1
|
Hanami Y, Kimura S, Suga T, Okamoto T, Ogawa E, Ashina K, Nakamura N, Kai S, Okajima H, Hatano E, Egi M, Takita J. Postoperative fluid balance and outcomes in pediatric living-donor liver transplant recipients: a retrospective cohort study. J Anesth 2025:10.1007/s00540-025-03515-9. [PMID: 40411562 DOI: 10.1007/s00540-025-03515-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Accepted: 05/06/2025] [Indexed: 05/26/2025]
Abstract
PURPOSE This study aimed to investigate the relationship between postoperative fluid balance (FB) and clinical outcomes in pediatric living-donor liver transplant (LDLT) recipients. METHODS This retrospective study was conducted at a tertiary care center. Patients aged ≤ 18 years who underwent LDLT between January 2010 and September 2023 were included. Postoperative FB was calculated as [(total fluid intake-total fluid output) / body weight] × 100 for 48 h. Patients were categorized into four groups: < 5%, 5-10%, 10-15%, and ≥ 15% FB. The primary outcome was ventilator-free days (VFD) within 30 days post-transplantation. Secondary outcomes included acute kidney injury (AKI), reintubation, hepatic arterial thrombosis, acute rejection, primary graft dysfunction, intensive care unit (ICU) length of stay (LOS), and mortality. RESULTS The study included 200 patients with a median weight of 9.0 (interquartile range [IQR]: 6.9-19.3) kg. Median VFD did not significantly differ across the FB groups: < 5% FB, 29.3 (IQR, 28.3-29.4) days; 5-10% FB, 29.3 (IQR, 28.3-29.4) days; 10-15% FB, 29.3 (IQR, 28.3-29.4) days; and ≥ 15% FB, 27.4 (IQR, 23.3-29.4) days (p = 0.27). However, multivariable analysis showed ≥ 15% FB was associated with 4.59 days shorter VFD (p = 0.004) and higher AKI incidence (odds ratio: 6.60, p = 0.012). Thrombosis occurred in 7 patients (3.5%) with no significant differences among groups (p = 0.61). Other secondary outcomes showed no significant differences. CONCLUSION Excessive postoperative FB (≥ 15%) in pediatric LDLT recipients was significantly associated with reduced VFD and increased AKI incidence, whereas other adverse outcomes were not significantly affected.
Collapse
Affiliation(s)
- Yotaro Hanami
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Kimura
- Department of Anesthesiology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Takenori Suga
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tatsuya Okamoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Eri Ogawa
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kazushige Ashina
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Natsumi Nakamura
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinichi Kai
- Department of Anesthesiology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hideaki Okajima
- Department of Pediatric Surgery, Kanazawa Medical University, Ishikawa, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Moritoki Egi
- Department of Anesthesiology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Junko Takita
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| |
Collapse
|
2
|
Alqahtani SA, Shpoliansky M, Vandriel SM, Johara F, Quammie C, Lurz E, Alonso EM, Daniel JF, Venkat VL, Leung DH, Economides J, Hsu EK, Loomes KM, Gupta NA, Mannino D, Menendez J, Ng VL, Kamath BM. Frailty in Pediatric Liver Disease May Be Associated With an Increased Incidence of Readmissions After Pediatric Liver Transplantation. Pediatr Transplant 2025; 29:e70077. [PMID: 40230032 DOI: 10.1111/petr.70077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 03/24/2025] [Accepted: 03/27/2025] [Indexed: 04/16/2025]
Abstract
BACKGROUND Frailty is a phenotype of cumulative decline leading to decreased physiologic reserve and vulnerability to stressors. Frailty is associated with adverse outcomes after liver transplantation (LT) in adults, but similar data are not available in children. A prospective multicenter study previously determined that frailty is present in 46% of children with end-stage liver disease (ESLD). We utilized this cohort to evaluate the impact of pre-transplant frailty on post-LT outcomes. METHODS The study included pediatric participants from the original frailty study across 10 North American transplant centers who had subsequently undergone LT. Clinical outcomes were collected up to 1 year post LT. Participants were stratified by their pre-transplant frailty score (defined by a pre-LT frailty score of ≥ 6.0) and long-term outcomes were compared between groups. RESULTS 28 (60.7% female, 46.4% biliary atresia) pediatric LT recipients were included, and 54% of children met criteria for frailty (n = 15). Baseline characteristics were comparable between groups; however, those with frailty were significantly more likely to have pre-transplant failure to thrive (33.3% vs. 0%, p = 0.044). Thirty-four hospital readmissions (22 in frail and 12 in non-frail children) occurred in 20 patients. Higher pre-transplant frailty scores were also significantly associated with an increased number of readmissions after transplantation (p = 0.034). CONCLUSIONS Pediatric frailty may be associated with the adverse outcome of increased frequency of hospitalization in the first year after pediatric liver transplantation. These data support the concept that frail children should be identified and targeted for prehabilitation prior to LT.
Collapse
Affiliation(s)
- Saleh A Alqahtani
- Department of Pediatrics, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Michael Shpoliansky
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
- Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Shannon M Vandriel
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Fatema Johara
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Claudia Quammie
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Eberhard Lurz
- Department of Pediatrics, Division of Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, University Hospital, LMU, Munich, Germany
| | - Estella M Alonso
- Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
| | - James F Daniel
- Division of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, Missouri, USA
| | - Veena L Venkat
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Daniel H Leung
- Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Julie Economides
- Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Evelyn K Hsu
- Division of Gastroenterology and Hepatology, University of Washington-Seattle Children's Hospital, Seattle, Washington, USA
| | - Kathleen M Loomes
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nitika A Gupta
- Division of Gastroenterology, Hepatology and Nutrition, Children's Healthcare of Atlanta Emory University School of Medicine, Atlanta, Georgia, USA
| | - Dana Mannino
- Division of Solid Organ Transplantation, Nemours Children's Hospital, Wilmington, Delaware, USA
| | - Jerome Menendez
- Division of Pediatric Gastroenterology, Levine Children's Hospital Carolinas Health Care Center, Charlotte, North Carolina, USA
| | - Vicky L Ng
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
- Transplant and Regenerative Medicine Centre, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Binita M Kamath
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| |
Collapse
|
3
|
Hwang CS, Aqul AA, Kwon YK. Expanding pediatric liver transplants: the role of split grafts, allocation policies, and machine perfusion. Curr Opin Organ Transplant 2025:00075200-990000000-00174. [PMID: 40173002 DOI: 10.1097/mot.0000000000001220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2025]
Abstract
PURPOSE OF REVIEW Pediatric liver transplant waitlist mortality remains disproportionately high, particularly among infants under one year old. Despite the success of split liver transplantation (SLT) in improving pediatric access to transplants, its utilization remains limited. This review examines barriers to SLT adoption, explores the impact of pediatric-focused allocation policies, and evaluates the potential of machine perfusion technology in expanding the pediatric donor pool. RECENT FINDINGS Studies have demonstrated that SLT outcomes are comparable to whole graft transplants when performed at experienced centers. However, logistical challenges, technical expertise, and policy limitations hinder its widespread adoption. Countries with pediatric-prioritized allocation and mandatory SLT policies, such as Italy and the United Kingdom, have significantly reduced pediatric waitlist mortality. Additionally, machine perfusion technology has emerged as a promising solution, allowing for ex vivo graft splitting and reducing ischemic injury, which may enhance graft utilization. SUMMARY A multifaceted approach is necessary to improve pediatric liver transplant outcomes, including stronger pediatric-first allocation policies, SLT training expansion, and integration of machine perfusion technologies. Implementing these strategies in the United States could significantly reduce pediatric waitlist mortality without negatively impacting adult transplant candidates.
