title: Requirement of protocol biopsy before and after complete cessation of immunosuppression after liver transplantation.
abstract: BACKGROUND
  Operational tolerance is defined as long-term acceptance of a transplanted organ after complete cessation of immunosuppression (IS), but may not always protect against antigen-dependent changes in graft morphology.
  
  
  METHODS
  IS free patients after living-donor liver transplantation (LDLT) underwent protocol biopsy (tolerance group [Gr-Tol]) and were evaluated for rejection and fibrosis. The degree of fibrosis was compared with those in the patients on maintenance IS group (Gr-IS) and the base line normal liver group (Gr-BS). When bridging fibrosis or progression of fibrosis was observed, IS was reintroduced or increased in Gr-Tol or in the patients in the weaning process.
  
  
  RESULTS
  Neither acute nor chronic rejection was observed. The degree of fibrosis, however, was significantly greater in Gr-Tol than those in Gr-IS and Gr-BS. In Gr-Tol, the number of graft infiltrating FOXP3 cells was significantly increased, the interval between LDLT and biopsy plus the donor age was significantly longer, and recipient age at LDLT was significantly younger, compared with those in Gr-IS. However, none of these three parameters correlated with the degree of fibrosis. In 7 of 11 patients in whom IS was reintroduced or increased, the improvement of fibrosis was observed by the subsequent biopsy.
  
  
  CONCLUSIONS
  Grafts of operationally tolerant patients after LDLT did not exhibit acute or chronic rejection, but they exhibited fibrosis. It remains elusive whether fibrosis observed in tolerant grafts is antigen dependent. The finding that after [corrected] the reintroduction or the increase of IS fibrosis was improved supported the possibility that fibrosis in operationally tolerant patients was antigen dependent.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Yoshitomi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Koshiba
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhao
authors.forename: Donghua
authors.initials: D
authors.lastname: Cheng
authors.forename: Aya
authors.initials: A
authors.lastname: Miyagawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakashita
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohe
authors.forename: Mikiko
authors.initials: M
authors.lastname: Ueda
authors.forename: Shinya
authors.initials: S
authors.lastname: Okamoto
authors.forename: Hiroto
authors.initials: H
authors.lastname: Egawa
authors.forename: Kathryn
authors.initials: K
authors.lastname: Wood
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Manabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D001706:Biopsy / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D005260:Female; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology*; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology*; D008297:Male; D011183:Postoperative Complications / Q000453:epidemiology / Q000473:pathology; D012189:Retrospective Studies; D014019:Tissue Donors / Q000706:statistics & numerical data
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents