title: Successful resolution of inflammation and increased regulatory T cells in sirolimus-treated post-transplant allograft hepatitis.
abstract: This retrospective case series reviews our center's experience with sirolimus and a CNI as alternative therapy for the treatment of PTAH. It also characterizes regulatory T cells (Tregs) in PTAH. LT recipients with PTAH who had received or were receiving treatment with sirolimus were retrospectively identified (n = 12). Liver enzymes, immunohistochemistry, and histology were compared in all 12 patients. Immunophenotyping for Tregs in peripheral blood mononuclear cells was performed on LT recipients with PTAH on conventional therapy with CNI, azathioprine ± prednisone (CT) (n = 11), recipients with PTAH on sirolimus, CNI ± prednisone (n = 8), recipients without PTAH (n = 25), and pre-transplant patients (n = 5). Severity of necro-inflammatory changes markedly improved with sirolimus. Treg frequency and number were significantly lower in recipients with PTAH on CT compared to (i) those on sirolimus (p = 0.002 and p = 0.01, respectively), and (ii) recipients without PTAH (p = 0.07 and p = 0.009, respectively). Treg frequency was significantly higher in recipients with PTAH on sirolimus compared to recipients without PTAH under CNI therapy (p = 0.027). Sirolimus in addition to a CNI is successful in reversing inflammation in LT recipients with PTAH. This is associated with significantly higher circulating Tregs.
authors.affiliation: Siragusa Transplant Center, Department of Surgery, Northwestern University, Chicago, IL, USA. u-ekong@md.northwestern.edu
authors.forename: Udeme D
authors.initials: UD
authors.lastname: Ekong
authors.forename: James
authors.initials: J
authors.lastname: Mathew
authors.forename: Hector
authors.initials: H
authors.lastname: Melin-Aldana
authors.forename: Deli
authors.initials: D
authors.lastname: Wang
authors.forename: Estella M
authors.initials: EM
authors.lastname: Alonso
mesh_terms: D001379:Azathioprine / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006505:Hepatitis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007223:Infant; D008099:Liver / Q000276:immunology / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D011183:Postoperative Complications / Q000188:drug therapy* / Q000276:immunology; D011241:Prednisone / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D016037:Single-Blind Method; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone; D020123:Sirolimus; D016559:Tacrolimus