Collapse
Affiliation(s)
- Christine S Hwang
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center
- Division of Pediatric Transplantation, Children's Medical Center
| | - Amal A Aqul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Texas Southwestern, Dallas, Texas, USA
| | - Yong Kyong Kwon
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center
- Division of Pediatric Transplantation, Children's Medical Center
| |
Collapse
|
4
|
Donnelly C, Patel SS, Jaffe IS, Akizhanov D, Chiang TPY, Long JJ, Liyanage L, Griesemer A, Segev DL, Massie AB. Association of Functional, Academic, Motor, and Cognitive Deficits in Graft Failure in Pediatric Liver Transplantation. Clin Transplant 2025; 39:e70132. [PMID: 40152814 DOI: 10.1111/ctr.70132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 02/03/2025] [Accepted: 03/02/2025] [Indexed: 03/29/2025]
Abstract
INTRODUCTION Predicting graft failure risk in pediatric liver transplantation (LT) recipients could identify areas for improving management. Persistent cognitive, motor, academic, and functional deficits are common in recipients and their impact on graft survival following LT helps inform risk prediction. METHODS Using SRTR data 2008-2023, we evaluated the cognitive, motor, academic, and functional deficits of LT recipients at time of transplant to 14 years post-LT. We compared all cause graft failure (ACGF) among patients with versus without pre-LT and 1-year post-LT deficits using Cox regression, adjusting for recipient characteristics. We calculated an individual risk score for ACGF. RESULTS In 8062 pediatric LT recipients median age 3 (IQR: 1, 10), 28.0%, 29.5%, 35.0%, and 79.8% of recipients had pre-LT deficits in cognition, motor, academic activity, and functional status respectively. This decreased to 23.0%, 18.1%, 14.2%, and 38.7% 1-year post-LT. Increased hazard of ACGF was noted in recipients with pre-LT decreased functional status (aHR = 1.13 (per 10% decrease), 95% CI: 1.10-1.15, p < 0.001), definite motor delay (aHR = 1.60, 95% CI: 1.21-2.10, p < 0.001), and inability to participate in academics (aHR = 1.49, 95% CI: 1.08-1.89, p = 0.01), but not delays in cognition (aHR = 0.91, 95% CI: 0.69-1.21, p = 0.19). Our risk score predicting ACGF demonstrated improved predictive performance compared to clinical parameters alone (C-statistic = 0.70 (0.67, 0.72) vs. 0.66 (0.64, 0.69), p < 0.001). CONCLUSIONS Pediatric LT recipients with pre- or post-LT motor, academic, and functional deficits are at higher risk for ACGF. Care should be taken to assess deficits to identify patients who may benefit from functional intervention to potentially reduce ACGF risk.
Collapse
Affiliation(s)
- Conor Donnelly
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Suhani S Patel
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Ian S Jaffe
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Daniyar Akizhanov
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Teresa Po-Yu Chiang
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Jane J Long
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Luckmini Liyanage
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Adam Griesemer
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Dorry L Segev
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
- Scientific Registry of Transplant Recipients, Minneapolis, Minnesota, USA
| | - Allan B Massie
- Department of Surgery, Transplant Institute, NYU Langone Health, New York, New York, USA
| |
Collapse
|
5
|
Sun X, Sun X, Zhou T, Li P, Wang B, Pan Q, Zhou A, Qian Y, Liu Y, Liu Y, Xia Q. Long-term outcomes and risk factors for early bacterial infection after pediatric liver transplantation: a prospective cohort study. Int J Surg 2024; 110:5452-5462. [PMID: 38833358 PMCID: PMC11392112 DOI: 10.1097/js9.0000000000001670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 05/09/2024] [Indexed: 06/06/2024]
Abstract
BACKGROUND Liver transplantation (LT) is the most efficient treatment for pediatric patients with end-stage liver diseases, while bacterial infection is the leading reason for post-transplant mortality. The present study is to explore the outcomes and risk factors of early bacterial infection (within 1 months) after pediatric LT. METHODS In this prospective cohort study, 1316 pediatric recipients [median (IQR) age: 9.1 (6.3-28.0) months; male: 48.0%; median (IQR) follow-up time: 40.6 (29.1-51.4) months] who received LT from September 2018 to April 2022 were included. Bacterial culture samples such as sputum, abdominal drainage, blood, and so on were collected when recipients were presented with infective symptoms. Kaplan-Meier analysis was applied to estimate the long-term survival rates and logistic regression was used to identify independent risk factors. To explore the role of pretransplant rectal swab culture (RSC) in reducing post-transplant bacterial infection rate, 188 infant LT recipients [median (IQR) age: 6.8 (5.5-8.1) months; male: 50.5%] from May 2022 to September 2023 were included. Log-binomial regression was used to measure the association of pretransplant RSC screening and post-transplant bacterial infection. The 'Expectation Maximization' algorithm was used to impute the missing data. RESULTS Bacterial infection was the primary cause for early (38.9%) and overall mortality (35.6%) after pediatric LT. Kaplan-Meier analysis revealed inferior 1-year and 5-year survival rates for recipients with post-transplant bacterial infection (92.6 vs. 97.1%, 91.8 vs. 96.4%, respectively; P <0.001). Among all detected bacteria, Staphylococcus spp. (34.3%) and methicillin-resistant coagulase-negative Staphylococci (43.2%) were the dominant species and multidrug resistant organisms, respectively. Multivariable analysis revealed that infant recipients [adjusted odds ratio (aOR) 1.49; 95% CI: 1.01-2.20], male recipients (aOR, 1.43; 95% CI: 1.08-1.89), high graft-to-recipient weight ratio (aOR, 1.64; 95% CI: 1.17-2.30), positive post-transplant RSC (aOR, 1.45; 95% CI: 1.04-2.02) and nasopharyngeal swab culture (aOR 2.46; 95% CI: 1.72-3.52) were independent risk factors for early bacterial infection. Furthermore, RSC screening and antibiotic prophylaxis before transplantation could result in a relatively lower post-transplant infection rate, albeit without statistical significance (adjusted RR, 0.53; 95% CI: 0.25-1.16). CONCLUSION In this cohort study, post-transplant bacterial infection resulted in an inferior long-term patient survival rate. The five identified independent risk factors for post-transplant bacterial infection could guide the prophylaxis strategy of post-transplant bacterial infection in the future. Additionally, pretransplant RSC might decrease post-transplant bacterial infection rate.
Collapse
Affiliation(s)
- Xicheng Sun
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
| | - Xiaowei Sun
- Clinical Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine
| | - Tao Zhou
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
| | - Peiying Li
- Clinical Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine
| | - Bingran Wang
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
| | - Qi Pan
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
| | - Aiwei Zhou
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
| | - Yongbing Qian
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
| | - Yongbo Liu
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Shanghai Institute of Transplantation
| | - Yuan Liu
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Shanghai Immune Therapy Institute
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Shanghai Institute of Transplantation
- Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai, People's Republic of China
| |
Collapse
|
6
|
Hartjes K, Koo D, Al-Ibraheemi A, Sweeny KF, Wehrman A, Elisofon S, Lee CK, Cuenca AG, Kim HB, Lee EJ. Early Graft Loss With Suspected Seventh-Day Syndrome Following Pediatric Liver Transplantation. Pediatr Transplant 2024; 28:e14818. [PMID: 38940480 DOI: 10.1111/petr.14818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 06/10/2024] [Accepted: 06/14/2024] [Indexed: 06/29/2024]
Abstract
INTRODUCTION Allograft dysfunction within the first week posttransplant is an uncommon but known complication following liver transplantation. Seventh-Day Syndrome (7DS) is a rare complication of allograft dysfunction following liver transplantation characterized by the rapid clinical deterioration of a formerly well-functioning allograft within the first week posttransplant. The etiology of 7DS is unknown, and treatment options remain limited. While cases of graft survival have been reported, the risk of mortality remains exceedingly high without urgent retransplantation. METHODS Patient data was retrospectively analyzed and a literature review performed. RESULTS We present a unique case of split liver transplantation into two pediatric recipients in which one recipient developed rapidly progressive graft failure approximately 1 week postoperatively requiring urgent retransplantation while the other recipient had an unremarkable postoperative course. Upon clinical manifestation of progressive graft failure, the patient was treated with thymoglobulin, rituximab, intravenous immunoglobulin, and plasmapheresis. Despite this, the patient's clinical status continued to decline and she underwent retransplantation 11 days following her initial liver transplant. CONCLUSION Seventh-Day Syndrome is a rare complication following liver transplantation that is associated with a high risk of morbidity and mortality. Our case adds to the limited literature on 7DS in children and is the first to report a comparative posttransplant clinical course in two recipients who received split grafts from the same donor.
