Cost-Effectiveness of Primary Liver Transplantation Versus Hepatoportoenterostomy in the Management of Biliary Atresia in the United States.

Biliary atresia (BA) is the leading indication to perform a pediatric liver transplantation (LT). Timely hepatoportoenterostomy (HPE) attempts to interrupt the natural history and allow for enteric bile flow; however, most patients who are treated with HPE require LT by the age of 10 years. We determined the cost-effectiveness of foregoing HPE to perform primary LT (pLT) in children with BA compared with standard-of-care HPE management. A Markov model was developed to simulate BA treatment over 10 years. Costs were measured in 2018 US dollars and effectiveness in life-years (LYs). The primary outcome was incremental cost-effectiveness ratio (ICER) between treatments. Model parameters were derived from the literature. In the base model, we assumed similar LT outcomes after HPE and pLT. Sensitivity analyses on all model parameters were performed, including a scenario in which pLT led to 100% patient and graft survival after LT. Children undergoing HPE accumulated $316,692 in costs and 8.17 LYs per patient. Children undergoing pLT accumulated $458,059 in costs and 8.24 LYs per patient, costing $1,869,164 per LY gained compared with HPE. With parameter variation over plausible ranges, only post-HPE and post-LT costs reduced the ICER below a typical threshold of $100,000 per LY gained. On probabilistic sensitivity analysis, 93% of iterations favored HPE at that threshold. With 100% patient and graft survival after pLT, pLT cost $283,478 per LY gained. HPE is more economically favorable than pLT for BA. pLT is unfavorable even with no graft or patient loss. The ability to predict those patients who may experience high costs after HPE or low costs after LT may help identify those patients for whom pLT could be considered.

The Health Care Transition of Youth With Liver Disease Into the Adult Health System: Position Paper From ESPGHAN and EASL.

BACKGROUND: Medical advances have dramatically improved the long-term prognosis of children and adolescents with once-fatal hepatobiliary diseases. However, there is no generally accepted optimal pathway of care for the transition from paediatric care to the adult health system. AIM: The purpose of this position paper is to propose a transition process for young people with paediatric onset hepatobiliary diseases from child-centred to adult-centred healthcare services. METHODS: Seventeen ESPGHAN/EASL physicians from 13 countries (Austria, Belgium, France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Spain, Sweden, Switzerland, and United Kingdom) formulated and answered questions after examining the currently published literature on transition from childhood to adulthood. PubMed and Google Scholar were systematically searched between 1980 and January 2018. Quality of evidence was assessed by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) system. Expert opinions were used to support recommendations whenever the evidence was graded weak. All authors voted on each recommendation, using the nominal voting technique. RESULTS: We reviewed the literature regarding the optimal timing for the initiation of the transition process and the transfer of the patient to adult services, principal documents, transition multi-professional team components, main barriers, and goals of the general transition process. A transition plan based on available evidence was agreed focusing on the individual young people's readiness and on coordinated teamwork, with transition monitoring continuing until the first year of adult services.We further agreed on selected features of transitioning processes inherent to the most frequent paediatric-onset hepatobiliary diseases. The discussion highlights specific clinical issues that will probably present to adult gastrointestinal specialists and that should be considered, according to published evidence, in the long-term tracking of patients. CONCLUSIONS: Transfer of medical care of individuals with paediatric onset hepatobiliary chronic diseases to adult facilities is a complex task requiring multiple involvements of patients and both paediatric and adult care providers.

UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care.

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included.These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings;1. Patient populations involved in AYP transition2. Risks of failing transition or poor transition3. Models of AYP transition4. Patient and carer/parent perspective in AYP transition5. Surgical perspective.

Early and Late Factors Impacting Patient and Graft Outcome in Pediatric Liver Transplantation: Summary of an ESPGHAN Monothematic Conference.

As pediatric liver transplantation comes of age, experts gathered to discuss current paradigms and define gaps in knowledge warranting research to further improve patient and graft outcomes. Identified areas ripe for collaborative research include understanding the molecular and cellular mechanisms of tolerance and the role of donor-specific antibodies, considering ways to expand donor pool, minimizing long-term side effects of immunosuppression, and fine-tuning surgical techniques to minimize biliary and vascular complications.

