Atypical Acute Liver Failure in Acute Myeloid Leukemia

Abstract

Gastroent Question: A 65-yearold white womanwith therapy-related acute myeloid leukemia was admitted to the intensive care unit with altered mental status 33 days after completing induction chemotherapy with azacitadine, high-dose cytarabine, and mitoxantrone. She had a history of breast cancer treated 12 years prior with 4 cycles of cyclophosphamide and doxorubicin, local radiation therapy, and tamoxifen, as well as mantle cell lymphoma treated 6 years prior with bendamustine, rituximab, and radiation therapy to a lytic lesion of the L1 vertebrae. On physical examination, she was afebrile, normotensive (133/89 mmHg), but obtunded. She had scleral icterus as well as mild abdominal distension with minimal ascites. There were no recent additions to her medication list; the only potentially hepatotoxic agent present was prophylactic posaconazole, which had been discontinued several days prior. Her laboratory studies revealed neutropenia (absolute neutrophil count, 90 K/mL) and evidence of acute hepatic dysfunction (aspartate aminotransferase [AST], 4,891 U/L; alanine aminotransferase [ALT], 2,070 U/L; International Normalized Ratio [INR], 3.3). The total bilirubin (TB) was 5.4 mg/dL, alkaline phosphatase (AP) 90 U/L, and serum ammonia 61 mg/dL. There was no serologic evidence of acute varicella zoster or hepatitis A, B, C, D, or E infections. Furthermore, polymerase chain reaction assays for herpes simplex virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and adenovirus were all negative. Thick and thin blood smears ruled out a transfusion-related trypanosomiasis infection; a urine toxicology screen was unremarkable, and a serum acetaminophen level was <3.0 mg/mL. Abdominal ultrasound revealed hepatomegaly (18.7 cm), ascites, a large right pleural effusion and patent hepatic vasculature. A liver biopsy had been deferred given her coagulopathy and persistent thrombocytopenia (<10 K/mL). Thus, the etiology of her acute hepatic dysfunction remained unknown. Thirteen days later, despite improvements in coagulopathy (INR 1.5), aminotransferases (AST, 68 U/L; ALT, 36 U/L) and mental status, she continued to have worsening cholestasis (TB,16.6 mg/dL; conjugated, 12.6 mg/dL; AP, 175 U/L, which peaked at 492 U/L days later). Thus, a liver biopsy was finally obtained (Figure A, B). What was the elusive etiology of this patient’s acute liver failure? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.