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11 pages, 567 KiB

Open AccessArticle

Cold Ischemia Time and Graft Fibrosis Are Associated with Autoantibodies after Pediatric Liver Transplantation: A Retrospective Cohort Study of the European Reference Network TransplantChild

by Norman Junge, Angelo Di Giorgio, Muriel Girard, Zeynep Demir, Diana Kaminska, Maria Janowska, Vaidotas Urbonas, Dominykas Varnas, Giuseppe Maggiore, Tommaso Alterio, Christoph Leiskau, Florian W. R. Vondran, Nicolas Richter, Lorenzo D’Antiga, Rafael Mikolajczyk, Eva-Doreen Pfister and Ulrich Baumann

Children 2022, 9(2), 275; https://doi.org/10.3390/children9020275 - 17 Feb 2022

Cited by 1 | Viewed by 1995

Abstract

The reported prevalence of autoantibodies (AAB) (ANA, SMA, LKM, SLA) after pediatric liver transplantation (pLTX) varies considerably from 26–75%, but their clinical impact on outcome is uncertain. We aimed to study the prevalence of AAB after pLTX, their association with donor-, transplant-, and [...] Read more.

The reported prevalence of autoantibodies (AAB) (ANA, SMA, LKM, SLA) after pediatric liver transplantation (pLTX) varies considerably from 26–75%, but their clinical impact on outcome is uncertain. We aimed to study the prevalence of AAB after pLTX, their association with donor-, transplant-, and recipient-characteristics, and their relation to outcome. In our multicenter retrospective study, we aimed to clarify conflicting results from earlier studies. Six ERN TransplantChild centers reported data on 242 patients, of whom 61% were AAB positive. Prevalence varied across these centers. Independent of the interval between pLTX and AAB analysis, a one-hour increase in CIT resulted in an odds ratio (OR) of 1.37 (95% CI 1.11–1.69) for SMA positivity and an OR of 1.42 (95%CI 1.18–1.72) for ANA positivity. Steroid-free immunosuppression (IS) versus steroid-including IS (OR 5.28; 95% CI 1.45–19.28) was a risk factor for SMA positivity. Liver enzymes were not associated with ANA or SMA positivity. We did not observe an association of rejection activity index with ANA or SMA. However, the liver fibrosis score in follow-up biopsies was associated with ANA titer and donor age. In conclusion, this first multicenter study on AAB after pLTX showed high AAB prevalence and varied widely between centers. Longer CIT and prednisolone-free-IS were associated with AAB positivity, whereas AAB were not indicative of rejection, but instead were associated with graft fibrosis. The detection of AAB may be a marker of liver fibrosis and may be taken into consideration when indications for liver biopsy and immunosuppressive regimes, or reduction of immunosuppression in long-term follow-up, are being discussed. Prospective immunological profiling of pLTX patients, including AAB, is important to further improve our understanding of transplant immunology and silent graft fibrosis. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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11 pages, 1794 KiB

Open AccessArticle

Long-Term Varicella Zoster Virus Immunity in Paediatric Liver Transplant Patients Can Be Achieved by Booster Vaccinations—A Single-Centre, Retrospective, Observational Analysis

by Tobias Laue, Elisabeth Oms, Johanna Ohlendorf and Ulrich Baumann

Children 2022, 9(2), 130; https://doi.org/10.3390/children9020130 - 19 Jan 2022

Cited by 5 | Viewed by 2972

Abstract

Varicella is one of the most common vaccine-preventable infections after paediatric solid organ transplantation; thus, vaccination offers simple and cheap protection. However, children with liver disease often progress to liver transplantation (LT) before they reach the recommended vaccination age. As a live vaccine, [...] Read more.

Varicella is one of the most common vaccine-preventable infections after paediatric solid organ transplantation; thus, vaccination offers simple and cheap protection. However, children with liver disease often progress to liver transplantation (LT) before they reach the recommended vaccination age. As a live vaccine, varicella zoster virus (VZV) vaccination after transplantation is controversial; however, many case series demonstrate that vaccination may be safe and effective in paediatric liver transplant recipients. Only limited data exists describing long-term vaccination response in such immunocompromised patients. We investigated retrospectively vaccination response in paediatric patients before and after transplantation and describe long-term immunity over ten years, including the influence of booster-vaccinations. In this retrospective, single-centre study, 458 LT recipients were analysed between September 2004 and June 2021. Of these, 53 were re-transplantations. Patients with no available vaccination records and with a history of post-transplant lymphoproliferative disease, after hematopoietic stem cell transplantation and clinical chickenpox were excluded from this analysis (n = 198). In total, data on 207 children with a median annual follow-up of 6.2 years was available: 95 patients (45.9%) were unvaccinated prior to LT. Compared to healthy children, the response to vaccination, measured by seroconversion, is weaker in children with liver disease: almost 70% after one vaccination and 93% after two vaccinations. One year after transplantation, the mean titres and the number of children with protective antibody levels (VZV IgG ≥ 50 IU/L) decreased from 77.5% to 41.3%. Neither diagnosis, gender, nor age were predictors of vaccination response. Booster-vaccination was recommended for children after seroreversion using annual titre measurements and led to a significant increase in mean titre and number of protected children. Response to vaccination shows no difference from monotherapy with a calcineurin inhibitor to intensified immunosuppression by adding prednisolone or mycophenolate mofetil. Children with liver disease show weaker seroconversion rates to VZV vaccination compared to healthy children. Therefore, VZV-naïve children should receive basic immunization with two vaccine doses as well as those vaccinated only once before transplantation. An average of 2–3 vaccine doses are required in order to achieve a long-term seroconversion and protective antibody levels in 95% of children. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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12 pages, 267 KiB

