2 groups were compared for anthropometric, clinical, and biochemical features and insulin resistance estimated by the homeostasis model assessment index (HOMA-IR). Sixty-one percent of the AA patients and 65% of the CA patients had hepatic steatosis (P โซุโฌ 0.38). In univariable analysis, steatosis was associated with HOMA-IR, body mass index, waist circumference, serum triglycerides, aminotransferase level, and histological scores for inflammation and fibrosis. After adjusting for these features, AA patients had a lower risk of steatosis than did CA patients (OR 0.54, 95% CI 0.32-0.91, P โซุโฌ 0.02). Insulin resistance but not steatosis was associated with a lower rate of sustained virological response when adjusted for known factors that predict response (relative risk 0.87, 95% CI 0.77-0.99, P โซุโฌ 0.028). Conclusion: After adjusting for the higher prevalence of features associated with hepatic steatosis, AA patients had a lower prevalence of hepatic steatosis than did CA patients with chronic hepatitis C, genotype 1. Insulin resistance but not steatosis was independently associated with lower sustained virological response. (HEPATOLOGY 2007;45:80-87.) H epatic steatosis is a common histological finding in chronic hepatitis C virus (HCV) infection, found in 40%-70% of patients. [1][2][3] In the largest series reported, the prevalence of steatosis was 65%, and its presence was associated with more advanced disease, especially in patients with genotype 1 infection. 4 The mechanisms of hepatic steatosis in HCV are thought to be multifactorial. [5][6][7][8][9][10][11][12][13][14] Several possibilities have been proposed including the presence of insulin resistance. Insulin resistance is a key factor in the development of steatosis in nonalcoholic fatty liver disease (NAFLD) and has been observed in individuals with HCV, especially in HCV, genotype 1 infection (referred to as metabolic steatosis). 15 Compared to other racial groups, African Americans (AA) appear to have a lower prevalence of fatty liver, 16,17 despite a higher prevalence of risk factors for NAFLD. Clinical series have also found an unexplained low representation of African Americans among patients with nonalcoholic steatohepatitis (NASH), the most severe form of NAFLD. 18 There have been no large studies of African Americans and Caucasian Americans (CA) designed to compare risk factors for and the presence of NAFLD determined by histopathology. Among patients with HCV, the relationship between race and the presence or severity of steatosis is unknown in genotype 1 infection, which is the predominant type found among both AA and CA. The aim of this study was to compare the prevalence and severity of hepatic steatosis according to anthropometry and other measures of insulin resistance among a large cohort of AA and CA with chronic hepatitis C, genotype