Evaluating diagnosis and clinical outcome for antibody-mediated rejection in liver transplantation: performance of the 2016 Banff Working Group criteria

Tom Z Liang; Kevin H Toomer; Alison Gareau; Jacqueline E Birkness-Gartman; Ahmet Gurakar; Robert A Anders; Keiichi Kinowaki; Kiyoko Oshima

doi:10.1007/s00428-025-04356-3

Evaluating diagnosis and clinical outcome for antibody-mediated rejection in liver transplantation: performance of the 2016 Banff Working Group criteria

Virchows Arch. 2026 Jan 2. doi: 10.1007/s00428-025-04356-3. Online ahead of print.

Authors

Tom Z Liang¹, Kevin H Toomer^{1

2}, Alison Gareau^{1

3}, Jacqueline E Birkness-Gartman¹, Ahmet Gurakar⁴, Robert A Anders¹, Keiichi Kinowaki^{1

5

6}, Kiyoko Oshima⁷

Affiliations

¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Department of Pathology, University of Wisconsin, Madison, WI, USA.
⁴ Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Pathology, Toranomon Hospital, Tokyo, Japan.
⁶ Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
⁷ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. koshima3@jhmi.edu.

PMID: 41483300
DOI: 10.1007/s00428-025-04356-3

Abstract

Antibody-mediated rejection (AMR) presents a rare but complex challenge following liver transplantation, characterized by histopathologic features lacking specificity. The 2016 Banff Working Group criteria aimed to standardize AMR diagnosis, focusing on histologic findings and C4d staining interpretation. Our retrospective analysis of 463 liver transplant recipients between 2017-2023 identified 13 donor specific antibody (DSA)-positive cases (2.8%) with matched liver biopsy available: 3 (23.1%) were classified as definite AMR, 7 (53.8%) as suspicious, and 3 (23.1%) as indeterminate. The incidence of AMR was found to be only 0.6%. 7 of these 13 cases were clinically treated as mixed AMR and T cell mediated rejection (TCMR), and 4 cases were treated as TCMR. Four cases treated as AMR/TCMR responded well, and no subsequent rejection episodes occurred during the follow-up period (20.3-96.5 months). Three patients failed to respond and expired after biopsy (6 days to 2.5 months), an outcome attributable to other complications in addition to liver dysfunction. Of note, among the cases classified as "definite" according to the Banff criteria, two cases had an h-score of 1. This discordance between h-score and C4d staining suggests diagnostic challenges in current practice, highlighting the necessity for C4d immunostaining in all allograft biopsies with microvasculitis to prevent misdiagnosis. Although integrated evaluation of DSA positivity, histologic pattern of injury, and C4d staining was generally reliable for distinguishing definite/suspicious categories from the indeterminate group, this study argues for further refinement of diagnostic criteria to enhance the accuracy of AMR detection and improve patient outcomes in liver transplantation.

Keywords: Antibody-mediated rejection (AMR); Banff Working Group criteria; C4d staining; Donor specific antibody (DSA); Liver rejection; Liver transplantation.