title: Telomere shortening and karyotypic alterations in hepatocytes in long-term transplanted human liver allografts.
abstract: The long-term fate of aged liver allografts in young recipients who received grafts from older donors is unknown. We evaluated graft aging by analyzing hepatocytic telomere length and karyotypic changes. Seventeen pediatric individuals who underwent living-donor liver transplantation for congenital biliary diseases were selected. At a median of 10.4 years post-transplant, ten had tolerated grafts with weaned off immunosuppressants, and seven had idiopathic post-transplantation hepatitis. Fluorescence in situ hybridization was used to evaluate the telomere signal intensity (TI) and karyotypic changes. First, we measured predictive age-dependent TI decline with regression analysis of donor livers. The mean TI at the earliest (within a year) and latest biopsies was significantly lower than the predicted TI of the studied allografts. With univariate analysis, a higher abnormal karyotype ratio in the donor liver was correlated with development of idiopathic post-transplantation hepatitis. With multivariate analysis that included clinical parameters, a greater TI decline at the earliest biopsy was correlated with the development of idiopathic post-transplantation hepatitis. In conclusion, graft aging as measured by TI decline and donor abnormal karyotype ratio was associated with idiopathic post-transplantation hepatitis of long-term transplanted liver allografts.
authors: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors: Wulamujiang
authors: W
authors: Aini
authors: Aya
authors: A
authors: Miyagawa-Hayashino
authors: Tatsuaki
authors: T
authors: Tsuruyama
authors: Seiji
authors: S
authors: Hashimoto
authors: Shinji
authors: S
authors: Sumiyoshi
authors: Munetaka
authors: M
authors: Ozeki
authors: Keiji
authors: K
authors: Tamaki
authors: Shinji
authors: S
authors: Uemoto
authors: Hironori
authors: H
authors: Haga
mesh_terms: D000293:Adolescent; D000782:Aneuploidy; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006505:Hepatitis / Q000150:complications / Q000209:etiology; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D007166:Immunosuppressive Agents; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D017093:Liver Failure / Q000235:genetics* / Q000628:therapy*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D015999:Multivariate Analysis; D016615:Telomere / Q000648:ultrastructure*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents