Complete remission of paraneoplastic vanishing bile duct syndrome after the successful treatment of Hodgkin’s lymphoma: a case report and review of the literature

Abstract

BackgroundVanishing bile duct syndrome has been associated with different pathologic conditions (adverse drug reactions, autoimmune diseases, graft versus host disease, and cancer). Though its causes are unknown, an immune-related pathogenesis is the most likely one. Vanishing bile duct syndrome can evolve to hepatic failure and, eventually, to death. The treatment is uncertain, but it needs the resolution of the underlying pathologic condition.Case presentationWe describe the association of Hodgkin’s lymphoma with a syndrome characterized by cholestasis, aminotransferase elevation and an histological picture of bile duct loss. All other causes of hepatic function impairment were excluded (in particular, drugs, viral and autoimmune related diseases) eventually leading to the diagnosis of vanishing bile duct syndrome. Despite the fact that the dysfunction is not caused by hepatic Hodgkin’s lymphoma involvement, liver impairment can limit the optimal therapy of Hodgkin’s lymphoma. A treatment consisting of ursodeoxycholic acid, prednisone, and full dose chemotherapy restored hepatic function and achieved complete and long-lasting remission of Hodgkin’s lymphoma.ConclusionWe reviewed all case reports showing that vanishing bile duct syndrome is a dismal paraneoplastic syndrome being fatal in a high proportion of patients if not adequately treated. Indeed, this syndrome requires both an early recognition and an appropriate aggressive treatment consisting of full dose upfront chemotherapy which is the only way to achieve a resolution of the vanishing bile duct syndrome. Delayed or reduced intensity treatments unfavorably correlate with survival.

Liver Involvement in Hodgkin's Lymphoma: Types of Injuries and Therapeutic Implications

“…An exception is a 17-year-old man who was successfully treated with chemotherapy, after which the initial greatly increased serum bilirubin level normalized and he had a good clinical outcome [8]. Other authors also consider that full dose chemotherapy associated with ursodeoxycholic acid and prednisone could restore the liver function, with a resolution of VBDS, and contribute to HL complete remission [56]. Good results have also been obtained with MOPP-ABV regimen, however the transplant represents the only curative treatment in cases with progressive liver disease [53].…”

“…Even if the treatment is appropriate, many patients experience progressive disease or liver failure, which can lead to death [8,56]. An exception is a 17-year-old man who was successfully treated with chemotherapy, after which the initial greatly increased serum bilirubin level normalized and he had a good clinical outcome [8].…”

“…The cholestasis can progress to biliary cirrhosis and liver failure [55]. VBDS can be found in autoimmune diseases, adverse drug reactions, graft versus host disease, and malignancies [56].…”

“…VBDS is manifested by cholestatic jaundice [8,54,56] increased aminotransferases, and an histological aspect of bile duct loss [56] in the absence of liver infiltration by lymphoma cells [8,54,56] or obstructive adenopathies [54], so that it is believed to be the expression of a paraneoplastic syndrome [8,54,56], consequence of cytokine release from lymphoma cells [54]. HL occurrence may be preceded by a VBDS [53,57] even by several months [53].…”

Paraneoplastic Manifestations of Lymphoproliferative Neoplasms

“…Clinically, it is characterized by hepatic failure. 128 Hepatic sinusoidal dilatation, a feature of VBDS, was shown to be present in HL patients presenting with systemic symptoms 121 without any direct involvement of liver by the lymphoma. There is evidence that the expression of intercellular adhesion molecules and the major histocompatibility complex antigens in response to the cytokines produced by the HL result in cytotoxicity to the biliary epithelium.…”