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Rajasekar JS, Rammohan A, Rela M. Special Techniques of Liver Transplantation: Living Donor Liver Transplantation With Right Posterior Sector Grafts and Extended Left Lobe Grafts; Auxiliary Partial Orthotopic Liver Transplantation, and Dual-Lobe Liver Transplantation. J Clin Exp Hepatol 2025; 15:102451. [PMID: 39722781 PMCID: PMC11666944 DOI: 10.1016/j.jceh.2024.102451] [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: 08/15/2024] [Accepted: 11/05/2024] [Indexed: 12/28/2024] Open
Abstract
Living donor liver transplantation (LDLT) constitutes the majority of liver transplants in Asia and advancements in LDLT techniques have expanded the range of allografts beyond the commonly used right lobe (RL). This review provides a comprehensive overview of lesser-known variants of allografts and LDLT techniques which include right posterior sector grafts (RPSG), dual-lobe liver transplantation (DLLT), auxiliary partial orthotopic liver transplantation (APOLT), and extended left lobe grafts with caudate concentrating on the technical aspects, current evidence, and their indications in contemporary practice of LDLT. The first section examines RPSGs, focussing on their potential as an alternative to RL grafts particularly when volumetric studies indicate a larger right posterior sector in donors. It addresses donor selection, surgical techniques, and potential complications. Next, the article explores DLLT, which optimizes graft volume through partial grafts from two donors. The emphasis is on the ethical considerations, surgical challenges, and haemodynamic risks, such as graft atrophy, highlighting the importance of careful donor selection and meticulous planning. The section on APOLT covers its application in treating acute liver failure (ALF) and metabolic liver diseases. The technique's ability to support liver function in ALF while avoiding long-term immunosuppression when the native liver regenerates is discussed, along with patient selection criteria and follow-up requirements. Finally, the review addresses left lobe grafts with caudate used in smaller adults and older children to increase functional graft volume and improve outcomes.
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Affiliation(s)
- Jasper S. Rajasekar
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India
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Hegarty R, Thompson RJ. Genetic aetiologies of acute liver failure. J Inherit Metab Dis 2024; 47:582-597. [PMID: 38499319 DOI: 10.1002/jimd.12733] [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: 12/01/2023] [Revised: 03/11/2024] [Accepted: 03/12/2024] [Indexed: 03/20/2024]
Abstract
Acute liver failure (ALF) is a rare, rapidly evolving, clinical syndrome with devastating consequences where definitive treatment is by emergency liver transplantation. Establishing a diagnosis can be challenging and, historically, the cause of ALF was unidentified in up to half of children. However, recent technological and clinical advances in genomic medicine have led to an increasing proportion being diagnosed with monogenic aetiologies of ALF. The conditions encountered include a diverse group of inherited metabolic disorders each with prognostic and treatment implications. Often these disorders are clinically indistinguishable and may even mimic disorders of immune regulation or red cell disorders. Rapid genomic sequencing for children with ALF is, therefore, a key component in the diagnostic work up today. This review focuses on the monogenic aetiologies of ALF.
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Affiliation(s)
- Robert Hegarty
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK
- Institute of Liver Studies, King's College London, London, UK
| | - Richard J Thompson
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK
- Institute of Liver Studies, King's College London, London, UK
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Cillo U, Lauterio A, Furlanetto A, Canitano N, Polacco M, Buscemi V, De Carlis R, Boetto R, D'Amico FE, Bassi D, De Carlis L, Gringeri E. Full-left/Full-right Liver Splitting With Middle Hepatic Vein and Caval Partition During Dual Hypothermic Oxygenated Machine Perfusion. Transplantation 2024; 108:1417-1421. [PMID: 38755751 DOI: 10.1097/tp.0000000000005039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2024]
Abstract
BACKGROUND Split liver transplantation is a valuable means of mitigating organ scarcity but requires significant surgical and logistical effort. Ex vivo splitting is associated with prolonged cold ischemia, with potentially negative effects on organ viability. Machine perfusion can mitigate the effects of ischemia-reperfusion injury by restoring cellular energy and improving outcomes. METHODS We describe a novel technique of full-left/full-right liver splitting, with splitting and reconstruction of the vena cava and middle hepatic vein, with dual arterial and portal hypothermic oxygenated machine perfusion. The accompanying video depicts the main surgical passages, notably the splitting of the vena cava and middle hepatic vein, the parenchymal transection, and the venous reconstruction. RESULTS The left graft was allocated to a pediatric patient having methylmalonic aciduria, whereas the right graft was allocated to an adult patient affected by hepatocellular carcinoma and cirrhosis. CONCLUSIONS This technique allows ex situ splitting, counterbalancing prolonged ischemia with the positive effects of hypothermic oxygenated machine perfusion on graft viability. The venous outflow is preserved, safeguarding both grafts from venous congestion; all reconstructions can be performed ex situ, minimizing warm ischemia. Moreover, there is no need for highly skilled surgeons to reach the donor hospital, thereby simplifying logistical aspects.
