Editorial introductions

Objective To summarize the experiences of diagnosing and treating portal vein stenosis (PVS) after pediatric liver transplantation from China donation after citizen’s death (CDCD) grafts. Methods Retrospective analysis was performed for 30 cases of pediatric CDCD liver transplantation recipients with PVS. The screening, diagnosis, treatment and prognosis of PVS were analyzed. Results Among 218 pediatric liver transplantation recipients with CDCD grafts, PVS was diagnosed in 30 cases with an incidence rate of 13.8% (30/218). The initial diagnosis of PVS ranged from 5 days to 27 months post-operation with a median age of 2.9 months. Ultrasonography indicated that stenotic rate of anastomotic site diameter was (41.28±12.93)% and blood flow velocity ratio (358.77±117.82)%. Intervention examination showed average pressure gradient was (9.06±5.34) mmHg between both sides of stenosis. All cases underwent percutaneous intrahepatic balloon dilatation. The recipients were followed up for a median follow-up time of 23(3-63) months. For three cases of restenosis, percutaneous intrahepatic balloon dilatation was repeated. Two cases underwent stent implantation due to ineffective balloon dilation. After treatment, the stenotic rate of anastomotic site diameter was (34.69±8.82) and blood flow velocity ratio (61.18±63.11)% on ultrasound while the average pressure gradient was (1.03±0.85) mmHg. Conclusions PVS is a common vascular complication after pediatric CDCD liver transplantation. Portal vein balloon dilation is both safe and efficacious. However, some cases require repeated balloon dilation and stent implantation serves as the last option for intractable PVS. Color ultrasound is both convenient and effective for making a primary diagnosis and evaluating outcomes. Key words: pediatric liver transplantation; portal vein stenosis; balloon dilation

Current American Association for the Study of Liver Diseases (AASLD) liver transplant evaluation guidelines include both adult and pediatric patients. While pediatric liver transplants account for 7.8% of all liver transplants in the United States, sufficient differences between pediatric and adult patients seeking liver transplantation (LT) now require independent, yet complementary documents. This document will focus on pediatric issues at each level of the evaluation process. Disease categories suitable for referral to a pediatric LT program are similar to adults: acute liver failure, autoimmune, cholestasis, metabolic or genetic, oncologic, vascular, and infectious. However, specific etiologies and outcomes differ widely from adult patients, justifying independent pediatric guidelines. Data supporting our recommendations are based on a Medline search of the English language literature from 1997 to the present. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the available evidence supporting the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The classifications and recommendations are based on three categories: the source of evidence in levels I through III; the Abbreviations: ALF, acute liver failure; GRADE, Grading of Recommendation Assessment, Development, and Evaluation; HB, hepatoblastoma; HCC, hepatocellular carcinoma; HPE, hepatoportoenterostomy; LT, liver transplantation; OTPN, Organ Procurement and Transplantation Network; PFIC, progressive familial intrahepatic cholestasis; TIPS, transjugular intrahepatic portosystemic shunt. From the Department of Pediatrics, University of Pittsburgh School of Medicine; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA; Department of Pediatrics, University of Toronto; Division of Pediatric Gastroenterology, Hepatology and Nutrition, SickKids Transplant and Regenerative Medicine Center, Hospital for Sick Children, Toronto, Canada; Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Emory University School of Medicine; Children’s Healthcare of Atlanta, Atlanta, GA; Department of Pediatrics, Division of Pediatric Gastroenterology and Hepatology, Yale School of Medicine, New Haven, CT; Department of Paediatrics, University of Melbourne; Department of Gastroenterology, Royal Children’s Hospital, Melbourne, Australia; Department of Surgery, Section of Transplantation and Immunology, Yale School of Medicine, New Haven, CT; Department of Surgery, University of Pittsburgh School of Medicine; Division of Pediatric Transplantation, Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA. Financial support to develop this practice guideline was provided by the American Association for the Study of Liver Diseases. All AASLD Practice Guidelines are updated annually. If you are viewing a Practice Guideline that is more than 12 months old, please visit www.aasld.org for an update in the material. Received April 22, 2014; accepted April 22, 2014. Address reprint requests to: Robert H. Squires, M.D., Professor of Pediatrics, University of Pittsburgh, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Ave., Pittsburgh, PA 15224. E-mail: squiresr@upmc.edu Copyright VC 2014 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27191 Potential conflict of interest: Dr. Romero received grants from Bristol-Myers Squibb.

