Liver Fibrosis in Heart Failure: Prevalence, Outcomes and Proteomic Pathway Analysis from the BIOSTAT-CHF Cohort

Liver disease is highly prevalent in heart failure (HF) and is associated with worse outcomes, although the pathophysiological mechanisms remain poorly understood. In 3,017 HF patients from the index and validation cohorts of BIOSTAT-CHF, the prevalence of liver fibrosis was 552 (18.3%) as estimated by FIB-4 ≥2.67. Patients with liver fibrosis showed greater signs of systemic congestion, hepatomegaly, jugular venous distension, and elevated right heart pressures. Liver fibrosis significantly predicted mortality or HF re-hospitalisation, with "burnt-out" fibrosis (advanced fibrosis with minimal steatosis) carrying the highest risk (LiverRisk score ≥10 and Hepatic steatosis index <30: HR 7.86 [4.03–15.1]). Proteomic pathway analysis of 359 biomarkers identified αv integrin and TGFβ receptor II as central mediators of fibrogenesis, linking extracellular matrix remodelling, suppressed angiogenesis and inflammation. These findings position αv integrin as a therapeutic target amenable to selective inhibition in patients with concomitant HF and liver fibrosis.