Extrahepatic multimorbidity, disease clusters and overall and cause-specific mortality in people with steatotic liver diseases: a prospective analysis of UK Biobank

BackgroundSteatotic liver disease (SLD) is a prevalent chronic liver disease linked to increased risks of various liver and extrahepatic diseases. However, the clustering of extrahepatic conditions and their impact on mortality in individuals with SLD remain poorly understood. MethodsWe used UK Biobank data to identify disease clusters among individuals with SLD and multimorbidity (having >= 2 extrahepatic diseases) using latent class analysis, conducted separately in males and females. Multivariable Cox models were used to assess associations between multimorbidity, derived disease clusters and all-cause mortality and cause-specific mortality of cardiovascular diseases, extrahepatic cancers, hepatocellular carcinoma and liver related diseases, with individuals without multimorbidity as reference group. ResultsAmong 36002 SLD individuals with multimorbidity, we identified five disease clusters in both sexes: respiratory, mental health, cancer/osteoarthritis, and cardiovascular clusters. Males had separate heart and stroke clusters, whereas females had a combined heart/stroke cluster and a unique thyroid cluster. During a median follow-up of 13.8 years, cardiovascular disease was the leading cause of death in cardiovascular clusters, whereas extrahepatic cancers were the most common cause of death in other clusters. Multimorbidity was associated with increased mortality by 100% (HR (95%CI): 2.00 (1.93, 2.08)), as well as mortality of cardiovascular diseases, extrahepatic cancers, and liver-related diseases. Among all disease clusters, cardiovascular clusters exhibited the highest mortality risk: 2.36 (2.16, 2.58) for the stroke cluster, 2.63 (2.48, 2.78) for the heart cluster in males, and 2.90 (2.64, 3.20) for heart/stroke cluster in females. ConclusionsMultimorbidity clusters in SLD exhibit sex differences, with cardiovascular-related clusters showing the highest mortality. These findings highlight the need for tailored prevention and management strategies in SLD populations.