Multisystem inflammatory syndrome in children associated with SARS-CoV-2 in a solid organ transplant recipient.

INTRODUCTION: Pediatric liver transplantation provides substantial survival benefit. An emphasis on value-based practices has become a central theme in many surgical fields, but value-based practices have not been well studied in pediatric transplantation. Given an increasing focus on optimizing outcomes with containing costs, defining value in pediatric liver transplantation warrants investigation. METHODS: Pediatric End-stage Liver Disease (PELD) era pediatric liver transplant recipients from February 2002 to February 2019 were identified using United Network for Organ Sharing (UNOS) STAR file data (n = 5,770). Liver centers were divided into volume tertiles (small, medium, large) and recipients were stratified by age (0 to 4, 5 to 11, 12 to 18 years). Value for the index transplant episode was defined as % graft survival ≥1 year divided by mean post-transplant length-of-stay (LOS). Nearest-neighbor Mahalanobis metric matching was used to account for confounding when assessing the impact of center volume on value. RESULTS: Compared with small centers, large centers delivered better outcomes (1-year graft survival 93.7% vs 89.4%, p = 0.017) without increased resource utilization (LOS 20.8 ± 15.6 days vs 19.6 ± 17.0, p = 0.281) during the 17-year study period. Mahalanobois-matched cohorts demonstrated a volume-value relationship (higher value care with better outcomes and decreased resource utilization) in the 0 to 4 age group, but not in older recipients (Table). The 0 to 4 age group comprised the largest proportion of status 1B patients (20.8%, p < 0.001) and the highest utilization rate of partial liver allografts (40.9%, p < 0.001). CONCLUSION: There is value in liver transplant volume in very young (0 to 4 years) pediatric patients. Given improved survival of these patients in higher-volume centers, regionalization of care may benefit this specific population of recipients. Table. - Matched Comparison of Length of Stay and 1-Year Graft Survival after Liver Transplant 1-year graft survival Small (%) Large (%) p Value Pediatric 0–4 y 87.1% 94.7% 0.011 Pediatric 5–11 y 92.0% 95.9% 0.252 Pediatric 12–18 y 92.4% 90.8% 0.704 Length of stay, days Small, mean (SD) Large, mean (SD) Pediatric 0–4 y 28.29 (22.8) 22.40 (14.8) 0.003 Pediatric 5–11 y 16.05 (12.6) 18.57 (13.8) 0.182 Pediatric 12–18 y 13.67 (12.3) 19.87 (15.0) 0.003

Living donor liver transplantation

Lymphoproliferative disorders after liver transplantation

Pediatric liver transplant is a life-saving procedure, but risks remain for children in the pre-, peri-, and post-transplant period-impacting survival, graft, and child health, and quality of life. Learning health networks offer a structure that multi-disciplinary teams across many centers can use to collaborate on improving outcomes for children with rare diseases-with a mantra of "sharing seamlessly" to coordinate across centers and "stealing shamelessly" from best practices within or outside of the network. We describe the development of the Starzl Network for Excellence in Pediatric Transplantation (SNEPT) as a learning health network dedicated to improving health and quality of life for children with liver transplants and their families. SNEPT was founded in 2017 as a collaborative effort between pediatric liver transplant centers and the families that they serve, initially at 10 and then 16 centers across the US and Canada. Stakeholders identified four priority projects: Peri-Operative and Surgical Practices, Optimizing Immunosuppression, Quality of Life, and Transition of Care. Over the last 8 years, we built SNEPT infrastructure to efficiently support work on each project. Our four working groups each developed methods to improve practice by sharing protocols, data, and experience between centers and adapting best-practice strategies from other centers for efficient improvement. Coordination as a learning health network has improved transparency and enhanced collaboration between SNEPT centers, creating opportunities for best-practices development and better outcomes in pediatric liver transplant.

