Impact of Cardiometabolic Risk Factor Burden and Therapeutic Control on the Prognosis of Alcohol‐Related Hepatitis: A Biopsy‐Proven Cohort Study With External Multicentre Validation

Abstract

ABSTRACT Background and Aims Cardiometabolic risk factors (CMRF) have traditionally been overlooked in alcohol‐related liver disease (ALD) and their prognostic impact in alcohol‐related hepatitis (AH) remains poorly defined. We evaluated the influence of CMRF burden and therapeutic control on complications and mortality in AH. Methods We prospectively enrolled 100 patients with biopsy‐proven AH. CMRF (obesity, hypertension, diabetes, hyper‐triglyceridaemia, low HDL cholesterol) and therapeutic control prior to admission were assessed. A cardiometabolic burden (CMB) score (0–10), incorporating CMRF number and control, was constructed. External validity was tested in an independent multicentre cohort of 332 patients with clinically diagnosed AH. Results In the primary cohort, patients with CMRF had higher 1‐year mortality than those without (48% vs. 25%, p  = 0.030) and more frequent in‐hospital complications. Clustered CMRF (≥ 3) independently predicted 1‐year mortality after adjustment for MELD, age and sex (HR = 4.1, 95% CI: 1.66–10, p  = 0.002). Increasing CMB scores (≥ 5) similarly associated with higher mortality (HR = 4.4, 95% CI: 1.76–11, p  = 0.002). These findings were reproduced in the external cohort, where ≥ 3 CMRF predicted 1‐year mortality (HR = 3.0, 95% CI: 1.97–4.7, p  < 0.001). Furthermore, ≥ 3 CMRF independently predicted 1‐year mortality beyond MELD and Lille response in treated patients (HR = 2.6, 95% CI: 1.46–4.5, p  = 0.001). Conclusions Clustered (≥ 3) and poorly controlled CMRF significantly impair survival and increase complication rates in AH. These findings, confirmed in an independent multicentre cohort, support integrating systematic cardiometabolic evaluation into routine clinical ALD management.