Open AccessArticle

Parental Disease Specific Knowledge and Its Impact on Health-Related Quality of Life

by Luisa Stasch, Johanna Ohlendorf, Ulrich Baumann, Gundula Ernst, Karin Lange, Christiane Konietzny, Eva-Doreen Pfister, Kirsten Sautmann and Imeke Goldschmidt

Children 2022, 9(1), 98; https://doi.org/10.3390/children9010098 - 11 Jan 2022

Cited by 1 | Viewed by 1313

Abstract

Objective: Structured education programs have been shown to improve somatic outcome and health-related quality of life (HRQOL) in a variety of chronic childhood diseases. Similar data are scarce in paediatric liver transplantation (pLTx). The purpose of this study was to examine the relationship [...] Read more.

Objective: Structured education programs have been shown to improve somatic outcome and health-related quality of life (HRQOL) in a variety of chronic childhood diseases. Similar data are scarce in paediatric liver transplantation (pLTx). The purpose of this study was to examine the relationship of parental disease-specific knowledge and psychosocial disease outcome in patients after pLTx. Methods: Parents of 113 children (chronic liver disease n = 25, after pLTx n = 88) completed the transplant module of the HRQOL questionnaire PedsQL, the “Ulm quality of life inventory for parents of children with chronic diseases” ULQUI, and a tailor-made questionnaire to test disease-specific knowledge. Results: Parental knowledge was highest on the topic of “liver transplantation” and lowest in “basic background knowledge” (76% and 56% correct answers respectively). Knowledge performance was only marginally associated with HRQOL scores, with better knowledge being related to worse HRQOL outcomes. In contrast, self-estimation of knowledge performance showed significant positive correlations with both PedsQL and ULQUI results. Conclusion: Patient HRQOL and parental emotional wellbeing after pLTx are associated with positive self-estimation of parental disease-specific knowledge. Objective disease-specific knowledge has little impact on HRQOL. Parental education programs need to overcome language barriers and address self-efficacy in order to improve HRQOL after pLTx. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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16 pages, 1032 KiB

Open AccessArticle

Two Sides of a Coin: Parental Disease-Specific Training as Seen by Health Care Practitioners and Parents in Pediatric Liver Transplantation

by Johanna Ohlendorf, Luisa Stasch, Ulrich Baumann, Christiane Konietzny, Eva-Doreen Pfister, Gundula Ernst, Karin Lange, Kirsten Sautmann and Imeke Goldschmidt

Children 2021, 8(9), 827; https://doi.org/10.3390/children8090827 - 21 Sep 2021

Cited by 1 | Viewed by 1622

Abstract

In the absence of widely accepted education standards for parents of children after liver transplantation (LTx), the content and structure of parental training are influenced by health care practitioners’ (HCP) individual knowledge and assessment of the relevance of its contents. This study examines [...] Read more.

In the absence of widely accepted education standards for parents of children after liver transplantation (LTx), the content and structure of parental training are influenced by health care practitioners’ (HCP) individual knowledge and assessment of the relevance of its contents. This study examines the hypothesis that expectations towards training differ between HCPs and parents, and that the quality of parental training affects the job-satisfaction of HCPs. Attitudes towards disease-specific education were assessed by tailor-made questionnaires in HCPs (n = 20) and parents of children with chronic liver disease or after LTx (n = 113). These were supplemented by focused interviews in n = 7 HCPs and n = 16 parents. Parents were more satisfied with current counseling than HCP. Language barriers and low parental educational background were perceived as obstacles by 43% of HCPs. The quality of parental knowledge was felt to have a strong influence on HCPs job satisfaction. The expectations towards the content of disease-specific education largely overlap but are not synonymous. HCP and parents agreed with regards to the importance of medication knowledge. Parents rated the importance about the meaning of laboratory values and diagnostic procedures significantly higher (3.50 vs. 2.85, p < 0.001 and 3.42 vs. 2.80, p < 0.001) than HCPs. Parents and HCPs would prefer a structured framework with sufficient staff resources for disease-specific counseling. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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8 pages, 225 KiB

Open AccessArticle

A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C

by Line Modin, Vicky Ng, Paul Gissen, Julian Raiman, Eva Doreen Pfister, Anibh Das, René Santer, Hanna Faghfoury, Saikat Santra and Ulrich Baumann

Children 2021, 8(9), 819; https://doi.org/10.3390/children8090819 - 17 Sep 2021

Cited by 2 | Viewed by 1931

Abstract

Background: To report on clinical presentation and outcomes of children who underwent liver transplantation (LTx) and were subsequently diagnosed to have Niemann-Pick type C (NPC). Methods: Retrospective, descriptive, multi-centre review of children diagnosed with NPC who underwent LTx (2003–2018). Diagnosis was made by [...] Read more.

