Utility and limitations of noninvasive fibrosis markers for predicting prognosis in biopsy-proven Japanese non-alcoholic fatty liver disease patients

The fibrosis stage of non-alcoholic fatty liver disease (NAFLD) is closely associated with long-term prognosis, including liver-related mortality. However, it is not yet clear whether noninvasive fibrosis markers can predict the incidence of non-liver-related complications in Japanese NAFLD. In this study, we clarified the prognosis of NAFLD patients, including non-liver-related diseases, based on hepatic pathology and noninvasive fibrosis markers.A total of 246 Japanese patients with NAFLD diagnosed by liver biopsy were enrolled. We investigated their prognosis based on hepatic pathology and noninvasive fibrosis markers.When these patients were categorized based on the severity of liver fibrosis as F0-2 (n = 196) and F3-4 (n = 50), the patients with F3-4 had significantly poorer prognosis in overall survival rates and all complications (P < 0.05). The fibrosis-4 (FIB-4) index was useful to predict overall survival and the incidence of hepatocellular carcinoma and liver cirrhosis (LC)-related complications but not extrahepatic malignancies. Multiple logistic regression analyses revealed the following risk factors: total bilirubin ≥ 1.2 (hazard ratio [HR] 6.362, 95% confidence interval [CI] 1.393-29.052) and severe liver fibrosis (HR 6.512, 95% CI 1.433-29.592) for overall survival; liver fibrosis (F3-4) (HR 13.370, 95% CI 2.775-64.427) for hepatocellular carcinoma; FIB-4 index (HR 26.560, 95% CI 3.320-212.494) for LC-related complications, and liver inflammation (A2-3) (HR 4.214, 95% CI 1.354-13.116) for extrahepatic malignancies.Severe liver fibrosis was associated not only with the hepatocarcinogenesis and LC-related complications but also with extrahepatic malignancies. The FIB-4 index was useful for predicting liver-related diseases but had limitations in predicting extrahepatic malignancies.