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.

Fungal infections in liver cirrhosis

“…However, when narrowing this data to examine IFIs, the pooled prevalence was 9.5%, suggesting that the majority of fungal infections in cirrhosis were invasive ( 7 ). Moreover, there was an observed correlation between the severity of liver disease and the risk for developing fungal infection, with rates of IFI ranging from 10–14% in patients with evidence of decompensation or critical illness ( 13 ).…”

“…Cryptococcus is observed as the third most common IFI in patients with evidence of decompensated cirrhosis ( 7 ). However, Cryptococcus often has a delayed diagnosis and as such often carries a poor prognosis when identified in patients with decompensated disease ( 13 ).…”

“…Iatrogenic factors such as corticosteroid use, and prolonged antibiotic therapy predispose patients to the development of multi-drug-resistant organisms. The culmination of these factors creates a state of immune dysfunction, the degree of which influences both the severity and progression of liver disease ( 13 ).…”

“…At the level of the gut, lack of immune surveillance compromises the intestinal barrier resulting in alterations in the gut microbiome, along with translocation of endotoxins such as lipopolysaccharide (LPS). The release of endotoxins is further exacerbated by portosystemic shunting that is observed with progression of liver disease ( 13 ). Collectively, this process can be defined as cirrhosis-associated immune dysfunction (CAID) ( 5 ).…”

“…Chronic activation of innate immune cells, such as neutrophils, results from continued circulation of pro-inflammatory molecules like LPS, along with other pathogen-associated molecular patterns (PAMPs). These pro-inflammatory molecules interact with the toll-like receptors located on the surface of neutrophils, resulting in increased production of reactive oxygen species (ROS) ( 13 ). Interestingly, Taylor et al studied neutrophil function in patients with cirrhosis by examining phagocytic activity and production of ROS.…”