Society: AASLD

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.

Table 1: Comparison of Baseline Variables and Acute Characteristics Between Fungal and Bacterial Infection.

Table 1: Comparison of Baseline Variables and Acute Characteristics Between Fungal and Bacterial Infection.

Figure 1. Comparison in survival from time of ICU admission between patients with fungal vs bacterial illness, as demonstrated in this Kaplan Meier curve.

Figure 1. Comparison in survival from time of ICU admission between patients with fungal vs bacterial illness, as demonstrated in this Kaplan Meier curve.

Introduction:
Studies show that fungal infections in cirrhotics have increased mortality, but early detection and treatment has shown mortality benefit. Cirrhotic patients with candidemia are more likely to develop acute on chronic liver failure(ACLF) and experience mortality. In studies of candidemia, the sensitivity of cultures was 21%-71%. Given the increase in mortality of fungal infections, it is vital to have a reliable test in those with cirrhosis. Our study evaluates mortality of early detection, MELD score, and organ dysfunction in cirrhotic patients positive for T2 panel.

Methods:
We performed a retrospective study and included cirrhotic patients admitted from 2017-2021. Data collected includes baseline characteristics, type of cirrhosis, MELD score, mortality outcomes with early T2 detection, INR, bilirubin(Bili), creatinine(Cr), hepatic encephalopathy(HE), mean arterial pressure(MAP), and PaO2/FiO2(P/F)ratio. Factors such as HE, MAPs, and P/F ratio were graded based on CLIF-C ACLF criteria(Table 1). Univariate and multivariate regression analysis was performed for these outcomes.

Results:
Our cohort(n=734) had a mean age 56.13 ± 11.81, BMI 29.77 ± 8.91, and male gender of 52%. Majority of the cohort had NASH (29%) or alcoholic(39%) cirrhosis. Out of 734 cohort, 94 (12.8%) had a positive T2 with the majority being NASH(25%) and alcohol(37%) cirrhosis. Mean number of days between admission and positive T2 in the expired group was 13.20 ± 17.45 vs 8.53 ± 10.24 in the alive group(p-value of 0.1152)(Table 2). Admission MELD of 23.47 ± 9.65 changed to MELD of 26.52 ± 9.81 when T2 turned positive(p-value 0.0001)(Table 3). Positive T2 expired vs positive T2 alive cohort shows an increase in the following: Bili by 3.32 ± 8.70 vs 0.39 ± 2.17(p-value 0.0323), INR by 0.71 ± 1.17 vs -0.10 ± 0.52(p-value 0.0001), Cr by 0.31 ± 1.13 vs -0.62 ± 2.62 (p-value of 0.0374), HE grade by 1.04 ± 1.10 vs 0.62 ± 0.91 (p-value 0.0461), MAP rating by 1.23 ± 0.88 vs 0.57 ± 0.77 (p-value 0.0002), and P/F ratio rating by 1.08 ± 0.97 vs 0.67 ± 0.82(p-value 0.0282)(Table 4).

Conclusion:
Fungal infections play a large role in mortality in cirrhotic patients, and early detection and early treatment have mortality benefits. Positive T2 panels were more common in those with NASH and alcoholic cirrhosis. Positive T2 patients had an elevation of MELD from admission to positive T2. In expired T2 positive patients, there was an elevation of bilirubin, INR, creatinine, HE grade, P/F ratio rating, and MAP rating. This shows that once a cirrhotic patient had candidemia there was a high chance of mortality and development of ACLF. This study shows the diagnostic value of obtaining T2 in cirrhotic patients especially those with worsening organ dysfunction. Other factors such as earlier detection of fungemia and detection time of T2 positivity mortality were not statistically significant.

Atul Lodh

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