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Ushijima K, Sanada Y, Otomo S, Ogaki K, Wakiya T, Okada N, Hirata Y, Onishi Y, Sakuma Y, Wada Y, Fujimura A, Mizuta K. Night-Time Chronotherapy with Methylprednisolone Prevents an Acute Rejection in Pediatric Patients with Liver Transplantation: A Randomized Clinical Trial. Clin Pharmacol Ther 2025. [PMID: 40091338 DOI: 10.1002/cpt.3640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 03/03/2025] [Indexed: 03/19/2025]
Abstract
While endogenous cortisol secretion rises in the early morning, the number of lymphocytes in the blood is higher at night, thus exhibiting an antiphase pattern to cortisol secretion. Therefore, compared with the daytime, the infiltration of lymphocytes into immune-reactive tissues is enhanced at night. This study aimed to determine whether the administration of methylprednisolone (mPSL) in the evening is more effective against T cell-mediated rejection (TCMR) after liver transplantation compared with morning administration. This study used a randomized, open-label, parallel-group comparison design. Pediatric patients scheduled to undergo living-donor liver transplantation were randomly divided into morning (8:00 a.m.) and evening (8:00 p.m.) mPSL administration groups. The primary endpoint was the occurrence of TCMR within 14 days of surgery. Sixty-two patients were enrolled between 2014 and 2023, and six patients were excluded from the analysis as their dose of mPSL deviated from the protocol within 14 days after surgery. Of the 56 subjects analyzed, TCMR was detected in 10 of the morning group (n = 29) and three of the evening group (n = 27) within 14 days after surgery. Stratified analysis of patients who did not receive preoperative rituximab treatment showed that none of the evening group and 36.4% of the morning group developed TCMR within 14 days after surgery (P < 0.01, 95% confidence interval; 2.00-infinity). Safety evaluation results were comparable between the two groups. This study shows that the evening administration of mPSL is an effective approach for suppressing TCMR. This study is hypothesis generating, and replication in further studies is needed.
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Affiliation(s)
- Kentaro Ushijima
- Division of Clinical Pharmacology, Jichi Medical University, Tochigi, Japan
- Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan
| | - Yukihiro Sanada
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Shinya Otomo
- Pharmacy of Jichi Medical University Hospital, Tochigi, Japan
| | - Keiko Ogaki
- Pharmacy of Jichi Medical University Hospital, Tochigi, Japan
| | - Taiichi Wakiya
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Noriki Okada
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yuta Hirata
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yasuharu Onishi
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yasunaru Sakuma
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yukiyo Wada
- Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan
| | - Akio Fujimura
- Division of Clinical Pharmacology, Jichi Medical University, Tochigi, Japan
- Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan
| | - Koichi Mizuta
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
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Ushijima K, Sanada Y, Otomo S, Ogaki K, Wakiya T, Okada N, Hirata Y, Horiuchi T, Omameuda T, Takadra K, Akimoto R, Onishi Y, Sakuma Y, Mizuta K. Inherited metabolic diseases are a potent risk factor for cytomegalovirus infection in pediatric living donor liver transplantation. BMC Infect Dis 2025; 25:97. [PMID: 39838300 PMCID: PMC11753104 DOI: 10.1186/s12879-025-10507-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 01/15/2025] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) is a major infectious complication in solid-organ transplant recipients, particularly in the context of pediatric liver transplantation. CMV serostatus is a well-established risk factor for postoperative CMV infection, with CMV seronegative recipients who receive organs from seropositive donors (D+/R-) being at the highest risk. Our previous research indicated a higher incidence of CMV infection in recipients with inherited metabolic diseases (IMDs) compared with those with biliary atresia (BA). This study aimed to determine whether IMDs constitute an independent risk factor for postoperative CMV infection. METHODS We retrospectively analyzed data from 45 IMD and 230 BA recipients. We collected information on the occurrence and timing of episodes of CMV infections, methylprednisolone (mPSL) pulse therapy, patient characteristics, and peri- and postoperative data. RESULTS Multivariable analysis identified mPSL pulse therapy (Odds Ratio (OR): 4.43), CMV serostatus (D+/R-) (OR: 6.03), and underlying IMDs (OR: 3.28) as independent risk factors for CMV infection. Further stratified analysis, which considered the timing of CMV infection diagnosis relative to mPSL pulse therapy, confirmed that CMV serostatus with (D+/R-) (OR: 5.61) and underlying IMDs (OR: 2.83) remained independent predictors of CMV infection, even when excluding the influence of mPSL pulse therapy. CONCLUSIONS This study demonstrates that IMDs are a potent independent risk factor for CMV infection following pediatric liver transplantation. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Kentaro Ushijima
- Division of Clinical Pharmacology, Jichi Medical University, Tochigi, Japan.
- Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan.
| | - Yukihiro Sanada
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Shinya Otomo
- Pharmacy of Jichi Medical University Hospital, Tochigi, Japan
| | - Keiko Ogaki
- Pharmacy of Jichi Medical University Hospital, Tochigi, Japan
| | - Taiichi Wakiya
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Noriki Okada
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yuta Hirata
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Toshio Horiuchi
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Takahiko Omameuda
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Kiichiro Takadra
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Ryosuke Akimoto
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yasuharu Onishi
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yasunaru Sakuma
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Koichi Mizuta
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
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Kakembo N, Loy JI, Fitzgerald TN, Antiel RM. Biliary atresia in Uganda: Current ethical challenges and advancement of public policy. World J Surg 2024; 48:2317-2321. [PMID: 38557980 DOI: 10.1002/wjs.12166] [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: 09/16/2023] [Accepted: 03/17/2024] [Indexed: 04/04/2024]
Abstract
Biliary atresia is a progressive cholangiopathy in neonates, which often results in liver failure. In high-income countries, initial treatment requires prompt diagnosis followed by Kasai portoenterostomy. For those with a late diagnosis, or those in whom Kasai portoenterostomy fails, liver transplantation is the only lifesaving treatment. Unfortunately, in low- and middle-income countries, timely diagnosis is a challenge and liver transplantation is rarely accessible. Here, we discuss the ethical dilemmas surrounding treatment of babies with biliary atresia in Uganda. Issues that require careful consideration include: risk of catastrophic health expenditure to families, ethical dilemmas of transplant tourism, medical risks of maintaining the transplant in a low-resourced health system, and difficult decisions encountered by the surgeon caring for these patients. Four distinct models of the patient-physician relationship are applied to biliary atresia in Uganda. These models describe differences in patient and physician roles, and patient values and autonomy. Solid organ transplantation is a rapidly evolving segment of healthcare in Uganda and ongoing policy advancements may shift ethical considerations in the future.
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Affiliation(s)
- Nasser Kakembo
- Department of Surgery, Makerere University, Kampala, Uganda
| | - J Isaac Loy
- Initiative for Science & Society, Duke University, Durham, North Carolina, USA
- College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Tamara N Fitzgerald
- Department of Surgery, Duke University, Durham, North Carolina, USA
- Duke Global Health Institute, Duke University, Durham, North Carolina, USA
| | - Ryan M Antiel
- Department of Surgery, Duke University, Durham, North Carolina, USA
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Utz Melere M, Sanha V, Farina M, da Silva CS, Nader L, Trein C, Lucchese AM, Ferreira C, Kalil AN, Feier FH. Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort. World J Transplant 2024; 14:88734. [PMID: 38576759 PMCID: PMC10989469 DOI: 10.5500/wjt.v14.i1.88734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/14/2023] [Accepted: 12/18/2023] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Biliary atresia (BA) is the most common indication for pediatric liver trans plantation, although portoenterostomy is usually performed first. However, due to the high failure rate of portoenterostomy, liver transplantation has been advocated as the primary procedure for patients with BA. It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes. AIM To investigate the effect of prior portoenterostomy in infants un dergoing liver transplantation for BA. METHODS This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil. Patients with BA were divided into two groups: Those under going primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy. Continuous variables were compared using the Student's t-test or the Kruskal-Wallis test, and categorical variables were compared using the χ2 or Fisher's exact test, as appropriate. Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis. Patient and graft survival analyses were conducted with the Kaplan-Meier product-limit estimator, and patient subgroups were compared using the two-sided log-rank test. RESULTS Forty-two patients were included in the study (25 [60%] girls), 23 undergoing liver transplantation without prior portoenterostomy, and 19 undergoing liver transplantation with prior portoenterostomy. Patients with prior portoenterostomy were older (12 vs 8 months; P = 0.02) at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores (13.2 vs 21.4; P = 0.01). The majority of the patients (35/42, 83%) underwent living-donor liver transplantation. The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis (39 vs 11%), but this result did not reach statistical significance. Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation, graft-to-recipient weight ratio, and use of vascular grafts. Finally, the groups did not significantly differ in terms of post-transplant survival. CONCLUSION In our study, prior portoenterostomy did not significantly affect the outcomes of liver transplantation.
