Fibrosis-4 index efficiently predicts chronic hepatitis and liver cirrhosis development based on a large-scale data of general population in Japan

A non-invasive method to evaluate the fibrosis stage and the risk stratification of non-alcoholic fatty liver disease (NAFLD) is required. A total of 416,066 generally healthy subjects who underwent health check-ups between 1990 and 2019 were investigated. Fatty liver prevalence greatly increased from the 1990s (21.9%) to the 2000s (37.1%) but showed no considerable change between 2001–2010 (39.2%) and 2011–2019 (35.5%). During the 30 years, the rate of high FIB-4 index (≥2.67) and mean body mass index (BMI) did not markedly change. Fatty liver was significantly associated with BMI, but not with alcohol intake or FIB-4 index. Cox regression analyses for development of chronic hepatitis or liver cirrhosis identified that the risk of developing chronic hepatitis and liver cirrhosis was higher in subjects without fatty liver than in those with it (hazard ratio [HR]=0.09; 95% confidence interval [CI], 0.03–0.22, p <0.001 and HR=0.04; 95% CI, 0.01–0.26, p =0.001, respectively), and much larger in subjects with a high FIB-4 index (≥ 2.67) than in those without it (HR=78.6; 95% CI, 29.0–213.1, p <0.001 and HR=5950.7; 95% CI,761.7–46,491.4, p <0.001, respectively). Adjusted survival curves for Cox proportional hazards regression further reinforced these results. In conclusion, the FIB-4 index is a useful indicator of chronic hepatitis and liver cirrhosis development in the general population.