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Alpha-fetoprotein is often measured in subjects with chronic hepatitis C for diagnosing hepatocellular carcinoma. However, its prevalence and clinical significance remain inconclusive in subjects without hepatocellular carcinoma. The study was to assess the clinical, virologic, and histopathological significance of elevated AFP in chronic hepatitis C without the presence of hepatocellular carcinoma.The retrospective study enrolled 102 consecutive subjects with a histological diagnosis of chronic hepatitis C. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 6 months' follow-up. The correlation between serum alpha-fetoprotein level and clinical, virologic, or histopathological records was reviewed.The prevalence of elevated serum alpha-fetoprotein (or = 13.6 ug/L) was 28.4% (29/102) in this study. Hepatic steatosis (or = 5% hepatocytes), hepatic fibrosis (or = stage II), uric acidor = 6.3 mg/dL, asparate aminotransferaseor = 40 IU/L, albumin3.5 g/dL, and fasting plasma glucose126 mg/dL were significantly associated with elevated AFP in multivariate analysis. However, neither hepatitis C virus genotype Ib infection nor viral loador = 1x10(6) copies/ml was related to elevated AFP. A serum alpha-fetoprotein level of 15.6 ug/L was 34.3% sensitive and 83.6% specific for hepatic steatosis, was 28.2% sensitive and 95.8% specific foror = stage II hepatic fibrosis in Chronic hepatitis C.Elevated alpha-fetoprotein is independently associated with hepatic steatosis (or = 5% hepatocytes),or = stage II hepatic fibrosis, increased level of uric acid (or = 6.3 mg/dL) or asparate aminotransferase (or = 40 IU/L), and decreased level of albumin (3.5 g/dL) or fasting plasma glucose (126 mg/ dL). Viral factors, including hepatitis C virus genotype 1b infection and viral load, are not related to elevated alpha-fetoprotein in hepatitis C virus-infected subjects.