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Affiliation(s)
- Melina Utz Melere
- Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Brazil
| | - Valberto Sanha
- Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Brazil
| | - Marco Farina
- Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Brazil
| | - Carolina Soares da Silva
- Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Brazil
| | - Luiza Nader
- Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Brazil
| | - Cristine Trein
- Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Brazil
| | - Angelica Maria Lucchese
- Department of Hepato-biliary-pancreatic Surgery and Liver Transplantation, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Cristina Ferreira
- Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Brazil
| | - Antonio Nocchi Kalil
- Department of Surgical Oncology, Santa Rita Hospital/Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90050-170, Rio Grande do Sul, Brazil
| | - Flavia Heinz Feier
- Department of Hepato-biliary-pancreatic Surgery and Liver Transplantation, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
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Gad EH, Sallam AN, Soliman H, Ibrahim T, Salem TAH, Ali MAH, Al-Sayed Abd-same M, Ayoub I. Pediatric living donor liver transplantation (LDLT): Short- and long-term outcomes during sixteen years period at a single centre- A retrospective cohort study. Ann Med Surg (Lond) 2022; 79:103938. [PMID: 35860167 PMCID: PMC9289343 DOI: 10.1016/j.amsu.2022.103938] [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: 05/01/2022] [Revised: 06/01/2022] [Accepted: 06/02/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Pediatric living donor liver transplantation (LDLT) is an effective tool for managing pediatric patients with end-stage liver disease (ESLD) with good long-term graft and patient survival, especially after improvement in peri-operative care, surgical tools and techniques; however, the morbidity and mortality after such a procedure are still a challenging matter. The study aimed to analyze short-and long-term outcomes after pediatric LDLT in a single centre. METHODS We retrospectively analyzed 67 pediatric patients who underwent LDLT in the period from April 2003 to July 2018. The overall male/female ratio was 40/27. RESULTS Forty-one (61.2%) of patients had ≥1 early and/or late morbidities; the early (less than 3months) and late (≥3months) ones affected 36(53.7%) and 12(17.9%) of them respectively. The 16-year graft and patient survivals were 35(52.2%) while early and late mortalities were 23(34.3%) and 9(13.4%) respectively. Sepsis and chronic rejection were the most frequent causes of early and late mortalities respectively. Moreover, more packed RBCs transfusion units, bacterial infections, and pulmonary complications were independent predictors of poor patient survival. CONCLUSIONS More packed RBCs transfusion units intra-operatively, and post-liver transplant (LT) bacterial infection, sepsis, chronic rejection, as well as pulmonary complications had a negative insult on our patients' outcomes, so proper management of them is mandatory for improving outcomes after pediatric LDLT.
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Affiliation(s)
- Emad Hamdy Gad
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
| | - Ahmed Nabil Sallam
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
| | - Hosam Soliman
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
| | - Tarek Ibrahim
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
| | | | | | | | - Islam Ayoub
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
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6
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Song W, Sun LY, Zhu ZJ. Effects of Previous Kasai Surgery on Gut Microbiota and Bile Acid in Biliary Atresia With End-Stage Liver Disease. Front Med (Lausanne) 2021; 8:704328. [PMID: 34646837 PMCID: PMC8502819 DOI: 10.3389/fmed.2021.704328] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 08/31/2021] [Indexed: 12/12/2022] Open
Abstract
Background and Aims: Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Although the Kasai procedure can improve temporary biliary drainage in some cases, complications and liver fibrosis still develop. Liver transplantation is the ultimate treatment. The current study aimed to investigate the effect of previous Kasai surgery on gut microbiota and bile acid in BA with end-stage liver disease. Methods: Patients with BA with end-stage liver disease were divided into two groups according to whether they had previously undergone Kasai surgery (non-Kasai: n = 8, post-Kasai: n = 8). Metagenomic sequencing and ultraperformance liquid chromatography/tandem mass spectrometry were performed to identify the gut microbiota and bile acid. Results: Previous Kasai surgery had some effects on gut microbiota and bile acid in BA with end-stage liver disease. In the gut microbiome, the differential species were mainly distributed at the species level. Veillonella atypica had a significant increase in the non-Kasai group (P < 0.05). Bacteroides spp., Prevotella spp., Barnesiella spp., Parabacteroides spp., Heliobacterium spp., Erysipelatoclostridium spp. and Diaporthe spp. were increased in the post-Kasai group (P < 0.05). Concerning functional profiles, methionine biosynthesis was enriched in the non-Kasai group, while pyridoxal biosynthesis and riboflavin biosynthesis were enriched in the post-Kasai group (linear discriminant analysis > 2, P < 0.05). In stools, 17 bile acids were distinctly elevated in the post-Kasai group, such as cholic acid, chenodeoxycholic acid, β-muricholic acid and tauro α-muricholate (P < 0.05). Spearman correlation test showed that V. atypica had an enormously positive correlation with liver enzymes. Faecalibacterium prausnitzii and Escherichia coli were associated with derivatives of the alternative pathway of bile acid metabolism. Conclusion: Previous Kasai surgery can improve the gut microbiota and bile acid in patients with BA with end-stage liver disease. This improvement contributes to maintaining the intestinal barrier.
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Affiliation(s)
- Wei Song
- 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.,Department of Intensive Care Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhi-Jun Zhu
- 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
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7
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Yamada N, Karasawa T, Wakiya T, Sadatomo A, Ito H, Kamata R, Watanabe S, Komada T, Kimura H, Sanada Y, Sakuma Y, Mizuta K, Ohno N, Sata N, Takahashi M. Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis. Am J Transplant 2020; 20:1606-1618. [PMID: 31909544 DOI: 10.1111/ajt.15773] [Citation(s) in RCA: 190] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 12/06/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023]
Abstract
Hepatic ischemia-reperfusion (I/R) injury is a major problem in liver transplantation (LT). Although hepatocyte cell death is the initial event in hepatic I/R injury, the underlying mechanism remains unclear. In the present study, we retrospectively analyzed the clinical data of 202 pediatric living donor LT and found that a high serum ferritin level, a marker of iron overload, of the donor is an independent risk factor for liver damage after LT. Since ferroptosis has been recently discovered as an iron-dependent cell death that is triggered by a loss of cellular redox homeostasis, we investigated the role of ferroptosis in a murine model of hepatic I/R injury, and found that liver damage, lipid peroxidation, and upregulation of the ferroptosis marker Ptgs2 were induced by I/R, and all of these manifestations were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or α-tocopherol. Fer-1 also inhibited hepatic I/R-induced inflammatory responses. Furthermore, hepatic I/R injury was attenuated by iron chelation by deferoxamine and exacerbated by iron overload with a high iron diet. These findings demonstrate that iron overload is a novel risk factor for hepatic I/R injury in LT, and ferroptosis contributes to the pathogenesis of hepatic I/R injury.
