Burden of Invasive Fungal Diseases in Patients With Alcohol-Related Hepatitis and Organ Failure.

Abstract

Background: The burden of invasive fungal diseases (IFDs) in patients with complicated alcoholic hepatitis (CAH)-defined by ≥ 2 hepatic (ascites, jaundice, liver failure, encephalopathy) or extrahepatic (coagulopathy, shock, kidney or respiratory failure) dysfunctions within 30 days-remains poorly characterised.

Aims: To assess the burden of IFDs in CAH and compare it with bacterial pneumonia (BP).

Methods: We conducted a retrospective nationwide cohort study of adult CAH patients in France (2012-2021). The primary exposure were IFDs. The primary outcome was 3-month mortality or liver transplantation. Associations were assessed with adjusted odds ratios (aORs) in complete-case and propensity score-matched cohorts. A 6-week landmark analysis and time-dependent Cox models were used to evaluate time-varying effects.

Results: Among 11,434 CAH patients (median age 55 years; 72% male), 2.2% and 15% developed IFDs and BP, respectively. Three-month survival was 17.5% (95% CI: 13.0-23.0) in IFDs, 46.8% (44.3-49.3) in BP and 60.0% (59.4-61.4) in those without either (p < 0.001). IFDs occurred in 44.3% of patients with BP, and BP increased IFD risk (aOR 2.93, 95% CI: 2.23-3.84). In matched analyses, IFDs were associated with a fourfold increase in mortality (aOR 4.58, 95% CI: 3.02-7.20), while BP showed a lower association (aOR 1.23, 95% CI: 1.06-1.43). IFDs were strong time-dependent predictors of death.

Conclusions: IFDs affected 1 in 50 CAH patients and carried a disproportionate mortality risk, compared with BP. These findings support the implementation of targeted screening and early antifungal strategies in CAH management, as for BP.