Background: To report on clinical presentation and outcomes of children who underwent liver transplantation (LTx) and were subsequently diagnosed to have Niemann-Pick type C (NPC). Methods: Retrospective, descriptive, multi-centre review of children diagnosed with NPC who underwent LTx (2003–2018). Diagnosis was made by filipin skin test or genetic testing. Results: Nine children were identified (six centres). Neonatal acute liver failure was the most common indication for LTx (seven children). Median age at first presentation: 7 days (range: 0–37). The most prevalent presenting symptoms: jaundice (8/9), hepatosplenomegaly (8/9) and ascites (6/9). 8/9 children had a LTx before the diagnosis of NPC. Genetic testing revealed mutations in NPC1 correlating with a severe biochemical phenotype in 5 patients. All 9 children survived beyond early infancy. Seven children are still alive (median follow-up time of 9 (range: 6–13) years). Neurological symptoms developed in 4/7 (57%) patients at median 9 (range: 5–13) years following LTx. Conclusion: Early diagnosis of NPC continues to be a challenge and a definitive diagnosis is often made only after LTx. Neurological disease is not prevented in the majority of patients. Genotype does not appear to predict neurological outcome after LTx. LTx still remains controversial in NPC. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

15 pages, 4205 KiB

Open AccessArticle

ABO Incompatible Liver Transplantation in Children: A 20 Year Experience from Centres in the TransplantChild European Reference Network

by Małgorzata Markiewicz-Kijewska, Piotr Kaliciński, Juan Torres Canizales, Angelo Di Giorgio, Ulrich Baumann, Carl Jorns, Alastair Baker, Maria Francelina Lopes, Esteban Frauca Remacha, Eduardo Lopez-Granados, Paloma Jara Vega, Maria-Sole Basso, Grzegorz Kowalewski, Diana Kamińska, Sandra Ferreira, Daniela Liccardo, Andrea Pietrobattista, Marco Spada and on behalf of ERN TransplantChild Healthcare Working Group

Children 2021, 8(9), 760; https://doi.org/10.3390/children8090760 - 31 Aug 2021

Cited by 6 | Viewed by 2165

Abstract

An increasing number of AB0-incompatible (AB0i) liver transplantations (LT) are being undertaken internationally in recent years due to organ shortages and the need for urgent transplantation. The aim of our study was establish the value of ABOi LT from available retrospective results of [...] Read more.

An increasing number of AB0-incompatible (AB0i) liver transplantations (LT) are being undertaken internationally in recent years due to organ shortages and the need for urgent transplantation. The aim of our study was establish the value of ABOi LT from available retrospective results of AB0i pediatric liver transplantations performed in European reference centers now belonging to the TransplantChild, European Reference Network (ERN). Data from medical records were analyzed, including demographic data, diagnosis, urgency of transplantation, time on the waiting list, PELD/MELD score, desensitization procedures, immunosuppression, selected post-transplant complications, and patient and graft survival. A total of 142 patients (pts) with transplants between 1986 and 2018 in 8 European transplant centers were included in the study. The indications for liver transplantation were: cholestatic diseases in 62 pts, acute liver failure in 42 pts, and other conditions in the remaining 38 pts. Sixty-six patients received grafts from living donors, and seventy-six received grafts from deceased donors. Both patient and graft survival were significantly affected by deceased donor type, urgent transplantation, and the development of vascular complications. In the multivariate analysis, vascular complications had a negative impact on patient and graft survival, while a longer time from the first AB0i LT in the study showed better results, suggesting an international learning experience. In conclusion, we believe that AB0i LT in children is now a safe procedure that may be adopted more readily in children. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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18 pages, 1956 KiB

Open AccessArticle

Social Resources for Transplanted Children and Families in European Union Hospitals of ERN TransplantChild

by María Jesús Pascau, Laura Pruneda, Ilaria de Barbieri, Matilde Correia, Belén López, Erika Guijarro, Gonzalo Sofío, Esteban Frauca Remacha, Paloma Jara Vega and on behalf of ERN TransplantChild Healthcare Working Group

Children 2021, 8(9), 723; https://doi.org/10.3390/children8090723 - 24 Aug 2021

Viewed by 1790

Abstract

Social well-being is an intrinsic part of the current concept of health. In the context of chronic disease, there are many challenges we face in order to provide social well-being to patients and their families, even more if we talk about rare diseases. [...] Read more.

Social well-being is an intrinsic part of the current concept of health. In the context of chronic disease, there are many challenges we face in order to provide social well-being to patients and their families, even more if we talk about rare diseases. TransplantChild, a European Reference Network (ERN) in paediatric transplantation, works to improve the quality of life of transplanted children. It is not possible to improve the quality of life if the human and material resources are not available. With this study, we want to identify the economic aids, facilities, services, and financed products that are offered to families in different European centres. We also want to find out who provides these resources and the accessibility to them. We designed an ad hoc survey using the EU Survey software tool. The survey was sent to representatives of the 26 ERN members. In this article we present the results obtained in relation to two of the aspects analysed: long-term financial assistance and drugs, pharmaceuticals and medical devices. Some resources are equally available in all participating centres but there are significant differences in others, such as education aids or parapharmacy product financing. A local analysis of these differences is necessary to find feasible solutions for equal opportunities for all transplanted children in Europe. The experience of centres that already provide certain solutions successfully may facilitate the implementation of these solutions in other hospitals. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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12 pages, 282 KiB

Open AccessArticle

A Sorrow Shared Is a Sorrow Halved? Patient and Parental Anxiety Associated with Venipuncture in Children before and after Liver Transplantation

by Antonia J. Kaluza, Anna Lisa Aydin, Berrit L. Cordes, Gianna Ebers, Albert Fuchs, Christiane Konietzny, Rolf van Dick and Ulrich Baumann

Children 2021, 8(8), 691; https://doi.org/10.3390/children8080691 - 11 Aug 2021

Cited by 3 | Viewed by 2243

Abstract

Taking blood via venipuncture is part of the necessary surveillance before and after liver transplantation. The spectrum of response from children and their parents is variable, ranging from a short and limited aversion to paralyzing phobia. The aim of this retrospective, cross-sectional study [...] Read more.