Learning health systems (LHS) integrate research, improvement, management, and patient care, such that every child receives "the right care at the right time...every time," that is, evidence-based, personalized medicine. Here, we report our efforts to establish a sustainable, productive, multicenter LHS focused on pediatric liver transplantation. The Starzl Network for Excellence in Pediatric Transplantation (SNEPT) is the first multicenter effort by pediatric liver transplant families and providers to develop shared priorities and a shared agenda for innovation in clinical care. This report outlines SNEPT's structure, accomplishments, and challenges as an LHS. We prioritized 4 initial projects: immunosuppression, perioperative anticoagulation, quality of life, and transition of care. We shared center protocols/management to identify areas of practice variability between centers. We prioritized actionable items that address barriers to providing "the right care at the right time" to every pediatric liver transplant recipient: facilitating transparency of practice variation and the connection of practices to patient outcomes, harnessing existing datasets to reduce the burden of tracking outcomes, incorporating patient-reported outcomes into outcome metrics, and accelerating the implementation of knowledge into clinical practice. This has allowed us to strengthen collaborative relationships, design quality improvement projects, and collect pilot data for each of our priority projects. The field of pediatric liver transplantation can be advanced through application of LHS principles. Going forward, SNEPT will continue to unite patient advocacy, big data, technology, and transplant thought leaders to deliver the best care, while developing new, scalable solutions to pediatric transplantation's most challenging problems.

Racial and socioeconomic disparities exist in liver transplantation (LT) outcomes among adults, but little research exists for pediatric LT populations. We examined racial differences in graft survival and mortality within a retrospective cohort of pediatric and young adult LT recipients at a large children's transplant center in the Southeast between 1998 and 2011. The association between race/ethnicity and rates of graft failure and mortality was examined with Cox proportional hazards models that were adjusted for demographic and clinical factors as well as individual-level and census tract-level socioeconomic status (SES). Among the 208 LT recipients, 51.0% were white, 34.6% were black, and 14.4% were other race/ethnicity. Graft survival and patient survival were higher for whites versus minorities 1, 3, 5, and 10 years after transplantation. The 10-year graft survival rates were 84% [95% confidence interval (CI) = 76%-91%] for white patients, 60% (95% CI = 46%-74%) for black patients, and 49% (95% CI = 23%-77%) for other race/ethnicity patients. The 10-year patient survival rates were 92% (95% CI = 84%-96%), 65% (95% CI = 52%-79%), and 76% (95% CI = 54%-97%) for the white, black, and other race/ethnicity groups, respectively. In analyses adjusted for demographic, clinical, and socioeconomic characteristics, the rates of graft failure [black: hazard ratio (HR) = 2.59, 95% CI = 1.29-5.45; other: HR = 3.01, 95% CI = 1.23-7.35] and mortality (black: HR = 4.24, 95% CI = 1.54-11.69; other: HR = 3.09, 95% CI = 0.78-12.19) were higher for minority groups versus whites. In conclusion, at a large pediatric transplant center in the Southeastern United States, racial/ethnic disparities exist in pediatric and young adult LT outcomes that are not fully explained by measured SES and clinical factors.

