Abstract
Patients with liver disease in the intensive care unit (ICU) face a unique susceptibility to infection due to the complex immune dysfunction resulting from hepatic failure. Bacterial infections are commonly present in these patients upon arrival to the hospital, often being the primary reason for ICU admission. In contrast, invasive fungal infections (IFIs) afflict a smaller percentage of patients and are usually discovered in the course of the ICU stay. IFI diagnosis in the ICU, particularly in patients with liver disease, is often delayed or overlooked, contributing to the extremely high ICU mortality associated with IFI in these patients despite the availability of effective (and largely safe) antifungal therapy. Thus, to improve outcomes, it is crucial for intensive care clinicians to be vigilant for IFIs in patients with liver disease. This review aims to contribute to the intensive care literature in this regard. We begin with an overview of normal antifungal immunity followed by a summary of how it may become compromised in the setting of hepatic dysfunction. Next, a general discussion of IFIs in liver disease is presented and then the three most relevant fungal pathogens, namely Candida, Aspergillus, and Cryptococcus, are individually examined. This review concludes by highlighting key knowledge and practice gaps that require attention by the scientific and clinical communities in the coming years.
Key Points
- Increased ICU Admissions for Liver Disease: The proportion of ICU admissions for cirrhotic patients has risen over time, with infections being a major driver of hospitalizations.
- Immune Dysfunction in Liver Disease: Hepatic failure impairs both innate and adaptive immunity, leading to increased susceptibility to fungal infections. Defects in neutrophil function, antigen presentation, and cytokine responses contribute to IFI risk.
- Candida Infections in Cirrhotic Patients: Candida is the most frequent fungal pathogen in liver disease patients, often manifesting as candidemia or spontaneous fungal peritonitis (SFP). IFIs in cirrhosis patients have an extremely high mortality rate.
- Aspergillus and Invasive Pulmonary Aspergillosis (IPA): Critically ill cirrhotic patients have a high risk of developing IPA, with studies suggesting a prevalence of 1.7% to 14% in ICU patients. Diagnosis is challenging due to the lack of classical CT findings in non-neutropenic hosts.
- Cryptococcus and Disseminated Disease: Cryptococcal infections are rare but can present as disseminated disease, including meningitis or peritonitis, in cirrhotic patients. Liver disease is a significant risk factor for cryptococcal fungemia.
- Challenges in Diagnosing IFIs: IFIs in liver disease patients often go unrecognized, leading to delayed treatment and increased mortality. Autopsy studies reveal a high rate of undiagnosed fungal infections in cirrhotic ICU patients.
- Antifungal Treatment Considerations: Liver disease complicates antifungal therapy due to drug metabolism concerns. Voriconazole carries a high risk of hepatotoxicity, whereas echinocandins and newer triazoles like isavuconazole are safer options.
- Impact of Antibiotics on Mycobiome: Broad-spectrum antibiotic use in cirrhotic patients disrupts gut fungal balance, increasing colonization and risk for invasive fungal infections.
- Prognostic Implications of IFIs: IFIs in liver disease patients are associated with mortality rates exceeding 60%, with invasive candidiasis and IPA carrying the highest risk.
- Future Directions in ICU Management: Improved diagnostic tools, better risk stratification models, and increased awareness among ICU clinicians are essential to reducing the burden of IFIs in liver disease patients.