Taking blood via venipuncture is part of the necessary surveillance before and after liver transplantation. The spectrum of response from children and their parents is variable, ranging from a short and limited aversion to paralyzing phobia. The aim of this retrospective, cross-sectional study was to determine the level of anxiety amongst children during venipuncture, to compare the anxiety reported by children and parents, and to identify the factors affecting the children’s and parents’ anxiety in order to develop therapeutic strategies. In total, 147 children (aged 0–17 years, 78 female) and their parents completed questionnaires. Statistical analysis was performed using qualitative and quantitative methods. Results showed that the majority of children reported anxiety and pain during venipuncture. Younger children had more anxiety (self-reported or assessed by parents). Children and parental reports of anxiety were highly correlated. However, the child’s anxiety was often reported as higher by parents than by the children themselves. The child’s general anxiety as well as the parents’ perceived stress from surgical interventions (but not the number of surgical interventions) prompted parental report of child anxiety. For children, the main stressors that correlated with anxiety and pain were factors during the blood collection itself (e.g., feeling the puncture, seeing the syringe). Parental anxiety was mainly related to circumstances before the blood collection (e.g., approaching the clinic, sitting in the waiting room). The main stressors mentioned by parents were the child’s discomfort and their inability to calm the child. Results indicate that the children’s fear of factors during the blood collection, along with the parents’ perceived stress and helplessness as well as their anticipatory anxiety are important starting points for facilitating the drawing of blood from children before and after liver transplantation, thereby supporting a better disease course in the future. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

12 pages, 406 KiB

Open AccessArticle

Under-Vaccination in Pediatric Liver Transplant Candidates with Acute and Chronic Liver Disease—A Retrospective Observational Study of the European Reference Network TransplantChild

by Tobias Laue, Zeynep Demir, Dominique Debray, Mara Cananzi, Paola Gaio, Valeria Casotti, Lorenzo D’Antiga, Vaidotas Urbonas and Ulrich Baumann

Children 2021, 8(8), 675; https://doi.org/10.3390/children8080675 - 03 Aug 2021

Cited by 11 | Viewed by 3022

Abstract

Infection is a serious concern in the short and long term after pediatric liver transplantation. Vaccination represents an easy and cheap opportunity to reduce morbidity and mortality due to vaccine-preventable infection. This retrospective, observational, multi-center study examines the immunization status in pediatric liver [...] Read more.

Infection is a serious concern in the short and long term after pediatric liver transplantation. Vaccination represents an easy and cheap opportunity to reduce morbidity and mortality due to vaccine-preventable infection. This retrospective, observational, multi-center study examines the immunization status in pediatric liver transplant candidates at the time of transplantation and compares it to a control group of children with acute liver disease. Findings show only 80% were vaccinated age-appropriately, defined as having received the recommended number of vaccination doses for their age prior to transplantation; for DTP-PV-Hib, less than 75% for Hepatitis B and two-thirds for pneumococcal conjugate vaccine in children with chronic liver disease. Vaccination coverage for live vaccines is better compared to the acute control group with 81% versus 62% for measles, mumps and rubella (p = 0.003) and 65% versus 55% for varicella (p = 0.171). Nevertheless, a country-specific comparison with national reference data suggests a lower vaccination coverage in children with chronic liver disease. Our study reveals an under-vaccination in this high-risk group prior to transplantation and underlines the need to improve vaccination. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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10 pages, 1570 KiB

Open AccessArticle

Liver Histopathology in Late Protocol Biopsies after Pediatric Liver Transplantation

by Małgorzata Markiewicz-Kijewska, Sylwia Szymańska, Michal Pyzlak, Piotr Kaliciński, Joanna Teisseyre, Adam Kowalski, Irena Jankowska, Piotr Czubkowski and Hor Ismail

Children 2021, 8(8), 671; https://doi.org/10.3390/children8080671 - 01 Aug 2021

Cited by 3 | Viewed by 2339

Abstract

Liver transplantation has become a routine treatment for children with end stage liver failure. Recently, the long term survival of pediatric patients after liver transplantation has improved, with a life expectancy much longer than that of adult recipients, but also with longer exposition [...] Read more.

