Metabolic dysfunction-associated steatotic liver disease and risk of four intrahepatic and extrahepatic diseases

INTRODUCTION AND OBJECTIVES: Recently, Delphi consensus proposed an overarching term steatotic liver disease (SLD), with various subcategories such as MASLD, MetALD and ALD. Our aim was to investigate the association between MASLD/MetALD/ALD and four intrahepatic and extrahepatic diseases (liver diseases, renal diseases, cardiovascular diseases, and cancers) in the UK Biobank cohort. PATIENTS AND METHODS: By defining hepatic steatosis as image-derived phenotype (IDP)-PDFF >5.21%, we used data from the UK Biobank to diagnose MASLD/ MetALD/ALD. The odd ratio (OR) and the hazard ratio (HR) were calculated using the logistic regression modals and Cox regression models, respectively. RESULTS: Among 39,230 eligible individuals, 6,865 MASLD subjects, 2,379 MetALD subjects and 884 ALD subjects were diagnosed. The last follow-up time was October 13, 2023. Consistent with the logistic analyses, MASLD/MetALD/ALD were significantly associated with a higher risk of liver diseases (HR=3.04 [95%CI:2.60-3.56], HR = 2.69 [95% CI: 2.12-3.42] and HR =3.99 [95%CI:2.92-5.45], respectively). Subjects with MASLD also had an increased higher risk of renal diseases (HR = 1.40 [95%CI:1.20-1.64]) and subjects with ALD had an increased higher risk of cancers (HR = 1.36 [95%CI:1.15-1.60]). CONCLUSION: It is the first study to report the association between MASLD, MetALD, ALD and common intrahepatic and extrahepatic diseases based on magnetic resonance imaging data-PDFF. We found that MASLD, MetALD and ALD were risk factors for liver diseases. Meanwhile, MASLD was also a risk factor for renal diseases and ALD was a risk factor for cancers.