Collapse
Affiliation(s)
- Kayla Hartjes
- Division of Gastroenterology, Hepatology, & Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Donna Koo
- Department of Surgery, Pediatric Transplant Center, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Alyaa Al-Ibraheemi
- Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Katherine F Sweeny
- Division of Gastroenterology, Hepatology, & Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Andrew Wehrman
- Division of Gastroenterology, Hepatology, & Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Scott Elisofon
- Division of Gastroenterology, Hepatology, & Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Christine K Lee
- Division of Gastroenterology, Hepatology, & Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Alex G Cuenca
- Department of Surgery, Pediatric Transplant Center, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Heung Bae Kim
- Department of Surgery, Pediatric Transplant Center, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Eliza J Lee
- Department of Surgery, Pediatric Transplant Center, Boston Children's Hospital, Boston, Massachusetts, USA
| |
Collapse
|
7
|
Wells J, Shah A, Gillis H, Gustafson S, Powell C, Krasaelap A, Hanna S, Hoefert JA, Bigelow A, Sherwin J, Lewis EC, Bline KE. Tiny patients, huge impact: a call to action. Front Public Health 2024; 12:1423736. [PMID: 38952729 PMCID: PMC11215126 DOI: 10.3389/fpubh.2024.1423736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 06/06/2024] [Indexed: 07/03/2024] Open
Abstract
The continuation of high-quality care is under threat for the over 70 million children in the United States. Inequities between Medicaid and Medicare payments and the current procedural-based reimbursement model have resulted in the undervaluing of pediatric medical care and lack of prioritization of children's health by institutions. The number of pediatricians, including pediatric subspecialists, and pediatric healthcare centers are declining due to mounting financial obstacles and this crucial healthcare supply is no longer able to keep up with demand. The reasons contributing to these inequities are clear and rational: Medicaid has significantly lower rates of reimbursement compared to Medicare, yet Medicaid covers almost half of children in the United States and creates the natural incentive for medical institutions to prioritize the care of adults. Additionally, certain aspects of children's healthcare are unique from adults and are not adequately covered in the current payment model. The result of decades of devaluing children's healthcare has led to a substantial decrease in the availability of services, medications, and equipment needed to provide healthcare to children across the nation. Fortunately, the solution is just as clear as the problem: we must value the healthcare of children as much as that of adults by increasing Medicaid funding to be on par with Medicare and appreciate the complexities of care beyond procedures. If these changes are not made, the high-quality care for children in the US will continue to decline and increase strain on the overall healthcare system as these children age into adulthood.
Collapse
Affiliation(s)
- Jordee Wells
- Department of Pediatrics, Division of Emergency Medicine, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, United States
| | - Anita Shah
- Division of Hospital Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
| | - Holly Gillis
- Department of Anesthesiology, Division of Pediatric Anesthestiology, University of Minnesota, Minneapolis, MN, United States
| | - Sarah Gustafson
- Division of Pediatric Hospital Medicine, Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
| | - Carmin Powell
- Division of Pediatric Hospital Medicine, Stanford University School of Medicine, Stanford, CA, United States
| | - Amornluck Krasaelap
- Department of Gastroenterology and Hepatology, SeattleChildren’s Hospital, Seattle, WA, United States
| | - Samantha Hanna
- Saint Louis University School of Medicine, SSM Health Cardinal Glennon Children's Hospital, St. Louis, MO, United States
| | - Jennifer A. Hoefert
- Saint Louis University School of Medicine, SSM Health Cardinal Glennon Children's Hospital, St. Louis, MO, United States
| | - Amee Bigelow
- The Heart Center, Nationwide Children’s Hospital, Columbus, OH, United States
| | - Jennifer Sherwin
- Division of Cardiovascular and Thoracic Surgery,Duke University Medical Center, Durham, NC, United States
| | - Emilee C. Lewis
- Division of Hospital Pediatrics, Department of Pediatrics,University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Katherine E. Bline
- Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, United States
| |
Collapse
|
8
|
Zhou AW, Jin J, Liu Y. Cellular strategies to induce immune tolerance after liver transplantation: Clinical perspectives. World J Gastroenterol 2024; 30:1791-1800. [PMID: 38659486 PMCID: PMC11036497 DOI: 10.3748/wjg.v30.i13.1791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 02/03/2024] [Accepted: 03/14/2024] [Indexed: 04/03/2024] Open
Abstract
Liver transplantation (LT) has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management. However, long-term side-effects of immunosuppressants, like infection, metabolic disorders and malignant tumor are gaining more attention. Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants, but the liver function and intrahepatic histology maintain normal. The approaches to achieve immune tolerance after transplantation include spontaneous, operational and induced tolerance. The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up. No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation. With the understanding to the underlying mechanisms of immune tolerance, many strategies have been developed to induce tolerance in LT recipients. Cellular strategy is one of the most promising methods for immune tolerance induction, including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells. The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials, while obstacles still exist before translating into clinical practice. Here, we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.
Collapse
Affiliation(s)
- Ai-Wei Zhou
- Department of Liver Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Jing Jin
- Department of Nursing, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Yuan Liu
- Department of Liver Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- Department of Liver Transplantation, Shanghai Immune Therapy Institute, Shanghai 200127, China
| |
Collapse
|
9
|
Kim PH, Yoon HM, Jung AY, Lee JS, Cho YA, Oh SH, Namgoong JM. Diagnostic accuracy of CT and Doppler US for hepatic outflow obstruction after pediatric liver transplantation using left lobe or left lateral section grafts. Ultrasonography 2024; 43:110-120. [PMID: 38369738 PMCID: PMC10915118 DOI: 10.14366/usg.23190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 12/22/2023] [Accepted: 01/11/2024] [Indexed: 02/20/2024] Open
Abstract
PURPOSE The aim of this study was to evaluate diagnostic accuracy and to establish computed tomography (CT) and Doppler ultrasonography (US) criteria for hepatic outflow obstruction after pediatric liver transplantation (LT) using left lobe (LL) or left lateral section (LLS) grafts. METHODS Pediatric patients who underwent LT using LL or LLS grafts between January 1999 and December 2021 were retrospectively included. The diagnostic performance of Doppler US and CT parameters for hepatic outflow obstruction was calculated using receiver operating characteristic (ROC) curve analysis. A diagnostic decision tree model combining the imaging parameters was developed. RESULTS In total, 288 patients (150 girls; median age at LT, 1.8 years [interquartile range, 0.9 to 3.6 years]) were included. Among the Doppler US parameters, venous pulsatility index (VPI) showed excellent diagnostic performance (area under the ROC curve [AUROC], 0.90; 95% confidence interval [CI], 0.86 to 0.93; Youden cut-off value, 0.40). Among the CT parameters, anastomotic site diameter (AUROC, 0.92; 95% CI, 0.88 to 0.95; Youden cut-off, 4.2 mm) and percentage of anastomotic site stenosis (AUROC, 0.88; 95% CI, 0.84 to 0.92; Youden cut-off, 35%) showed excellent and good diagnostic performance, respectively. A decision tree model combining the VPI, peak systolic velocity, and percentage of anastomotic site stenosis stratified patients according to the risk of hepatic outflow obstruction. CONCLUSION VPI, anastomotic site diameter, and percentage of anastomotic site stenosis were reliable imaging parameters for diagnosing hepatic outflow obstruction after pediatric LT using LL or LLS grafts.
Collapse
Affiliation(s)
- Pyeong Hwa Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Mang Yoon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ah Young Jung
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Seong Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Ah Cho
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seak Hee Oh
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung-Man Namgoong
- Department of Pediatric Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
10
|
Abstract
В педиатрической практике трансплантация фрагментов печени позволяет достичь высоких результатов [Bowring M.G., 2020] и, при этом, полностью гарантировать безопасность родственных доноров. В то же время, при выполнении трансплантации «взрослый – ребенок», практически отсутствуют этические вопросы, поскольку, чаще всего, донором является один из родителей реципиента. Тем не менее, важной задачей остается создание условий для ускорения реабилитации и минимизации хирургической травмы у донора, в этой связи, внедрение миниинвазивных методов имеет особое значение.
