Exploring the interaction between metabolic dysfunction and alcohol-associated hepatitis: A global study

Although the role of cardiometabolic risk factors (CMRFs) has been characterized in steatotic liver disease, their role in the severity of alcohol-associated hepatitis (AH) remains unclear. We aimed to evaluate the impact of CMRFs on mortality.

Multinational prospective cohort study (2015-2024) including hospitalized patients with AH across 32 centers in 14 countries. Diagnosis of AH was made using the National Institute on Alcohol Abuse and Alcoholism criteria. Analyses included adjusted competing-risk models by age, sex, ethnicity, history of cirrhosis, CMRF, corticosteroid use, MELD, and acute-on-chronic liver failure grade, with liver transplantation as a competing risk. Nine hundred thirty-six participants were included; the mean age was 48±11.2 years, and 88.9% were male. At least 1 CMRF was present in 46.6%; median body mass index was 24.2 kg/m 2 [IQR: 22.8-28.2], prevalence of diabetes 17.6%, hypertension 16.5%, and dyslipidemia 5.8%. Median MELD was 24.4 (19.3-31.4), 86.7% had severe AH, and 180-day survival was 72.9%. Survival did not differ by CMRF status (log-rank p =0.453). In adjusted competing-risk models, higher age (subdistribution hazard ratio [sHR] 1.03; 95% CI: 1.01-1.04), greater alcohol intake (per g/day; sHR: 1.001; 95% CI: 1.000-1.002), MELD (sHR: 1.04; 95% CI: 1.01-1.06), and acute-on-chronic liver failure grade 2-3 (sHR: 2.34 and 4.34) predicted mortality. However, no individual CMRF independently increased mortality. A prespecified nonlinear body mass index analysis showed modestly lower mortality between 25 and 40 kg/m², with a higher risk above 40 kg/m².

Among patients with severe AH, metabolic dysfunction was not associated with increased mortality. Although a higher body mass index was associated with slightly lower mortality in AH, this may reflect better nutritional status rather than a true protective effect.