title: Polymorphisms in ABCB11 and ATP8B1 Associated with Development of Severe Intrahepatic Cholestasis in Hodgkin's Lymphoma.
abstract: We report a young man presenting with jaundice and severe debilitating intrahepatic cholestasis 7 months before the diagnosis of Hodgkin's lymphoma. Serum gamma-glutamyl transferase (GGT) activity was not raised. Liver biopsy demonstrated deficiency of canalicular GGT and bile salt export pump expression, which suggested "benign" recurrent intrahepatic cholestasis. Direct sequencing of genomic DNA was therefore undertaken to look for mutations in ATP8B1 and ABCB11. Cholestasis and pruritus are well recognized presenting features of Hodgkin's lymphoma. However, striking in this case is that the intrahepatic cholestasis presented and resolved 7 months before the diagnosis. Furthermore, 4 polymorphisms were identified in ATP8B1 in this patient-c.696T > C (rs319438), c.811A > C (rs319438), c.2855G > A (rs1296811) and c.3454G > A (rs222581)-and two polymorphisms in ABCB11-c.1331T > C (rs2287622) and c.3084A > G (rs497692); 2 of which have been associated with intrahepatic cholestasis of pregnancy. We therefore postulate that these polymorphisms predisposed this patient to the development of intrahepatic cholestasis within the abnormal pro-inflammatory cytokine milieu typical for Hodgkin's lymphoma. This case shows for the first time that some polymorphisms in ABCB11 and ATP8B1 may predispose to the development of intrahepatic cholestasis in Hodgkin's lymphoma. It also demonstrates the importance of close clinical surveillance for the development of Hodgkin's lymphoma in patients presenting with unexplained intrahepatic cholestasis.
authors.affiliation: Institute of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, Denmark Hill, London SE5 9RS, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Blackmore
authors.affiliation: Histopathology, Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Knisely
authors.affiliation: Department of Paediatric Hepatology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Hartley
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, UK.
authors.forename: Kirsten
authors.initials: K
authors.lastname: McKay
authors.affiliation: Honorary Consultant in Paediatric Metabolic Medicine, Great Ormond Street Hospital and MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Gissen
authors.affiliation: Department of Haematological Medicine, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Marcus
authors.affiliation: Institute of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, Denmark Hill, London SE5 9RS, UK.
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Shawcross
keywords: BRIC, “benign” recurrent intrahepatic cholestasis; BSEP, bile salt export pump; CT, computerized tomography; GGT, gamma-glutamyl transferase; Hodgkin's; ICP, intrahepatic cholestasis of pregnancy; PFIC, progressive familial intrahepatic cholestasis; UDCA, ursodeoxycholic acid; intrahepatic cholestasis; lymphoma; polymorphism