Liver transplantation has become a routine treatment for children with end stage liver failure. Recently, the long term survival of pediatric patients after liver transplantation has improved, with a life expectancy much longer than that of adult recipients, but also with longer exposition of the graft to various injuries, including immunological, inflammatory and others. Biochemical tests, although important, do not always reflect graft injury. The aim of our study was to analyze the histopathology of the graft in late protocol biopsies and correlate it with the clinical and biochemical status of these patients. We analyzed 61 protocol liver biopsies taken from 61 patients. Biopsies were taken 9.03–17.09 years (mean 12.68, median 11.74 years) after transplantation. Liver specimens were examined particularly for the presence and stage of liver fibrosis, inflammation, steatosis, and acute or chronic cellular and humoral rejection. We did not find any abnormalities in 26 (42.6%) liver specimens. None of the patients had signs of cellular or antibody mediated rejection or chronic rejection. In 23 liver biopsies (37.7%), we found non-specific lymphoid infiltrates. Another problem was fibrosis (equal to or more than three on the Ishak scale)—we found it in 17 patients, including seven liver specimens (11.5%) with severe fibrosis (Ishak 5–6). Conclusions: Various pathomorphological abnormalities were found in more than half of patients with a median 11.74 years post-transplant follow-up. Most of them presented normal laboratory liver tests at the same time, suggesting a slow subclinical process leading to pathomorphological abnormalities. No single factor for the development of these abnormalities was found, but our study supports the need for protocol liver biopsies even in patients with normal/almost normal biochemical liver tests. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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14 pages, 311 KiB

Open AccessArticle

Current Practices on Diagnosis, Prevention and Treatment of Post-Transplant Lymphoproliferative Disorder in Pediatric Patients after Solid Organ Transplantation: Results of ERN TransplantChild Healthcare Working Group Survey

by Alastair Baker, Esteban Frauca Remacha, Juan Torres Canizales, Luz Yadira Bravo-Gallego, Emer Fitzpatrick, Angel Alonso Melgar, Gema Muñoz Bartolo, Luis Garcia Guereta, Esther Ramos Boluda, Yasmina Mozo, Dorota Broniszczak, Wioletta Jarmużek, Piotr Kalicinski, Britta Maecker-Kolhoff, Julia Carlens, Ulrich Baumann, Charlotte Roy, Christophe Chardot, Elisa Benetti, Mara Cananzi, Elisabetta Calore, Luca Dello Strologo, Manila Candusso, Maria Francelina Lopes, Manuel João Brito, Cristina Gonçalves, Carmen Do Carmo, Xavier Stephenne, Lars Wennberg, Rosário Stone, Jelena Rascon, Caroline Lindemans, Dominik Turkiewicz, Eugenia Giraldi, Emanuele Nicastro, Lorenzo D’Antiga, Oanez Ackermann and Paloma Jara Vega Show full author list Hide full author list

Children 2021, 8(8), 661; https://doi.org/10.3390/children8080661 - 29 Jul 2021

Cited by 16 | Viewed by 3481

Abstract

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems [...] Read more.

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities; (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers’ approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases; (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012–2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived; (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

16 pages, 639 KiB

Open AccessArticle

Recipient-Specific Risk Factors Impairing Patient and Graft Outcome after Pediatric Liver Transplantation—Analysis of 858 Transplantations in 38 Years

by Christoph Leiskau, Norman Junge, Eva-Doreen Pfister, Imeke Goldschmidt, Frauke Mutschler, Tobias Laue, Johanna Ohlendorf, Hamoud Nasser, Jan Beneke, Nicolas Richter, Florian Vondran and Ulrich Baumann

Children 2021, 8(8), 641; https://doi.org/10.3390/children8080641 - 27 Jul 2021

Cited by 11 | Viewed by 1711

Abstract

(1) Background and Aim: Despite excellent long-term results in pediatric liver transplantation (pLTx), mortality and graft loss still are to be diminished. We aim to describe time-dependent changes and long-term outcome of a large single-center pLTx cohort and to identify independent recipient-related risk [...] Read more.

(1) Background and Aim: Despite excellent long-term results in pediatric liver transplantation (pLTx), mortality and graft loss still are to be diminished. We aim to describe time-dependent changes and long-term outcome of a large single-center pLTx cohort and to identify independent recipient-related risk factors impairing patient and graft survival. (2) Methods: This is a retrospective single-center study analyzing all pediatric liver transplants from 1983–2020. Risk factors for mortality and graft loss were identified by univariable and multi-linear regression analysis. (3) Results: We analyzed 858 liver transplantations in 705 pediatric patients. Five-year patient/graft survival increased from 60.9%/48.0% (1983–1992) to 97.5%/86.5% (OR = 12.5; p < 0.0001/OR = 6.5; p < 0.0001) (2014–2020). Indications changed significantly over time, with a higher proportion of patients being transplanted for malignancies and metabolic disease and indications of PFIC and α1AT-deficiency declining. The era of transplantation (log7.378/9.657; p < 0.0001) and indication of acute liver failure (log = 1.944/2.667; HR = 2.015/1.772; p = 0.0114/0.002) impairs patient/graft survival significantly in the multivariate analysis. Furthermore, patient survival is worsened by re-transplantation (log = 1.755; HR = 1.744; p = 0.0176) and prolonged waiting times in high-urgency status (log = 2.588; HR = 1.073; p = 0.0026), whereas the indication of biliary atresia improved outcome (log = 1.502; HR = 0.575; p = 0.0315). Graft survival was additionally impaired by pre-existing portal vein thrombosis (log = 1.482; HR = 2.016; p = 0.0330). (4) Conclusions: Despite more complex indications, patient and graft survival after pLTx continue to improve.. Acute liver failure remains the indication with poorest outcome, and listing for high urgency liver transplantation should be considered carefully and early to keep waiting time on HU list short. Furthermore, pre-transplant portal vein thrombosis should be prevented whenever possible to improve graft survival. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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12 pages, 794 KiB

