COMPARISON OF FUNGAL VS BACTERIAL INFECTIONS IN ACUTE ON CHRONIC LIVER FAILURE: CAUSE OR COROLLARY FOR HIGH MORTALITY?

Background: Due to development of an immune dysregulated phenotype, advanced liver disease in all its forms predisposes to sepsis acquisition and related mortality. Immunodeficiency develops despite immune activation, predisposing patients to opportunistic infections, including invasive fungal infections. Despite high mortality, little data exists on fungal infection within a medical liver intensive unit (MILU). Specifically, data is lacking describing such infection in acute on chronic liver failure.
We aimed to characterize epidemiology, baseline factors and outcomes of fungal infections in our MILU.

Methods: From our prospective registry of patients admitted to our MILU, we identified 17 fungal and 183 bacterial culture-positive infections between August 2018-September 2022. Data on baseline comorbidities, acute characteristics of infection and clinical outcomes was manually extracted. Univariate analysis was used to compare fungal infections to bacterial counterparts.

Results: Patients with fungal infections were younger than bacterial counterparts (mean age 51.5±14.2 vs 58.4±11.6, p=0.024, table 1). Etiology of liver disease in fungal cases included cirrhosis, acute liver failure (11.6%) and Byler's disease post-transplant (5.8%); five patients had acute surgical illnesses including pancreatitis, cholecystitis and perforated viscus. Patients with fungal infections more frequently had hepatorenal syndrome, hepatic encephalopathy, thrombocytopenia, and malnutrition as complications of underlying liver disease (p=0.012-0.048, table 1). Fungal cases were associated with higher bilirubin (16.8±10.5 vs 9.4±10.1, p=0.05) and presence of central lines (75.5% vs 39.7%, p=0.003). Most patients with fungal infections had acute on chronic liver failure (ACLF) grade 3 compared to bacterial (70.6% vs 34.8%, p=0.029). MELD-Na and Child Pugh scores at infection were higher in case of fungal vs bacterial infection. Mean admission MELD-Na for fungal cases was 29.6±7.24, and medial survival time was 1 week relative to 4 weeks for bacterial infections (p<0.0001, fig 1). More patients with fungal infections required pressors (100% vs 72%, p=0.011) and intubation (95.2% vs 66.3%, p=0.013); 12 (71%) of patients had received at least 5 days of antibiotics prior to positive fungal culture.

Conclusion:
All patients with fungal infections passed away within 2 weeks, reflecting 100% mortality. Majority of cases of fungal infection also had severe ACLF, likely accounting for the significantly worse survival relative to bacterial counterparts. Further prospective studies examining timing of early antifungal therapy and empiric antifungal coverage are critical. Our findings suggest antifungal coverage should be considered in patients with ACLF-3 who fail to improve on antibiotic therapy.