Effects of diabetes, obesity, and metabolic syndrome on alcohol-associated liver disease: A systematic review

Hepatol Commun. 2026 Aug 20;10(9):e01029. doi: 10.1097/HC9.0000000000001029. eCollection 2026 Sep 1.

ABSTRACT

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading cause of advanced liver disease and liver transplantation worldwide. Cardiometabolic risk factors (CMRFs) may worsen ALD prognosis. While recent nomenclature acknowledges the impact of CMRFs in steatotic liver disease with low-to-moderate alcohol use, individuals with high alcohol intake are still classified as having ALD regardless of CMRF status. We conducted a systematic review to evaluate the impact of CMRFs, primarily diabetes, obesity, and metabolic syndrome, on clinical outcomes in patients with ALD.

METHODS: We performed a systematic review of peer-reviewed studies published through October 21, 2025, as well as abstracts from the AASLD, EASL, DDW, ACG, and APASL conferences from 2023 to 2025. We included studies involving adults (≥18 y) with ALD that assessed at least one CMRF (eg, diabetes, obesity, metabolic syndrome) and reported longitudinal clinical outcomes. Primary outcomes included incident cirrhosis, hepatocellular carcinoma (HCC), overall and cause-specific mortality, cardiovascular events, liver-related complications, and liver transplantation.

RESULTS: Nineteen studies comprising 132,054 patients with ALD met the inclusion criteria. Diabetes was consistently associated with increased risks of overall mortality [adjusted hazard ratio (aHR) 3.00], liver-related mortality (aHR 3.60), HCC (hazard ratios 1.6-21.7), and cardiovascular mortality (aHR 19.91). Elevated BMI was linked to higher all-cause mortality (aHR 1.16-1.58), cardiovascular mortality (aHR 3.76), HCC incidence (HR 2.0-2.9), and liver-related mortality (aHR 16.22). Metabolic syndrome was associated with increased overall (HR 1.27-2.37) and liver-related mortality (HR 1.47-2.06). A greater burden of CMRFs was correlated with lower transplant-free survival and reduced rates of hepatic recompensation.

CONCLUSION: Diabetes, obesity, and metabolic syndrome are associated with worse hepatic and extrahepatic outcomes in ALD.

PMID:42623525 | DOI:10.1097/HC9.0000000000001029