Durable Clinical and Immunologic Advantage of Living Donor Liver Transplantation in Children

Przybyszewski, Eric M.; Verna, Elizabeth C.; Lobritto, Steven; Martínez, Mercedes; Vittorio, Jennifer; Fox, Alyson N.; Samstein, Benjamin; Kato, Tomoaki; Griesemer, Adam; Emond, Jean C.

doi:10.1097/tp.0000000000002110

Cited by 16 publications

(20 citation statements)

References 31 publications

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“…Thus, it has yet to be determined whether the secondarily observed reduction in PTLD is related to improved tolerance of maternal grafts, and by inference, lower levels of immunosuppression. It is also worth noting that in this retrospective study, patients with BA were more likely to undergo LDLT compared to non‐BA recipients …”

Section: Potential Impact Of Maternal Donormentioning

confidence: 86%

“…It is also worth noting that in this retrospective study, patients with BA were more likely to undergo LDLT compared to non-BA recipients. 18 Taken together, these four retrospective, observational studies suggest that there may be a potential immunologic benefit to recipients of maternal donor allografts. In these limited cohorts, no association was made with HLA compatibility, which would be the most obvious potential immunologic benefit when receiving a maternal donor allograft.…”

Section: Post-transplant Patient Survival Between Ldlt and Ddlt Was Notmentioning

confidence: 95%

“…More recently, several groups have reported an unexpected finding: improved graft and patient survival in pediatric recipients of maternal living donor liver allografts (Table ) . This is in contrast to modern era observations in kidney transplantation, in which maternal living donor allografts have been associated with worse outcomes .…”

Section: Improved Outcomes In Ldltmentioning

confidence: 97%

“…Another recent report investigating maternal donor benefit in pediatric LDLT included non‐BA patients in its analysis of rejection‐free survival . These authors demonstrated that LDLT was associated with a significantly lower rate of ACR, chronic rejection, and a greater likelihood to achieve immunosuppression monotherapy.…”

Section: Potential Impact Of Maternal Donormentioning

confidence: 99%

“…16 More recently, several groups have reported an unexpected finding: improved graft and patient survival in pediatric recipients of maternal living donor liver allografts (Table 1). [17][18][19][20][21] This is in contrast to modern era observations in kidney transplantation, in which maternal living donor allografts have been associated with worse outcomes. 22 However, the lower rate of graft survival in maternal kidney transplantation could be attributed to non-immunologic donor-related factors such as smaller graft size and nephron underdosing as observed in prior studies of donor-recipient sex-mismatched allografts.…”

Section: Improved Outcome S In Ldltmentioning

confidence: 99%

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Immunologic benefit of maternal donors in pediatric living donor liver transplantation

Kim

Akbari

Genyk

et al. 2019

Pediatric Transplantation

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Purpose of review Long‐term follow‐up has suggested that pediatric LDLT may have superior outcomes compared to deceased donor recipients. In this review, we describe the subset of LDLT recipients with maternal donors that have lower reported rates of rejection and improved allograft survival. Recent findings Pediatric LDLT recipients, particularly those with a primary diagnosis of biliary atresia who receive grafts from their mothers, have been reported to have lower rates of acute cellular rejection post‐transplant and graft failure. Maternal‐fetal microchimerism and the persistence of regulatory T cells may be related to improved outcomes observed in recipients with maternal donors. Further, recent studies have shown that up to 60% of pediatric LDLT recipients can undergo intentional withdrawal of immunosuppression and achieve long‐term operational tolerance. The impact of graft type on operational tolerance has not been thoroughly investigated; however, investigation of tolerant pediatric LDLT patients with maternal donors may provide key insights into the mechanisms of immune tolerance. Summary While excellent outcomes can be achieved in pediatric LDLT, there is still a measurable decrease in graft and patient survival over time post‐transplant. Recipients of maternal donor liver transplants are a subset of patients who may be advantaged toward improved outcomes by means of immune tolerance.

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Section: Potential Impact Of Maternal Donormentioning

confidence: 86%

Section: Post-transplant Patient Survival Between Ldlt and Ddlt Was Notmentioning

confidence: 95%

Section: Improved Outcomes In Ldltmentioning

confidence: 97%

Section: Potential Impact Of Maternal Donormentioning

confidence: 99%

Section: Improved Outcome S In Ldltmentioning

confidence: 99%

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Immunologic benefit of maternal donors in pediatric living donor liver transplantation

Kim

Akbari

Genyk

et al. 2019

Pediatric Transplantation

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Living Donor Liver Transplant in Children

Adeyemi

Rand

Olthoff

2021

Liver Transplantation

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Long‐term Outcomes of Pediatric Living Versus Deceased Donor Liver Transplantation Recipients: A Systematic Review and Meta‐analysis

et al. 2021

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Living donor liver transplantation (LDLT) emerged in the 1980s as a viable alternative to scarce cadaveric organs for pediatric patients. However, pediatric waitlist mortality remains high. Long‐term outcomes of living and deceased donor liver transplantation (DDLT) are inconsistently described in the literature. Our aim was to systematically review the safety and efficacy of LDLT after 1 year of transplantation among pediatric patients with all causes of liver failure. We searched the MEDLINE, Medline‐in‐Process, MEDLINE Epub Ahead of Print, Embase + Embase Classic (OvidSP), and Cochrane (Wiley) from February 1, 1947 to February 26, 2020, without language restrictions. The primary outcomes were patient and graft survival beyond 1 year following transplantation. A meta‐analysis of unadjusted and adjusted odds and hazard ratios was performed using a random‐effects model. A total of 24 studies with 3677 patients who underwent LDLT and 9098 patients who underwent DDLT were included for analysis. In patients with chronic or combined chronic liver failure and acute liver failure (ALF), 1‐year (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.53‐0.88), 3‐year (OR, 0.73; 95% CI, 0.61‐0.89), 5‐year (OR, 0.71; 95% CI, 0.57‐0.89), and 10‐year (OR, 0.42; 95% CI, 0.18‐1.00) patient and 1‐year (OR, 0.50; 95% CI, 0.35‐0.70), 3‐year (OR, 0.55; 95% CI, 0.37‐0.83), 5‐year (OR, 0.5; 95% CI, 0.32‐0.76), and 10‐year (OR, 0.26; 95% CI, 0.14‐0.49) graft survival were consistently better in LDLT recipients compared with those in DDLT recipients. In patients with ALF, no difference was seen between the 2 groups except for 5‐year patient survival (OR, 0.60; 95% CI, 0.38‐0.95), which favored LDLT. Sensitivity analysis by era showed improved survival in the most recent cohort of patients, consistent with the well‐described learning curve for the LDLT technique. LDLT provides superior patient and graft survival outcomes relative to DDLT in pediatric patients with chronic liver failure and ALF. More resources may be needed to develop infrastructures and health care systems to support living liver donation.

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Durable Clinical and Immunologic Advantage of Living Donor Liver Transplantation in Children

Abstract: This study demonstrates the potential benefit of LDLT, particularly with maternal grafts, for pediatric liver transplant recipients on multiple clinical parameters over long-term follow-up.

Cited by 16 publications

References 31 publications

Immunologic benefit of maternal donors in pediatric living donor liver transplantation

Immunologic benefit of maternal donors in pediatric living donor liver transplantation

Living Donor Liver Transplant in Children

Long‐term Outcomes of Pediatric Living Versus Deceased Donor Liver Transplantation Recipients: A Systematic Review and Meta‐analysis

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