S5494 Vanishing Bile Duct Syndrome in the Setting of Valproic Acid Use: A Case Report of Progressive Ductopenia

Introduction: Vanishing bile duct syndrome (VBDS) is an uncommon but severe form of chronic liver disease, defined as loss of intralobular bile ducts in >50% of portal areas of the liver. Development of VBDS has been associated with drugs, herbs, and natural supplements, infectious diseases including hepatitis B, hepatitis C, Epstein-Barr virus, and cytomegalovirus and immune-mediated reactions, though it can also have genetic causes. All etiologies are marked by chronic cholestasis and destruction of intrahepatic bile ducts. Progressive destruction and disappearance of intrahepatic bile ducts can lead to ductopenia. Here, we report a case of VBDS in the setting of valproic acid use. Case Description/Methods: A 64-year-old man on divalproex acid for bipolar disorder presented with acute jaundice with bilateral flank pain. Laboratory evaluation revealed total bilirubin of 6.3 mg/dl; direct bilirubin of 5.1 mg/dL, indirect bilirubin of 1.2 mg/dL; alkaline phosphatase 674 U/L; aspartate aminotransferase 189 U/L; alanine aminotransferase 170 U/L. Viral hepatitis panel was negative. Anti-smooth muscle, Alpha-1 Antitrypsin, and antimitochondrial antibody were negative. A right upper quadrant ultrasound showed mildly dilated common bile duct measuring 8 mm. Computed tomography of the abdomen and pelvis showed mild intrahepatic ductal dilation. magnetic resonance cholangiopancreatography was negative for obstruction and re-confirmed mild dilation of the common bile duct with no significant intrahepatic biliary dilation. Given rising bilirubin without a cause, liver biopsy was obtained which showed acute cholestasis with ductular reaction and lymphocytic inflammation, thought to be secondary to medications. Histologic changes of autoimmune hepatitis were not appreciated. With concern for hepatic injury secondary to divalproex sodium use, the medication was tapered and switched to paliperidone. L-Carnitine was not initiated due to chronic exposure to divalproex sodium. Discussion: This case highlights the importance of Divalproex as a potential cause of VBDS. Progressive destruction and disappearance of intrahepatic bile ducts can lead to ductopenia, a hall mark of VBDS. Providers should have increased awareness regarding the possibility of VBDS in patients chronically exposed to divalproex sodium since the progression of this syndrome can lead to an overall paucity of bile ducts with the potential to progress to cholestatic liver disease and possibly biliary cirrhosis.