In 10% of the patients with chronic abnormal alanine aminotransferase (ALT) levels no cause is found. The prognosis of this liver disease, the increased risk of liver fibrosis regardless of the types of histological lesions and the need for a liver biopsy are unknown. Nearly 50% of these cases are explained by non-alcoholic steatohepatitis (NASH). The aim of this study was to evaluate, in patients with accidentally detected chronically elevated ALT levels, the prevalence of fibrosis and NASH, and the clinical and biological factors associated with each entity. Retrospectively, 67 patients (mean age, 46.6 +/- 12.1 years; 45 males) were included. All patients had a liver biopsy and were hepatitis B virus, hepatitis C virus, human immunodeficiency virus seronegative without alcohol, drug, autoimmune or genetically induced liver disease, with ALT > N (the upper limit of normal). NASH was evaluated according to necroinflammatory lesions and fibrosis. Fibrosis was evaluated according to the METAVIR score. Statistical analyses were performed using Student's t test, the Mann-Whitney rank-sum test and the chi-square test. Fibrosis scores were: F0, 37.3%; F1, 32.8%; F2, 26.9%; F3, 1.5%; and F4, 1.5%. NASH was absent in 59.7% and present in 40.3%. Significant differences were observed between F < 2 and F > or = 2 fibrosis patients for aspartate aminotransferase (AST) and ALT and between patients with NASH or without for body mass index. Overall, the risk of F > or = 2 fibrosis was increased in patients with AST > N, ALT > 2N or AST > N and ALT > 2N. The prevalence of F > or = 2 fibrosis and NASH in patients with unexplained chronic abnormal ALT are 30% and 40%, respectively. Since the risk of F > or = 2 fibrosis is significantly increased in patients with AST > N and/or ALT > 2N, liver biopsy should be performed only in patients with AST > N or ALT > 2N.