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Affiliation(s)
- Naoya Yamada
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.,Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Tadayoshi Karasawa
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Taiichi Wakiya
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Ai Sadatomo
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Homare Ito
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Ryo Kamata
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Sachiko Watanabe
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Takanori Komada
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Hiroaki Kimura
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
| | - Yukihiro Sanada
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yasunaru Sakuma
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Koichi Mizuta
- Department of Transplant Surgery, Saitama Children's Medical Center, Saitama, Japan
| | - Nobuhiko Ohno
- Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University, Tochigi, Japan.,Division of Ultrastructural Research, National Institute for Physiological Sciences, Aichi, Japan
| | - Naohiro Sata
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Masafumi Takahashi
- Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
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Abstract
We present the most recent research results on the creation of pigs that can accept human cells. Pigs in which grafted human cells can flourish are essential for studies of the production of human organs in the pig and for verification of the efficacy of cells and tissues of human origin for use in regenerative therapy. First, against the background of a worldwide shortage of donor organs, the need for future medical technology to produce human organs for transplantation is discussed. We then describe proof-of-concept studies in small animals used to produce human organs. An overview of the history of studies examining the induction of immune tolerance by techniques involving fertilized animal eggs and the injection of human cells into fetuses or neonatal animals is also presented. Finally, current and future prospects for producing pigs that can accept human cells and tissues for experimental purposes are discussed.
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Okada N, Sanada Y, Onishi Y, Urahashi T, Ihara Y, Yamada N, Hirata Y, Katano T, Imai T, Ushijima K, Ogaki K, Otomo S, Mizuta K. The Causes and Outcomes of Early Relaparotomy Following Pediatric Living Donor Liver Transplantation. Liver Transpl 2019; 25:1066-1073. [PMID: 30865366 DOI: 10.1002/lt.25446] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 03/07/2019] [Indexed: 12/25/2022]
Abstract
Early relaparotomy of adult recipients after living donor liver transplantation (LDLT) is significantly associated with poor prognosis. However, there are few reports focusing on pediatric recipients after LDLT. The aim of this study is to clarify the causes and outcomes of early relaparotomy after pediatric LDLT. A total of 265 pediatric recipients (272 LDLTs) transplanted from May 2001 to October 2015 were retrospectively analyzed. Early relaparotomy was defined as surgical intervention performed within 3 months after LDLT. Early relaparotomy was performed 49 times for 33 recipients (12.5%). The recipient and graft survival rates in the early relaparotomy group were significantly lower than those in the nonearly relaparotomy group, respectively (75.0% and 63.6% versus 96.6% and 95.8%; both P < 0.001). Left lateral segment grafts were used significantly more frequently in the nonrelaparotomy group (P = 0.01). According to the multivariate analysis, the preoperative Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) score of the early relaparotomy group was significantly higher than that of the nonearly relaparotomy group (13.7 versus 6.3; P = 0.04). According to the receiver operating characteristic curve, the preoperative PELD/MELD score cutoff point was 17.2. Early relaparotomy due to infectious causes led to significantly poorer graft survival than that due to noninfectious causes (P = 0.04). In conclusion, the recipient and graft survival rates of the early relaparotomy group were significantly lower than those of the nonearly relaparotomy group. A high preoperative PELD/MELD score was a risk factor for early relaparotomy. In particular, early relaparotomy due to infection showed a poor prognosis.
