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Liu X, Shen J, Yan H, Hu J, Liao G, Liu D, Zhou S, Zhang J, Liao J, Guo Z, Li Y, Yang S, Li S, Chen H, Guo Y, Li M, Fan L, Li L, Luo P, Zhao M, Liu Y. Posttransplant complications: molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2024; 5:e669. [PMID: 39224537 PMCID: PMC11366828 DOI: 10.1002/mco2.669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 07/02/2024] [Accepted: 07/08/2024] [Indexed: 09/04/2024] Open
Abstract
Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.
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Affiliation(s)
- Xiaoyou Liu
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Junyi Shen
- Department of OncologyZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Hongyan Yan
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Jianmin Hu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Guorong Liao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ding Liu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Song Zhou
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Jie Zhang
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Jun Liao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Zefeng Guo
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yuzhu Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Siqiang Yang
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Shichao Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Hua Chen
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ying Guo
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Min Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Lipei Fan
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Liuyang Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Peng Luo
- Department of OncologyZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ming Zhao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yongguang Liu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
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Nabulsi S, Otunla AA, Salciccioli J, Marshall DC, Villani V, Shanmugarajah K, Shalhoub J. HLA matching between donors and recipients improves clinical liver transplant graft survival. Liver Int 2024; 44:411-421. [PMID: 38010995 DOI: 10.1111/liv.15774] [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: 07/06/2023] [Revised: 10/03/2023] [Accepted: 10/16/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND AND AIMS The importance of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large-scale multi-centre database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication and donor status. METHODS This retrospective observational analysis was performed using 22 702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs. 4-6 mismatches) and then subcategorized by indication and donor status. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. RESULTS Allograft survival and risk of acute rejection were associated with degree of HLA mismatch. This association between HLA mismatch and graft survival persisted in individuals who underwent transplant for hepatitis, metabolic, drug toxicity, and congenital indications. Donor status also influenced the relationship between HLA mismatch and graft survival. Graft survival in DBD recipients was longer than in DCD in the 4-6 HLA mismatch group, whereas no significant difference was found in the 0-3 HLA mismatch group. CONCLUSION HLA mismatch significantly reduced graft survival and increased risk of acute rejection. This association was noted only in specific indications. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols, and transplant surveillance.
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Affiliation(s)
- Sarah Nabulsi
- Department of Life Sciences, Imperial College London, London, UK
| | | | - Justin Salciccioli
- Department of Critical Care, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | - Vincenzo Villani
- Department of Transplantation, Memorial Hermann Health System, Houston, Texas, USA
| | | | - Joseph Shalhoub
- Academic Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College London, London, UK
- Imperial Vascular Unit, Imperial College Healthcare NHS Trust, London, UK
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Kok G, Ilcken EF, Houwen RH, Lindemans CA, Nieuwenhuis EE, Spierings E, Fuchs SA. The Effect of Genetic HLA Matching on Liver Transplantation Outcome: A Systematic Review and Meta-Analysis. ANNALS OF SURGERY OPEN 2023; 4:e334. [PMID: 37746594 PMCID: PMC10513352 DOI: 10.1097/as9.0000000000000334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 08/11/2023] [Indexed: 09/26/2023] Open
Abstract
Objective We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation. Background Liver transplantation is a common treatment for patients with end-stage liver disease. In contrast to most other solid organ transplantations, there is no conclusive evidence supporting human leukocyte antigen (HLA) matching for liver transplantations. With emerging alternatives such as transplantation of bankable (stem) cells, HLA matching becomes feasible, which may decrease the need for immunosuppressive therapy and improve transplantation outcomes. Methods We systematically searched the PubMed, Embase, and Cochrane databases and performed a meta-analysis investigating the effect of genetic HLA matching on liver transplantation outcomes (acute/chronic rejection, graft failure, and mortality). Results We included 14 studies with 2682 patients. HLA-C mismatching significantly increased the risk of acute rejection (full mismatching: risk ratio = 1.90, 95% confidence interval = 1.08 to 3.33, P = 0.03; partial mismatching: risk ratio = 1.33, 95% confidence interval = 1.07 to 1.66, P = 0.01). We did not discern any significant effect of HLA mismatching per locus on acute rejection for HLA-A, -B, -DR, and -DQ, nor on chronic rejection, graft failure, or mortality for HLA-DR, and -DQ. Conclusions We found evidence that genetic HLA-C matching reduces the risk of acute rejection after liver transplantation while matching for other loci does not reduce the risk of acute rejection, chronic rejection, graft failure, or mortality.
