Liver Fibrosis Assessed Via Noninvasive Tests Is Associated With Incident Heart Failure in a General Population Cohort

BACKGROUND & AIMS: The aim of this study was to determine whether liver fi brosis is associated with heart failure in a general population cohort, and if genetic polymorphisms ( PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fi brosis and decreased risk of coronary artery disease, modify this association. METHODS: Using UK Biobank data, we prospectively examined the relationship between noninvasive fi brosis markers (nonalcoholic fatty liver disease [NAFLD] fi brosis score [NFS], Fibrosis-4 [FIB- 4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n [ 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fi brosis and heart failure were estimated by stratifying for genotype and testing for an interaction between genotype and liver fi brosis using a likelihood ratio test. RESULTS: A total of 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fi brosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high-risk NFS score HR, 1.59; 95% confidence fi dence interval [CI],1.47-1.76; P < .0001; FIB-4 HR, 1.69; 95% CI, 1.55-1.84; P < .0001; APRI HR, 1.85; 95% CI, 1.56-2.19; P < .0001; combined fi brosis scores HR, 1.90; 95% CI, 1.44-2.49; P < .0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD), and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fi brosis markers and heart failure. For PNPLA3, , a statistically significant fi cant interaction was found between PNPLA3 rs738409, FIB-4, APRI score, and heart failure. CONCLUSION: In the general population, serum markers of liver fi brosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fi brosis were not positively associated with elevated heart failure risk.