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. 2025 Sep 9:10.1097/HEP.0000000000001513.
doi: 10.1097/HEP.0000000000001513. Online ahead of print.

Natural history and development of a novel composite endpoint in patients with alcohol-associated hepatitis: Data from a prospective multicenter study

Srinivasan Dasarathy  1 , Wanzhu Tu  2 , Nicole Welch  1 , Samer Gawrieh  2 , Yunpeng Yu  2 , Qing Tang  2 , Carla Kettler  2 , Arun J Sanyal  3 , Gyongyi Szabo  4 , Vijay H Shah  5 , Ramon Bataller  6 , Laura E Nagy  1 , Craig J McClain  7   8 , Naga Chalasani  2 , Thomas Kerr  9 , Mack C Mitchell  9 ; for AlcHepNet Investigators
Collaborators, Affiliations

Natural history and development of a novel composite endpoint in patients with alcohol-associated hepatitis: Data from a prospective multicenter study

Srinivasan Dasarathy et al. Hepatology. .

Abstract

Background aims: The clinical course and outcomes of alcohol-associated hepatitis (AH) remain poorly understood. Major adverse liver outcomes do not capture the added risk of return to drinking. We examined the natural history of AH and developed a composite endpoint using a contemporary observational cohort of AH.

Approach results: A cohort of 1127 participants: 712 AH patients, 256 heavy drinking controls without clinically evident liver disease, and 159 healthy controls, were prospectively followed for 6 months at 8 United States centers as part of the Alcoholic Hepatitis Network (AlcHepNet) consortium. Outcomes included mortality and a composite endpoint (AlcHepNet composite index) that included death, liver transplantation, hepatic decompensation (new onset/worsening ascites, HE, variceal bleeding), liver-related hospital admission, MELD increase ≥5, and return to drinking. Of 712 AH patients (age 45±10.7 y; 59.1% male), 558 (79.0%) had severe and 148 (21.0%) had moderate AH, 232 (32.5%) died, and 86 (12.1%) underwent liver transplantation. Mortality rates in moderate AH and severe AH were 0.7% versus 17.2% (30 d), 3.4% versus 26.5% (90 d), and 8.8% versus 30.5% (180 d), respectively (all p <0.001). Composite liver/alcohol use events were noted in 459 (64.5%) AH patients. Higher MELD score, lower mean arterial pressure, and baseline leukocytosis were associated with higher 90-day mortality in AH (all p <0.05). College education and higher ALP were associated with lower mortality. Heavy drinking controls had low mortality (n=3; 1.2%).

Conclusions: This large observational study showed a high incidence of composite liver and alcohol-use events within 6 months, reiterating the need for early interventions.

Keywords: alcohol-associated hepatitis; composite event; multicenter; outcomes; prospective.

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Conflict of interest statement

Conflicts of interest. Naga Chalasani has consulting agreements with Madrigal, Zydus, Altimmune, Ipsen, Biomed Fusion, GSK, Pfizer, Akero, and Boston Pharmaceuticals. He receives research support from Exact Sciences, Boehringer-Ingelheim. He has equity in Avant Sante, a contract research organization, and Heligenics, a drug discovery start-up company.

Figures

Fig. 1.
Fig. 1.
Participant enrollment in AlcHepNet observational study.
Fig. 2.
Fig. 2.
Kaplan-Meier estimates of overall survival in patients with AH, stratified by baseline MELD scores.
Fig. 3.
Fig. 3.
(A) Kaplan-Meier curves of composite endpoints (including return to drinking) within 180 days among patients with AH. (B) Kaplan-Meier curves of composite endpoints (excluding return to drinking) within 180 days among patients with AH.
See this image and copyright information in PMC

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