Transfusion-Free Surgical Program Reduces Use of Blood Products for Patients Undergoing Liver Transplantation

Immunosuppression is paramount to prevent acute rejection in solid organ transplant but also poses a risk for infection and malignancy. Identifying factors that influence rejection may allow for personalization of treatment and avoidance of an unnecessary degree of immunosuppression for the vulnerable pediatric population. We conducted a retrospective review analyzing public data provided by the Organ Procurement and Transplantation Network for pediatric patients listed for solid organ transplantation (kidney, liver, lung, and heart) from March 1998 to December 2022. Univariate and multivariate logistic regression was used to identify independent risk factors for treated acute rejection at 6 months and/or 1 year for liver, lung, kidney, and heart transplants. The study population consisted of the following pediatric patients for each organ studied: liver (n = 8993), lung (n = 846), heart (n = 7118), and kidney (n = 14 600). At 1 year, 28.4% and 31.7% of males and females, respectively, were treated for rejection in liver transplant, 24.1% and 34.5%, respectively, for lung, 14.8% and 16.2%, respectively, for kidney, and 25.2% for both in heart transplant. In multivariate analysis, male recipient status was a statistically significant protective factor against rejection in liver transplant, OR = 0.85 (p < 0.001), lung transplant, OR = 0.61 (p = 0.004), and kidney transplant, OR = 0.91 (p = 0.040), but not heart transplant, OR = 0.96 (p = 0.460). Our study demonstrates that pediatric males may have a lower risk of acute rejection in liver, lung, and kidney transplant yet not in heart transplant. These findings may have implications for the level of maintenance immunosuppression for pediatric male transplant recipients.

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Johnny C. HongJohnny C. HongJohnny C. Hong, MD, FACS, is Associate Professor of Surgery and holds the inaugural Mark Adams Chair in Surgery at the Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Dr Hong also serves as Director, Solid Organ Transplantation Service Line; a joint program of Froedtert & Medical College of Wisconsin, USA, Children's Hospital of Wisconsin, USA, and Blood Center of Wisconsin, USA. In this position, Dr Hong oversees the liver, kidney, pancreas, heart, and lung transplantation programs for both adults and children. Dr Hong completed a general surgery residency as well as an immunology and organ transplantation fellowship at the University of Texas Houston Health Science Center, Houston, Texas, USA. He also obtained additional fellowship training in multi-organ transplantation and hepatobiliary surgery at the University of California, Los Angeles (UCLA), USA. Prior to his recruitment to the Medical College of Wisconsin, he served as associate professor of surgery and program director of the multi-organ transplantation and hepatobiliary surgery fellowship program at UCLA. Dr Hong is internationally known for his expertise in all aspects of abdominal transplantation and hepatobiliary surgery, especially adult and pediatric liver transplantation including split liver and live donor liver transplantation. He is recognized for his expertise in the surgical management of benign and malignant liver and bile duct diseases and tumors. Dr Hong's professional career has been devoted to advancing the care of patients with end stage liver disease and surgical diseases involving the liver and bile duct. He is widely published in the peer-reviewed literature and maintains a research laboratory studying ways to improve graft function and treat reperfusion injury. His innovative work on liver resuscitation through regulated hepatic reperfusion has great potential for clinical application in human liver surgery and transplantation. In addition, Dr Hong is an active member of national and international surgical and transplantation societies and has held key leadership positions at these national and international organizations. Marc R. HammermanMarc R. HammermanDr Marc R. Hammerman is the Chromalloy Professor of Renal Diseases in Medicine at Washington University School of Medicine, USA. For the past 24 years he has served as Director of the Washington University Renal Division in the Department of Internal Medicine. He is Nephrologist in Chief at Barnes Jewish Hospital in St. Louis Missouri, USA. Dr Hammerman, a native of St. Louis, was born at Barnes Hospital, the institution at which he has spent his entire professional career. He is a graduate of Washington University and its school of medicine, trained in internal medicine at the former Barnes Hospital/Washington University and at Massachusetts General Hospital/Harvard, USA, in endocrinology and metabolism at Baltimore City Hospital/Johns Hopkins, USA, and later at Washington University, and served in the United States Public Health Service Commissioned Corps at the National Institutes of Health. Dr Hammerman's research is directed towards the development of a technology for ‘growing’ new organs in situ using transplanted embryonic organ primordia from animal embryos as starting material (organogenesis). The goal of his work is to develop novel replacement therapies for end-stage renal disease and transplantation therapies for types 1 and 2 diabetes mellitus. In this regard, he has successfully pioneered growing renal and endocrine pancreas replacement organs in situ after transplantation of precursor organs from embryonic pigs into rats and into non-human primates. He is the inventor for several patents in the field of renal and pancreatic organogenesis. Dr Hammerman is a member of Alpha Omega Alpha, the American Society of Clinical Investigation, the Association of American Physicians, Phi Beta Kappa and Sigma Xi and was recognized as an Established Investigator of the American Heart Association. Dr Hammerman has published more than 200 original manuscripts, reviews and book chapters and has spoken at more than 100 national and international venues. Kathy L. CoffmanKathy L. CoffmanDr Kathy L. Coffman is an attending psychiatrist at the Cleveland Clinic Foundation, USA. She attended Wayne State School of Medicine, USA, and completed an internship in internal medicine at Michael Reese Hospital in Chicago, USA, and a psychiatry residency at University of Chicago, USA. She also completed a two-year fellowship in consultation liaison psychiatry at University of Michigan. She is board certified in Addiction Psychiatry, Geriatric Psychiatry and Psychosomatic Medicine. She has been involved with the field of transplant psychiatry since her residency over the last twenty years. Dr Coffman's research interests include maintaining sobriety in alcoholic liver transplant recipients, HIV, and psychological issues in lung disease. She is a current member of the psychiatry committee for the National Board of Psychiatry and Neurology for development of test questions for the US Medical Licensing Examination. She has been involved in grant review for the National Institute of Mental Health, and has been a reviewer for Psychomatics and other journals.

