The natural history of nonalcoholic fatty liver disease: a clinical histopathological study

OBJECTIVES: We aimed to define nonalcoholic steatohepatitis (NASH) histopathological change over time and to correlate changes with clinical characteristics. METHODS: We retrieved nonalcoholic fatty liver cases from our histopathology database covering 1985 to 2001. We also identified patients in clinic with NASH on biopsy >1 yr prior. All patients were evaluated and clinical data obtained in clinic. Those patients qualifying for NASH therapeutic trials underwent liver biopsy pretreatment. One pathologist (S.T.) read all slides using a NASH grading and staging system. RESULTS: A total of 22 patients had repeat biopsies a mean of 5.7 yr (range 1.4-15.7 yr) after the first biopsy. Nine were women, nine had diabetes, 11 had hypertension, and 14 had hyperlipidemia. Mean body mass index was 33.8 kg/m(2) (range 26.5-48.6 yr). Mean age was 50.6 yr (range 33-64 yr). Ten patients (45%) had fibrosis stage 1 or 2, and two patients (9%) had bridging fibrosis or cirrhosis (stage 3 or 4) on first biopsy. Seven (32%) had increases in fibrosis score. Four patients (18%) had decreases in fibrosis score. The percentage of patients with stage 3 or 4 increased from 9% to 18%. In two patients the disease progressed rapidly (fibrosis scores from 1 to 3 in 1.4 yr and from 2 to 4 in 2.6 yr). Only serum AST at last biopsy correlated with histological change, being higher in those with disease progression. Three patients progressed from steatosis to steatohepatitis with fibrosis. CONCLUSIONS: NASH has a variable histological course. However, one third of patients have fibrosis progression, and one third of these have rapid progression to advanced fibrosis. Histological progression correlated with higher serum AST but no other clinical factors. Steatosis alone may progress to NASH with fibrosis.