BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) and metabolic dysfunction-associated steatotic liver disease (MASLD) are both associated with liver fibrosis. HFrEF patients may develop liver fibrosis due to hepatic congestion, MASLD, or a combination of both. The Fibrosis-4 (FIB-4) score calculated using age, aspartate aminotransferase, alanine aminotransferase, and platelet count, serves as a screening tool for advanced liver fibrosis. This study examines the association between the FIB-4 score and all-cause mortality, cardiovascular mortality, and major adverse liver outcomes (MALO) in patients with HFrEF. METHOD AND RESULTS: This study included 4523 HFrEF patients from the Danish Heart Failure Registry. Based on FIB-4 score, 25.5 % were low-risk, 45.7 % were indeterminate-risk, and 28.8 % were high-risk for advanced liver fibrosis. After five years, the cumulative incidence of all-cause mortality was 43 % for the high-risk group, 36 % for the indeterminate-risk group, and 23 % for the low-risk group. The indeterminate-risk and high-risk group had an increased hazard ratio (HR) for all-cause mortality (HR 1.33, 95 % confidence interval [CI] 1.16-1.52
HR 1.51, 95 % CI 1.31-1.74) compared to the low-risk group. Similarly, HRs were elevated for cardiovascular mortality (HR 1.61, 95 % CI 1.27-2.05
HR 2.14, 95 % CI 1.67-2.74) and MALO (HR 1.77, 95 % CI 1.01-3.31
HR 2.54, 95 % CI 1.43-4.52). CONCLUSION: A high FIB-4 score in patients with HFrEF is associated with increased mortality and MALO.