Liver transplantation: Rejection and tolerance

Taner, Timuçin

doi:10.1002/lt.24840

Cited by 31 publications

(25 citation statements)

References 23 publications

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“…Our data suggest that because of the unique time‐ and histologic severity–dependent outcomes, it is important to describe TCMR after LT in the context of its timing and histologic grade. Our finding that early moderate‐to‐severe or steroid‐resistant rejection may play a role in late TCMR is new but supports the historic observation that multiple or inadequately treated TCMR episodes are risk factors for chronic rejection . For this small subset of patients, the risk appears substantial, and closer longer‐term clinical follow‐up may be warranted.…”

Section: Discussionsupporting

confidence: 77%

Not All Cellular Rejections Are the Same: Differences in Early and Late Hepatic Allograft Rejection

Jadlowiec¹,

Morgan²,

Nehra³

et al. 2019

Liver Transpl

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T cell-mediated rejection (TCMR) is common after liver transplantation (LT), and it is often thought to have a minimum impact on outcomes. Because alloimmune response changes over time, we investigated the role of the timing of TCMR on patient and allograft survival and examined the risk factors for early and late TCMR. We reviewed protocol liver biopsies for 787 consecutive LT recipients with an 8.6-year follow-up. The incidence of early TCMR (≤6 weeks after LT) was 33.5% with nonalcoholic steatohepatitis patients having the lowest incidence. Younger recipient age (P < 0.01), number of human leukocyte antigen mismatches (P < 0.01), and use of deceased donor allografts (P = 0.01) were associated with increased risk of early TCMR, which had no impact on allograft (hazard ratio [HR], 1.02; 95% CI, 0.79-1.32; P = 0.89) or overall survival (HR, 1.03; 95% CI, 0.78-1.34; P = 0.86). Late TCMR (>6 weeks after LT) was less common (17.7%) and was associated with different risk factors. The majority of late TCMR (56.2%) episodes had no antecedent early TCMR, although moderateto-severe early TCMR (HR, 2.85; 95% CI, 1.55-5.23; P < 0.01) and steroid resistance (HR, 3.62; 95% CI, 1.87-6.99; P < 0.01) were associated with late TCMR. Late TCMR increased risk of mortality (HR, 1.89; 95% CI, 1.35-2.65; P = 0.001) and graft loss (HR, 1.71; 95% CI, 1.23-2.37; P = 0.001). Thus, these data suggest that the timing and histologic grade of TCMR determine its impact on patient and allograft survival. Early mild TCMR episodes after LT do not adversely impact patient or allograft survival provided that they are adequately treated. The occurrence of late TCMR carries deleterious effects with increased longterm risk of graft loss and decreased survival. Patients with moderate-to-severe early TCMR are at an increased risk for late TCMR and warrant closer clinical follow-up.

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Section: Discussionsupporting

confidence: 77%

Not All Cellular Rejections Are the Same: Differences in Early and Late Hepatic Allograft Rejection

Jadlowiec¹,

Morgan²,

Nehra³

et al. 2019

Liver Transpl

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“…Reasons for elevated liver enzymes reach from harmless findings to rather serious pathologies such as acute rejection or recurrence of the underlying disease . A timely and correct diagnosis of the reason for elevated liver enzymes is substantial because of the availability of effective treatment options (especially in case of viral hepatitis or acute rejection) .…”

Section: Discussionmentioning

confidence: 99%

Hepatitis E virus genotype 3 is a common finding in liver‐transplanted patients undergoing liver biopsy for elevated liver enzymes with a low De Ritis ratio and suspected acute rejection: A real‐world cohort

Darstein

Häuser

Straub

et al. 2018

Clinical Transplantation

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“…For these reasons, tolerance of LT has been an attractive and ultimate goal in transplant immunology. Approximately 20% of recipients could become completely tolerant without any immunosuppressant drugs after LT ( 5 – 7 ), whereas such “operational tolerance” is reported only anecdotally in recipients of other organs ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Immune Tolerance Induction Using Cell-Based Strategies in Liver Transplantation: Clinical Perspectives

et al. 2020

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Liver transplantation (LT) has become the best chance and a routine practice for patients with end-stage liver disease and small hepatocellular carcinoma. However, lifelong immunosuppressive regimens could lead to many post-LT complications, including cancer recurrence, infections, dysmetabolic syndrome, and renal injury. Impeccable management of immunosuppressive regimens is indispensable to ensure the best long-term prognosis for LT recipients. This is challenging for these patients, who probably have a post-LT graft survival of more than 10 or even 20 years. Approximately 20% of patients after LT could develop spontaneous operational tolerance. They could maintain normal graft function and histology without any immunosuppressive regimens. Operational tolerance after transplantation has been an attractive and ultimate goal in transplant immunology. The liver, as an immunoregulatory organ, generates an immune hyporesponsive microenvironment under physiological conditions. In this regard, LT recipients may be ideal candidates for studies focusing on operative tolerance. Cell-based strategies are one of the most promising methods for immune tolerance induction, including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory T cells, regulatory dendritic cells, regulatory macrophages, regulatory B cells, and mesenchymal stromal cells. The safety and the efficacy of many cell products have been evaluated by prospective clinical trials. In this review, we will summarize the latest perspectives on the clinical application of cell-based strategies in LT and will address a number of concerns and future directions regarding these cell products.

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Liver transplantation: Rejection and tolerance

Cited by 31 publications

References 23 publications

Not All Cellular Rejections Are the Same: Differences in Early and Late Hepatic Allograft Rejection

Not All Cellular Rejections Are the Same: Differences in Early and Late Hepatic Allograft Rejection

Hepatitis E virus genotype 3 is a common finding in liver‐transplanted patients undergoing liver biopsy for elevated liver enzymes with a low De Ritis ratio and suspected acute rejection: A real‐world cohort

Immune Tolerance Induction Using Cell-Based Strategies in Liver Transplantation: Clinical Perspectives

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