Acute and Chronic Rejection After Liver Transplantation: What A Clinician Needs to Know

Choudhary, Narendra S.; Saigal, Sanjiv; Bansal, Rinkesh Kumar; Saraf, Neeraj; Gautam, Dheeraj; Soin, Arvinder S.

doi:10.1016/j.jceh.2017.10.003

Cited by 128 publications

(102 citation statements)

References 67 publications

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“…The incidence of tBPAR is usually reported in the literature at 12 months after LT. However, many studies underline that the majority of tBPAR occurs early (initial 3 months) . Because the main feature of this study is the early introduction of EVR (POD 7), a completely unexplored scenario when the study was designed, we considered 3 months as a valuable and safe efficacy endpoint.…”

Section: Discussionmentioning

confidence: 99%

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial

et al. 2019

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Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open‐label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6‐12 ng/mL. The primary endpoint was the proportion of treated biopsy‐proven acute rejection (tBPAR)–free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR‐free (P = 0.09); composite endpoint‐free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.

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Section: Discussionmentioning

confidence: 99%

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial

et al. 2019

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“…What is striking however is that even in the modern era, despite the introduction of new immunosuppressive agents and strategies, chronic rejection continues to be reported as a cause of graft loss. 18,19 Neves Souza 17 observed the presence of an unspecified chronic hepatitis associated with bridging fibrosis in children, which progressed to graft failure. It is possible that histologic features like this will need to be evaluated as possibly a new form of "chronic rejection.…”

Section: Discussionmentioning

confidence: 99%

20‐ to 25‐year patient and graft survival following a single pediatric liver transplant—Analysis of the United Network of Organ Sharing database: Where to go from here

Ekong

Gupta

Urban³

et al. 2019

Pediatric Transplantation

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To understand factors contributing to liver graft loss and patient death, we queried a national database designed to follow pediatric patients transplanted between 1987 and 1995 till adulthood. A comparison was made to a cohort transplanted between 2000 and 2014. The 5‐, 10‐, 15‐, 20‐, and 25‐year patient survival and graft survival were 95.5%, 93.7%, 89.1%, 80.8%, and 73.1%, and 92.5%, 86.7%, 77.6%, 68.7%, and 62.2%, respectively. The twenty‐year patient/graft survival was significantly worse in those transplanted between 5 and 17 years of age compared to those transplanted at <5 years of age (P < 0.001). For the modern era cohort, the 3‐year patient survival was significantly lower in children transplanted at 16‐17 years of age compared to those transplanted at <5 and 11‐15 years of age (P ≤ 0.02). The 3‐year graft survival was similarly lower in children transplanted at 16‐17 years of age compared to those transplanted at <5, 5‐10, and 11‐15 years of age (P ≤ 0.001). Infection as a cause of death occurred either early or >15 years post‐transplant. Chronic rejection remained the leading cause of graft loss in both cohorts and the commonest indication for retransplantation 20‐25 years following primary transplant. Further research is required to identify modifiable factors contributing to development of chronic rejection.

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“…The incidence of acute rejection for liver transplant has been reported to be between 10% and 40%. We, therefore, chose to fix incidence rates at 15% and 30% for type I error and power analyses (Choudhary et al, 2017; Dogan et al, 2018). Phenotypes were generated using the model

logit \Pr (Y_{i} = 1 | X_{i}) = β_{0} + X_{i} β,

where

Y_{i}

denotes the outcome phenotype of recipient i in a sample of N total donor/recipient pairs and all other variables are defined in the Methods section.…”

Section: Methodsmentioning

confidence: 99%

Joint testing of donor and recipient genetic matching scores and recipient genotype has robust power for finding genes associated with transplant outcomes

Arthur

Guan

Loza

et al. 2020

Genetic Epidemiology

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Genetic matching between transplant donor and recipient pairs has traditionally focused on the human leukocyte antigen (HLA) regions of the genome, but recent studies suggest that matching for non‐HLA regions may be important as well. We assess four genetic matching scores for use in association analyses of transplant outcomes. These scores describe genetic ancestry distance using identity‐by‐state, or genetic incompatibility or mismatch of the two genomes and therefore may reflect different underlying biological mechanisms for donor and recipient genes to influence transplant outcomes. Our simulation studies show that jointly testing these scores with the recipient genotype is a powerful method for preliminary screening and discovery of transplant outcome related single nucleotide polymorphisms (SNPs) and gene regions. Following these joint tests with marginal testing of the recipient genotype and matching score separately can lead to further understanding of the biological mechanisms behind transplant outcomes. In addition, we present results of a liver transplant data analysis that shows joint testing can detect SNPs significantly associated with acute rejection in liver transplant.

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Acute and Chronic Rejection After Liver Transplantation: What A Clinician Needs to Know

Cited by 128 publications

References 67 publications

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial

20‐ to 25‐year patient and graft survival following a single pediatric liver transplant—Analysis of the United Network of Organ Sharing database: Where to go from here

Joint testing of donor and recipient genetic matching scores and recipient genotype has robust power for finding genes associated with transplant outcomes

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