В последние два десятилетия миниинвазивные подходы к резекциям печени прочно вошли в арсенал крупных гепатобилиарных центров. Это стало возможным благодаря накопленному опыту открытой хирургии печени, а также технологическому прогрессу [Morise Z., 2017]. Однако, применение лапароскопического подхода у родственных доноров фрагментов печени по-прежнему остается предметом живого интереса в трансплантологических центрах всего мира. Первые сравнительные исследования оказались весьма обнадеживающими и продемонстрировали перспективность этого подхода [Broering D. C., 2018]. Накопление подобного опыта, анализ кривой обучения, стандартизация хирургической техники по-прежнему являются важными вопросами развития данного направления.
В России лапароскопическое изъятие фрагмента печени для последующей трансплантации было впервые выполнено в ФГБУ «НМИЦ ТИО им. Академика В. И. Шумакова» в 2016 году. Также, в России впервые в мире произведено полностью лапароскопическое изъятие одновременно фрагмента печени и почки для последующей трансплантации детям [Готье С. В., 2016, Gautier S. V., 2019].
Цель исследования.
Оптимизация хирургической техники и результатов лапароскопического изъятия левого латерального сектора у прижизненных доноров фрагмента печени на основании анализа накопленного опыта.
Задачи исследования.
1. Сравнить результаты открытого и лапароскопического изъятия левого латерального сектора у прижизненных доноров.
2. Определить критерии селекции прижизненных доноров для лапароскопического изъятия левого латерального сектора печени.
3. Стандартизировать хирургическую технику выполнения лапароскопической латеральной секторэктомии печени.
4. Оценить результаты трансплантации левого латерального сектора, полученного открытым и лапароскопическим путём, у реципиентов.
5. Изучить кривую обучения выполнения лапароскопической латеральной секторэктомии печени у родственного донора.
Научная новизна.
На сегодняшний день, лапароскопическое изъятие левого латерального сектора печени у прижизненных доноров выполняется лишь в нескольких центрах в мире. Суммарный накопленный опыт по всему миру не превышает 500 операций. В настоящее время, по данным литературы, существует лишь несколько исследований, посвященных данной тематике. Проведение псевдорандомизации позволило объективизировать результаты и увеличить их достоверность. Изучение кривой обучения выполнения лапароскопической латеральной секторэктомии печени позволяет оценить потенциал внедрения данной методики в клинические центры.
Новыми являются данные сравнительного анализа клинических результатов проведения открытого и лапароскопического изъятия левого латерального сектора печени у живых доноров, а также сравнительного анализа результатов трансплантаций у реципиентов, получивших соответствующие трансплантаты.
Новыми являются разработанные рекомендации по селекции доноров для лапароскопического изъятия левого латерального сектора.
Впервые разработаны алгоритмы, протоколы и рекомендации по выполнению хирургического вмешательства лапароскопической резекции левого латерального сектора печени у родственного донора.
Практическая значимость исследования.
Впервые в России на основании доказательной медицины установлена клиническая эффективность и безопасность лапароскопической левой латеральной секторэктомии у прижизненных доноров фрагмента печени.
Разработана и стандартизирована хирургическая техника, позволяющая максимально снизить интра- и послеоперационные осложнения у доноров левого латерального сектора печени, а также получать трансплантаты высокого качества.
Внедрение научных разработок в клиническую практику позволит:
• обезопасить хиругическое пособие у доноров путем снижения интраоперационой кровопотери и минимизации хирургической травмы;
• ускорить послеоперационную реабилитацию у доноров;
• получить хороший косметический эффект после оперативного пособия.
Методология и методы исследования.
В исследовании проведен статистический анализ клинических данных, результатов оперативного вмешательства, лабораторных и инструментальных исследований до, во время и после резекции левого латерального сектора печени у родственных доноров и трансплантации левого латерального сектора
детям. Проведен статистический анализ клинических данных, результатов трансплантаций левого латерального сектора печени у реципиентов, получивших трансплантат от доноров, оперированных открыто и лапароскопически.
Основные положения, выносимые на защиту
1. Лапароскопическое изъятие левого латерального сектора является эффективным и безопасным методом, позволяющим уменьшить операционную травму и ускорить реабилитацию, а также получить хороший косметический эффект.
2. Результаты трансплантации левого латерального сектора печени детям от доноров, оперированных лапароскопически, сопоставимы с аналогичными от доноров, оперированных по классической открытой методике.
3. Унификация хирургической методики позволяет уменьшить длительность операции, а также позволяет добиться максимального снижения интра- и послеоперационных осложнений у доноров.
4. Более строгая селекция доноров для лапароскопического изъятия левого латерального сектора позволяет снизить риск интраоперационных осложнений на этапе становления методики и наработки хирургического опыта.
Степень достоверности и апробация результатов
Достоверность результатов определяется объемом проведенных исследований с использованием современных методов статистической обработки.
Апробация работы состоялась 15 июля 2020 года на совместной конференции научных и клинических подразделений федерального государственного бюджетного учреждения «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Министерства здравоохранения Российской Федерации (ФГБУ «НМИЦ ТИО им. ак. В.И. Шумакова» Минздрава России) и кафедры трансплантологии и искусственных органов Института клинической медицины имени Н.В. Склифосовского Федерального государственного автономного образовательного учреждения высшего образования Первый осковский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет).
Материалы диссертации доложены и обсуждены на III Российском национальном конгрессе «Трансплантация и донорство органов» (Москва 2017г.), на 15-м международном конгрессе по донорству органов (ISODP, Дубай, ОАЭ), на 10-м Всероссийском съезде трансплантологов (Москва, 2020 г.), и на международном съезде трансплантологического общества (The Transplantation Society, Сеул, Южная Корея, 2020г.).
Внедрение результатов исследования в практику
Результаты исследования используются в хирургическом отделении № 2 федерального государственного бюджетного учреждения «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Министерства здравоохранения Российской Федерации, в отделении онкологии и детской хирургии федерального государственного бюджетного учреждения «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии имени Дмитрия Рогачёва» Министерства здравоохранения Российской Федерации, а также в образовательной программе кафедры трансплантологии и искусственных органов Института клинической медицины имени Н.В. Склифосовского Федерального государственного автономного образовательного учреждения высшего образования Первый осковский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет).
Личный вклад автора.
Автор принимал непосредственное участие в разработке концепции и постановке задач исследования; в оперативных вмешательствах у родственных доноров печени и операциях по трансплантации печени; самостоятельно осуществлял сбор материала для исследования. Автором самостоятельно сформирована база данных, проведена статистическая обработка, анализ и интерпретация полученных результатов.
Публикации по теме диссертации
По теме диссертации опубликовано 15 научных работ, из них 3 статьи в центральных рецензируемых журналах, рекомендованных ВАК, а также 2 статьи в международных журналах.
Collapse
Affiliation(s)
- K.O. Semash
- V.I. Shumakov National Center of Transplantology and Artificial Organs
| |
Collapse
|
11
|
Seker Yilmaz B, Baruteau J, Chakrapani A, Champion M, Chronopoulou E, Claridge LC, Daly A, Davies C, Davison J, Dhawan A, Grunewald S, Gupte GL, Heaton N, Lemonde H, McKiernan P, Mills P, Morris AA, Mundy H, Pierre G, Rajwal S, Sivananthan S, Sreekantam S, Stepien KM, Vara R, Yeo M, Gissen P. Liver transplantation in ornithine transcarbamylase deficiency: A retrospective multicentre cohort study. Mol Genet Metab Rep 2023; 37:101020. [PMID: 38053940 PMCID: PMC10694733 DOI: 10.1016/j.ymgmr.2023.101020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 12/07/2023] Open
Abstract
Ornithine transcarbamylase deficiency (OTCD) is an X-linked defect of ureagenesis and the most common urea cycle disorder. Patients present with hyperammonemia causing neurological symptoms, which can lead to coma and death. Liver transplantation (LT) is the only curative therapy, but has several limitations including organ shortage, significant morbidity and requirement of lifelong immunosuppression. This study aims to identify the characteristics and outcomes of patients who underwent LT for OTCD. We conducted a retrospective study for OTCD patients from 5 UK centres receiving LT in 3 transplantation centres between 2010 and 2022. Patients' demographics, family history, initial presentation, age at LT, graft type and pre- and post-LT clinical, metabolic, and neurocognitive profile were collected from medical records. A total of 20 OTCD patients (11 males, 9 females) were enrolled in this study. 6/20 had neonatal and 14/20 late-onset presentation. 2/20 patients had positive family history for OTCD and one of them was diagnosed antenatally and received prospective treatment. All patients were managed with standard of care based on protein-restricted diet, ammonia scavengers and supplementation with arginine and/or citrulline before LT. 15/20 patients had neurodevelopmental problems before LT. The indication for LT was presence (or family history) of recurrent metabolic decompensations occurring despite standard medical therapy leading to neurodisability and quality of life impairment. Median age at LT was 10.5 months (6-24) and 66 months (35-156) in neonatal and late onset patients, respectively. 15/20 patients had deceased donor LT (DDLT) and 5/20 had living related donor LT (LDLT). Overall survival was 95% with one patient dying 6 h after LT. 13/20 had complications after LT and 2/20 patients required re-transplantation. All patients discontinued dietary restriction and ammonia scavengers after LT and remained metabolically stable. Patients who had neurodevelopmental problems before LT persisted to have difficulties after LT. 1/5 patients who was reported to have normal neurodevelopment before LT developed behavioural problems after LT, while the remaining 4 maintained their abilities without any reported issues. LT was found to be effective in correcting the metabolic defect, eliminates the risk of hyperammonemia and prolongs patients' survival.