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Affiliation(s)
- Noriki Okada
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Yukihiro Sanada
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Yasuharu Onishi
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Taizen Urahashi
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Yoshiyuki Ihara
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Naoya Yamada
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Yuta Hirata
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Takumi Katano
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Toshimi Imai
- Pharmacology, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Kentaro Ushijima
- Pharmacology, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Keiko Ogaki
- Pharmacy, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Shinya Otomo
- Pharmacy, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
| | - Koichi Mizuta
- Departments of Transplant Surgery, Jichi Medical University Hospital, Jichi Medical University, Shimotsuke City, Japan
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10
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Vitamin A can ameliorate fibrosis of liver in an established rat model of biliary atresia and Kasai portoenterostomy. J Pediatr Surg 2018; 53:2416-2422. [PMID: 30257812 DOI: 10.1016/j.jpedsurg.2018.08.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Accepted: 08/25/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Antifibrosis therapy may prevent progressive liver fibrosis after successful Kasai portoenterostomy (KPE) in biliary atresia (BA) patients. The aim of this study is to evaluate the efficacy of antifibrosis therapy in a rat model of BA and KPE. METHODS BA model was created on three-week-old Sprague-Dawley rats by intrabiliary alcohol injection as previously described, and KPE was performed at postoperative week (POW) 5 by cystoenterostomy. Liver biopsies were performed at the time of BA creation, during KPE, POW 9, and at sacrifice (POW 17). Prednisolone (0.1 mg/100 g/day, group 1, n = 20), Vitamin A (0.5 mg/100 g/day, group 2, n = 20), and ursodeoxycholic acid (UDCA, 1.5 mg/100 g/day, group 3, n = 20) were respectively given to three groups after KPE and continued daily until sacrifice. Histological evaluation of fibrosis and immunohistochemistry stains for 8 fibrosis markers were compared to the control group (without medication, n = 10). RESULTS Among the four markers, namely ɑ-smooth muscle actin (ɑ-SMA), glial fibrillary acidic protein (GFAP), tumor growth factor β1 (TGFβ1) receptors 1 and 2, which showed persistently high expression after successful KPE in the examined 8 markers, only the expression of ɑ-SMA was significantly reduced in all treatment groups at POW17. However, the fibrosis grade at POW 17 was only significantly reduced in group 2 in comparison with the control group (Vitamin A vs. control group, Ishak score 3 vs. 1.8, p < 0.05). CONCLUSION In our rat model of BA with KPE, Vitamin A was effective in reducing liver fibrosis, and the mechanisms deserve further study. LEVEL OF EVIDENCE Basic science.
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Okada N, Sanada Y, Urahashi T, Ihara Y, Yamada N, Hirata Y, Katano T, Otomo S, Ushijima K, Mizuta K. Endotoxin Metabolism Reflects Hepatic Functional Reserve in End-Stage Liver Disease. Transplant Proc 2018; 50:1360-1364. [PMID: 29705277 DOI: 10.1016/j.transproceed.2018.01.052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 12/29/2017] [Accepted: 01/23/2018] [Indexed: 01/29/2023]
Abstract
BACKGROUND The hepatic clearance of endotoxin (Et) may reflect hepatic functional reserve and ischemic injury to hepatocytes. Therefore, we examined the relationships between Et activity (EA) and the metrics Pediatric End-Stage Liver Disease (PELD)/Model of End-Stage Liver Disease (MELD) score and alanine transaminase (ALT) levels in the postoperative period. METHODS We performed 8 living-donor liver transplantations (LDLTs) for biliary atresia at our center from April 2012 to December 2012. EA was measured by means of an Et activity assay (EAA) in samples collected from a vein 1 day before LDLT, from the portal vein during the intraoperative anhepatic phase, from an artery 1 hour after reperfusion, from an artery on postoperative day (POD) 1, and from an artery or vein at PODs 7 and 14. RESULTS EAs generally remained at low levels. EA at the reperfusion period was significantly lowest. The correlation coefficient for the preoperative MELD/PELD score and the EAA was 0.837, and the corresponding P value was .009; thus, there was a significant relationship between the preoperative MELD/PELD score and the EAA. The correlation coefficients for ALT at POD 1 and EA during the anhepatic phase, at 1 hour after reperfusion, and at POD 1 were 0.64, 0.43, and 0.38, respectively, and the P values for these correlations were .08, .67, and .34. Thus, we observed that ALT and EA generally tended to be somewhat directly correlated, but no significant relationships between these 2 metrics were observed. CONCLUSIONS Endotoxin metabolism reflects the hepatic functional reserve capacity of end-stage liver disease.
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Affiliation(s)
- N Okada
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan.
| | - Y Sanada
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan
| | - T Urahashi
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan
| | - Y Ihara
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan
| | - N Yamada
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan
| | - Y Hirata
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan
| | - T Katano
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan
| | - S Otomo
- Department of Pharmacy, Jichi Medical University Hospital, Tochigi, Japan
| | - K Ushijima
- Department of Clinical Pharmacy, Jichi Medical University, Tochigi, Japan
| | - K Mizuta
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan
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Kitajima T, Sakamoto S, Sasaki K, Uchida H, Narumoto S, Fukuda A, Teramukai S, Uemoto S, Kasahara M. Living donor liver transplantation for post-Kasai biliary atresia: Analysis of pretransplant predictors of outcomes in infants. Liver Transpl 2017; 23:1199-1209. [PMID: 28590589 DOI: 10.1002/lt.24796] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 04/24/2017] [Accepted: 05/23/2017] [Indexed: 12/29/2022]
Abstract
After decades of dramatic surgical innovations in pediatric living donor liver transplantation (LDLT), LDLT for biliary atresia (BA) still poses various challenges. This study reviewed our experience with LDLT for children with post-Kasai BA and evaluated outcomes and prognostic factors. From 2005 to 2016, 168 post-Kasai BA LDLT patients were enrolled and divided into 3 groups by age. Patient characteristics and perioperative data were compared. Predictors of morbidity and mortality following LDLT were analyzed in 93 infants. Outcome was relatively worse in infants than older children, with overall survival at 1 and 5 years of 94.5% and 93.2%, respectively, and graft survival at 1 and 5 years of 91.1% each. Incidence of vascular complications was not significantly higher in infants. High Pediatric End-Stage Liver Disease (PELD) score (odds ratio [OR], 3.72; 95% confidence interval [CI], 1.30-10.67; P = 0.02) and portal vein (PV) hypoplasia (OR, 3.23; 95% CI, 1.10-9.52; P = 0.03) were independent risk factors for morbidity. Low weight-for-age z score (hazard ratio, 5.76; 95% CI, 1.05-31.47; P = 0.03) was identified as a significant risk factor for mortality after LDLT, but not age or absolute body weight (BW). Infants with BW deficit had a significantly smaller PV diameter (P = 0.005), greater blood loss (P = 0.001), and higher incidence of postoperative bacteremia (P = 0.01). In conclusion, high PELD score and PV hypoplasia were independent risk factors for morbidity, and BW deficit was associated with poor survival in infants with post-Kasai BA after LDLT. However, LDLT in these infants at the earliest possible time after referral is a feasible option with excellent patient survival in an experienced center. Liver Transplantation 23 1199-1209 2017 AASLD.
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Affiliation(s)
- Toshihiro Kitajima
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Seisuke Sakamoto
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Kengo Sasaki
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Hajime Uchida
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Soichi Narumoto
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Akinari Fukuda
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Satoshi Teramukai
- Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
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Yanagi Y, Matsuura T, Hayashida M, Takahashi Y, Yoshimaru K, Esumi G, Taguchi T. Bowel perforation after liver transplantation for biliary atresia: a retrospective study of care in the transition from children to adulthood. Pediatr Surg Int 2017; 33:155-163. [PMID: 27882406 PMCID: PMC5263240 DOI: 10.1007/s00383-016-4008-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2016] [Indexed: 02/07/2023]
Abstract
PURPOSE We evaluated the outcomes of liver transplantation (LT) in pediatric and adult patients with biliary atresia (BA). We focused on bowel perforation after LT (BPLT) as the most common surgical complication and analyzed its risk factors. METHODS This was a retrospective analysis of 70 BA patients who underwent LT. The patients were divided into three groups according to the timing of LT: within the first year of age (Group A), between 1 and 12 years of age (Group B), and after 12 years of age (Group C). The outcomes of LT and the clinical presentations of BPLT were compared. The surgical variables of patients with and without BPLT were analyzed to assess the risk factors. RESULTS The timing of LT did not affect patient survival. The incidence of BPLT was significantly higher in Group C. In Group C, BPLT progressed to severe peritonitis. No cases of BPLT-associated mortality were observed. A multivariate analysis revealed that a prolonged operative time for LT was an independent risk factor (p = 0.03). CONCLUSION The clinical course after transplantation was complicated after adolescence. BPLT should be strongly suspected and relaparotomy should be performed in a timely manner for patients undergoing LT after adolescence.
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Affiliation(s)
- Yusuke Yanagi
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Toshiharu Matsuura
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Makoto Hayashida
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Yoshiaki Takahashi
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Koichiro Yoshimaru
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Genshirou Esumi
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Tomoaki Taguchi
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
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Nacoti M, Corbella D, Fazzi F, Rapido F, Bonanomi E. Coagulopathy and transfusion therapy in pediatric liver transplantation. World J Gastroenterol 2016; 22:2005-23. [PMID: 26877606 PMCID: PMC4726674 DOI: 10.3748/wjg.v22.i6.2005] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Revised: 11/23/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, "developmental hemostasis", demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the "cell based model of coagulation", takes into account the interaction between plasma proteins and cells. In the last, the concept of "rebalanced coagulation" highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Data, however, are currently lacking regarding the use of anti-aggregation/anticoagulation therapies and how to best monitor for thrombosis in the early postoperative period in pediatric patients. Therefore, further studies are necessary to elucidate the interaction between the development of the coagulation system and cirrhosis in children. Moreover, strategies to optimize blood transfusion and anticoagulation must be tested specifically in pediatric patients. In conclusion, data from the adult world can be translated with difficulty into the pediatric field as indication for transplantation, baseline pathologies and levels of pro- and anticoagulation factors are not comparable between the two populations.
