title: Proposed Diagnostic Criteria for Chronic Antibody-Mediated Rejection in Liver Allografts.
abstract: Donor-specific alloantibodies (DSA) can cause acute antibody-mediated rejection (AMR) in all solid organ allografts. However, long-term outcome in patients with posttransplant DSA needs further study. We retrospectively evaluated prospectively collected paired serum, tissue, and data on 45 matched DSA- positive [DSA+; mean florescence intensity (MFI) ≥10,000] and -negative (DSA-) recipients of a primary liver-only allograft from January 2000 to April 2009. Blinded histopathologic evaluation demonstrated that DSA+ versus DSA- patients were more likely to have subtle inflammation and unique patterns of fibrosis, despite normal or near-normal liver function tests. Stepwise multivariable modeling developed a score (putatively named the chronic AMR [cAMR] score) that included interface activity, lobular inflammation, portal tract collagenization, portal venopathy, sinusoidal fibrosis, and hepatitis C virus status. The score was developed (c = 0.811) and cross-validated (c = 0.704) to predict allograft failure. Two cutoffs were employed to optimize sensitivity and specificity (80% each); a value >27.5 predicted 50% 10-year allograft failure. We propose chronic AMR as a potential new entity defined by (1) a high cAMR score, (2) DSA, and (3) elimination of other potential causes of a similar injury pattern. In conclusion, cAMR score calculation identified liver allograft recipients with DSA at highest risk for allograft loss, although independent validation is needed.
authors.affiliation: Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
authors.forename: J G
authors.initials: JG
authors.lastname: O'Leary
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA.
authors.forename: J
authors.initials: J
authors.lastname: Cai
authors.affiliation: Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
authors.forename: R
authors.initials: R
authors.lastname: Freeman
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA.
authors.forename: N
authors.initials: N
authors.lastname: Banuelos
authors.affiliation: Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
authors.forename: B
authors.initials: B
authors.lastname: Hart
authors.affiliation: Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
authors.forename: L W
authors.initials: LW
authors.lastname: Jennings
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA.
authors.forename: H
authors.initials: H
authors.lastname: Kaneku
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA.
authors.forename: P I
authors.initials: PI
authors.lastname: Terasaki
authors.affiliation: Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
authors.forename: G B
authors.initials: GB
authors.lastname: Klintmalm
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Demetris
mesh_terms: D064591:Allografts; D016022:Case-Control Studies; D058625:End Stage Liver Disease / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D006085:Graft Survival; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007518:Isoantibodies