Longterm outcome of the liver graft: The pathologist's perspective

Demetris, Anthony J.

doi:10.1002/lt.24851

Cited by 13 publications

(11 citation statements)

References 28 publications

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“…In our cohort, 18 cases of aAMR and 26 cases of cAMR were included. The vast majority of our patients have a history of TCMR, in some cases very close to the diagnosis and treatment of AMR; this strongly illustrates the links between TCMR and AMR, which can probably be frequently associated with LT recipients 19,20 . Considering cases of aAMR, the diagnosis was usually made early after LT (median 1 mo) but sometimes very late after LT.…”

Section: Discussionmentioning

confidence: 58%

“…The vast majority of our patients have a history of TCMR, in some cases very close to the diagnosis and treatment of AMR; this strongly illustrates the links between TCMR and AMR, which can probably be frequently associated with LT recipients. [19,20] Considering cases of aAMR, the diagnosis was usually made early after LT (median 1 mo) but sometimes very late after LT. This was related to the presence of preformed DSA but also to de novo DSA, which could have been detected after an immunological event, such as pregnancy [21] or immunosuppression withdrawal.…”

Section: Discussionmentioning

confidence: 99%

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Treatment of donor-specific anti-HLA antibodies-mediated rejection after liver transplantation: A French nationwide retrospective study

Dumortier

Conti

Hiriart

et al. 2023

Liver Transplantation

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The deleterious effect of donor-specific anti-HLA antibodies (DSA) after liver transplantation (LT) has been increasingly recognized during the past decade. Antibody-mediated rejection (AMR) represents a rare but severe complication in the presence of DSA. However, little is known concerning the treatment of AMR after LT. The nationwide French study aimed to describe LT recipients who received specific treatment of AMR. We performed a multicenter retrospective study on 44 patients who were treated with B-cell targeting agents from January 2008 to December 2020. Median patient age at the time of AMR treatment was 51.6 years (range: 17.9–68.0). AMR was classified as acute (n = 19) or chronic (n = 25). The diagnosis of AMR was made after a median time of 16.8 months (range: 0.4–274.2) after LT. The main therapeutic combination was plasma exchange/rituximab/IVIG (n = 25, 56.8%). The median follow-up after the treatment of AMR was 32 months (range: 1–115). After the treatment, 1-, 5- and 10-year patient and graft survivals were 77%, 55.9%, and 55.9%, and 69.5%, 47.0%, and 47.0%, respectively. Initial total bilirubin (Q1–Q3 vs. Q4) was significantly associated with patient survival (log-rank test, p = 0.005) and graft survival (log-rank test, p = 0.002). After a median follow-up of 21 months (range: 12–107), DSA became undetectable in 15/38 patients (39.5%) with available DSA monitoring. In conclusion, specific treatment of AMR in LT recipients has slowly emerged in France during the past decade and has probably been considered in the most severe patients; this explains the global poor outcome, even if the outcome was favorable in some cases.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Treatment of donor-specific anti-HLA antibodies-mediated rejection after liver transplantation: A French nationwide retrospective study

Dumortier

Conti

Hiriart

et al. 2023

Liver Transplantation

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“…In adults, liver rejection seems to be controlled by immunosuppressive drugs. However, liver transplants with normal histology are infrequent 24,25 and long-term prognosis is a major issue, especially in young recipients 26 . Selecting donors with low HED values for young recipients should enable better long-term histological results.…”

Section: Discussionmentioning

confidence: 99%

Donor HLA class 1 evolutionary divergence is a major predictor of liver allograft rejection: a retrospective cohort study

Féray

Taupin

Sebagh

et al. 2020

Preprint

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BackgroundRecognition of donor antigens by the recipient’s immune system leads to allograft rejection. HLA evolutionary divergence (HED) between an individual’s HLA alleles is a continuous metric that quantifies the differences between each amino acid of two homologous alleles and reflects the breadth of the immunopeptidome presented to T lymphocytes. We investigated whether or not HED of the donor or of the recipient has an impact on liver transplant rejection.MethodWe did a retrospective cohort study in 1154 adult and 113 children recipients of liver transplant. We considered the histological lesions in liver biopsies performed routinely 1,2 and 5 years after transplantation and in case of liver dysfunction. Donor-specific anti-HLA antibodies (DSA) were determined in children at the time of biopsy. HED was calculated using the physicochemical Grantham distance for class I (HLA-A, HLA-B) and class II (HLA-DRB1, HLA-DQB1) alleles. We assessed the incidence of rejection-related liver lesions using a multivariate Cox proportional hazards regression analysis.FindingsIn the adult cohort, recipients from donors with class I HED above the median had a higher risk of acute or chronic rejection, but not of other histological lesions. HED of the recipients was not related to any histological lesion. In multivariate analysis, a high donor class I HED was associated with acute rejection (hazard ratio [HR] 1.79; 95% confidence interval [CI]: 1.34-2.40; P<0.0001) or chronic rejection (HR 2.26, CI 1.45-3.51; P<0.0001) and was independent of age and HLA identities. In the pediatric cohort, class I HED of the donor was also associated with acute rejection (HR 1.81, 95% CI 1.12-3.14; P=0.013) independently of the presence of DSA.InterpretationClass I HED of the donor reflects graft immunogenicity and predicts rejection independently of donor-recipient HLA compatibility. This novel and easily accessible prognostic marker could improve donor selection and guide immunosuppression.

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“…The histopathology of AMR in LT can be extremely complex due to overlapping features seen in AMR and concomitant TCMR, particularly in smouldering injury seen in chronic AMR and late-onset TCMR. 55 AMR and TCMR (and sometimes even CDR) may all co-exist. Distinguishing the endothelialitis seen in TCMR from capillaritis and inlet venulitis seen in AMR may be extremely difficult.…”

Section: Histology Of Antibody-mediated Rejectionmentioning

confidence: 99%

Antibody-mediated rejection of the liver allograft: An update and a clinico-pathological perspective

Lee

Fiel

Schiano

2021

Journal of Hepatology

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Antibody-mediated rejection after liver transplantation is an under-recognised cause of allograft injury. While definitions of acute and chronic antibody-mediated rejection have increased clinical awareness, timely identification and management of antibody-mediated rejection remain difficult because of complexities in diagnosis and histopathology, lack of treatment protocols, and unclear long-term outcomes. While recent cohort studies assessing the importance of donor-specific antibodies have aided in its diagnosis, literature on the treatment of antibody-mediated rejection in liver transplantation remain limited to case reports and small series. Further increasing the awareness and timely recognition of antibody-mediated rejection post-liver transplantation is crucial in order to stimulate future research and the development of protocols for its diagnosis and treatment. This review will summarise recent advances in the clinical diagnosis and treatment of antibody-mediated rejection in liver transplantation, as well as some of the histopathologic features (on liver biopsy tissue) of acute and chronic antibodymediated rejection.

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Longterm outcome of the liver graft: The pathologist's perspective

Cited by 13 publications

References 28 publications

Treatment of donor-specific anti-HLA antibodies-mediated rejection after liver transplantation: A French nationwide retrospective study

Treatment of donor-specific anti-HLA antibodies-mediated rejection after liver transplantation: A French nationwide retrospective study

Donor HLA class 1 evolutionary divergence is a major predictor of liver allograft rejection: a retrospective cohort study

Antibody-mediated rejection of the liver allograft: An update and a clinico-pathological perspective

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