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Living Related Liver Transplantation for Biliary Atresia in the Last 5 years: Experience from the First Liver Transplant Program in India. Indian J Pediatr 2015; 82:884-9. [PMID: 25708058 DOI: 10.1007/s12098-014-1687-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2014] [Accepted: 12/31/2014] [Indexed: 02/01/2023]
Abstract
OBJECTIVE To study the clinical, biochemical profile and outcome of patients with biliary atresia (BA) who underwent living related liver transplantation (LRLT) at authors' institute in the last 5 y (2008-2013). METHODS Case records of the 20 patients diagnosed with biliary atresia who had undergone living related liver transplantation at authors' centre in the last 5 y were analysed. RESULTS Eighteen patients with BA with a failed Kasai procedure and 2 without a prior Kasai's portoenterostomy received a liver transplant. At a median follow up of 2 y and 6 mo, both the patient and graft survival rates were 90 %. The median age of the recipients at the time of LRLT was 8 mo and 12 (60 %) of the transplanted children were less than or equal to 1 y of age. The male-female ratio was 1.8:1. The median weight was 7.3 kg (5.8-48 kg); two thirds were less than 10 kg. The median pre-transplant total serum bilirubin (TSB) and international normalized ratio (INR) were 12.98 (0.5-48.3) mg/dl and 1.3 (1.0-3.9) respectively. All patients received a living related graft and there was no donor mortality. The median duration of postoperative ventilation was 14 h. The post-operative complications were infection (30 %), vascular complications (20 %) and acute rejection (20 %). The median duration of postoperative hospital stay was 21 d (17-42). Two patients died of combined hepatic and portal vein thrombosis in the early postoperative period. Late rejection was encountered in 1 patient and another developed chronic kidney disease necessitating a renal transplant. There were no late vascular occlusions or development of post transplant lymphoproliferative disease. CONCLUSIONS Thus, LRLT for BA with or without a prior portoenterostomy, is a feasible and successful treatment modality with good outcomes attained despite the challenges of age and size. This treatment modality is now well established in India.
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Okada N, Sanada Y, Hirata Y, Yamada N, Wakiya T, Ihara Y, Urahashi T, Miki A, Kaneda Y, Sasanuma H, Fujiwara T, Sakuma Y, Shimizu A, Hyodo M, Yasuda Y, Mizuta K. The impact of rituximab in ABO-incompatible pediatric living donor liver transplantation: the experience of a single center. Pediatr Transplant 2015; 19:279-86. [PMID: 25689881 DOI: 10.1111/petr.12445] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/16/2015] [Indexed: 01/08/2023]
Abstract
Previous studies have demonstrated the safety of ABO-incompatible pediatric LDLT using preoperative plasmapheresis and rituximab; however, no reports have described the timing and dosage of rituximab administration for pediatric LDLT. This study aimed to describe a safe and effective dosage and timing of rituximab for patients undergoing pediatric ABO-incompatible LDLT based on the experience of our single center. A total of 192 LDLTs in 187 patients were examined. These cases included 29 ABO-incompatible LDLTs in 28 patients. Rituximab was used beginning in January 2004 in recipients older than two yr of age (first period: 375 mg/m(2) in two cases; second period: 50 mg/m(2) in two cases; and 200 mg/m(2) in eight cases). Two patients who received 375 mg/m(2) rituximab died of Pneumocystis carinii pneumonia and hemophagocytic syndrome. One patient who received 50 mg/m(2) rituximab required retransplantation as a consequence of antibody-mediated complications. All eight patients administered 200 mg/m(2) survived, and the mean CD20(+) lymphocyte count was 0.1% at the time of LDLT. In the preoperative management of patients undergoing pediatric ABO-incompatible LDLT, the administration of 200 mg/m(2) rituximab three wk prior to LDLT was safe and effective.
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Affiliation(s)
- Noriki Okada
- Department of Transplant Surgery, Jichi Medical University, Shimotsuke-shi, Tochigi-ken, Japan
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Graft Regeneration in Pediatric Living Donor Liver Transplantation. Transplant Proc 2014; 46:767-9. [DOI: 10.1016/j.transproceed.2013.10.048] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Accepted: 10/28/2013] [Indexed: 02/07/2023]
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Management of neonatal cholestasis: Consensus statement of the pediatric gastroenterology chapter of Indian academy of pediatrics. Indian Pediatr 2014; 51:203-10. [DOI: 10.1007/s13312-014-0375-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Wang JB, Liu C, Yeh YC, Liu CP, Chang CJ, Chen CY, Chin T. A novel rat model simulating biliary atresia after a Kasai operation. J INVEST SURG 2014; 27:183-90. [PMID: 24476001 DOI: 10.3109/08941939.2013.856969] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
PURPOSE The mechanisms of liver fibrosis in biliary atresia (BA) after a Kasai operation deserve studying to improve the clinical outcomes. This study aimed to create a rat model simulating BA after a Kasai operation. METHODS We inserted a polyethylene tube (PE10) into the common hepatic duct (CHD) and ligated the common bile duct (CBD) in 30 newborn rats and injected 95% ethanol into IHD at postoperative week-one (POW-1). The PE10 was removed at POW-3. The rats were sacrificed at POW-5. The CBD cystojejunostomy was performed on another 10 rats at POW-5. RESULTS The IHD obliteration and CBD dilatation were noted at POW-3 cholangiography before removal of the PE tube. The gross findings at sacrifice in the rats without cystojejunostomy included biliary fibrosis, CBD cyst, and IHD obliteration. The microscopic findings of the liver were like BA. Seven of the 10 rats with CBD cystojejunostomy were jaundice-free at POW-8. The fibrosis grade at POW-8 of the rats with CBD cystojejunostomy was significantly lower in the jaundice-free rats (Ishak fibrosis score, 3.4 ± 0.9 and 1.5 ± 0.3 in the jaundiced rats and jaundice-free rats, respectively, p < .05). CONCLUSION Based on our study, CBD cystojejunostomy five weeks after CBD ligation with ethanol injection into the IHD in newborn rats can provide a model for investigating mechanisms and treatments of liver fibrosis in BA after a Kasai operation.