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Affiliation(s)
- Gautam Kok
- From the Department of Metabolic Diseases, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
| | - Eveline F. Ilcken
- From the Department of Metabolic Diseases, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
| | - Roderick H.J. Houwen
- Department of Pediatric Gastroenterology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
| | - Caroline A. Lindemans
- Department of Immunology, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Hematopoietic Cell Transplantation, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Edward E.S. Nieuwenhuis
- Department of Pediatric Gastroenterology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
| | - Eric Spierings
- Center of Translational Immunology, Utrecht University Medical Center, Utrecht, The Netherlands
| | - Sabine A. Fuchs
- From the Department of Metabolic Diseases, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
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Hu L, Lin J, Shi X, Wang A. Efficacy of transarterial therapy combined with first-line tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a network meta-analysis. World J Surg Oncol 2023; 21:208. [PMID: 37475030 PMCID: PMC10360255 DOI: 10.1186/s12957-023-03098-3] [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: 03/11/2023] [Accepted: 07/12/2023] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND Transarterial therapies, including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and selective internal radiation therapy, combined with first-line tyrosine kinase inhibitors (TKIs) are considered the standard therapy for unresectable hepatocellular carcinoma. However, inconsistent results have been reported in various studies assessing different combinations of targeted agents. METHODS A network meta-analysis (NMA) was performed by including 23 randomized controlled trials (RCTs) with 6175 patients to investigate the efficiency of transarterial therapies in combination with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), time to progression (TTP), and tumor objective response rate (ORR). A random-effects consistency model was used in this Bayesian NMA. Hazard ratio and odd risks with a 95% credible interval were calculated and agents were ranked based on ranking probability. RESULTS HAIC showed maximal OS and TTP and TACE plus lenvatinib showed maximal PFS, ORR, and disease control rate (DCR). HAIC and TACE plus lenvatinib were ranked highest based on their respective parameters, which were OS for HAIC and PFS, ORR, and DCR for TACE plus lenvatinib. CONCLUSION HAIC and TACE plus lenvatinib were relatively better choice for unresectable hepatocellular carcinoma. However, owing to the lack of statistically significant OS benefits among most agents, other agents should be considered as potential alternatives for unresectable hepatocellular carcinoma.
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Affiliation(s)
- Lingbo Hu
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
- Department of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center (Group), Zhejiang, China
| | - Jiangying Lin
- Department of Blood Purification, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
| | - Xingpeng Shi
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China
- Department of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center (Group), Zhejiang, China
| | - Aidong Wang
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Zhejiang, China.
- Department of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center (Group), Zhejiang, China.
