Requirement of protocol biopsy before and after complete cessation of immunosuppression after liver transplantation.
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.
Yoshitomi
Mami
M
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Koshiba
Takaaki
T
Haga
Hironori
H
Li
Ying
Y
Zhao
Xiangdong
X
Cheng
Donghua
D
Miyagawa
Aya
A
Sakashita
Hiromi
H
Tsuruyama
Tatsuaki
T
Ohe
Hidenori
H
Ueda
Mikiko
M
Okamoto
Shinya
S
Egawa
Hiroto
H
Wood
Kathryn
K
Sakaguchi
Shimon
S
Manabe
Toshiaki
T
Tanaka
Koichi
K
Uemoto
Shinji
S
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
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents