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

Background and Aim: 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. Methods: 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. Results: 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. Conclusions: 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.