S2472 Gone in a Flash: Infliximab-Induced Vanishing Bile Duct Syndrome

Abstract

INTRODUCTION: Vanishing bile duct syndrome (VBDS) is a group of acquired disorders that causes the destruction and disappearance of intrahepatic bile ducts and cholestasis. Infliximab has been reported to rarely cause adverse events of cholestasis due to ductopenia characteristic of VBDS. CASE DESCRIPTION/METHODS: Patient is a 51-year-old male with stage III melanoma treated with pembrolizumab, a programmed death 1 (PD-1) checkpoint inhibitor. The patient’s clinical course was complicated by pembrolizumab-induced colitis, and Infliximab therapy was initiated. He only received two doses before developing worsening bloody diarrhea greater than four times a day and dark urine. Vital signs on admission were within normal limits. His physical exam revealed jaundiced skin and right upper quadrant abdominal tenderness. Labs demonstrated a mixed pattern cholestasis with AST of 1408, ALT 627, total bilirubin 16, with an INR of 1.0. Liver biopsy on admission was consistent with a drug-induced liver injury or autoimmune hepatitis. An EGD was performed concerning for eosinophilic esophagitis but pathology report demonstrated rare (< 1/10HPF) intraepithelial eosinophils. Flexible sigmoidoscopy revealed CMV colitis by immunostaining biopsies from the rectosigmoid colon. MRCP showed no evidence of biliary obstruction or extra-hepatic ductal disease. However, repeat liver biopsy demonstrated extralobular and intralobular degeneration of bile ducts and acute cholestasis consistent with VBDS. No evidence of CMV by immunostaining was noted on this repeat liver biopsy. DISCUSSION: Infliximab can induce hepatotoxicity by causing cholestatic liver disease. This cholestasis has been typically described as self-limiting but can manifest with a prolonged clinical course of greater than six months. This is clinically distinct from that of (VBDS), which can progress to established biliary cirrhosis. VBDS is primarily a diagnosis of exclusion and although it is not commonly caused by infliximab, it has been recently reported. Diagnosing VBDS is challenging, and as our patient showed, requires multiple liver biopsies, MRCP, and extensive infectious and immunological workup to rule out alternate pathology. The mechanism of infliximab induced cholestatic hepatitis has been described in recent literature, however the pathophysiology of this condition remains unclear; further studies into this condition are important and will likely include both genetic and environmental factors.