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

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.