Collapse
Affiliation(s)
- Berna Seker Yilmaz
- Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK
| | - Julien Baruteau
- Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK
- Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| | - Anupam Chakrapani
- Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| | - Michael Champion
- Department of Inherited Metabolic Disease, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, SE1 7EH London, UK
| | - Efstathia Chronopoulou
- Department of Inherited Metabolic Disease, Division of Women's and Children's Services, University Hospitals Bristol NHS Foundation Trust, Bristol BS1 3NU, UK
| | | | - Anne Daly
- Birmingham Women's and Children's Hospital NHS Foundation Trust, B4 6NH, Birmingham, UK
| | - Catherine Davies
- Department of Inherited Metabolic Disease, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, SE1 7EH London, UK
| | - James Davison
- Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| | - Anil Dhawan
- Paediatric Liver Gastroenterology and Nutrition Centre and Mowat Labs, King's College Hospital NHS Foundation Trust, WC2R 2LS, London, UK
| | - Stephanie Grunewald
- Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| | - Girish L. Gupte
- Birmingham Women's and Children's Hospital NHS Foundation Trust, B4 6NH, Birmingham, UK
| | - Nigel Heaton
- Institute of Liver Studies, Kings College Hospital, Denmark Hill, WC2R 2LS London, UK
| | - Hugh Lemonde
- Department of Inherited Metabolic Disease, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, SE1 7EH London, UK
| | - Pat McKiernan
- Birmingham Women's and Children's Hospital NHS Foundation Trust, B4 6NH, Birmingham, UK
| | - Philippa Mills
- Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK
| | - Andrew A.M. Morris
- Willink Unit, Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK
| | - Helen Mundy
- Department of Inherited Metabolic Disease, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, SE1 7EH London, UK
| | - Germaine Pierre
- Department of Inherited Metabolic Disease, Division of Women's and Children's Services, University Hospitals Bristol NHS Foundation Trust, Bristol BS1 3NU, UK
| | - Sanjay Rajwal
- Leeds Teaching Hospitals NHS Trust, LS9 7TF Leeds, UK
| | - Siyamini Sivananthan
- Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| | - Srividya Sreekantam
- Birmingham Women's and Children's Hospital NHS Foundation Trust, B4 6NH, Birmingham, UK
| | - Karolina M. Stepien
- Adult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, M6 8HD Salford, UK
| | - Roshni Vara
- Department of Inherited Metabolic Disease, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, SE1 7EH London, UK
| | - Mildrid Yeo
- Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| | - Paul Gissen
- Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK
- Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| |
Collapse
|
12
|
Antala S, DiNorcia J, Bucuvalas J. Balancing immunosuppression in pediatric liver transplantation: Playing the long game. Pediatr Transplant 2023; 27:e14575. [PMID: 37439035 DOI: 10.1111/petr.14575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 07/03/2023] [Indexed: 07/14/2023]
Abstract
The overarching goal in the care of pediatric liver transplant recipients is to optimize allograft and patient health. Balancing immunosuppression to maintain allograft health while avoiding medication side effects is essential for long-term survival and optimal quality of life in pediatric liver transplant recipients. Utilizing precision medicine to personalize immunosuppression, which includes minimization and withdrawal, is core to this effort. The unique anatomy and physiology of the liver make it more tolerant to immune-mediated injury and a more favorable organ for immunosuppression minimization and withdrawal. However, several challenges exist. Standard biochemical values and histologic features may not reliably predict allograft health after a reduction in immunosuppression. Additionally, biochemical values alone do not reliably identify which patients can successfully develop operational tolerance, as there may be occult allograft injury despite normal liver enzymes. Finally, the durability of tolerance after successful reduction in immunosuppression remains uncertain over time. Innovative tools show promise in circumventing these challenges, but more research is needed to determine actual clinical utility. While immunosuppression-free transplant may not be a current reality for most pediatric liver transplant recipients, strategies to safely minimize immunosuppression without compromising allograft health are within reach. Each liver allograft and recipient pair requires a different degree of immune modulation, and through a structured process of minimization and withdrawal, immunosuppression can indeed be tailored in a precise, personalized way to optimize outcomes. This review focuses on the progress that has been made to individualize immunosuppression in pediatric liver transplantation to ensure optimal allograft and recipient health.
Collapse
Affiliation(s)
- Swati Antala
- Department of Pediatrics, Icahn School of Medicine, Kravis Children's Hospital at Mount Sinai, New York City, New York, USA
| | - Joseph DiNorcia
- Recanati-Miller Transplantation Institute, Mount Sinai Hospital, New York City, New York, USA
| | - John Bucuvalas
- Department of Pediatrics, Icahn School of Medicine, Kravis Children's Hospital at Mount Sinai, New York City, New York, USA
| |
Collapse
|
13
|
Patterson C, So S, Shipley K, Shivgulam ME, Avitzur Y, Ng VL. Physical function in children and adolescents pre- and 1-year post-liver transplant. Pediatr Transplant 2023; 27:e14573. [PMID: 37492021 DOI: 10.1111/petr.14573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/25/2023] [Accepted: 07/03/2023] [Indexed: 07/27/2023]
Abstract
BACKGROUND Several studies describe poorer motor developmental motor outcomes post-liver transplant (LT) in younger children. Limited studies examine physical function in older children and adolescents pre- and post-LT. METHODS Retrospective review of standard of care physical function outcome measures pre- and 1-year post-LT in children ≥6 years at LT. Measures include: 6-minute walk test (6MWT), grip strength, Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2) components, Physical Activity Questionnaire (PAQ), and Paediatric Quality of Life Multidimensional Fatigue Scale. Association of medical variables with outcomes was explored. RESULTS The study cohort included 23 (8 male, median (interquartile range) age 11.67 (8.25, 13.92) years at LT) participants. Top two primary diagnoses included biliary atresia (30.4%) and fulminant hepatic failure (21.7%). At 1-year post-LT, over one-third (36%) were overweight or obese. Compared with healthy norms, children had significantly lower pre-LT PAQ scores (p = .002), pre- and post-6MWT scores (p < .001) and post-LT BOT-2 strength and agility scores (p < .001). Pre-LT, lower balance scores were associated with abdominal distention/ascites (p = .009) and splenomegaly (p = .017). Lower pre-LT platelet count correlated with poorer balance (r = .532, p = .017) and lower strength and agility scores (r = .446, p = .043). Significant moderate inverse correlations were found between weight/body mass index z-scores and BOT-2 components. Post-LT children continue to demonstrate decreased levels of motor proficiency and functional capacity but report less fatigue and increased physical activity. CONCLUSIONS Older children and adolescents undergoing LT are at risk of decreased physical function, highlighting the need for pre- and post-LT rehabilitation to optimize long term outcomes.
