Liver fibrosis and poor outcome in patients with heart failure: new insights from the BIOSTAT-CHF study

Abstract Background/Introduction The cardio-hepatic axis is increasingly implicated in heart failure (HF) pathophysiology. Metabolic-Associated Steatotic Liver Disease (MASLD) has been shown to predict incident HF. Progression of MASLD to liver fibrosis represents an important prognostic shift, potentially through haemodynamic changes of advancing liver fibrosis or systemic pro-inflammatory perturbation. Detection of subclinical forms of liver fibrosis may therefore have prognostic value in patients with HF. Purpose In this study, we investigate the association between subclinical liver fibrosis, assessed using FIB-4 index, and clinical outcomes. Methods We evaluated 1,102 patients with worsening or new-onset HF from the BIOlogy Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study who had available measures of age, AST, ALT and platelet that were used to determine the FIB-4 index at baseline. Outcome assessed was All-Cause Mortality (ACM). Kaplan-Meier curves were used to illustrate time-to-event outcomes and proportional hazards models were used to calculate Hazard Ratios (HR) and 95% confidence intervals (95% CI). Adjustment for the inflammatory markers, IL-6 and TNF Receptor Superfamily 4 (TNFRSF4), was used to determine the contribution of inflammation on the association between FIB-4 and outcomes. Results Patients with a higher level of liver fibrosis had a higher risk of death compared to patients with a low risk of liver fibrosis (Intermediate, FIB-4 1.3-2.67: HR 1.46, p = 0.008; High, FIB-4 2.68-3.24: HR 2.11, p 0.001; Very High, FIB-4 ≥3.25: HR 2.63 p 0.001) (Figure). Adjustment for inflammatory markers attenuated the effect of fibrosis on outcomes (Table). However, even after adjustment for inflammation, fibrosis remained a strong independent predictor of outcomes (Table). After adjustment for fibrosis, TNFRSF4 remained strongly associated with adverse clinical outcomes (HR 1.58, p 0.001). Conclusion(s) These results indicate that subclinical liver fibrosis, assessed using FIB-4 index, is associated with poorer outcomes. Even after adjustment for inflammation, liver fibrosis remains a strong independent predictor of outcomes.Figure:Kaplan-Meier Curve Table:HRs by FIB-4 category