S5620 Vanishing Bile Duct Syndrome Following Oxaliplatin-Based Chemotherapy: A Rare Hepatotoxic Complication

Introduction: Vanishing bile duct syndrome (VBDS) is a rare yet well-documented disease resulting in the progressive destruction and loss of intrahepatic bile ducts and ultimately, cholestasis. The small ductules of the biliary tree are usually affected, thus hepatobiliary imaging may fail to provide a diagnosis. We present a case of a patient who developed VBDS after receiving oxaliplatin chemotherapy for metastatic gastric cancer. Case Description/Methods: A 55-year-old man with a past medical history of surgically unresectable stage IV gastric adenocarcinoma presented with epigastric abdominal pain and vomiting that progressed over 1 week. He had previously received 4 cycles of FOLFOX chemotherapy, including oxaliplatin. His last session was one week prior to presentation. He was not taking any other prescribed medications or supplements. Laboratory studies were significant for alkaline phosphatase 911 IU/L, total bilirubin 2.2 md/dL, albumin 2.2 gm/dL, alanine aminotransferase 607 IU/L, aspartate aminotransferase 230 IU/L and international normalized ratio 0.9. Acute viral hepatitis testing was negative and so was a urine toxicology screen. An magnetic resonance cholangiopancreatography was recommended by hepatology that demonstrated normal appearance of the biliary tree without evidence of biliary obstruction. Due to persistently elevated liver enzymes, the decision was made to pursue a liver biopsy which exhibited noncaseating granulomas that were rich in eosinophils with sinusoidal inflammation consistent with DILI. Importantly, there was bile duct inflammation and loss of bile duct architecture in over half of the examined portal tracts suggestive of evolving VBDS. Steroid therapy was initiated but halted after no improvement in liver enzymes. He was discharged and his liver enzymes eventually normalized after continued cessation of FOLFOX therapy. Discussion: The diagnosis of VBDS is established by histologic examination after liver biopsy and by excluding other conditions with imaging tests. VBDS is defined as loss of interlobular bile ducts in over 50 percent of portal areas, provided that the histologic specimen contains ≥10 portal tracts. Some patients with DILI may progress to VBDS despite discontinuing the offending agent. For patients with severe ductopenia without a clear etiology, initial therapy is UDCA or steroids. Improvement in symptoms is typically observed shortly after starting therapy, while liver biochemical tests may remain chronically elevated for months. Most patients either have a gradual recovery or a progressive and often irreversible bile duct loss which may lead to cirrhosis.