Non-invasive assessment of liver fibrosis with FIB-4 for risk stratification and prognosis in ambulatory heart failure

Background Liver dysfunction is increasingly recognized as a contributor to heart failure (HF) progression and adverse outcomes. The Fibrosis-4 (FIB-4) index, a simple non-invasive marker of advanced liver fibrosis, has been validated in metabolic liver disease and associated with cardiovascular risk and mortality. In HF, FIB-4 may reflect both underlying liver fibrosis and chronic hepatic congestion. However, its prognostic role in HF remains insufficiently characterized. Purpose To evaluate the association between FIB-4 and all-cause mortality in a cohort of ambulatory HF patients. Methods Retrospective analysis of ambulatory HF patients followed in a HF clinic between January 2010 and December 2023 was conducted. FIB-4 was calculated based on age, AST, ALT and platelet values. The FIB-4 index was interpreted according to age: in <65 years, values <1.3 ruled out advanced fibrosis, 1.3–2.67 were considered indeterminate, and >2.67 indicated advanced fibrosis; in those ≥65 years, values <2.0 ruled out advanced fibrosis, 2.0–2.67 were indeterminate, and >2.67 indicated advanced fibrosis. Continuous variables were summarized as mean ± standard deviation or median (P25-P75), and categorical variables as percentages. Multivariable Cox proportional hazards regression models were performed to evaluate the independent association between FIB-4 categories and all-cause mortality, adjusting for age, left ventricular ejection fraction (LVEF) and relevant comorbidities. Results 1233 patients were included (mean age 67.3± 12.5 years; 30.8 % women; 24% BMI >30 kg/m²; 69.7 % NYHA II; NT-proBNP 1999 (IQR 825-4197); LVEF 38.2 ±14.7%; 45% Type-2 DM; 61.6% dyslipidemia). During a median follow-up of 55 months 529 deaths (42.9%) occurred. Higher FIB-4 levels were associated with increased mortality in univariable analysis when modeled as a continuous variable (HR 1.025 per unit increase, 95% CI 1.004–1.047; p=0.022). When categorized into three strata (low <1.3, indeterminate 1.3–2.67, high >2.67), mortality increased progressively across FIB-4 categories (Figure 1). After adjustment for age, LVEF, HTA, DM, BMI and dyslipidemia, only the highest FIB-4 category (>2.67) remained independently associated with mortality (adjusted HR 1.24, 95% CI 1.03–1.49; p=0.021). When stratified by age, in patients <65 years, FIB-4 >2.67 was strongly and independently associated with mortality (adjusted HR 2.12, 95% CI 1.19-3.79; p=0.011). In patients ≥65 years, using age-specific thresholds, FIB-4 >2.67 remained independently associated with mortality (adjusted HR 1.45, 95% CI 1.11-1.89; p=0.007). Conclusion In ambulatory HF patients, elevated FIB-4 is independently associated with all-cause mortality. This simple and widely available index may enhance risk stratification and help identify high-risk individuals who could benefit from closer monitoring and more proactive management strategies.Baseline cohort characteristics