2484 Intravenous Acetaminophen Associated With Hepatotoxicity in an Orthotopic Liver Transplant Patient

Abstract

INTRODUCTION: Intravenous acetaminophen (IV APAP) is a commonly used post-operative analgesic. In adults, IV APAP administered at therapeutic doses of less than 4 g over 24 hours is considered safe. Five to ten percent of APAP is metabolized into N-acetyl-p-benzoquinone imine (NAPQI), the toxic metabolite responsible for APAP hepatotoxicity. NAPQI is inactivated when conjugated to tripeptide glutathione. CASE DESCRIPTION/METHODS: A 69 year old male with a history of secondary biliary liver cirrhosis status post orthotopic liver transplantation in 2006 and newly diagnosed prostate adenocarcinoma was admitted to the Urology service for planned robotic-assisted prostatectomy. He underwent uncomplicated robotic-assisted prostatectomy, requiring no fluid resuscitation, vasopressor support or blood products. Post-operatively, vital signs remained normal with no episodes of hypotension. He was started on IV APAP 1000 mg every 6 hours for 36 hours, followed by PO APAP 650 mg every 6 hours for post-operative pain. On post-operative day 2, AST was 2751 IU/L, ALT 3447 IU/L, TBili 1.9 mg/dL and INR 1.5 (Figure 1). All orders for acetaminophen were stopped. Liver Doppler ultrasound was normal. A serum acetaminophen level drawn 10 hours after the last IV APAP dose was <15 ug/mL. Work up for infectious etiologies was negative. The patient was started on IV NAC therapy. Following completion of IV NAC therapy, AST was 986 IU/L, ALT 2340 IU/L, TBili 1.9 mg/dL, and INR 1.4. The patient was discharged home on post-operative day 4. Labs during his outpatient Hepatology follow-up appointment 4 days after discharge were AST 62 IU/L, ALT 426 IU/L, TBili 1.3 mg/dL, and INR 1.1. DISCUSSION: This is the first case of acute liver toxicity in a post-OLT patient who received therapeutic doses of IV APAP. There was no evidence of hypotension or APAP overdose in the electronic medical records. All other etiologies for acute liver toxicity were ruled out, including shock liver, infection and vascular compromise. It is possible APAP metabolism is altered in transplant livers compared to native livers. A study on 13 liver transplant patients concluded APAP metabolism was transiently altered in orthotopic livers following liver transplantation, resulting in enhanced NAPQI production. It is possible transplant livers carry less glutathione stores due to cold storage preservation and post-transplant reperfusion, rendering them more susceptible to hepatotoxicty from NAPQI concentrations that a native liver would tolerate.