Invasive fungal infections in liver diseases

Abstract

Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.

FIGURE 1

Immune dysfunction and invasive fungal infections in liver disease. Alcohol use leads to immune paralysis and increase gut permeability, which, in turn, leads to increased LPS in the circulation. LPS in the cirrhotic liver leads to increased inflammation leading to further immune paralysis. The decreased immunoglobulin and complement production from cirrhotic livers leads to decreased opsonization by human macrophages. In addition, the neutrophil function is decreased in cirrhosis. Transplant medications, including calcineurin inhibitors, corticosteroids, and antimetabolites, decrease neutrophil, macrophage, and T-cell function. Abbreviations: CNI, calcineurin inhibitor; IFN, interferon; LPS, lipopolysaccharide; NET, neutrophil extracellular trap; ROS, reactive oxygen species. Illustration by Nicole Wolf, MS, ©2022.