Minimization or withdrawal of immunosuppressants in pediatric liver transplant recipients

Lin, Niang‐Cheng; Wang, Hsin‐Kai; Yeh, Yi‐Chen; Liu, Chia-Pei; Loong, Che‐Chuan; Tsai, Hsin Lin; Chen, Cheng‐Yen; Chin, Taiwai; Liu, Chinsu

doi:10.1016/j.jpedsurg.2015.08.043

Cited by 27 publications

(41 citation statements)

References 33 publications

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“…These promising results suggested that in selected pediatric OLT recipients, COT was feasible; yet selection criteria (such as clinical and biomarkers criteria) are needed to identify the children who could successfully attempt IS withdrawal. High rates (40%-42%) of successful COT were also reported by other series[120,121]. Likewise, Waki et al[120] demonstrated that Non-tol patients were associated with post-transplant human leukocyte antigen antibodies.…”

Section: Resultsmentioning

confidence: 58%

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

Manzia¹,

Angelico²,

Gazia³

et al. 2019

WJG

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BACKGROUNDImmunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients.AIMTo study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients.METHODSA systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTSEmerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences.CONCLUSIONThe selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.

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Section: Resultsmentioning

confidence: 58%

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

Manzia¹,

Angelico²,

Gazia³

et al. 2019

WJG

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“…It has been suggested that the chronic use of immunosuppressants is likely to increase the risk of hypertension, anemia, malignancy, bone disease, cardiovascular diseases, renal dysfunction and psychiatric disorders [16]. Our institute showed 5 MMA and 1 PA patients with metabolic disease after LT were eventually weaned off tacrolimus, and fiveremained tacrolimus-free for more than 2 years.. Pediatric patients are immunologically naïve thus render tacrolimus withdrawal likely in selected recipients (histologically stable graft function > 1 year if transplant at < 1 year of age, or stable up to 2 years if transplant at > 1 year of age) [27]. Two mut patients are prescribed sodium bicarbonate due to renal tubular acidosis that is secondary to their MMA, and three mut patients are prescribed an antihyperuricemic agent to control elevated uric acid that might be induced by the immunosuppressant [28] or secondary to methylmalonate deposition as an injury to renal tubule cells [29] The study in Lucile Packard Children’s Hospital at Stanford reported 6 from 14 patients MMA underwent LT and 8 patients received a combined liver-kidney transplantation (CLKT) with 100% survival rate at a mean follow-up of 3.25 ± 4.2 years [30].…”

Section: Discussionmentioning

confidence: 99%

Methylmalonic acidemia/propionic acidemia – the biochemical presentation and comparing the outcome between liver transplantation versus non-liver transplantation groups

Chu

Chien

Lin

et al. 2019

Orphanet J Rare Dis

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Background Most patients with isolated methylmalonic acidemia (MMA) /propionic acidemia (PA) presenting during the neonatal period with acute metabolic distress are at risk for death and significant neurodevelopmental disability. The nationwide newborn screening for MMA/PA has been in place in Taiwan from January, 2000 and data was collected until December, 2016. Results During the study period, 3,155,263 newborns were screened. The overall incidence of MMA mutase type cases was 1/121,356 ( n = 26), 1 cobalamin B was detected and that for PA cases ( n = 4) was 1/788,816. The time of referral is 8.8 days for MMA patients, and 7.5 days for PA patients. The MMA mutase type patients have higher AST, ALT, and NH 3 values as well as a lower pH value ( p < 0.05). The mean age for liver transplantation (LT) is 402 days (range from 0.6–6.7 yr) with 16 out of 20 cases (80.0%) using living donors. The mean admission length shortened from 90.6 days/year (pre-LT) to 5.3 days/year (at 3rd year post-LT) ( p < 0.0005). Similarly, the tube feeding ratio decreased from 67.8 to 0.50% ( p < 0.00005). The anxiety level of the caregiver was reduced from 33.4 to 27.2 after LT ( p = 0.001) and the DQ/IQ performance of the patients was improved after LT from 50 to 60.1 ( p = 0.07). Conclusion MMA/PA patients with LT do survive and have reduced admission time, reduced tube feeding and the caregiver is less anxious.

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“…(52) Multiple studies have examined this phenomenon, although pediatricspecific studies have been limited (Table 6). (53)(54)(55)(56)(57)(58) These reports demonstrated that a proportion of carefully selected LT recipients (15%-60%) can be successfully weaned off immunosuppression with normal allograft function 14-120 months after medication discontinuation. (51,52,54,55,(57)(58)(59)(60)(61) Currently, the Immunosuppression Withdrawal for Stable Pediatric LT Recipients study (iWITH NCT01638559) is ongoing and has completed patient recruitment.…”

Section: Tolerancementioning

confidence: 98%

“…Normal liver function was initially observed in some patients after required immunosuppression withdrawal due to complications such as PTLD or noncompliance . Multiple studies have examined this phenomenon, although pediatric‐specific studies have been limited (Table ) . These reports demonstrated that a proportion of carefully selected LT recipients (15%‐60%) can be successfully weaned off immunosuppression with normal allograft function 14‐120 months after medication discontinuation .…”

Section: Tolerancementioning

confidence: 99%

Immunosuppression in pediatric liver transplant recipients: Unique aspects

et al. 2017

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Pediatric liver transplantation has experienced improved outcomes over the last 50 years. This can be attributed in part to establishing optimal use of immunosuppressive agents to achieve a balance between minimizing the risks of allograft rejection and infection. The management of immunosuppression in children is generally more complex and can be challenging when compared with the use of these agents in adult liver transplant patients. Physiologic differences in children alter the pharmacokinetics of immunosuppressive agents, which affects absorption, distribution, metabolism, and drug excretion. Children also have a longer expected period of exposure to immunosuppression, which can impact growth, risk of infection (bacterial, viral, and fungal), carcinogenesis, and likelihood of nonadherence. This review discusses immunosuppressive options for pediatric liver transplant recipients and the unique issues that must be addressed when managing this population. Further advances in the field of tolerance and accommodation are needed to relieve the acute and cumulative burden of chronic immunosuppression in children.Liver Transplantation 23 244-256 2017 AASLD.

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Minimization or withdrawal of immunosuppressants in pediatric liver transplant recipients

Cited by 27 publications

References 33 publications

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

Methylmalonic acidemia/propionic acidemia – the biochemical presentation and comparing the outcome between liver transplantation versus non-liver transplantation groups

Immunosuppression in pediatric liver transplant recipients: Unique aspects

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