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Clinical Trial
. 2025 Jun;45(6):e70111.
doi: 10.1111/liv.70111.

Bacterial Infections in Patients With Severe Alcohol-Associated Hepatitis: Drivers of Organ Failure and Mortality

Laura Buttler  1 , Jan Stange  2 , Nikolaos Pyrsopoulos  3 , Tarek Hassanein  4 , Heiner Wedemeyer  1   5 , Benjamin Maasoumy  1   5 , Markus Busch  1 ; VTL‐308 study group
Affiliations
Clinical Trial

Bacterial Infections in Patients With Severe Alcohol-Associated Hepatitis: Drivers of Organ Failure and Mortality

Laura Buttler et al. Liver Int. 2025 Jun.

Abstract

Background: Severe alcohol-associated hepatitis (sAH) is a life-threatening condition with limited treatment options. Although corticosteroids offer some benefit in short-term survival, their use remains controversial due to concerns about increased infection risk. Infections are a major cause of mortality in sAH; however, the reasons for this remain unclear.

Methods: A post hoc analysis of the prospective VTL-308 multicentre trial on 151 patients with sAH was performed. Competing-risk models evaluated predictors of infections, the influence of corticosteroids on infection risk, and the impact of infections on the clinical outcomes up to 1 year of follow-up.

Results: Among 151 patients, 90 (59.6%) developed infections. The most frequent were urinary tract (34.4%) and bloodstream (30%) infections. The causative pathogen was isolated in 40 patients, with Enterococcus spp. being the most common (35%). Fungal infections were detected in 19 (12.6%) patients. Corticosteroid use was not associated with increased bacterial (subdistribution-hazard ratio [sHR] =0.74; 95% Confidence Interval (CI): 0.42-1.33; p = 0.32) or fungal infection risk (sHR = 1.74; 95% CI: 0.59-5.15; p = 0.31). Infections significantly increased multi-organ failure (MOF) in the univariate (sHR = 2.31; 95% CI: 1.03-5.17; p = 0.04) and multivariate models (sHR = 2.46; 95% CI: 1.12-5.39; p = 0.03). 37.8% of infected patients died versus 13.1% of non-infected patients. Bacterial infections strongly predicted mortality, with sHRs ranging from 5.22 to 7.78, indicating a five- to eight-fold increased risk of death (p < 0.001).

Conclusions: Infections in sAH are central drivers of MOF and mortality. Our findings highlight infections as an independent risk factor unaffected by corticosteroid use, addressing previous concerns about the safety of this treatment.

Keywords: alcohol‐associated liver disease (ALD); corticosteroids in alcohol‐associated hepatitis; fungal infections in sAH; infections in alcohol‐associated hepatitis; predictive modelling in sAH; severe alcohol‐associated hepatitis (sAH).

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Conflict of interest statement

J.S. served as the Chief Medical Officer of Vital Therapies Inc. at the time of the VTL‐308 study and is currently the Chief Medical Officer and Chairman of the Board of Albutec GmbH. H.W. served as a speaker/advisory board member for Abbott Laboratories & Abbott Molecular Inc., Bristol‐Myers Squibb, Gilead Sciences GmbH & Gilead Sciences Ltd., GlaxoSmithKline Services Unlimited, Janssen, Roche Diagnostics International Ltd., and Vir Biotechnology Inc.; received research support from Abbott Laboratories & Abbott Molecular Inc. and Biotest AG; and received lecture fees from Biotest AG and Gilead Sciences GmbH & Gilead Sciences Ltd. B.M. served as a speaker and/or advisory board member for AbbVIe, AstraZeneca, Falk, Fujirebio, Gilead, Luvos, MSD, Norgine, Roche, W. L. Gore & Associates and received research support from Altona Diagnostics, EWIMED, Fujirebio, and Roche, all unrelated to the present work.

Figures

FIGURE 1
FIGURE 1
Types of infections in the infection group (n = 90) (A). Frequency of different pathogens identified in infected patients (grampositive and gramnegative) (B). BSI, bloodstream infection; HR, hazard ratio; SBP, spontaneous bacterial peritonitisUTI, urinary tract infection.
FIGURE 2
FIGURE 2
Incidences of infections were not increased in patients receiving corticosteroid therapy. The figures illustrate the results of competing risk analyses. In a first approach, patients were divided into steroid or no steroid groups depending on their baseline medication (A). In a second model, the patients were also assigned to groups depending on their respective baseline medication, but were censored with the time point of steroid discontinuation or with the new onset of steroids within the observation period (B). HR, hazard ratio.
FIGURE 3
FIGURE 3
Corticosteroid was not linked to higher incidences of fungal infections. Steroid and no steroid groups were defined based on the respective baseline medication (A) and patients were censored if steroid therapy had been started/stopped during follow‐up (B).
FIGURE 4
FIGURE 4
Infections were strongly linked to a drastic increase in mortality (A) and multi‐organ failure (B). HR, hazard ratio; LTx, liver transplantation; MOF, multi‐organ failure.
See this image and copyright information in PMC

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