Multimorbidity in patients with chronic liver disease: A systematic review

Background Chronic liver disease (CLD) is a major global health threat traditionally managed through a “hepatocentric” lens, which often overlooks the systemic complexity of the disease. This systematic review aims to identify multimorbidity patterns (clusters) in adults with CLD and evaluate their specific impact on clinical outcomes and mortality risk. Methods A systematic search was performed across PubMed, Scopus, CINAHL, and Web of Science for studies published until July 2025. Following PRISMA guidelines, 19 high-quality studies (12 cohort and 7 cross-sectional) were selected. We analysed multimorbidity clusters, focusing on cardiometabolic, mental health, and musculoskeletal domains, and extracted effect sizes (HR and OR) to determine prognostic impact. Results Multimorbidity affects up to 99% of patients with CLD. Three primary clusters were identified: the cardiometabolic cluster, linked to the Liver-Cardio-Kidney-Metabolic (CKM) syndrome; the mental health cluster, where depression increases mortality risk by 49% (HR 1.49); and the musculoskeletal cluster, where myosteatosis is associated with a 2.9-fold increased risk of severe fibrosis (OR 2.9). Notably, the presence of two or more extrahepatic conditions doubles the mortality risk (HR 2.00). These findings demonstrate that extrahepatic clusters are independent predictors of poor prognosis in patients with liver dysfunction. Conclusion The survival of CLD patients depends on the totality of the disease network rather than isolated hepatic function. Effective management requires a transition to an integrated multidisciplinary model, incorporating routine screening for sarcopenia and mental health disorders to mitigate systemic frailty.