Vanishing bile duct syndrome in Hodgkin’s lymphoma: A case report and literature review

Abstract

Vanishing bile duct syndrome (VBDS) has been described in different pathologic conditions including infection, ischemia, adverse drug reactions, autoimmune diseases, allograft rejection, and humoral factors associated with malignancy. It is an acquired condition characterized by progressive destruction and loss of the intra-hepatic bile ducts leading to cholestasis. Prognosis is variable and partially dependent upon the etiology of bile duct injury. Irreversible bile duct loss leads to significant ductopenia, biliary cirrhosis, liver failure, and death. If biliary epithelial regeneration occurs, clinical recovery may occur over a period of months to years. VBDS has been described in a number of cases of patients with Hodgkin’s lymphoma (HL) where it is thought to be a paraneoplastic phenomenon. This case describes a 25-year-old man found on liver biopsy to have VBDS. Given poor response to medical treatment, the patient underwent transplant evaluation at that time and was found to have classical stage IIB HL. Early recognition of this underlying cause or association of VBDS, including laboratory screening, and physical exam for lymphadenopathy are paramount to identifying potential underlying VBDS-associated malignancy. Here we review the literature of HL-associated VBDS and report a case of diagnosed HL with biopsy proven VBDS.

Successful liver transplantation for drug-induced vanishing bile duct syndrome

“…It is classically linked to haematological malignancies, and in particular to Hodgkin’s lymphoma where up to 50% of cases have some degree of liver infiltration with lymphoma cells 1 2 7. A few of these reports described VBDS and severe ductopenic cholestatic liver damage as the initial and primary presentation of Hodgkin’s lymphoma 1 2 7. Moreover, VBDS in the context of Hodgkin’s lymphoma carries a high mortality 2.…”

“…A few of these reports described VBDS and severe ductopenic cholestatic liver damage as the initial and primary presentation of Hodgkin’s lymphoma 1 2 7. Moreover, VBDS in the context of Hodgkin’s lymphoma carries a high mortality 2. Other conditions associated with VBDS include macrophage activation syndrome and histiocytosis X. Immune-mediated aetiologies in the context of organ transplantation often result in severe ductopenia and this includes chronic graft versus host disease in the context of allogenic bone marrow transplantation, acute T-cell-mediated rejection and the rare chronic ductopenic rejection 1–3…”

“…The typical diagnostic features for drug-induced VBDS were present in this patient as demonstrated by the persistent elevation of ALP and bilirubin for greater than 6 months and the lack of evidence of biliary disorders such as PBC, PSC or malignancy and indeed paucity of intralobular bile ducts on the second biopsy. The standard diagnostic histopathological criterion for VBDS is loss of 50% or more of the intrahepatic bile ducts on a specimen containing at least 10 portal tracts 1–5. Nevertheless, a milder form can be diagnosed when the duct loss is significant but still less than 50%.…”

“…In one report, idiopathic biliary ductopenia progressed slowly over 9 years but with no apparentclinical deterioration or significant symptoms of biliary disease 12. In other cases, incomplete clinical recovery may take place but with persistent cholestatic markers and evidence of hepatic fibrosis and rarely progression to advanced chronic liver disease 1–3 13. Those patients may also develop complications of cholestasis such as gallstone formation, hyperlipidaemia, xanthelasmas and vitamin deficiencies.…”

“…Vanishing bile duct syndrome (VBDS) is a rare disorder that leads to progressive loss and destruction of intrahepatic bile ducts and severe ductopenia or bile duct paucity. Despite the scarcity of cases, VBDS is a recognised complication of cholestatic drug-induced liver injury (DILI) 1–3. Most cases improve with conservative management, and only a very small proportion of patients develop progressive systemic symptoms and chronic liver disease.…”