Collapse
Affiliation(s)
- Catherine Patterson
- Rehabilitation Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
- Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Stephanie So
- Rehabilitation Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
- Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | | | - Madeline E Shivgulam
- Division of Kinesiology, School of Health and Human Performance, Faculty of Health, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Yaron Avitzur
- Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Vicky Lee Ng
- Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| |
Collapse
|
14
|
Batsis I, Elisofon S, Ferguson M, Jonas M, Kimball B, Lee C, Mitchell P, Fawaz R. A quality improvement intervention to decrease the decline in renal function in pediatric liver transplant recipients. Pediatr Transplant 2023; 27:e14506. [PMID: 36938904 DOI: 10.1111/petr.14506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 02/01/2023] [Accepted: 02/24/2023] [Indexed: 03/21/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) impacts long-term morbidity in pediatric liver transplant (LT) recipients. The prevalence of estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (eGFR < 90) at our institution was 25% at 1 year post-LT; thus, quality improvement (QI) project was initiated, aiming to decrease the prevalence of eGFR < 90 by at least 20% at 1 year-post LT. METHODS Children post-LT under 19 years from 2010 to 2018 were included. Three QI interventions were implemented starting 1/2016: documentation of blood pressure percentile (BP%) and eGFR, documentation of a kidney management plan if either was abnormal, and amlodipine initiation prior to hospital discharge after LT. We compared the prevalence of eGFR < 90 at 3, 12, and 24 months after LT in the pre- and post-intervention period. RESULTS 68 patients in pre- and 42 in post-intervention periods met inclusion criteria. Pre-intervention BP%, eGFR, and kidney management plan were documented at 25%, 10%, and 22%, compared to 71%, 83%, and 71% post-intervention, respectively. 22% of patients were started on amlodipine prior to discharge from LT in the pre- versus 74% in the post-intervention period. Prevalence of eGFR < 90 at 3 m post-LT was 19% in pre- versus 14% in the post-intervention period (p = .31); at 12 months 24% versus 7% (p = .01) and at 24 months 16% versus 6% (p = .13), respectively. Significant non-modifiable risk factors for eGFR < 90 were malignancy (RR = 4.5, p < .0001), metabolic disorder (RR = 2.6, p = .02), and age at transplant (7% increased risk per year of age, p = .007). CONCLUSION By improving documentation of BP%, eGFR, and kidney management plan, the prevalence of eGFR < 90 was decreased by a relative 74% and 60% at 12 and 24 months post-LT, respectively.
Collapse
Affiliation(s)
- Irini Batsis
- Division of Hepatology, Mount Sinai Kravis Children's Hospital, New York, New York, USA
| | - Scott Elisofon
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Michael Ferguson
- Division of Pediatric Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Maureen Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Brendan Kimball
- Department of Quality Improvement, Pediatric Transplant Center, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Christine Lee
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Paul Mitchell
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Rima Fawaz
- Division of Gastroenterology, Hepatology and Nutrition, Yale New Haven Children's Hospital, New Haven, Connecticut, USA
| |
Collapse
|
15
|
Rajasekaran V, McCaffer C, Bishop J, Van Der Meer G, Toll EC, Evans H. Late airway complications following pediatric liver transplantation: A case series. Pediatr Transplant 2023; 27:e14473. [PMID: 36694298 DOI: 10.1111/petr.14473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/09/2022] [Accepted: 01/09/2023] [Indexed: 01/26/2023]
Abstract
BACKGROUND Late airway complications, as consequence of immunosuppression following pediatric liver transplantation are uncommonly reported. METHODS In this retrospective case series, we describe two young children presenting with symptoms of airway obstruction, secondary to differing pathologies in the supraglottic airway, as a result of immunosuppression following liver transplantation. RESULTS Case 1, a 2-year-old girl who presented with stridor 12-months following liver transplantation, was found to have a proliferative soft tissue mass involving the supraglottic larynx. Biopsies were consistent with infiltrative eosinophilic laryngitis and associated eosinophilic esophagitis. Case 2, a 12-month-old female who presented with stridor 5-months following liver transplantation, was found to have an exophytic soft tissue mass involving the supraglottis and hypopharynx. Biopsies revealed polymorphic Epstein-Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD). Case 1 was managed with local resection and high dose oral corticosteroids. Case 2 responded to debulking of the necrotic supraglottic mass, reduction of immunosuppression and rituximab. CONCLUSION A high index of suspicion needs to be maintained for complications of immunosuppression for appropriate diagnosis of airway presentations following pediatric liver transplantation. Further research is necessary to improve early detection and consolidate management strategies for these airway lesions.
Collapse
Affiliation(s)
- Vivek Rajasekaran
- Department of Paediatric Gastroenterology and Hepatology, Starship Child Health, Auckland, New Zealand.,Department of Paediatrics, Child and Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Craig McCaffer
- Department of Paediatric Otolaryngology, Starship Child Health, Auckland, New Zealand
| | - Jonathan Bishop
- Department of Paediatric Gastroenterology and Hepatology, Starship Child Health, Auckland, New Zealand
| | - Graeme Van Der Meer
- Department of Paediatric Otolaryngology, Starship Child Health, Auckland, New Zealand
| | - Edward C Toll
- Department of Paediatric Otolaryngology, Starship Child Health, Auckland, New Zealand
| | - Helen Evans
- Department of Paediatric Gastroenterology and Hepatology, Starship Child Health, Auckland, New Zealand.,Department of Paediatrics, Child and Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| |
Collapse
|
16
|
Baumann U, Karam V, Adam R, Fondevila C, Dhawan A, Sokal E, Jacquemin E, Kelly DA, Grabhorn E, Pawlowska J, D'Antiga L, Jara Vega P, Debray D, Polak WG, de Ville de Goyet J, Verkade HJ. Prognosis of Children Undergoing Liver Transplantation: A 30-Year European Study. Pediatrics 2022; 150:189501. [PMID: 36111446 DOI: 10.1542/peds.2022-057424] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/14/2022] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVES The European Liver Transplant Registry has been collecting data on virtually all pediatric liver transplant (PLT) procedures in Europe since 1968. We analyzed patient outcome over time and identified parameters associated with long-term patient outcome. METHODS Participating centers and European organ-sharing organizations provided retrospective data to the European Liver Transplant Registry. To identify trends, data were grouped into consecutive time spans: era A: before 2000, era B: 2000 to 2009, and the current era, era C: since 2010. RESULTS From June 1968 until December 2017, 16 641 PLT were performed on 14 515 children by 133 centers. The children <7 years of age represented 58% in era A, and 66% in the current era (P <.01). The main indications for PLT were congenital biliary diseases (44%) and metabolic diseases (18%). Patient survival at 5 years is currently 86% overall and 97% in children who survive the first year after PLT. The survival rate has improved from 74% in era A to 83% in era B and 85% in era C (P <.0001). Low-volume centers (<5 PLT/year) represented 75% of centers but performed only 19% of PLT and were associated with a decreased survival rate. In the current era, however, survival rates has become irrespective of volume. Infection is the leading cause of death (4.1%), followed by primary nonfunction of the graft (1.4%). CONCLUSIONS PLT has become a highly successful medical treatment that should be considered for all children with end-stage liver disease. The main challenge for further improving the prognosis remains the early postoperative period.
