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

Cari V.; Perez M.I.; Tellez I.; Idalsoaga F.; Valsan A.; Nair G.; Soni K.; Rhoads S.F.; Arnold J.; Ayala-Valverde M.; Ramirez-Cadiz C.; Jalal P.K.; Ibrahim M.A.; Elfeki M.A.; Roblero J.P.; Simian D.; Velarde-Ruiz Velasco J.A.; Cordova J.; Higuera-de-la-Tijera F.; Silva R.; Rocha C.M.; Araujo R.C.; Fontani G.M.; Pereira G.H.; Bessone F.; Tanno M.; Kisch A.; Mendizabal M.; Marciano S.; Gomez-Perdiguero G.; Montes P.; Guerra Salazar P.; Ramos G.; Chacko K.R.; Skladaný L.; Maiwall R.; Simonetto D.; Sanyal A.J.; Shah V.H.; Singal A.K.; Dunn W.; Kamath P.S.; Loomba R.; Arrese M.; Bataller R.; Díaz L.A.; Arab J.P. · Hepatology (2026) · DOI: 10.1097/hep.0000000000001780

Resumen

Introduction: – Although the role of cardiometabolic risk factors (CMRF) 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 CMRF on mortality. Methods: – Multinational prospective cohort study (2015–2024) including hospitalized patients with severe AH across 32 centers in 14 countries. Diagnosis of AH was made using the NIAAA criteria. Analyses included adjusted competing-risk models by age, sex, ethnicity, history of cirrhosis, CMRF, corticosteroid use, MELD, and ACLF grade, with liver transplantation as a competing risk. Results: – 936 participants were included; mean age 48±11.2 years, and 88.9% were male. At least one CMRF was present in 46.6% median body mass index (BMI) was 24.2 kg/m2 [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 (sHR 1.02; 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 ACLF grade 2–3 (sHR 2.34 and 4.34) predicted mortality. However, no individual CMRF independently increased mortality. A prespecified non-linear BMI analysis showed modestly lower mortality between 25–40 kg/m², with a higher risk above 40 kg/m². Conclusion: – Among patients with severe AH, metabolic dysfunction was not associated with increased mortality. Although a higher BMI was associated with slightly lower mortality in AH, this may reflect better nutritional status rather than a true protective effect. Copyright