Open AccessArticle

Long-Term Follow-Up of Renal Function in Children after Liver Transplantation—A Single Center Retrospective Study

by Grzegorz Kowalewski, Piotr Kaliciński, Marek Stefanowicz, Ryszard Grenda, Piotr Czubkowski and Marek Szymczak

Children 2021, 8(8), 633; https://doi.org/10.3390/children8080633 - 25 Jul 2021

Cited by 3 | Viewed by 1803

Abstract

Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). Its prevalence with modern immunosuppression regimens, especially in children, is variable depending on the transplantation era. The study included 61 pediatric patients with at least 10 years of follow-up after liver [...] Read more.

Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). Its prevalence with modern immunosuppression regimens, especially in children, is variable depending on the transplantation era. The study included 61 pediatric patients with at least 10 years of follow-up after liver transplantation remaining under constant care of the Department of Pediatric Surgery and Organ Transplantation. The analysis included several tests: estimated glomerular function (eGFR), results of screening for renal tubular defects and blood concentrations of basic immunosuppressive drug-tacrolimus. CKD was diagnosed in 3% of children at 12 years after LT. The maintaining of tacrolimus concentrations >4 ng/mL in long-term observation was associated with a significant increase of microalbuminuria. The presence of microalbuminuria, regarded as a risk factor of CKD, confirmed the necessity of regular comprehensive assessment of patients in long-term follow-up. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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9 pages, 360 KiB

Open AccessArticle

Influence of Parental Attitudes on Formation of Psychological Resilience and Adherence to Medical Regime in Adolescents after Liver or Renal Transplantation

by Marta Biernacka, Anna Jakubowska-Winecka and Piotr Kaliciński

Children 2021, 8(8), 619; https://doi.org/10.3390/children8080619 - 22 Jul 2021

Cited by 2 | Viewed by 1582

Abstract

Identifying the causes of poor disease control and medication non-adherence is indispensable so that patients can benefit from treatment. The aim of our study was to determine the relationship between parental attitudes, the development of psychological resilience, and systematic medication adherence in a [...] Read more.

Identifying the causes of poor disease control and medication non-adherence is indispensable so that patients can benefit from treatment. The aim of our study was to determine the relationship between parental attitudes, the development of psychological resilience, and systematic medication adherence in a group of adolescents after kidney and liver transplantation. The analysis included the results obtained from 96 families. A total of 52 patients after kidney transplantation and 44 patients after liver transplantation, aged 12–18 years and their parents were examined. The types of parental attitudes were assessed using the Parental Attitude Scale. The patient’s resilience was determined with the Resiliency Assessment Scale. The MMAS-8 was used to assess the regularity of medication-taking behavior. A total of 61% of the patients in the study group displayed high levels of psychological resilience. The analyses showed a positive correlation between resilience and the systematic taking of medication by the patients. Moreover, it was found that the analyzed link between psychological resilience on the degree of the regularity of medication intake was enhanced by a specific type of parental attitude. The obtained results confirm the importance of psychological resources in developing better disease control. The relationship between the type of parental attitudes and medication adherence indicates the need to take into account the family context during the child’s treatment. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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9 pages, 671 KiB

Open AccessArticle

Vitamin D Insufficiency Prior to Paediatric Liver Transplantation Is Associated with Early T-Cell Mediated Rejection

by Nathalie M. Rock, Elisa Anghileri, Vladimir L. Cousin, Laetitia-Marie Petit and Valérie A. McLin

Children 2021, 8(7), 612; https://doi.org/10.3390/children8070612 - 20 Jul 2021

Cited by 3 | Viewed by 1645

Abstract

Objectives: T-cell mediated rejection (TCMR) can compromise long-term liver allograft survival. The immunomodulatory properties of vitamin D are increasingly recognized. We investigated whether perturbations in vitamin D metabolism prior to LT may predispose to TCMR in a representative cohort of paediatric LT [...] Read more.

Objectives: T-cell mediated rejection (TCMR) can compromise long-term liver allograft survival. The immunomodulatory properties of vitamin D are increasingly recognized. We investigated whether perturbations in vitamin D metabolism prior to LT may predispose to TCMR in a representative cohort of paediatric LT recipients. Methods: In this retrospective single-center study of children who underwent liver transplantation between 2005 and 2017, we collected serum 25(OH) vitamin D levels and other parameters related to vitamin D metabolism. Post-transplant variables were collected from medical records during the first year following LT. Results: Eighty-two patients were included. Twenty-six (32%) developed TCMR, 52 (65%) presented at least one event of 25(OH) D insufficiency during the year before the transplant, while 23 (32%) had at least one documented elevated plasma parathyroid hormone level. Forty-six patients benefited from nutritional support (56%). The development of TCMR was associated with vitamin D insufficiency pre-LT (p = 0.01). No significant correlations were identified between PTH levels and incidence of TCMR. The association was stronger in patients transplanted for cholestatic diseases (p = 0.004). Conclusions: Vitamin D insufficiency before a liver transplant may be associated with TCMR during the first year post-LT. These findings warrant further investigation. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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14 pages, 2029 KiB

