Diabetes mellitus is linked to higher mortality in alcohol-related acute-on-chronic liver failure

Background: Acute-on-chronic liver failure (ACLF) is a rapidly progressive syndrome marked by high short-term mortality. While diabetes mellitus (DM) is known to worsen liver-related outcomes, its specific impact on alcohol-related ACLF (ALD-ACLF) remains underexplored. This study aimed to assess the prognostic impact of DM on 90-day outcomes in ALD-ACLF using data from the APASL ACLF Research Consortium (AARC) database. Methods: This observational study involved data from 5612 ACLF patients with documented 90-day outcomes. We identified 2096 patients with ALD-ACLF precipitated by alcoholic hepatitis. Patients with non-ALD etiologies, mixed etiologies, or non-alcoholic precipitants were excluded. Diabetic and non-diabetic patients were compared using 1:2 propensity score matching based on key baseline covariates. Survival outcomes were assessed using Kaplan–Meier analysis and multivariable Cox regression. Results: After matching, 109 diabetic patients were compared with 218 well-matched non-diabetic controls. Diabetic patients had significantly lower overall survival (32 vs. 57%) and transplant-free survival (31 vs. 50%) compared to non-diabetics (log-rank p < 0.001). On multivariable Cox regression, DM was independently associated with increased 90-day mortality (HR 1.739, 95% CI 1.262–2.395, p < 0.001), along with elevated serum lactate (HR 1.187 per mmol/L, p < 0.001) and creatinine (HR 1.267 per mg/dL, p < 0.001). Conclusion: Diabetes mellitus is a significant independent predictor of mortality in patients with ALD-ACLF. These findings highlight the need for early identification and integrated management of diabetes in ACLF care pathways to improve clinical outcomes.