Tacrolimus is beneficial in liver transplantation for reversing steroid-resistant acute rejection, and for controlling the process of chronic rejection in allograft recipients receiving Cyclosporine- (CyA) based regimens. Very little is known about the long-term efficacy of tacrolimus in pediatric transplantation after conversion from CyA. Our study examines the long-term outcome after conversion to tacrolimus for acute or chronic rejection in pediatric liver transplant (LTx) recipients. Seventy-three children (age < 18 years) receiving their primary LTx under CyA between August 1989 and April 1996 were converted to tacrolimus for ongoing acute rejection (n=22, group I) or chronic rejection (n=51, group II). Mean age at the time of conversion was 10.2+/-5.5 years with a mean interval from LTx to conversion of 3.5+/-2.9 (range 0.5-10.1 years). There were 33 boys and 40 girls. All patients were followed until June 1999. Mean follow-up was 97.3+/-17.4 months (range 62.4-118.9 months). Overall 5-year actual patient survival was 78.1% and 8-year actuarial survival was 74.6%. Patients converted to tacrolimus therapy to resolve acute rejection (group I) experience significantly better patient and graft survival at 5 and 8 years than those converted to resolve chronic rejection (group II). Eight-year patient survival and graft survival was 95.5 and 90.9% for group I compared to 74.6 and 53.5% for group II, respectively (long rank P=0.035 and 0.01, respectively). Nearly 75% of children were weaned off steroids after conversion. There was a marked improvement in hypertension, gum hyperplasia, hirsutism, and cushingoid appearance. One child in group I (4.5%) and four children in group II (7.8%) developed posttransplant lymphoproliferative disorder after conversion. There was an improvement in growth in children who were less than the age of 12 years at the time of conversion and who were weaned off steroids; more significantly girls responded more favorably than boys. The benefit of transplantation is maintained long-term after conversion to tacrolimus for acute or chronic rejection. The response rate was significantly better in group I as compared with group 11. Marked improvement in growth, hypertension, and reversal of the brutalizing effects of CyA was noted after conversion to tacrolimus. The results suggest that early conversion of pediatric liver transplant patients is warranted for the treatment of acute and chronic rejection, and for improvements in quality of life.

Not everything that counts can be counted: Tracking long-term outcomes in pediatric liver transplant recipients

Systemic lupus erythematosus in a 15-year-old with graft-versus-host disease following liver transplant and unexpected full hematopoietic engraftment