Vanishing Bile Duct Syndrome in a Hodgkin's Lymphoma Patient with Fatal Outcome Despite Lymphoma Remission
A previously healthy 33-year-old Saudi man was admitted with a progressive left-sided neck swelling for 1 year. He developed yellowish discoloration of the skin and sclera, pale stools, and dark urine associated with abdominal distension 1 week prior to admission. He also complained of unexplained weight loss of 8 kg, low-grade fever, and fatigability. There was no history of liver disease or use of any herbs or other medication. Physical examination revealed pallor, jaundice, and a nontender, firm lymph node in the neck measuring 5 × 5 cm with unremarkable examination of other systems.\nComplete blood count showed mild leukopenia with a total WBC count of 3.1 × 109/L (normal 4-11), neutrophils 2 × 109/L, lymphocytes 0.7 × 109/L, mild normocytic normochromic anemia (Hb 12.6 g/dL), and a normal platelet count. Liver function tests (LFT) revealed a predominant cholestatic pattern with a total bilirubin (TBil) of 88 μmol/L (normal up to 18 μmol/L), direct bilirubin 74 umol/L, alkaline phosphatase 524 U/L, gamma-glutamyl transferase (GGT) 518 U/L, alanine aminotransferase 194 U/L, aspartate aminotransferase 106 U/L, and serum albumin 42 g/L. His renal function tests were normal and autoimmune work up was negative. Virology screening revealed negative results for hepatitis A, B, C, HIV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV).\nAbdominal ultrasound showed a normal-sized liver (13 cm) with multiple hyper-echoic lesions seen in both lobes; the largest one in the left lobe (3.8 × 2.7 cm), and mild splenomegaly (14.9 cm). Common bile duct (CBD), portal vein, and hepatic veins were normal. Baseline computed tomography (CT) scan of the neck, chest, abdomen, and pelvis revealed multiple lymph nodes in the left side of the neck (largest 4.8 × 4.1 cm), left supraclavicular, mediastinal, both hilar areas, and intra-abdominal regions, suggestive of lymphoma. In addition, at least three hypodense focal hepatic lesions were present (largest 4 × 3.6 cm) with features suggestive of hemangiomas. Other findings were noncontributory.\nThe patient underwent left cervical lymph node excisional biopsy, which showed classical HL of nodular sclerosis type [] with a positive immunohistochemical staining for CD 30 and CD 15 but negative for CD 45 and CD 20. Bone marrow biopsy showed no evidence of lymphoma infiltration, so he was staged as III-B.\nThe patient received first cycle of chemotherapy, ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) with 30% dose reduction due to liver dysfunction. His jaundice improved initially but after 1 week he presented again with generalized weakness, anorexia, nausea, and worsening of jaundice. Repeat liver function tests revealed deterioration with elevated bilirubin (159 μmol/L) and liver enzymes consistent with a cholestatic pattern. There was no evidence of intrahepatic biliary dilatation on ultrasound. He underwent endoscopic retrograde cholangiopancreatography (ERCP), which showed normal CBD and a sphincterotomy and insertion of a biliary stent were performed. No improvements in liver function were noted so an ultrasound-guided liver biopsy was performed, which revealed cholestasis and nonspecific portal inflammation with no evidence of lymphoma. CK7 staining showed significantly reduced number of bile ducts consistent with a diagnosis of VDBS [].\nIn view of the persistent liver dysfunction, the patient received a modified ESHAP chemotherapy regimen (methylprednisolone 250 mg IV daily for 4 days, cisplatin 25 mg/m2 IV continuous infusion for 4 days and cytarabine 2 g/m2 IV on day 5 but without etoposide) because of the liver friendly nature of this regimen to prevent any further liver damage. The patient remained jaundiced with TBil fluctuating between 400 and 600 μmol/L, although a drop in TBil was noted (232 μmol/L) for a brief period. A repeat CT scan performed after the second chemotherapy cycle revealed significant regression of the lymph nodes in the neck, supraclavicular, mediastinal and retroperitoneal areas.\nAt this stage he received the second cycle of modified ESHAP chemotherapy (3rd cycle in total) but with a higher dose of methylprednisolone (500 mg daily for 4 days). After 2 weeks, he developed febrile neutropenia with positive blood cultures for Klebsiella species. He was treated with broad spectrum antibiotics. He also sustained drug-induced acute kidney injury, which improved initially but serum creatinine remained elevated, which hindered administration of further chemotherapy. His liver function showed no improvement. A positron emission tomography-CT of the whole body did not show significant fluorodeoxyglucose activity suggesting remission of HL. He was referred for a liver transplant but his condition rapidly deteriorated. He developed severe coagulopathy and hepatic encephalopathy, and died 4 months after the initial diagnosis of HL.