Vanishing Bile Duct Syndrome: A Rare Cause of Cholestasis in Hodgkinʼs Lymphoma

Abstract

Case: A 46 year-old Hispanic male presented with a 3-day history of jaundice, poor appetite, and abdominal pain. Past medical history was unremarkable, and the patient was not taking medications, illicit drugs, or alcohol. He denied B symptoms. Physical exam was unremarkable except for jaundice; no stigmata of chronic liver disease. Investigations showed total bilirubin of 14.2 mg/dL (direct 9mg/dL), GGT 362, AP 581, AST 120, ALT 248, albumin 4.1g/dL. Serology was negative for HIV, hepatitis A, B and C. CT showed normal liver without intra or extra-hepatic duct dilatation, and multiple large para-aortic and peri-hepatic lymph nodes (LN). Biopsy of a LN showed mixed cellularity Hodgkin lymphoma (HL), stage I/II. Bilirubin continued to rise to 27.2 mg/dL, and despite two cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), bilirubin increased to 41 g/dL, which lead to ABVD cessation and initiation of radiotherapy (RT) to the abdomen. An ERCP was normal. A liver biopsy showed marked canalicular and focal hepatocytic cholestasis, minimal inflammation, and ductopenia; no malignant cells, steatosis or iron deposition were seen, and a diagnosis of vanishing bile duct dyndrome (VBDS) as the cause of cholestasis was established. Ursodeoxycholic acid was started, RT was completed, and ABVD was restarted when bilirrubin decreased. Treatment was completed and a followup CT showed a decrease of LN size, and a PET scan was negative. Currently,18 months after diagnosis, the patient remains well and in remission. His bilirubin has normalized, and LFT have improved to near normal. Discussion: Cholestasis as the presenting symptom of HL is very uncommon (<4%). It can be caused by lymphomatous infiltration of the liver, extrahepatic biliary obstruction by lymphadenopathy, concurrent viral infections, or drug toxicities. Rarely, it can be due to a paraneoplastic phenomenon, which can be divided into VBDS and pure intrahepatic cholestasis without ductopenia. The pathophysiology of VBDS is unknown, but is thought to be caused by release of toxic cytokines from lymphoma cells, leading to destruction of bile ducts without significant inflammation. Diagnosed by exclusion and supported by histology in the absence of liver involvement by HL. VBDS is rare, and usually fatal. Only 18 cases of VBDS have been reported since its description in 1993. The overall mortality is 65%, liver failure being the leading cause, followed by sepsis and recurrence of HL. However, 30% of cases have normal LFT without recurrence at 24 months. There is no difference in outcome across sex, age, type of HL, B-symptoms, or chemotherapy or steroids, but those who are stage I/II at presentation and receive radiotherapy appear to have a better outcome.