Collapse
Affiliation(s)
- Ulrich Baumann
- Hannover Medical School, Divisions of Paediatric Gastroenterology and Hepatology, Department for Paediatric Kidney, Liver, and Metabolic Diseases, Hannover, Germany.,Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom.,European Liver Transplant Registry, AP-HP Hôpital Paul Brousse, Research Unit "Chronotherapy, cancers and transplantation," University Paris-Saclay, Villejuif, France.,European Liver and Intestine Transplant Association, Padova, Italy.,European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain
| | - Vincent Karam
- European Liver Transplant Registry, AP-HP Hôpital Paul Brousse, Research Unit "Chronotherapy, cancers and transplantation," University Paris-Saclay, Villejuif, France.,European Liver and Intestine Transplant Association, Padova, Italy
| | - René Adam
- European Liver Transplant Registry, AP-HP Hôpital Paul Brousse, Research Unit "Chronotherapy, cancers and transplantation," University Paris-Saclay, Villejuif, France.,European Liver and Intestine Transplant Association, Padova, Italy
| | - Constantino Fondevila
- European Liver Transplant Registry, AP-HP Hôpital Paul Brousse, Research Unit "Chronotherapy, cancers and transplantation," University Paris-Saclay, Villejuif, France.,Department of General and Digestive Surgery, Hospital Universitario La Paz, IDIPAZ, CIBERehd, Madrid, Spain
| | - Anil Dhawan
- King's College Hospital, London, United Kingdom
| | - Etienne Sokal
- Cliniques Universitaires Saint Luc, Catholic University of Louvain, Brussels, Belgium
| | - Emmanuel Jacquemin
- Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Biliary Atresia and Genetic Cholestasis, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, Assistance Publique: Hôpitaux de Paris, University Paris-Saclay, Le Kremlin-Bicêtre; Inserm U1193, Hepatinov, University Paris-Saclay, Orsay, France
| | - Deirdre A Kelly
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - Enke Grabhorn
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Childreńs Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Joanna Pawlowska
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Lorenzo D'Antiga
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Paediatric Hepatology, Gastroenterology, and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Paloma Jara Vega
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Paediatric Hepatology Service, Coordinator ERN TransplantChild, Hospital Infantil Universitario La Paz, Madrid, Spain
| | - Dominique Debray
- European Reference Network TransplantChild, La Paz University Hospital, Madrid, Spain.,Pediatric Liver Unit and Reference Center for Biliary Atresia and Genetic Cholestasis, APHP-Hôpital Necker, Université de Paris, Paris, France
| | - Wojciech G Polak
- European Liver and Intestine Transplant Association, Padova, Italy.,Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jean de Ville de Goyet
- Department for the Treatment and Study of Pediatric Abdominal Diseases and Abdominal Transplantation, ISMETT, Palermo, Italy
| | - Henkjan J Verkade
- European Liver and Intestine Transplant Association, Padova, Italy.,Dept. of Pediatrics, Beatrix Children's Hospital/University Medical Center Groningen, University of Groningen, ERN RareLiver, Groningen, The Netherlands
| | | |
Collapse
|
17
|
Trier C, Schaffalitzky de Muckadell V, Borgwardt L, Rasmussen A, Hørby Jørgensen M. Markers of obesity in Danish pediatric liver transplantation recipients. Pediatr Transplant 2022; 26:e14320. [PMID: 35669999 DOI: 10.1111/petr.14320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 03/22/2022] [Accepted: 05/05/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Long-time survivors of pediatric liver transplantation have an increased incidence of the metabolic syndrome. Adult recipients have an increased risk of post-transplantation obesity; however, pediatric data are limited. METHODS The study included 42 recipients of pediatric liver transplantation in Denmark, transplanted between 1990 and 2014. The study participants were examined with anthropometric measures, dual-energy X-ray scans and blood samples. From the anthropometric measures, body mass index (BMI) and BMI standard deviation score (SDS) were calculated. From the dual-energy X-ray scans, fat percent was assessed, and body fat mass index (BFMI) was calculated. RESULTS The median age was 17.4 years (range 4.1-38.9) at the time of the study, and the median time since transplantation was 8.5 years (range 0.4-23.9). The prevalence of overweight and obesity was 31.0% based on BMI SDS (age below 18) and BMI (age 18 and above). When compared to the participants with normal weight, the participants with overweight and obesity had a higher BFMI (9.29 vs 5.57 kg/m2 , p < .001) and fat percent (38.35% vs 29.50%, p = .006). They had higher levels of total cholesterol (4.3 vs 3.6 mmol/L, p = .023) and low-density lipoprotein (2.5 vs 1.7, p = .015), and had had longer time since transplantation (15.6 vs 8.5 years respectively, p = .045). CONCLUSIONS Long-time survivors of pediatric liver transplantation have a higher BMI or BMI SDS than the general pediatric population. The obesity is characterized by a higher BFMI, fat percent, and cholesterols levels, when compared to recipients without overweight or obesity.
Collapse
Affiliation(s)
- Caecilie Trier
- Department of Pediatric and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.,Department of Pediatric and Adolescent Medicine, University Hospital Holbaek, Holbaek, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Vibeke Schaffalitzky de Muckadell
- Department of Pediatric and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.,Department of Gynecology and Obstetrics, Hospital of Lillebaelt, Kolding, Denmark
| | - Lise Borgwardt
- Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Denmark
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen, Denmark
| | | |
Collapse
|
18
|
Gavriilidis P, Hidalgo E. Alternatives to left lateral sector in paediatric liver transplantation-a systematic review on monosegmental and reduced grafts. Hepatobiliary Surg Nutr 2022; 11:567-576. [PMID: 36016740 PMCID: PMC9396086 DOI: 10.21037/hbsn-20-792] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 02/05/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND Paediatric liver transplantation (pLT) is the treatment of choice for many liver conditions. However, it still poses relevant challenges, mainly related to the size of the recipients. Unlike in adults, excessive graft volume might represent an issue when the estimated graft-recipient-weight-ratio (GRWR) is significantly disproportionate. In this situation, the traditional left lateral sector (LLS) grafts are too big and other alternatives are required, such as monosegmental or reduced (including hyper-reduced) grafts (RLLS/HRLLS). Results with conventional LLS-pLT are excellent and replicating them with monosegmental or RLLS is challenging given (I) the technical complexity and (II) the need to overcome the large-for-size scenario. This article is to review the existing experience with monosegmental, RLLS/HRLLS grafts and appraise its results. METHODS Systematic search of the electronic databases, conducted from their inception until May 2020. RESULTS After scrutiny of the available literature, 16 studies were included reporting 330 patients transplanted with monosegmental and RLLS/HRLLS grafts. There were 10 re-grafts (6 of them <90 days); 90% of grafts were LDLT. Overall, median recipient's age and weight were 7 months (range, 5 days-22 months) and 5.8 kg (range, 2.6-8 kg) respectively. Median graft weight was 209 grams (range, 124-264 grams) and median GRWR was 3.5% (range, 2.7-5.6%). Hepatic artery and portal vein thrombosis overall incidence were 1.5% and 4.2%; 120 out of the 330 pLT were monosegmental (37%) producing a smaller graft (median of 164 grams) and accordingly a lower GRWR (median 3.2%) compared to reduced LLS. With a median follow-up of 39 months (range, 6-87 months), the overall graft and patient survival were 84% (285/340) and 89% (295/330). DISCUSSION Monosegmental and RLLS/HRLLS grafts provide access to liver transplantation for very small recipients with excellent results comparable to the standard LLS.
Collapse
Affiliation(s)
- Paschalis Gavriilidis
- Department of Hepatopanceaticobiliary Surgery. Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
| | - Ernest Hidalgo
- Department of Hepato-Pancreatic-Biliary Surgery and Liver Transplantation, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| |
Collapse
|
19
|
Patterson C, So S, Rogers A, Ng VL. Motor outcomes in young children pre-and one-year post-liver transplant. Pediatr Transplant 2022; 26:e14200. [PMID: 34874102 DOI: 10.1111/petr.14200] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 08/11/2021] [Accepted: 11/12/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Motor skill acquisition plays an important role in physical activity participation and overall social and physical health. Limited studies have examined motor development in children pre-and post-liver transplant (LT). METHODS Retrospective review of motor outcomes in children <6 years old with cholestatic liver disease assessed pre-and 1-year post-isolated LT. Measures include Alberta Infant Motor Scale and Peabody Developmental Motor Scales (gross motor quotient (GMQ), fine motor quotient (FMQ), and total motor quotient (TMQ)). Association of medical variables with motor outcomes was explored. RESULTS Participants included 33 (58% male) children with diagnoses of biliary atresia (70%), Alagille syndrome (21%), and others (9%). Median age at LT was 10 (IQR 7.0-20.5) months. Pre-LT >75% of children were at risk for motor delay (≤10th percentile on AIMS/ ≥1SD below mean GMQ). Post-LT, 52% scored ≥1 SD below the mean GMQ compared with 22% FMQ. Children at risk/delayed pre-LT had an increased risk of motor delay on GMQ post-LT (odds ratio 11.43, 95% CI 1.12-116.7, p = .017). Higher INR pre-LT correlated with lower TMQ post-LT (r = -.51, p = .003). Longer waitlist time correlated with lower FMQ post-LT (r = .41, p = .03). GMQ post-LT and height z-scores pre-LT (r = .46, p = .02) and post-LT (r = .45, p < .01) were positively correlated. There was no correlation with presence of ascites, weight z-score, length of hospitalization, and age at LT. CONCLUSIONS Young children have increased risk of motor delay pre-LT, which may persist post-LT. Severity of liver disease and growth delays may impact motor development, highlighting the need for ongoing rehabilitation pre- and post-LT.
