S2568 DDD: Diagnostic Dilemma in Drug Induced Liver Injury: Adverse Reaction of Abiraterone in Treatment of Metastatic Prostate Cancer

Abstract

INTRODUCTION: Drug-induced liver injury (DILI) is a benign and reversible form of liver injury that occurs as an adverse reaction to medication use. It is a leading cause of acute liver failure and requires prompt recognition and discontinuation of the offending agent to avoid development of chronic disease. We present a case of severe DILI secondary to Abiraterone use in a patient with prostate cancer. CASE DESCRIPTION/METHODS: A 67 year-old-male without known liver disease was seen for severely elevated liver enzymes, jaundice and abdominal pain. Pertinent history includes stage IV prostate cancer with metastasis to the bone and lymph nodes with initiation of Abiraterone four months prior. He denies excessive alcohol, acetaminophen or herbal supplement use. Initial liver panel results: AST 1668 (peak 2379), ALT 3093 (peak 3330), alk phos 185 (peak 361) and TB 14.3 (peak 29). INR was 1.40 (peak 1.65). While transplant center transfer was considered, given patient's stability and not meeting King's College Criteria for acute liver failure, this decision was deferred and he was placed on NAC for 48 hours. Extensive workup for other causes of elevated liver enzymes were negative including: Wilson’s disease, autoimmune hepatitis, HAV, HBV, HCV, EBV, HSV, CMV, alpha 1 antitrypsin deficiency, portal vasculature thrombosis and acetaminophen toxicity. Core needle biopsies revealed acute hepatitis with confluent and bridging necrosis as well as mild Kupffer cell siderosis with iron accumulation. Serum ferritin level was 28,441 and IgG4 was mildly elevated, which prompted concern for hemophagocytic lymphohistiocytosis(HLH), hemochromatosis and autoimmune cholangiopathy. Patient did not meet criteria for HLH, hemochromatosis types I-IV in the absence of HFE, HFE2, TFR2, HAMP and SLC40A1 gene mutations, nor did MRI or pathology staining reveal IgG4 cholangiopathy. LFTs normalized within four months and ferritin within six months. Abiraterone was not restarted. DISCUSSION: Abiraterone is an antiandrogen that inhibits CYP17. Although the mechanism of hepatic injury is unknown, Abiraterone has been shown to cause elevations in serum aminotransferase levels in up to 13% of patients and ALT elevations above 5x the ULN in 6% of patients, however only few documented cases are known in which patients displayed associated symptoms such as jaundice and no documentation of severe elevations in serum ferritin as seen in our patient. This case also highlights the diagnostic challenge in DILI.Figure 1.: A. Mild to moderate predominantly lymphocytic inflammation. B. Intact bile ducts.Figure 2.: Confluent necrosis with areas of bridging necrosis.Figure 3.: Iron stain with Kupffer cell siderosis.