2356 Severe Allopurinol-Induced Liver Injury

Abstract

INTRODUCTION: The severity of drug-induced liver injury (DILI), a diagnosis of exclusion, can vary greatly from mild to life-threatening. Allopurinol is a commonly used medication that rarely causes serious hepatotoxicity. Objective data, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total serum bilirubin, have been used to grade the severity of liver injury. We present a case of idiosyncratic allopurinol-induced cholestatic injury that meets diagnostic criteria for severe and life-threatening. CASE DESCRIPTION/METHODS: A 70-year-old African American woman with gouty arthritis, hypertension, and dyslipidemia presented to the Emergency Room with two weeks of abdominal pain. The patient was started on allopurinol for acute gout flare one month prior to presentation. In the interim, she developed malaise, anorexia (3 kg weight loss), and pruritus. She had no personal or family history of liver disease. Physical examination was notable for scleral icterus and mild, diffuse abdominal tenderness. Complete blood count was remarkable for absolute eosinophilia of 3.0 thou/cu mm, confirmed on peripheral blood smear. Liver function tests revealed a cholestatic pattern, with AST 259 u/L (normal 5-34), ALT 411 u/L (10-60), ALP 817 u/L (4-121), GGT 766 u/L (9-36), total bilirubin 15.7 mg/dL (0.2-1.2) and direct bilirubin 10.6 mg/dL (0.1-0.5). Synthetic liver function was normal. Toxicology screens, ceruloplasmin level, hepatitis serologies, and autoimmune workup were unremarkable. Imaging studies did not reveal acute pathology. Liver biopsy showed mild/moderate expansion of mixed inflammatory infiltrate with increased number of eosinophils. After discontinuation of allopurinol, absolute eosinophil count and liver function tests trended down with clinical resolution of symptoms. DISCUSSION: Among DILI literature, few reports exist of severe, life-threatening cholestatic liver injury after allopurinol initiation. This patient had 8x the upper limit of normal AST, 7x ALT, 7x ALP, 21x GGT, and 21x direct bilirubin. According to multiple DILI severity grading tools, this case is classified between severe (grade 3) and life-threatening (grade 4). Beyond discontinuation of the medication, there are limited treatment options available for idiosyncratic DILI other than liver transplantation. Therefore, prompt discontinuation of the offending medication along with close monitoring for progression to fulminant liver failure is crucial.