Collapse
Affiliation(s)
- Catherine Patterson
- Rehabilitation Medicine, The Hospital for Sick Children, Toronto, ON, Canada.,Transplant and Regenerative Medicine, The Hospital for Sick Children, Toronto, ON, Canada.,University of Toronto, Toronto, ON, Canada
| | - Stephanie So
- Rehabilitation Medicine, The Hospital for Sick Children, Toronto, ON, Canada.,Transplant and Regenerative Medicine, The Hospital for Sick Children, Toronto, ON, Canada.,University of Toronto, Toronto, ON, Canada
| | - Alaine Rogers
- Rehabilitation Medicine, The Hospital for Sick Children, Toronto, ON, Canada.,Transplant and Regenerative Medicine, The Hospital for Sick Children, Toronto, ON, Canada.,University of Toronto, Toronto, ON, Canada
| | - Vicky L Ng
- Transplant and Regenerative Medicine, The Hospital for Sick Children, Toronto, ON, Canada.,University of Toronto, Toronto, ON, Canada.,Division of Pediatric Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada
| |
Collapse
|
20
|
de Ville de Goyet J, Baumann U, Karam V, Adam R, Nadalin S, Heaton N, Reding R, Branchereau S, Mirza D, Klempnauer JL, Fischer L, Kalicinski P, Colledan M, Lopez Santamaria M, de Kleine RH, Chardot C, Yilmaz S, Kilic M, Boillot O, di Francesco F, Polak WG, Verkade HJ. European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children. Hepatology 2022; 75:634-645. [PMID: 34724224 DOI: 10.1002/hep.32223] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 09/12/2021] [Accepted: 10/16/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS The European Liver Transplant Registry (ELTR) has collected data on liver transplant procedures performed in Europe since 1968. APPROACH AND RESULTS Over a 50-year period (1968-2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children). Data were analyzed according to three successive periods (A, before 2000; B, 2000-2009; and C, since 2010), studying donor and graft characteristics and graft outcome. The use of living donors steadily increased from A to C (A, n = 296 [7%]; B, n = 1131 [23%]; and C, n = 1985 [39%]; p = 0.0001). Overall, the 5-year graft survival rate has improved from 65% in group A to 75% in group B (p < 0.0001) and to 79% in group C (B versus C, p < 0.0001). Graft half-life was 31 years, overall; it was 41 years for children who survived the first year after transplant. The late annual graft loss rate in teenagers is higher than that in children aged <12 years and similar to that of young adults. No evidence for accelerated graft loss after age 18 years was found. CONCLUSIONS Pediatric liver transplantation has reached a high efficacy as a cure or treatment for severe liver disease in infants and children. Grafts that survived the first year had a half-life similar to standard human half-life. Transplantation before or after puberty may be the pivot-point for lower long-term outcome in children. Further studies are necessary to revisit some old concepts regarding transplant benefit (survival time) for small children, the role of recipient pathophysiology versus graft aging, and risk at transition to adult age.
Collapse
Affiliation(s)
- Jean de Ville de Goyet
- Department for the Treatment and Study of Pediatric Abdominal Diseases and Abdominal Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Palermo, Italy
| | - Ulrich Baumann
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.,Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany.,European Liver and Intestine Transplant Association, Padua, Italy
| | - Vincent Karam
- European Liver Transplant Registry, Assistance Publique-Hôpitaux de Paris Hôpital Paul Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - René Adam
- European Liver and Intestine Transplant Association, Padua, Italy.,European Liver Transplant Registry, Assistance Publique-Hôpitaux de Paris Hôpital Paul Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| | - Silvio Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | | | - Raymond Reding
- Cliniques Universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium
| | - Sophie Branchereau
- Service de Chirurgie Viscérale Pédiatrique Bicêtre University Hospital, Faculty of Medicine Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France
| | - Darius Mirza
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jürgen L Klempnauer
- Klinik für Viszeral und Transplantations-chirurgie, Hannover Medical School, Hannover, Germany
| | - Lutz Fischer
- Department of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Piotr Kalicinski
- Department of Pediatric and Transplant Surgery, Children's Memorial Health Institute, Warsaw, Poland
| | - Michele Colledan
- Università degli studi di Milano Bicocca, ASST Giovanni XXIII, Department of Organ Failure and Transplantation, Bergamo, Italy
| | | | - Ruben H de Kleine
- Department of Surgery, Section of Hepato-Pancreatico-Biliary Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Christophe Chardot
- Service de Chirurgie Pediatrique, Hôpital Necker Enfants Malades, Paris, France
| | - Sezai Yilmaz
- Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Murat Kilic
- Liver Transplant Program, Izmir Kent Hospital, Izmir, Turkey
| | - Olivier Boillot
- Pediatric Liver Transplant Surgery, Hôpital Edouard Herriot, Lyon, France
| | - Fabrizio di Francesco
- Department for the Treatment and Study of Pediatric Abdominal Diseases and Abdominal Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico, Palermo, Italy
| | - Wojciech G Polak
- European Liver and Intestine Transplant Association, Padua, Italy.,Erasmus MC, Transplant Institute, Division of Hepatopancreatobiliary and Transplant Surgery, Department of Surgery, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Henkjan J Verkade
- European Liver and Intestine Transplant Association, Padua, Italy.,Department of Pediatrics, University Medical Center Groningen, University of Groningen, Hospital, Groningen, the Netherlands
| | -
- European Liver Transplant Registry, Assistance Publique-Hôpitaux de Paris Hôpital Paul Brousse, Université Paris-Sud, Inserm U 935, Villejuif, France
| |
Collapse
|
21
|
Over 30 Years of Pediatric Liver Transplantation at the Charité-Universitätsmedizin Berlin. J Clin Med 2022; 11:jcm11040900. [PMID: 35207173 PMCID: PMC8880346 DOI: 10.3390/jcm11040900] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/01/2022] [Accepted: 02/07/2022] [Indexed: 12/11/2022] Open
Abstract
Background: Pediatric liver transplantation (LT) is the treatment of choice for children with end-stage liver disease and in certain cases of hepatic malignancies. Due to low case numbers, a technically demanding procedure, the need for highly specialized perioperative intensive care, and immunological, as well as infectious, challenges, the highest level of interdisciplinary cooperation is required. The aim of our study was to analyze short- and long-term outcomes of pediatric LT in our center. Methods: We conducted a retrospective single-center analysis of all liver transplantations in pediatric patients (≤16 years) performed at the Department of Surgery, Charité – Universitätsmedizin Berlin between 1991 and 2021. Three historic cohorts (1991–2004, 2005–2014 and 2015–2021) were defined. Graft- and patient survival, as well as perioperative parameters were analyzed. The study was approved by the institutional ethics board. Results: Over the course of the 30-year study period, 212 pediatric LTs were performed at our center. The median patient age was 2 years (IQR 11 years). Gender was equally distributed (52% female patients). The main indications for liver transplantation were biliary atresia (34%), acute hepatic necrosis (27%) and metabolic diseases (13%). The rate of living donor LT was 25%. The median cold ischemia time for donation after brain death (DBD) LT was 9 h and 33 min (IQR 3 h and 46 min). The overall donor age was 15 years for DBD donors and 32 years for living donors. Overall, respective 1, 5, 10 and 30-year patient and graft survivals were 86%, 82%, 78% and 65%, and 78%, 74%, 69% and 55%. One-year patient survival was 85%, 84% and 93% in the first, second and third cohort, respectively (p = 0.14). The overall re-transplantation rate was 12% (n = 26), with 5 patients (2%) requiring re-transplantation within the first 30 days. Conclusion: The excellent long-term survival over 30 years showcases the effectiveness of liver transplantation in pediatric patients. Despite a decrease in DBD organ donation, patient survival improved, attributed, besides refinements in surgical technique, mainly to improved interdisciplinary collaboration and management of perioperative complications.
Collapse
|
22
|
Neuberger J. Retransplantation should be offered to children with liver graft failure. Med J Aust 2020; 213:456-457. [PMID: 33089493 DOI: 10.5694/mja2.50833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- James Neuberger
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, The United Kingdom
| |
Collapse
|