Researchers reported that a good correlation between donor specific antibody, histology, and C4d staining results validates the Banff criteria for acute antibody-mediated rejection in patients who have undergone liver transplantation, as published in Human Pathology.

The Banff Working Group published guidance in 2016 with the goal of standardizing the diagnostic criteria for antibody-mediated rejection in liver transplantation. In addition, it contains recommendations for C4d staining and accompanying interpretations. In the guidance published, acute and chronic antibody-mediated rejection were differentiated based on a number of criteria.

Antibody-mediated rejection can occur with any organ transplantation, but it is rarer in liver transplantation due to the so-called ‘immune privileged’ nature of the liver. Liver transplantation is sometimes needed in diseases such as Alagille syndrome (ALGS). However, there has been much uncertainty regarding the diagnostic criteria for antibody-mediated rejection, of which the 2016 Banff criteria aims to resolve.

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“This study was conducted in order to investigate how [donor specific antibody] results are correlated with [antibody-mediated rejection]-related microscopic changes and how the diagnosis of acute [antibody-mediated rejection] potentially impacts clinical management,” the authors wrote.

The research team identified patients who had undergone liver transplantation at King’s College Hospital in London. In addition, participants must have had donor-specific assays performed and a matched liver biopsy for review. A total of 109 patients met the inclusion criteria.

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“The present study identified a good correlation between [donor-specific antigen] results and liver biopsy findings. Morphological microvascular injuries were almost exclusively observed in [donor-specific antigen]-positive cases; cases with significant C4d staining were all [donor-specific antigen]-positive,” wrote the authors of the study. 

In this study, 9% of patients who were positive for donor-specific antigen post-liver transplantation met the Banff criteria for acute antibody-mediated rejection. The vast majority of cases were T cell-mediated rejection. The research team reported that the careful assessment of microvascular injury using C4d immunostaining is important, both in cases of antibody-mediated rejection and T cell-mediated rejection. 


Maurice JB, Nwaogu A, Gouda M, Shaw O, Sanchez-Fueyo A, Zen Y. Acute antibody-mediated rejection in liver transplantation: impact and applicability of the Banff Working Group on Liver Allograft Pathology 2016 CriteriaHum Pathol. Published online June 18, 2022. doi:10.1016/j.humpath.2022.06.015