Clinicopathologic Characteristics of Late Acute Antibody-mediated Rejection in Pediatric Liver Transplantation

Abstract

Background. An early and accurate diagnosis of liver antibody-mediated rejection (AMR) followed by timely intervention is important for clinical management but remains challenging. The aim of this study was to assess the clinicopathologic characteristics and outcomes of late acute AMR in pediatric liver transplantation recipients. Methods. We performed a retrospective review of 739 ABO-identical/compatible allograft liver biopsies from 199 pediatric transplantation recipients. Results. Based on Banff 2016 AMR criteria, 3 recipients fulfilled the criteria for definite for late acute AMR, 2 met the criteria for suspicious for AMR, and 2 were indeterminate for AMR. We further assessed the clinicopathologic characteristics of these 7 patients. All 7 patients had at least 1 biopsy with a histopathologic pattern compatible with acute AMR. Additionally, we observed accompanied moderately to markedly dilated portal/central veins and endothelialitis disproportionate to the degree of bile duct injury in all 7 patients; periportal/perivenular hepatocyte necrosis was seen in 6 of 7 patients; and arteritis was seen in 3 of 7 patients. In each case, microvascular C4d deposition was present in at least 1 biopsy. Posttransplant donor specific anti-HLA antibodies were detected in 5 patients. Two of 7 patients were retransplanted, and 2 died after developing refractory AMR. The remaining 5 patients were alive with stable graft function at a median follow-up of 4.1 years. Conclusions. Our data suggest that acute AMR in pediatric liver grafts is rare, can develop late, and may be associated with graft loss or patient death. The recurrent histopathologic findings of moderately to markedly dilated portal/central veins and endothelialitis disproportionate to the degree of bile duct injury are features that appear unique to pediatric acute AMR of liver grafts.

Immunologic benefits of maternal living donor allografts in pediatric liver transplantation: fewer rejection episodes and no evidence of de novo allosensitization

“…All but one of these patients received a DDLT graft, and none received a maternal‐LLD graft. Patient characteristics and histological findings of the patients with AMR have been previously described 26 . When we investigated the effect of post‐LT DSA on graft, patient, and ACR‐free survival, we did not detect any difference between positive and negative DSA patients (Figure S2).…”

“…In the present study, 80% of children tested for post‐LT DSA were positive, which may represent a selection bias as they were likely being tested in the context of graft dysfunction or a rejection episode. Despite this high rate, AMR was diagnosed in only three childrenl 26 . Musat et al showed that in the adult population, preformed DSA was associated with an increased risk of ACR; however, only 2 out of 109 patients (1.8%) developed a rejection episode that fulfills the criteria for an AMR diagnosis 35 .…”

“…Despite this high rate, AMR was diagnosed in only three childrenl. 26 Musat et al showed that in the adult population, preformed DSA was associated with an increased risk of ACR; however, only 2 out of 109 patients (1.8%) developed a rejection episode that fulfills the criteria for an AMR diagnosis. 35 In another study, DSA was detected in 54% (n = 27) of long-term survivors of pediatric LT, and non-tolerant patients were more likely to have class II DSA, especially against HLA-DQ.…”

Not only a small liver - The pathologist’s perspective in the pediatric liver transplant setting

“…In addition to the histopathology picture of an acute injury, the complement fragment 4d (C4d) linear and granular vascular deposition (demonstrated through specific immunohistochemical or immunofluorescence stain) ( Fig. 3 ) and positive serum Donor-Specific Antibodies (DSA) are required criteria to obtain a definitive diagnosis 48 , 55 , 59 , 60 …”

A network-based approach to identify expression modules underlying rejection in pediatric liver transplantation

“… 11 As a result, surveillance biopsies performed after the first year after Tx can reveal fibrosis, antibody-mediated chronic allograft injury; this can be with or without cellular infiltrates and circulating donor-specific antibodies. 12 , 13 , 14 …”