Open AccessArticle

Is ABO-Incompatible Living Donor Liver Transplantation Really a Good Alternative for Pediatric Recipients?

by Catherine de Magnée, Louise Brunée, Roberto Tambucci, Aurore Pire, Isabelle Scheers, Etienne M. Sokal, Pamela Baldin, Francis Zech, Stéphane Eeckhoudt, Raymond Reding and Xavier Stephenne

Children 2021, 8(7), 600; https://doi.org/10.3390/children8070600 - 16 Jul 2021

Cited by 5 | Viewed by 2323

Abstract

Background: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been proposed to compensate for donor shortage. To date, few studies have reported detailed ABOi LDLT results in large series of pediatric patients. C4d complement deposition in graft capillaries has been reported to be [...] Read more.

Background: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been proposed to compensate for donor shortage. To date, few studies have reported detailed ABOi LDLT results in large series of pediatric patients. C4d complement deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in solid organ transplantation. Methods: A retrospective case–control study was conducted, comparing clinical outcomes of each of 34 consecutive pediatric ABOi LDLT recipients with those of 2 non-ABOi pairs (n = 68), matched according to pre-transplant diagnostic criteria, age, and date of transplantation. In addition, we studied the C4d immunostaining pattern in 22 ABOi and in 36 non-ABOi recipients whose liver biopsy was performed within the first 4 post-transplant weeks for suspected acute rejection. Results: The incidence of biliary complications was higher in ABOi recipients (p < 0.05), as were the incidence of acute humoral rejection (p < 0.01) and the incidence of retransplantation (p < 0.05). All children who required retransplantation were older than 1 year at the time of ABOi LDLT. Positive C4d immunostaining was observed in 13/22 (59%) ABOi recipients versus 3/36 (8.3%) non-ABOi recipients (p < 0.0001). Conclusions: ABOi LDLT is a feasible option for pediatric end-stage liver disease but carries increased risks for the recipient, especially for children older than 1 year, even with a specific preparation protocol. C4d immunostaining may be a hallmark of acute humoral rejection in ABOi liver transplantation. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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14 pages, 860 KiB

Open AccessArticle

Impact of Graft Size Matching on the Early Post-Transplant Complications and Patients Survival in Children after Living Donor Liver Transplantations

by Marek Stefanowicz, Grzegorz Kowalewski, Marek Szymczak, Waldemar Patkowski, Krzysztof Zieniewicz, Ireneusz Grzelak, Adam Kowalski, Hor Ismail, Diana Kamińska and Piotr Kaliciński

Children 2021, 8(7), 579; https://doi.org/10.3390/children8070579 - 06 Jul 2021

Cited by 4 | Viewed by 2166

Abstract

We aimed to assess the impact of the graft-recipient weight ratio (GRWR) on early post-transplant complications and patient survival rates in children after living donor liver transplantation (LDLT). We retrospectively analyzed 321 patients who underwent LDLT from 2004 to 2019. The recipients were [...] Read more.

We aimed to assess the impact of the graft-recipient weight ratio (GRWR) on early post-transplant complications and patient survival rates in children after living donor liver transplantation (LDLT). We retrospectively analyzed 321 patients who underwent LDLT from 2004 to 2019. The recipients were categorized into four groups: 37 patients had a GRWR ≤ 1.5% (Group A), 196 patients had a GRWR > 1.5% and ≤3.5% (Group B), 73 patients had a GRWR > 3.5% and <5% (Group C) and 15 patients had a GRWR ≥ 5% (Group D). Incidence of early surgical complications including vascular complications, biliary complications, postoperative bleedings, gastrointestinal perforations and graft loss were comparable among groups with a different GRWR. Delayed abdominal wound closure was more common in patients with a GRWR > 3.5%. Recipients with a GRWR < 5% had a significantly better prognosis concerning patients and graft survival. Using grafts with a GRWR < 5% allows us to expand the donor pool and decrease the risk of mortality while on the waiting list, when patients at the time of transplantation have less advanced liver disease. LDLT with a GRWR ≥ 5% is related to a higher risk of poor outcome, and thus should be an option for treating selected patients when the risk of a delayed transplantation is high and access to deceased donors is limited. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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14 pages, 1189 KiB

Open AccessArticle

Identification of Impaired Executive Functioning after Pediatric Liver Transplantation Using Two Short and Easily Applicable Tests: Cognitive Functioning Module PedsQL and Children’s Color Trail Test

by Imeke Goldschmidt, Rolf van Dick, Christoph Jacobi, Eva Doreen Pfister and Ulrich Baumann

Children 2021, 8(7), 571; https://doi.org/10.3390/children8070571 - 02 Jul 2021

Cited by 3 | Viewed by 2247

Abstract

We aimed to assess executive functioning in children after liver transplantation compared with healthy controls and in relation to real-life school performance using the PedsQL^TM Cognitive Functioning Scale (CogPedsQL) and the Childrens’ Color Trail Test (CCTT). One hundred and fifty five children [...] Read more.

