A Case of Cryptococcal Hepatitis in an HIV Patient with a Negative Serum Cryptococcal Antigen

Infectious Cryptococcus neoformans occurs primarily in immunocompromised patients. The primary organ affected is the lungs, but the infection of the central nervous system (CNS) is also be seen. Disseminated cryptococcosis can involve any organ in the body. However, hepatic involvement is rare. Here we discuss a case of cryptococcal hepatitis in a patient who presented with persistently elevated liver enzymes. A 56-year-old Ecuadorian female with no known past medical history presented with fever, abdominal pain, nausea, unintentional weight loss, and diarrhea for two months. Her liver function tests (LFTs) revealed elevated aspartate aminotransferase (AST: 415 U/L), elevated alanine aminotransferase (ALT: 201 U/L), elevated alkaline phosphatase (ALP: 763 U/L), but normal total bilirubin (0.9 mg/dl). Her HIV antigen screening was reactive, and the absolute cluster of differentiation 4 (CD4) helper count was 22 cell/µL. Over the course of her hospital stay, the patient's liver enzymes continued to trend upward, with negative Histoplasma antibodies and negative serum cryptococcal antigen titers. During the second week of hospitalization, her liver enzymes continued to rise with an ALP of 4046 U/L, AST of 436 U/L, and ALT of 276 U/L. With a persistent elevation of the liver enzymes without any definitive cause, an ultrasound-guided biopsy was performed. Pathology revealed cryptococcal hepatitis, and the patient was started on a 15-day course of amphotericin B with an eight-week course of fluconazole 400 mg with LFTs nearly normalizing at six weeks. This case demonstrates an unusual manifestation of cryptococcosis. Our patient did not present with the typical cryptococcal pulmonary or central nervous system infection. Additionally, our patient's serum cryptococcal antigen titers were negative, but biopsy results revealed cryptococcal hepatitis, despite a very high sensitivity and specificity of the serum cryptococcal antigen test. This case demonstrates the importance of maintaining a broad differential, specifically in immunocompromised patients.