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Affiliation(s)
- Umberto Cillo
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Alessandro Furlanetto
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Nicola Canitano
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Marina Polacco
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Vincenzo Buscemi
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Riccardo Boetto
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Francesco Enrico D'Amico
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Domenico Bassi
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Enrico Gringeri
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
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Marchuk H, Wang Y, Ladd ZA, Chen X, Zhang GF. Pathophysiological mechanisms of complications associated with propionic acidemia. Pharmacol Ther 2023; 249:108501. [PMID: 37482098 PMCID: PMC10529999 DOI: 10.1016/j.pharmthera.2023.108501] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 07/06/2023] [Accepted: 07/18/2023] [Indexed: 07/25/2023]
Abstract
Propionic acidemia (PA) is a genetic metabolic disorder caused by mutations in the mitochondrial enzyme, propionyl-CoA carboxylase (PCC), which is responsible for converting propionyl-CoA to methylmalonyl-CoA for further metabolism in the tricarboxylic acid cycle. When this process is disrupted, propionyl-CoA and its metabolites accumulate, leading to a variety of complications including life-threatening cardiac diseases and other metabolic strokes. While the clinical symptoms and diagnosis of PA are well established, the underlying pathophysiological mechanisms of PA-induced diseases are not fully understood. As a result, there are currently few effective therapies for PA beyond dietary restriction. This review focuses on the pathophysiological mechanisms of the various complications associated with PA, drawing on extensive research and clinical reports. Most research suggests that propionyl-CoA and its metabolites can impair mitochondrial energy metabolism and cause cellular damage by inducing oxidative stress. However, direct evidence from in vivo studies is still lacking. Additionally, elevated levels of ammonia can be toxic, although not all PA patients develop hyperammonemia. The discovery of pathophysiological mechanisms underlying various complications associated with PA can aid in the development of more effective therapeutic treatments. The consequences of elevated odd-chain fatty acids in lipid metabolism and potential gene expression changes mediated by histone propionylation also warrant further investigation.
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Affiliation(s)
- Hannah Marchuk
- Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA
| | - You Wang
- Jining Key Laboratory of Pharmacology, Jining Medical University, Shandong 272067, China.; School of Basic Medicine, Jining Medical University, Shandong 272067, China
| | - Zachary Alec Ladd
- Surgical Research Lab, Department of Surgery, Cooper University Healthcare and Cooper Medical School of Rowan University, Camden, NJ 08103, USA
| | - Xiaoxin Chen
- Surgical Research Lab, Department of Surgery, Cooper University Healthcare and Cooper Medical School of Rowan University, Camden, NJ 08103, USA; Coriell Institute for Medical Research, Camden, NJ 08103, USA; MD Anderson Cancer Center at Cooper, Camden, NJ 08103, USA.
| | - Guo-Fang Zhang
- Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA; Department of Medicine, Division of Endocrinology, and Metabolism Nutrition, Duke University Medical Center, Durham, NC 27710, USA.
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Auxiliary Partial Orthotopic Liver Transplantation for Acute Liver Failure: Not Supportive Enough? Indian J Surg 2022. [DOI: 10.1007/s12262-021-02925-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Zeng ZG, Zhou GP, Wei L, Qu W, Liu Y, Tan YL, Wang J, Sun LY, Zhu ZJ. Therapeutic potential of living donor liver transplantation from heterozygous carrier donors in children with propionic acidemia. Orphanet J Rare Dis 2022; 17:62. [PMID: 35189944 PMCID: PMC8862340 DOI: 10.1186/s13023-022-02233-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 02/06/2022] [Indexed: 02/08/2023] Open
Abstract
Background Current world experience regarding living donor liver transplantation (LDLT) in the treatment of propionic acidemia (PA) is limited, especially in terms of using obligate heterozygous carriers as donors. This study aimed to evaluate the clinical outcomes of LDLT in children with PA.
