Kinetics of host immune responses and cytomegalovirus resistance in a liver transplant patient.

Hdl Handle:
http://hdl.handle.net/10147/207590
Title:
Kinetics of host immune responses and cytomegalovirus resistance in a liver transplant patient.
Authors:
Schaffer, Kirsten; Moran, Julie; Duffy, Margaret; McCormick, Aiden P; Hall, William W; Hassan, Jaythoon
Affiliation:
Department of Microbiology, St. Vincent's University Hospital, Elm Park, Dublin, , Ireland. kirsten.e.schaffer@ucd.ie
Citation:
Liver Transpl. 2009 Oct;15(10):1199-203.
Journal:
Liver transplantation : official publication of the American Association for the , Study of Liver Diseases and the International Liver Transplantation Society
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207590
DOI:
10.1002/lt.21832
PubMed ID:
19790144
Abstract:
Among solid organ transplant (SOT) recipients, donor-seropositive/recipient-seronegative (D+/R-) cytomegalovirus (CMV) status is associated with the highest risk of ganciclovir-resistant CMV disease, which has been reported for patients receiving oral ganciclovir but not valganciclovir prophylaxis. We report a case of CMV breakthrough infection in a D+/R- liver transplant patient while he was receiving oral valganciclovir. Forty samples collected over 6 months were analyzed for the CMV viral load, lymphocyte counts, cytokine levels, and lymphocyte differentiation status. Genotypic resistance testing of the viral UL97 gene was performed when the patient failed to respond. CMV viremia occurred on day 50 post-transplant, and 5 samples taken between days 50 and 85 showed the wild-type UL97 genotype. The appearance of deletion 594-595 was observed from day 114 post-transplant. Viral loads declined when foscarnet was commenced and remained below 10,000 copies/mL when the lymphocyte count was greater than 1000/microL (P = 0.02). T cell responses revealed significant expansion of CD8+ terminal effector memory cells. CD4+ cells were largely populations of naive and central memory cells. Circulating interleukin 10 (IL-10) levels correlated with the viral load (P < 0.0001). Seroconversion occurred on day 230. The CMV viral load in combination with lymphocyte counts and IL-10 may be a predictive marker for the risk of development of resistant CMV disease in D+/R- SOT patients.
Language:
eng
MeSH:
Administration, Oral; Cytomegalovirus/*metabolism; Cytomegalovirus Infections/diagnosis/etiology; Ganciclovir/analogs & derivatives/pharmacology; Genotype; Humans; Immune System; Immunosuppressive Agents/therapeutic use; Kinetics; Liver Diseases/therapy/virology; Liver Transplantation/*adverse effects/methods; Male; Middle Aged; Time Factors; Viral Load
ISSN:
1527-6473 (Electronic); 1527-6465 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchaffer, Kirstenen_GB
dc.contributor.authorMoran, Julieen_GB
dc.contributor.authorDuffy, Margareten_GB
dc.contributor.authorMcCormick, Aiden Pen_GB
dc.contributor.authorHall, William Wen_GB
dc.contributor.authorHassan, Jaythoonen_GB
dc.date.accessioned2012-02-01T10:32:15Z-
dc.date.available2012-02-01T10:32:15Z-
dc.date.issued2012-02-01T10:32:15Z-
dc.identifier.citationLiver Transpl. 2009 Oct;15(10):1199-203.en_GB
dc.identifier.issn1527-6473 (Electronic)en_GB
dc.identifier.issn1527-6465 (Linking)en_GB
dc.identifier.pmid19790144en_GB
dc.identifier.doi10.1002/lt.21832en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207590-
dc.description.abstractAmong solid organ transplant (SOT) recipients, donor-seropositive/recipient-seronegative (D+/R-) cytomegalovirus (CMV) status is associated with the highest risk of ganciclovir-resistant CMV disease, which has been reported for patients receiving oral ganciclovir but not valganciclovir prophylaxis. We report a case of CMV breakthrough infection in a D+/R- liver transplant patient while he was receiving oral valganciclovir. Forty samples collected over 6 months were analyzed for the CMV viral load, lymphocyte counts, cytokine levels, and lymphocyte differentiation status. Genotypic resistance testing of the viral UL97 gene was performed when the patient failed to respond. CMV viremia occurred on day 50 post-transplant, and 5 samples taken between days 50 and 85 showed the wild-type UL97 genotype. The appearance of deletion 594-595 was observed from day 114 post-transplant. Viral loads declined when foscarnet was commenced and remained below 10,000 copies/mL when the lymphocyte count was greater than 1000/microL (P = 0.02). T cell responses revealed significant expansion of CD8+ terminal effector memory cells. CD4+ cells were largely populations of naive and central memory cells. Circulating interleukin 10 (IL-10) levels correlated with the viral load (P < 0.0001). Seroconversion occurred on day 230. The CMV viral load in combination with lymphocyte counts and IL-10 may be a predictive marker for the risk of development of resistant CMV disease in D+/R- SOT patients.en_GB
dc.language.isoengen_GB
dc.subject.meshAdministration, Oralen_GB
dc.subject.meshCytomegalovirus/*metabolismen_GB
dc.subject.meshCytomegalovirus Infections/diagnosis/etiologyen_GB
dc.subject.meshGanciclovir/analogs & derivatives/pharmacologyen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmune Systemen_GB
dc.subject.meshImmunosuppressive Agents/therapeutic useen_GB
dc.subject.meshKineticsen_GB
dc.subject.meshLiver Diseases/therapy/virologyen_GB
dc.subject.meshLiver Transplantation/*adverse effects/methodsen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshTime Factorsen_GB
dc.subject.meshViral Loaden_GB
dc.titleKinetics of host immune responses and cytomegalovirus resistance in a liver transplant patient.en_GB
dc.contributor.departmentDepartment of Microbiology, St. Vincent's University Hospital, Elm Park, Dublin, , Ireland. kirsten.e.schaffer@ucd.ieen_GB
dc.identifier.journalLiver transplantation : official publication of the American Association for the , Study of Liver Diseases and the International Liver Transplantation Societyen_GB
dc.description.provinceLeinster-

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