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Affiliation(s)
- Jen-Bin Wang
- 1Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, School of Medicine , Taipei , Taiwan
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Chardot C, Buet C, Serinet MO, Golmard JL, Lachaux A, Roquelaure B, Gottrand F, Broué P, Dabadie A, Gauthier F, Jacquemin E. Improving outcomes of biliary atresia: French national series 1986-2009. J Hepatol 2013; 58:1209-17. [PMID: 23402746 DOI: 10.1016/j.jhep.2013.01.040] [Citation(s) in RCA: 167] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2012] [Revised: 01/22/2013] [Accepted: 01/27/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS This study analyses the prognosis of biliary atresia (BA) in France since liver transplantation (LT) became widely available. METHODS The charts of all BA patients living in France and born between 1986 and 2009 were reviewed. Patients were divided into 3 cohorts according to their years of birth: 1986-1996, 1997-2002, and 2003-2009. RESULTS 1107 BA children were identified, 990 born in metropolitan France (incidence 1/18,400 live births). Kasai operation was performed in 1044 (94%), leading to complete clearance of jaundice (total serum bilirubin ≤ 20 μmol/L) in 38% of patients. Survival with native liver (SNL) after Kasai operation was 40%, 36%, and 30% at 5, 10, and 20 years, stable in the 3 cohorts. Median age at Kasai operation was 59 days, unchanged over time. Twenty-year SNL was 39%, 32%, 28%, and 19% after Kasai operation performed in the first, second, third months of life or thereafter (p=0.0002). 588 children underwent 692 LTs. Mortality without transplantation decreased over time: 16%, 7%, and 4% in the 3 cohorts (p<0.0001). Survival after transplantation was 83%, 82%, and 77% at 5, 10, and 20 years in the whole series. Five-year post-transplant survival was 75%, 90%, and 89% in the 3 cohorts (p<0.0001). In the whole series, overall BA patient survival was 81%, 80%, and 77% at 5, 10, and 20 years. Five-year BA patient overall survival increased over time: 72%, 88%, and 89% in the 3 cohorts (p<0.0001). CONCLUSIONS BA patients currently have an 89% live expectancy, and a 30% chance to reach adulthood without transplantation. Early Kasai operation, without age threshold, reduces the need for liver transplantation until adulthood.
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Affiliation(s)
- Christophe Chardot
- Observatoire français de l'atrésie des voies biliaires, Hôpital Necker - Enfants malades, Université Paris Descartes, Paris, France.
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Zhu JJ, Xia Q, Zhang JJ, Xue F, Chen XS, Li QG, Xu N. Living donor liver transplantation in 43 children with biliary atresia: a single-center experience from the mainland of China. Hepatobiliary Pancreat Dis Int 2012; 11:250-5. [PMID: 22672817 DOI: 10.1016/s1499-3872(12)60156-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND There is no large-cohort report on living donor liver transplantation (LDLT) for biliary atresia (BA) patients from the mainland of China. This single-center study describes our initial experience with 43 LDLTs for BA patients aged two years or younger. METHODS In this study, the eligibility criteria were BA as the primary diagnosis and two years of age or younger. From October 2006 to December 2010, the clinical data of 43 LDLTs, including pre-operative evaluations, surgical techniques, postoperative complications and outcomes of donors and recipients, were retrospectively analyzed. RESULTS Donor graft type was the left lateral segment with compatible ABO blood groups. Forty-three recipients were selected in this study. The median patient age at operation was 9 months (range 6-24), and the median body weight was 8 kg (range 5.7-12.5). Fourteen (32.6%) recipients received Kasai operations before liver transplantation. The overall one- and two-year cumulative survival rates for grafts and recipients were 81%, 81% and 76%, 76%, respectively. No donor mortality was encountered, with a minimal morbidity and no long-term sequelae. Nine out of 43 recipients died. Postoperative complications of recipients were biliary leakage and refluxing cholangitis (11/43, 25.6%), hepatic artery thrombosis (4, 9.3%), pulmonary infections (4, 9.3%), portal vein thrombosis (3, 7.0%), wound disruption (3, 7.0%), acute rejection (3, 7.0%), cytomegalovirus infection (2, 4.7%), and intra-abdominal bleeding (1, 2.3%). CONCLUSION Despite the relatively low survival rates due to lack of experience initially, LDLT still provides encouraging outcomes for pediatric recipients with BA, even small children under two years old.
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Affiliation(s)
- Jian-Jun Zhu
- Department of Liver Surgery, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Mizuta K, Urahashi T, Ihara Y, Sanada Y, Wakiya T, Yamada N, Okada N, Egami S, Hishikawa S, Hyodo M, Sakuma Y, Fujiwara T, Kawarasaki H, Yasuda Y. Living Donor Liver Transplantation in Children With Cholestatic Liver Disease: A Single-Center Experience. Transplant Proc 2012; 44:469-72. [DOI: 10.1016/j.transproceed.2011.11.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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