Using Mobile Phone Technology to Support Young Liver Transplant Recipients Moving to Adult Services.

BACKGROUND: The process and preparation of moving from child to adult services (transition) is a challenging period of time for young people and represents significant changes in care and support systems. The proliferation of mobile phone applications for health purposes suggests that it is an area for further investigation. OBJECTIVE: The review explores the potential to use mobile phone technology to help support young liver transplant recipients moving to adult services. It represents the first review conducted in this specialism and considers a new model of support for young liver patients. METHODS: A systematic rapid review of the published peer-reviewed literature. RESULTS: Two searches were conducted: Search 1: the use of technology to support transition to adult services (6 studies) and Search 2: how best to support liver transplant recipients during transition (6 studies). DISCUSSION: Research shows that to achieve positive transition young people need information about their condition and transition. The process needs to be guided by transition readiness, rather than the young persons' age. Although parents and support networks should be in place and are valued, transition should build upon self-management and independence. Results suggest that there appears to be scope to use mobile phone technology to support transition. This is the first time a review has explored the types of issues or concerns facing liver transplant patients and how these can be addressed through mobile phone technology.

Primary prophylaxis of variceal hemorrhage in children with portal hypertension: a framework for future research.

Nonselective ß-blocker therapy and endoscopic variceal ligation reduce the incidence of variceal hemorrhage in cirrhotic adults, but their use in children is controversial. There are no evidence-based recommendations for the prophylactic management of children at risk of variceal hemorrhage due to the lack of appropriate randomized controlled trials. In a recent gathering of experts at the American Association for the Study of Liver Diseases annual meeting, significant challenges were identified in attempting to design and implement a clinical trial of primary prophylaxis in children using either of these therapies. These challenges render such a trial unfeasible, primarily due to the large sample size required, inadequate knowledge of appropriate dosing of ß-blockers, and difficulty in recruiting to a trial of endoscopic variceal ligation. Pediatric research should focus on addressing questions of natural history and diagnosis of varices, prediction of variceal bleeding, optimal approaches to ß-blocker and ligation therapy, and alternative study designs to explore therapeutic efficacy in children.

Portal hypertension and its management in children.

Portal hypertension (PHT), defined as raised intravascular pressure in the portal system, is a complication of chronic liver disease or liver vascular occlusion. Advances in our ability to diagnose and monitor the condition but also predict the risk of gastrointestinal bleeding have enabled us to optimise the management of children with PHT either at a surveillance or at a postbleeding stage. A consensus among paediatric centres in the classification of varices can be beneficial in streamlining future paediatric studies. New invasive (endoscopic and surgical procedures) and non-invasive (pharmacotherapy) techniques are currently used enabling clinicians to reduce mortality and morbidity in children with PHT.

Nitisinone in the treatment of hereditary tyrosinaemia type 1.

Hereditary tyrosinaemia type 1 (HT-1) is a rare genetic disease caused by mutations in the gene for the enzyme fumarylacetoacetase. It usually presents with liver failure but can be manifest as chronic liver disease. Rarely, it may present with nonhepatic manifestations such as renal dysfunction, porphyria-like illness or cardiomyopathy. There is a high lifetime risk of developing hepatocellular carcinoma (HCC). Prior to the development of liver transplantation, most patients died in childhood.The clinical manifestations stem from the cytotoxicity of tyrosine metabolites accumulating proximal to the metabolic defect. Nitisinone acts on tyrosine metabolism upstream of the defect to prevent the production of these metabolites. Nitisinone is used in combination with a tyrosine- and phenylalanine-restricted diet. Nitisinone has transformed the natural history of tyrosinaemia. Liver failure is controlled in 90% of patients, those with chronic liver disease improve and nonhepatic manifestations are abolished. Nitisinone is well tolerated and has few adverse effects other than a predictable rise in plasma tyrosine levels. Nitisinone provides protection against HCC if it is started in infancy, but if commenced after the age of 2 years, a significant risk of HCC remains. Furthermore, where nitisinone is used pre-emptively, liver disease appears to be prevented, suggesting the importance of neonatal screening for tyrosinaemia where possible. Nitisinone is indicated for all children with HT-1, and liver transplantation is only indicated where nitisinone fails, or where the development of HCC is likely or suspected.