We aimed to assess executive functioning in children after liver transplantation compared with healthy controls and in relation to real-life school performance using the PedsQL^TM Cognitive Functioning Scale (CogPedsQL) and the Childrens’ Color Trail Test (CCTT). One hundred and fifty five children (78f, median age 10.4 (1.2–18.3) years) underwent testing with CogPedsQL and/or CCTT 4.9 (0.1–17.0) years after transplantation. Results were compared to those of 296 healthy children (165f, median age 10.0 (2.0–18.0) years). Liver transplanted children displayed significantly reduced scores for cogPedsQL and CCTT1&2 compared to healthy controls. Overall, school performance was lower in patients compared to controls. In both patients and controls, results of CCTT2 and CogPedsQL correlated strongly with school performance. In contrast to controls, school performance in patients correlated with the level of maternal but not paternal primary education degree (r = −0.21, p = 0.03). None of the patient CCTT or CogPedsQL test results correlated with parental school education. Conclusion: CogPedsQL and CCTT 1&2 were easily applicable in children after OLT and revealed reduced executive functioning compared to controls. Results reflect real life school performance. The association of parental education with school performance is reduced in transplanted children, which possibly indicates the overriding impact of transplant-associated morbidity on cognitive outcomes. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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10 pages, 2073 KiB

Open AccessCase Report

Ileal Bile Acid Transporter Inhibition Reduces Post-Transplant Diarrhea and Growth Failure in FIC1 Disease—A Case Report

by Johanna Ohlendorf, Imeke Goldschmidt, Norman Junge, Tobias Laue, Hamoud Nasser, Elmar Jäckel, Frauke Mutschler, Eva-Doreen Pfister, Diran Herebian, Verena Keitel and Ulrich Baumann

Children 2022, 9(5), 669; https://doi.org/10.3390/children9050669 - 05 May 2022

Cited by 5 | Viewed by 2338

Abstract

Familial intrahepatic cholestasis 1 (FIC1) disease is a genetic disorder characterized by hepatic and gastrointestinal disease due to ATP8B1 deficiency, often requiring liver transplantation (LT). Extrahepatic symptoms, such as diarrhea, malabsorption, and failure to thrive, do not improve and instead may be aggravated [...] Read more.

Familial intrahepatic cholestasis 1 (FIC1) disease is a genetic disorder characterized by hepatic and gastrointestinal disease due to ATP8B1 deficiency, often requiring liver transplantation (LT). Extrahepatic symptoms, such as diarrhea, malabsorption, and failure to thrive, do not improve and instead may be aggravated after LT. We describe a patient with FIC1 disease who underwent LT at 2 years, 8 months of age. After LT, the child developed severe refractory diarrhea and failed to thrive. The response to bile acid resins was unsatisfactory, and the parents declined our recommendation for partial external biliary diversion (PEBD). Quality of life was extremely impaired, especially due to severe diarrhea, making school attendance impossible. Attempting to reduce the total bile acids, we initiated off-label use of the ileal bile acid transporter (IBAT) inhibitor Elobixibat (Goofice^™), later converted to Odevixibat (Bylvay^™). After six months of treatment, the patient showed less stool output, increased weight and height, and improved physical energy levels. The child could now pursue higher undergraduate education. In our patient with FIC1 disease, the use of IBAT inhibitors was effective in treating chronic diarrhea and failure to thrive. This approach is novel; further investigations are needed to clarify the exact mode of action in this condition. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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8 pages, 191 KiB

Open AccessCase Report

Successful Liver Transplantation in Two Polish Brothers with Transaldolase Deficiency

by Marek Stefanowicz, Maria Janowska, Joanna Pawłowska, Anna Tylki-Szymańska, Adam Kowalski, Marek Szymczak, Piotr Kaliciński and Irena Jankowska

Children 2021, 8(9), 746; https://doi.org/10.3390/children8090746 - 29 Aug 2021

Cited by 2 | Viewed by 1448

Abstract

Transaldolase deficiency (TALDO; OMIM 606003) is a rare inborn autosomal-recessive error of the pentose phosphate pathway. It is an early-onset multisystem disease with dysmorphic features, anaemia, coagulopathy, thrombocytopenia, tubulopathy, hepatosplenomegaly and end-stage liver disease. We present a case of two Polish brothers, born [...] Read more.

Transaldolase deficiency (TALDO; OMIM 606003) is a rare inborn autosomal-recessive error of the pentose phosphate pathway. It is an early-onset multisystem disease with dysmorphic features, anaemia, coagulopathy, thrombocytopenia, tubulopathy, hepatosplenomegaly and end-stage liver disease. We present a case of two Polish brothers, born to consanguineous parents, with early-onset TALDO. The dominant feature of disease was an early severe liver injury, with subsequent renal tubulopathy. Nodular liver fibrosis developed in the course of the underlying disease. The older brother presented stable liver function, however, he was qualified for deceased donor liver transplantation (DDLT) because of a liver tumour and suspicion of hepatocarcinoma. The boy was transplanted at the age of 14. The younger brother was qualified for DDLT due to end-stage liver disease and transplanted at the age of 11. Currently, both our patients are alive and in a good condition with normal graft function 23 and 20 months after DDLT respectively. Liver transplantation can be a therapeutic option in TALDO and should be considered in patients with coexisting severe chronic and end-stage liver disease. Long term follow-up is necessary to assess the impact of liver transplantation for quality of life, survival time and the course of the disease. Full article

(This article belongs to the Special Issue Multidisciplinary Problems and Research in Pediatric Liver Transplantation)

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