Methods From November 2017 to January 2020, 7 of the 192 children who underwent LDLT at our institution had been diagnosed with PA (median age, 2.1 years; range, 1.1–5.8 years). The primary indication for transplantation was frequent metabolic decompensations in 6 patients and preventative treatment in 1 patient. Of the seven parental living donors, six were genetically proven obligate heterozygous carriers. Results During a median follow-up of 23.9 months (range, 13.9–40.2 months), all patients were alive with 100% allograft survival, and no severe transplant-related complications occurred. In the case of liberalized protein intake, they did not suffer metabolic decompensation or disease-related complications and made progress in neurodevelopmental delay and body growth, as well as blood and urinary metabolite levels. In one patient with pre-existing mild dilated cardiomyopathy, her echocardiogram results completely normalized 13.8 months post-transplant. All living donors recovered well after surgery, with no metabolic decompensations or procedure-related complications. Western blotting revealed that the hepatic expressions of PCCA and PCCB in one of the heterozygous donors were comparable to those of the normal healthy control at the protein level. Conclusions LDLT using partial liver grafts from asymptomatic obligate heterozygous carrier donors is a viable therapeutic option for selected PA patients, with no negative impact on donors’ and recipients' clinical courses.
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Menon J, Vij M, Sachan D, Rammohan A, Shanmugam N, Kaliamoorthy I, Rela M. Pediatric metabolic liver diseases: Evolving role of liver transplantation. World J Transplant 2021; 11:161-179. [PMID: 34164292 PMCID: PMC8218348 DOI: 10.5500/wjt.v11.i6.161] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/13/2021] [Accepted: 06/03/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic liver diseases (MLD) are the second most common indication for liver transplantation (LT) in children. This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation. LT is also performed in metabolic disorders for end-stage liver disease, its sequelae including hepatocellular cancer. It is also performed for preventing metabolic crisis', arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia. Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis, cholestasis, inflammation, variable amount of fibrosis, and cirrhosis. The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT. A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters. Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver. The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.
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Affiliation(s)
- Jagadeesh Menon
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Mukul Vij
- Department of Pathology, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Deepti Sachan
- Department of Transfusion Medicine, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Ashwin Rammohan
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Naresh Shanmugam
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Ilankumaran Kaliamoorthy
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
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Forny P, Hörster F, Ballhausen D, Chakrapani A, Chapman KA, Dionisi‐Vici C, Dixon M, Grünert SC, Grunewald S, Haliloglu G, Hochuli M, Honzik T, Karall D, Martinelli D, Molema F, Sass JO, Scholl‐Bürgi S, Tal G, Williams M, Huemer M, Baumgartner MR. Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision. J Inherit Metab Dis 2021; 44:566-592. [PMID: 33595124 PMCID: PMC8252715 DOI: 10.1002/jimd.12370] [Citation(s) in RCA: 144] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 02/03/2021] [Accepted: 02/15/2021] [Indexed: 12/13/2022]
Abstract
Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re-evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well-informed decisions in the context of MMA and PA patient care.
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Affiliation(s)
- Patrick Forny
- Division of Metabolism and Children's Research CenterUniversity Children's Hospital Zurich, University of ZurichZurichSwitzerland
| | - Friederike Hörster
- Division of Neuropediatrics and Metabolic MedicineUniversity Hospital HeidelbergHeidelbergGermany
| | - Diana Ballhausen
- Paediatric Unit for Metabolic Diseases, Department of Woman‐Mother‐ChildUniversity Hospital LausanneLausanneSwitzerland
| | - Anupam Chakrapani
- Metabolic Medicine Department, Great Ormond Street Hospital for Children NHS Foundation Trust and Institute for Child HealthNIHR Biomedical Research Center (BRC), University College LondonLondonUK
| | - Kimberly A. Chapman
- Rare Disease Institute, Children's National Health SystemWashingtonDistrict of ColumbiaUSA
| | - Carlo Dionisi‐Vici
- Division of Metabolism, Department of Pediatric SpecialtiesBambino Gesù Children's HospitalRomeItaly
| | - Marjorie Dixon
- Dietetics, Great Ormond Street Hospital for Children NHS Foundation TrustLondonUK
| | - Sarah C. Grünert
- Department of General Paediatrics, Adolescent Medicine and Neonatology, Medical Centre‐University of FreiburgFaculty of MedicineFreiburgGermany
| | - Stephanie Grunewald
