Fibrosis-4 index predicts long-term all-cause, cardiovascular and liver-related mortality in the adult Korean population
Authors and Affiliations
Authors and Affiliations
Young-Gyun Seo MD., PhD. 1, Stergios A. Polyzos MD., PhD. 2, Kyung-Hee Park MD., PhD. 1, Christos S. Mantzoros MD., PhD. 3,4
1Department of Family Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea
2First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
3Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
4Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
Corresponding Author: Christos S. Mantzoros, MD, DSc, PhD hc
Background and 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 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 (KNHANES) and mortality data were retrieved from the Korean Cause of Death data registry. Adults (≥19 years) 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 (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox regression analysis, and Kaplan-Meier estimates of the cumulative mortality were evaluated.
Results: There were 46,456 individuals with median follow-up of 8.6 years (interquartile range 6.3-10.6 years). Kaplan-Meier curves for cumulative mortality showed that participants with FIB-4≥2.67 (versus 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 estimated alcohol intake ≥30 gr for males and ≥20 gr for females 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.