Fibrosis-4 Index Predicts Long-Term All-Cause, Cardiovascular and Liver-Related Mortality in the Adult Korean Population

Background & Aims Associations between hepatic fibrosis and mortality remain to be fully elucidated in large population-based studies. This study aimed to evaluate the associations of the fibrosis-4 index (FIB-4) with all-cause, cardiovascular, cancer, and liver-related mortality in the adult Korean population without viral hepatitis. Methods Baseline data were retrieved from the Korea National Health and Nutrition Examination Survey, and mortality data were retrieved from the Korean Cause of Death data registry. Adults (age, ≥19 y) without viral hepatitis B or C, liver cirrhosis, any cancer, stroke, myocardial infarction, angina pectoris, or renal failure at baseline were eligible. Presumed hepatic fibrosis was evaluated with FIB-4. Hazard ratios (HRs) and 95% CIs were calculated using multivariable Cox regression analysis, and Kaplan–Meier estimates of the cumulative mortality were evaluated. Results There were 46,456 individuals with a median follow-up period of 8.6 years (interquartile range, 6.3–10.6 y). Kaplan–Meier curves for cumulative mortality showed that participants with a FIB-4 of ≥2.67 (vs FIB-4, <2.67) had higher cumulative all-cause, cardiovascular, cancer, and liver-related mortality. In the fully adjusted model, Cox regression analysis revealed that presumed advanced hepatic fibrosis (FIB-4, ≥2.67) remained associated with all-cause mortality (HR, 1.64; 95% CI, 1.23–2.18), cardiovascular mortality (HR, 2.96; 95% CI, 1.60–5.46), and liver-related mortality (HR, 10.50; 95% CI, 4.70–23.44), but not cancer mortality, after adjusting for confounders including central obesity and insulin resistance. Excluding participants with an estimated alcohol intake of 30 grams or more for men and 20 grams or more for women did not affect the results. Conclusions At the population level, liver fibrosis estimated by FIB-4 was associated with increased cumulative all-cause, cardiovascular, and liver-related mortality. Associations between hepatic fibrosis and mortality remain to be fully elucidated in large population-based studies. This study aimed to evaluate the associations of the fibrosis-4 index (FIB-4) with all-cause, cardiovascular, cancer, and liver-related mortality in the adult Korean population without viral hepatitis. Baseline data were retrieved from the Korea National Health and Nutrition Examination Survey, and mortality data were retrieved from the Korean Cause of Death data registry. Adults (age, ≥19 y) without viral hepatitis B or C, liver cirrhosis, any cancer, stroke, myocardial infarction, angina pectoris, or renal failure at baseline were eligible. Presumed hepatic fibrosis was evaluated with FIB-4. Hazard ratios (HRs) and 95% CIs were calculated using multivariable Cox regression analysis, and Kaplan–Meier estimates of the cumulative mortality were evaluated. There were 46,456 individuals with a median follow-up period of 8.6 years (interquartile range, 6.3–10.6 y). Kaplan–Meier curves for cumulative mortality showed that participants with a FIB-4 of ≥2.67 (vs FIB-4, <2.67) had higher cumulative all-cause, cardiovascular, cancer, and liver-related mortality. In the fully adjusted model, Cox regression analysis revealed that presumed advanced hepatic fibrosis (FIB-4, ≥2.67) remained associated with all-cause mortality (HR, 1.64; 95% CI, 1.23–2.18), cardiovascular mortality (HR, 2.96; 95% CI, 1.60–5.46), and liver-related mortality (HR, 10.50; 95% CI, 4.70–23.44), but not cancer mortality, after adjusting for confounders including central obesity and insulin resistance. Excluding participants with an estimated alcohol intake of 30 grams or more for men and 20 grams or more for women did not affect the results. At the population level, liver fibrosis estimated by FIB-4 was associated with increased cumulative all-cause, cardiovascular, and liver-related mortality.