- Metabolic Medicine Department, Great Ormond Street Hospital for Children NHS Foundation Trust and Institute for Child HealthNIHR Biomedical Research Center (BRC), University College LondonLondonUK
| | - Goknur Haliloglu
- Department of Pediatrics, Division of Pediatric NeurologyHacettepe University Children's HospitalAnkaraTurkey
| | - Michel Hochuli
- Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, InselspitalBern University Hospital and University of BernBernSwitzerland
| | - Tomas Honzik
- Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of MedicineCharles University and General University Hospital in PraguePragueCzech Republic
| | - Daniela Karall
- Department of Paediatrics I, Inherited Metabolic DisordersMedical University of InnsbruckInnsbruckAustria
| | - Diego Martinelli
- Division of Metabolism, Department of Pediatric SpecialtiesBambino Gesù Children's HospitalRomeItaly
| | - Femke Molema
- Department of Pediatrics, Center for Lysosomal and Metabolic DiseasesErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Jörn Oliver Sass
- Department of Natural Sciences & Institute for Functional Gene Analytics (IFGA)Bonn‐Rhein Sieg University of Applied SciencesRheinbachGermany
| | - Sabine Scholl‐Bürgi
- Department of Paediatrics I, Inherited Metabolic DisordersMedical University of InnsbruckInnsbruckAustria
| | - Galit Tal
- Metabolic Unit, Ruth Rappaport Children's HospitalRambam Health Care CampusHaifaIsrael
| | - Monique Williams
- Department of Pediatrics, Center for Lysosomal and Metabolic DiseasesErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Martina Huemer
- Division of Metabolism and Children's Research CenterUniversity Children's Hospital Zurich, University of ZurichZurichSwitzerland
- Department of PaediatricsLandeskrankenhaus BregenzBregenzAustria
| | - Matthias R. Baumgartner
- Division of Metabolism and Children's Research CenterUniversity Children's Hospital Zurich, University of ZurichZurichSwitzerland
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Sood V, Squires JE, Mazariegos GV, Vockley J, McKiernan PJ. Living Related Liver Transplantation for Metabolic Liver Diseases in Children. J Pediatr Gastroenterol Nutr 2021; 72:11-17. [PMID: 32969959 PMCID: PMC10657650 DOI: 10.1097/mpg.0000000000002952] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
ABSTRACT Metabolic liver diseases (MLDs) are a heterogeneous group of inherited conditions for which liver transplantation can provide definitive treatment. The limited availability of deceased donor organs means some who could benefit from transplant do not have this option. Living related liver transplant (LrLT) using relatives as donors has emerged as one solution to this problem. This technique is established worldwide, especially in Asian countries, with shorter waiting times and patient and graft survival rates equivalent to deceased donor liver transplantation. However, living donors are underutilized for MLDs in many western countries, possibly due to the fear of limited efficacy using heterozygous donors. We have reviewed the published literature and shown that the use of heterozygous donors for liver transplantation is safe for the majority of MLDs with excellent metabolic correction. The use of LrLT should be encouraged to complement deceased donor liver transplantation (DDLT) for treatment of MLDs.
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Affiliation(s)
- Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - George V. Mazariegos
- Division of Pediatric Transplantation, Hillman Center for Pediatric Transplantation
| | - Jerry Vockley
- Center for Rare Disease Therapy, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA
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Zhou GP, Sun LY, Zhu ZJ. The concept of "domino" in liver and hepatocyte transplantation. Therap Adv Gastroenterol 2020; 13:1756284820968755. [PMID: 33149765 PMCID: PMC7586492 DOI: 10.1177/1756284820968755] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 10/01/2020] [Indexed: 02/04/2023] Open
Abstract
Although orthotopic liver transplantation remains the only proven treatment for end-stage liver disease and inherited metabolic liver disease, its application has been limited by the scarcity of donor organs available for transplantation. Among feasible approaches developed to expand the donor organ pool, domino liver transplantation is a strategy in which explanted genetically defective livers of liver transplant recipients are used as grafts in other patients. Another promising therapeutic strategy is hepatocyte transplantation, an alternative to liver transplantation for certain groups of patients. However, the availability of primary hepatocytes is also hindered by the shortage of donor liver tissues. Against this background, domino hepatocyte transplantation, a strategy that utilizes the hepatocytes derived from the explanted livers of liver transplant recipients with noncirrhotic inherited metabolic liver diseases as the source of primary hepatocytes, may help increase the supply of liver cells available for transplantation. In this review, we focus on the status quo of domino liver transplantation and domino hepatocyte transplantation. We also describe recent innovative transplant strategies based on domino transplantation.
