Vanishing Bile Duct Syndrome Leading to Biliary Cirrhosis in a Patient With Remote History of Non-Hodgkin Lymphoma

Abstract

We present a case of a 60-year-old man with a remote history of non-Hodgkin Lymphoma (NHL) who developed cirrhosis during the course of his lymphoma. Investigation into the underlying cause of cirrhosis was negative including viral and autoimmune serologic markers and imaging studies of biliary tree. He had no history of alcohol abuse. While his NHL was eventually successfully treated with chemotherapy, he developed multiple sequelae of end stage liver disease including variceal bandings, spontaneous bacterial peritonitis, and acute coagulopathic episodes before successful liver transplantation nearly two decades after his diagnosis of NHL. Histologic exam of the explanted liver showed a biliary pattern of cirrhosis with near total loss of interlobular bile ducts. Chronic biliary injury and cholestasis was confirmed by the presence of excess copper deposition and copper binding protein by copper and Victoria blue stains, respectively. There were no features of primary sclerosing cholangitis or primary biliary cirrhosis. There was no steatosis, no evidence of alpha-1-antitrypsin disease, hemochromatosis, or veno-occlusive disease. There was no evidence of lymphomatous involvement. It was determined that the patient had likely developed VBDS and biliary cirrhosis in association with his NHL. Vanishing bile duct syndrome (VBDS) refers to a clinicopathologic group of conditions resulting from progressive destruction and disappearance of intrahepatic bile ducts. It can be seen in a variety of conditions including primary liver disorders or manifestations of systemic illnesses. VBDS has also been reported in association with many drugs. VBDS is an uncommon but potentially fatal complication of Hodgkin lymphoma, and in exceptionally rare cases, NHL. The exact mechanism is unknown but is thought to be a paraneoplastic phenomenon, or possible sequelae of drug induced/chemotherapy injury. There are only 3 prior published cases of VBDS in association with NHL. In 2 of the cases the patients died, one of acute liver failure and the other of multiple organ failure secondary to his underlying lymphoma. The third case demonstrated reversibility of the VBDS with near normalization of total bilirubin levels 6 weeks after onset of chemotherapy. To our knowledge, our case is the first to demonstrate a prolonged course of VBDS in association with NHL, eventually leading to chronic end stage liver disease and biliary cirrhosis, despite complete remission of NHL.