Case Presentation: A 57-year-old man with decompensated cryptogenic cirrhosis and chronic kidney disease who was listed for simultaneous liver and kidney transplantation presented with two days of anorexia and malaise. He reported associated nausea, vomiting, and progressive weakness. He denied fever, confusion, cough, abdominal pain, dysuria.Vital signs were normal. He was fatigued, jaundiced, and chronically ill-appearing. Abdomen was distended, non-tender with moderate ascites. No asterixis. The patient was admitted for decompensated cirrhosis with acute kidney injury, MELD-Na was 27. Paracentesis revealed WBC of 228k/uL with 66% lymphocytes. Peritoneal fluid and blood cultures grew cryptococcus neoformans after 5 days. HIV testing was negative. Serum cryptococcal antigen was positive. Cerebrospinal fluid opening pressure was 33 mmHg with no leukocytes, protein 44 g/dL, glucose 59 mg/dL, and a positive cryptococcal antigen. Due to disseminated fungal infection, the patient was temporarily held from transplant listing. He was treated with intravenous amphotericin B and flucytosine as well as serial lumbar punctures. Unfortunately, he developed refractory shock, progressive renal and liver failure, acute respiratory distress and passed away.
Discussion: While well-known as an opportunistic infection affecting HIV positive and other immunocompromised patients, Cryptococcus neoformans is an insidious, under-recognized, and significantly more deadly fungal infection for cirrhotic patients. An estimated 21-36% of reported cryptococcal infections occur in patients with cirrhosis. Mortality rates have been reported as high as 81-100% in end-stage liver disease compared to the 12% mortality rate in US HIV-positive cryptococcosis. Decompensated liver disease is one very few independent risk factors for invasive cryptococcal infection, thought to be a result of impaired innate immunity and cell-mediated immune dysfunction. Treatment duration is extended, often requiring initial treatment with amphotericin B and 5-flucytosine, followed by consolidation with fluconazole for 6-12 months or more.Studies are ongoing about the implications of cryptococcal infection on transplant eligibility with no clear guidance at this time. In a recent case control study, a small number of successful transplantations in patients with recent or even undiscovered active infection at the time of transplant has been reported. Of these, transplant was associated with mortality benefit and interestingly none in this group developed relapsed or progressive infection. Whether recent cryptococcosis should be a categorical exclusion criterion for transplant listing is not clear. However, results imply that in an otherwise stable cirrhotic patient, transplantation could be pursued in the setting of appropriate infectious treatment. This would be importantly distinct from many other disseminated microbial infections in those awaiting transplant, most of which must be completely eliminated prior to initiation.
Conclusions: Internists should be aware that decompensated cirrhosis is a strong independent risk factor for invasive cryptococcal infection and is significantly more fatal in this population. Recent cryptococcosis in the setting of appropriate disease treatment may not be categorically exclusionary from life-saving liver transplantation, but instead should be an individualized decision.