title: Cytomegalovirus infection persists in the liver graft in the vanishing bile duct syndrome.
abstract: Cytomegalovirus infection is one factor implicated in the cause of the vanishing bile duct syndrome complicating liver transplantation. To further investigate the role of cytomegalovirus in this syndrome, we studied serial liver biopsy material by in situ hybridization for cytomegalovirus DNA using a highly sensitive technique that allows the localization of viral replication. Cytomegalovirus DNA was identified in hepatocytes in 10 of 12 patients with the vanishing bile duct syndrome, 1 of whom had no serological evidence of cytomegalovirus infection. It was also present in all 18 patients with uncomplicated cytomegalovirus infection but was not identified in any of 10 subjects with transplants who had neither complication. Nine of the patients in this series underwent a diagnostic liver biopsy at 1 wk and subsequently had cytomegalovirus infection develop; cytomegalovirus DNA was identified in liver tissue of all nine patients, indicating that cytomegalovirus replication commences at an early stage. In those with uncomplicated cytomegalovirus, infection occurred earlier (p less than 0.05) but was eliminated more quickly (p less than 0.0005), and the number of infected hepatocytes was greater (p less than 0.05) when compared with those with the vanishing bile duct syndrome; in these, cytomegalovirus DNA was detectable until death or retransplantation. Cytomegalovirus DNA was never identified in either biliary or endothelial tissue. These data indicate that the vanishing bile duct syndrome is associated with persistent cytomegalovirus replication within hepatocytes.
authors.affiliation: Institute of Liver Studies, King's College School of Medicine and Dentistry, London, United Kingdom.
authors.forename: J C
authors.initials: JC
authors.lastname: Arnold
authors.forename: B C
authors.initials: BC
authors.lastname: Portmann
authors.forename: J G
authors.initials: JG
authors.lastname: O'Grady
authors.forename: N V
authors.initials: NV
authors.lastname: Naoumov
authors.forename: G J
authors.initials: GJ
authors.lastname: Alexander
authors.forename: R
authors.initials: R
authors.lastname: Williams
mesh_terms: D002779:Cholestasis / Q000209:etiology*; D003586:Cytomegalovirus Infections / Q000150:complications*; D004279:DNA, Viral / Q000032:analysis; D006680:HLA Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007165:Immunosuppression Therapy; D008099:Liver / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects*; D009693:Nucleic Acid Hybridization; D013577:Syndrome
chemical_list: D004279:DNA, Viral; D006680:HLA Antigens; D006684:HLA-DR Antigens