AIMS:

The aim of our study was to elucidate the characteristics and natural history of Japanese nonalcoholic fatty liver disease (NAFLD).

PATIENTS AND METHODS:

Two hundred and forty-seven patients were diagnosed as having biopsy-proven NAFLD at Tokyo Women's Medical University or an affiliated hospital from 1990 to June 2004. Biopsies were scored for the severity of steatosis, necro-inflammation, and fibrosis according to modified Brunt criteria. We assessed the clinicopathological features and natural history of NAFLD in patients stratified by the stage of their fibrosis. Univariate and multivariate logistic analyses were performed, and the diagnostic ability was assessed by the area under the receiver operating characteristic curve.

RESULTS:

Clinicopathological features: The median age of the patients was 53 years, with a range from 10 to 89 years. There were 130 males and 117 females. Histologically, 46 patients were classified as F3 (bridging fibrosis), and 43 patients had F4 (cirrhosis). Females and older patients were more common in the F3-4 patients. Most of the F3-4 patients showed mild elevation of transaminases with significant deterioration of liver function tests compared with F0-2 patients. Ten patients were simultaneously diagnosed as having cirrhotic NASH and hepatocellular carcinoma (HCC). Natural history: During follow-up (median 44 months) of the F3-4 patients, 10 patients developed liver-related morbidity and five patients developed HCC. In the F3-4 patients, the 5-year cumulative incidence of HCC was 20%. Eight patients died (two of liver failure, four of HCC and two of other carcinomas). Serum markers for detecting F3-4: Serum hyaluronic acid levels can accurately evaluate NAFLD patients with F3-4.

CONCLUSIONS:

The most important consequence of NAFLD patients with advanced fibrosis was HCC. Regular screening for this complication is extremely important.