Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed—from diagnosis to LT—with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016–2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population

Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed—from diagnosis to LT—with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016–2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population

Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed-from diagnosis to LT-with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016-2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population.Peer reviewe

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

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

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 PedsQLTM 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

Accumulation of Postoperative Unexpected Events Assessed by the Comprehensive Complication Index&reg; as Prognostic Outcome Parameters for Kasai Procedure

Introduction The Kasai procedure in children with biliary atresia (BA) is associated with several complications in the short-term. The Comprehensive Complication Index (CCI&reg;) is a validated metric in adult surgery for the analysis of complications and morbidity in surgical patients. We aimed to analyze the CCI&reg; for the first time in BA infants and to correlate its association with outcomes. Material and Methods We conducted a retrospective review of medical records of infants with type III BA undergoing the Kasai procedure between January 2011 and December 2021 at our institution. All unexpected events were ranked according to the Clavien&ndash;Dindo classification, and the CCI&reg; per patient was subsequently calculated. Clavien&ndash;Dindo grades, individual events, CCI&reg;, and total event numbers per patient were correlated with one- and two-year outcomes post-surgery. Results A total of 131 events were identified in 101 patients (ranging 0&ndash;11 per patient). Forty-four Grade I (33.6%), 67 Grade II (51.1%), 18 Grade III (13.7%), and two sentinel events [&gt;Grade IV] (1.5%) were documented according to Clavien&ndash;Dindo, including one death in a cardiac-associated BA patient. None of the complications significantly correlated with a poor outcome. Sixty-three (62.4%) CCI&reg; scores were calculated (range 0&ndash;100). The mean CCI&reg; score during the in-patient treatment post-surgery was significantly higher in patients with a poorer outcome than patients with native liver survival at one- and two-year follow-up (22.7 &plusmn; 21.7 vs. 13.2 &plusmn; 18.1; p = 0.02). Conclusion Not the severity of complications, but the accumulation of numerous events related to Kasai procedure were associated with a poorer outcome. Therefore, the CCI&reg; is an excellent instrument for the postoperative morbidity assessment of BA patients

Evaluation of living liver donors using contrast enhanced multidetector CT – The radiologists impact on donor selection

Abstract Background Living donor liver transplantation (LDLT) is a valuable and legitimate treatment for patients with end-stage liver disease. Computed tomography (CT) has proven to be an important tool in the process of donor evaluation. The purpose of this study was to evaluate the significance of CT in the donor selection process. Methods Between May 1999 and October 2010 170 candidate donors underwent biphasic CT. We retrospectively reviewed the results of the CT and liver volumetry, and assessed reasons for rejection. Results 89 candidates underwent partial liver resection (52.4%). Based on the results of liver CT and volumetry 22 candidates were excluded as donors (31% of the cases). Reasons included fatty liver (n = 9), vascular anatomical variants (n = 4), incidental finding of hemangioma and focal nodular hyperplasia (n = 1) and small (n = 5) or large for size (n = 5) graft volume. Conclusion CT based imaging of the liver in combination with dedicated software plays a key role in the process of evaluation of candidates for LDLT. It may account for up to 1/3 of the contraindications for LDLT.</p

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

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

Long-Term Outcome Following Liver Transplantation for Primary Hepatic Tumors—A Single Centre Observational Study over 40 Years

The incidence of pediatric liver tumors in general has been rising over the last years and so is the number of children undergoing liver transplantation for this indication. To contribute to the ongoing improvement of pre- and post-transplant care, we aim to describe outcome and risk factors in our patient cohort. We have compared characteristics and outcome for patients transplanted for hepatoblastoma to other liver malignancies in our center between 1983 and 2022 and analysed influential factors on tumor recurrence and mortality using nominal logistic regression analysis. Of 39 children (16 f) who had transplants for liver malignancy, 31 were diagnosed with hepatoblastoma. The proportion of malignant tumors in the transplant cohort rose from 1.9% (1983–1992) to 9.1% in the current decade (p p > 0.0001). Hearing loss was a common side effect of ototoxic chemotherapy in hepatoblastoma patients (48%). The most common maintenance immunosuppression were mTor-inhibitors. Risk factors for tumor recurrence in patients with hepatoblastoma were higher AFP before transplant (AFPpre-LTX), a low ratio of AFPmax to AFPpre-LTX and salvage transplantation. Liver malignancies represent a rising number of indications for liver transplantation in childhood. Primary tumor resection can spare a liver transplant with all its long-term complications, but in case of tumor recurrence, transplantation might have inferior outcome. The rate of acute biopsy-proven rejections and biliary complications in comparison to our total transplant cohort needs further investigations

Psychosocial outcome and resilience after paediatric liver transplantation in young adults

Background and objective: The long-term psychosocial outcome of young adults after paediatric liver transplantation (LT) was investigated with the focus on day-to-day living. We aimed to capture patients’ subjective perceptions of well-being and autonomy based on key physical outcome parameters. Methods: All patients following paediatric LT at Hannover Medical School born before 2002 with a post-transplant follow-up of at least four years were included in this study. This retrospective observational study compared psychosocial parameters obtained from a self-designed 77-item questionnaire with standard clinical outcome variables. Results: Eighty-two patients (male: 57%) aged 13–41 years were included in the survey within a three-month period (response rate: 41%). With an adherence rate of 33%, all but two patients were immunosuppressed. In total, 53 patients had transitioned to adult care largely without problems. Eighty-three percent (n = 68) evaluated their current health status as “(very) good”. Sixty-seven patients (82%) did not experience health-related anxiety in daily life. Conclusions: Our results demonstrate psychological stability and high self-esteem of young patients, as well as good integration into society and a high degree of normality during daily life after LT. Adherence rates are lower than anticipated and do not correlate with patients’ understanding of their medical condition