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Affiliation(s)
- Guang-Peng Zhou
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China,Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
| | - Li-Ying Sun
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China,Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China,Intensive Care Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Liver Transplantation for Propionic Acidemia: Evidence from A Systematic Review and Meta-analysis. Transplantation 2020; 105:2272-2282. [PMID: 33093405 DOI: 10.1097/tp.0000000000003501] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND The worldwide experience of liver transplantation (LT) in the treatment of propionic acidemia (PA) remains limited and fragmented. This review aims to provide a comprehensive and quantitative understanding of post-transplant clinical outcomes in PA patients. METHODS MEDLINE, Embase and the Cochrane Library databases were searched for studies focusing on PA patients who underwent LT. The pooled estimate rates and 95% confidence intervals (CIs) were calculated using a random-effects model with Freeman-Tukey double arcsine transformation. RESULTS Twenty-one studies involving 70 individuals were included. The pooled estimate rates were 0.95 (95% CI, 0.80-1.00) for patient survival and 0.91 (95% CI, 0.72-1.00) for allograft survival. The pooled estimate rates were 0.20 (95% CI, 0.05-0.39) for rejection, 0.08 (95% CI, 0.00-0.21) for hepatic artery thrombosis, 0.14 (95% CI, 0.00-0.37) for cytomegalovirus/Epstein-Barr virus infection and 0.03 (95% CI, 0.00-0.15) for biliary complications. The pooled estimate rates were 0.98 (95% CI, 0.88-1.00) for metabolic stability, 1.00 (95% CI, 0.79-1.00) for reversal of pre-existing cardiomyopathy and 0.97 (95% CI, 0.78-1.00) for improvement of neurodevelopmental delay. A large proportion of patients achieved liberalization of protein intake posttransplant [pooled estimate rate 0.66 (95% CI, 0.35-0.93)]. CONCLUSIONS Despite the risk of transplant-related complications, LT is a viable therapeutic option in PA patients, with satisfactory survival rates and clinical outcomes. Given the diversity in neurological assessment methods and the inconsistency in achievement of dietary protein liberalization across different studies, consensus on neurological evaluation methods and post-transplant protein intake is necessary. Longer-term clinical outcomes of LT for PA warrants further investigation.
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Yap S, Vara R, Morais A. Post-transplantation Outcomes in Patients with PA or MMA: A Review of the Literature. Adv Ther 2020; 37:1866-1896. [PMID: 32270363 PMCID: PMC7141097 DOI: 10.1007/s12325-020-01305-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Indexed: 12/25/2022]
Abstract
Introduction Liver transplantation is recognised as a treatment option for patients with propionic acidemia (PA) and those with methylmalonic acidemia (MMA) without renal impairment. In patients with MMA and moderate-to-severe renal impairment, combined liver–kidney transplantation is indicated. However, clinical experience of these transplantation options in patients with PA and MMA remains limited and fragmented. We undertook an overview of post-transplantation outcomes in patients with PA and MMA using the current available evidence. Methods A literature search identified publications on the use of transplantation in patients with PA and MMA. Publications were considered if they presented adequate demographic and outcome data from patients with PA or MMA. Publications that did not report any specific outcomes for patients or provided insufficient data were excluded. Results Seventy publications were identified of which 38 were full papers. A total of 373 patients underwent liver/kidney/combined liver–kidney transplantation for PA or MMA. The most typical reason for transplantation was recurrent metabolic decompensation. A total of 27 post-transplant deaths were reported in patients with PA [14.0% (27/194)]. For patients with MMA, 18 post-transplant deaths were reported [11% (18/167)]. A total of 62 complications were reported in 115 patients with PA (54%) with cardiomyopathy (n = 12), hepatic arterial thrombosis (HAT; n = 14) and viral infections (n = 12) being the most commonly reported. A total of 52 complications were reported in 106 patients with MMA (49%) with viral infections (n = 14) and renal failure/impairment (n = 10) being the most commonly reported. Conclusions Liver transplantation and combined liver–kidney transplantation appears to benefit some patients with PA or MMA, respectively, but this approach does not provide complete correction of the metabolic defect and some patients remain at risk from disease-related and transplantation-related complications, including death. Thus, all treatment avenues should be exhausted before consideration of organ transplantation and the benefits of this approach must be weighed against the risk of perioperative complications on an individual basis.
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