title: Presence of occult cytomegalovirus infection in the brain after orthotopic liver transplantation. An autopsy study of 83 cases.
abstract: Cytomegalovirus (CMV) infection remains a highly prevalent systemic complication following orthotopic liver transplantation (LT), accounting for a significant increase in morbidity and affiliated costs. However, unlike other immunosuppressed groups of population, CMV infection of the central nervous system in LT is rarely diagnosed, either clinically or postmortem. Furthermore, in 20% of the LT patients who develop preterminal neurological complications, the etiology remains undetermined. With the hypothesis that at least some of these cases could be related to an occult CMV infection, we examined brain tissue from 83 unselected autopsies of LT patients by morphological, immunohistochemical (IHC), in situ hybridization (ISH), and nested polymerase chain reaction (nested PCR) techniques. Microglial nodules were observed in 17 brains of the LT group (20.4%) but in none of the 36 controls. Isolated positive cells by either IHC, ISH, or both techniques, were identified in 11 LT patients (13.2%) and in 2 controls (5.5%). CMV DNA amplification was obtained from paraffin-embedded tissues in 41 of 81 LT cases (50.6%), and in 5 controls (13.8%) (P=0.00017). Viral inclusion bodies, inflammatory infiltrates, or necrotizing changes were not identified in any case. Our findings indicate an increased susceptibility of the brain of LT patients to occult infection by CMV and suggest that a latent or low-grade infection of the central nervous system could operate as a reservoir of the CMV and play a role in some of the unexplained neurological symptoms that appear in the postoperative period.
authors.affiliation: Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona Medical School, Spain. tribalta@clinic.ub.es
authors.forename: Teresa
authors.initials: T
authors.lastname: Ribalta
authors.forename: A Julio
authors.initials: AJ
authors.lastname: Martinez
authors.forename: Pedro
authors.initials: P
authors.lastname: Jares
authors.forename: Jaume
authors.initials: J
authors.lastname: Muntané
authors.forename: Rosa
authors.initials: R
authors.lastname: Miquel
authors.forename: Xavier
authors.initials: X
authors.lastname: Claramonte
authors.forename: Antonio
authors.initials: A
authors.lastname: Cardesa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000473:pathology*; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D018792:Encephalitis, Viral / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D017403:In Situ Hybridization; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications; D012189:Retrospective Studies
chemical_list: D017931:DNA Primers; D004279:DNA, Viral