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Tajima T, Hata K, Kusakabe J, Miyauchi H, Yurugi K, Hishida R, Ogawa E, Okamoto T, Sonoda M, Kageyama S, Zhao X, Ito T, Seo S, Okajima H, Nagao M, Haga H, Uemoto S, Hatano E. The impact of human leukocyte antigen mismatch on recipient outcomes in living-donor liver transplantation. Liver Transpl 2022; 28:1588-1602. [PMID: 35603526 PMCID: PMC9796617 DOI: 10.1002/lt.26511] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/19/2022] [Accepted: 05/10/2022] [Indexed: 01/01/2023]
Abstract
Donor-recipient human leukocyte antigen (HLA) compatibility has not been considered to significantly affect liver transplantation (LT) outcomes; however, its significance in living-donor LT (LDLT), which is mostly performed between blood relatives, remains unclear. This retrospective cohort study included 1954 LDLTs at our institution (1990-2020). The primary and secondary endpoints were recipient survival and the incidence of T cell-mediated rejection (TCMR) after LDLT, respectively, according to the number of HLA mismatches at all five loci: HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ. Subgroup analyses were also performed in between-siblings that characteristically have widely distributed 0-10 HLA mismatches. A total of 1304 cases of primary LDLTs were finally enrolled, including 631 adults (recipient age at LT ≥18 years) and 673 children (<18 years). In adult-to-adult LDLT, the more HLA mismatches at each locus, the significantly worse the recipient survival was (p = 0.03, 0.01, 0.03, 0.001, and <0.001 for HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ, respectively). This trend was more pronounced when multiple loci were combined (all p < 0.001 for A + B + DR, A + B + C, DR + DQ, and A + B + C + DR + DQ). Notably, a total of three or more HLA-B + DR mismatches was an independent risk factor for both TCMR (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.21-5.87; p = 0.02) and recipient survival (HR 2.44, 95% CI 1.11-5.35; p = 0.03) in between-siblings. By contrast, HLA mismatch did not affect pediatric LDLT outcomes at any locus or in any combinations; however, it should be noted that all donor-recipient relationships are parent-to-child that characteristically possesses one or less HLA mismatch at each locus and maximally five or less mismatches in total. In conclusion, HLA mismatch significantly affects not only TCMR development but also recipient survival in adult LDLT, but not in children.
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Affiliation(s)
- Tetsuya Tajima
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Koichiro Hata
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Jiro Kusakabe
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Hidetaka Miyauchi
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kimiko Yurugi
- Department of Clinical Laboratory MedicineKyoto University HospitalKyotoJapan
| | - Rie Hishida
- Department of Clinical Laboratory MedicineKyoto University HospitalKyotoJapan
| | - Eri Ogawa
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Tatsuya Okamoto
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Mari Sonoda
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Shoichi Kageyama
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Xiangdong Zhao
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takashi Ito
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Satoru Seo
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Hideaki Okajima
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan,Department of Pediatric SurgeryKanazawa Medical UniversityKanazawaJapan
| | - Miki Nagao
- Department of Clinical Laboratory MedicineKyoto University HospitalKyotoJapan
| | - Hironori Haga
- Department of Diagnostic PathologyKyoto University HospitalKyotoJapan
| | - Shinji Uemoto
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan,Shiga University of Medical ScienceJapan
| | - Etsuro Hatano
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
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Bricogne C, Halliday N, Fernando R, Tsochatzis EA, Davidson BR, Harber M, Westbrook RH. Donor-recipient human leukocyte antigen A mismatching is associated with hepatic artery thrombosis, sepsis, graft loss, and reduced survival after liver transplant. Liver Transpl 2022; 28:1306-1320. [PMID: 35313059 PMCID: PMC9541857 DOI: 10.1002/lt.26458] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 01/13/2023]
Abstract
Human leukocyte antigen (HLA) matching is not routinely performed for liver transplantation as there is no consistent evidence of benefit; however, the impact of HLA mismatching remains uncertain. We explored the effect of class I and II HLA mismatching on graft failure and mortality. A total of 1042 liver transplants performed at a single center between 1999 and 2016 with available HLA typing data were included. The median follow-up period was 9.38 years (interquartile range 4.9-14) and 350/1042 (33.6%) transplants resulted in graft loss and 280/1042 (26.9%) in death. Graft loss and mortality were not associated with the overall number of mismatches at HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci. However, graft failure and mortality were both increased in HLA mismatching on graft failure and mortality the presence of one (p = 0.004 and p = 0.01, respectively) and two (p = 0.01 and p = 0.04, respectively) HLA-A mismatches. Elevated hazard ratios for graft failure and death were observed with HLA-A mismatches in univariate and multivariate Cox proportional hazard models. Excess graft loss with HLA-A mismatch (138/940 [14.7%] mismatched compared with 6/102 [5.9%] matched transplants) occurred within the first year following transplantation (odds ratio 2.75; p = 0.02). Strikingly, transplants performed at a single all grafts lost due to hepatic artery thrombosis were in HLA-A-mismatched transplants (31/940 vs. 0/102), as were those lost due to sepsis (35/940 vs. 0/102). In conclusion, HLA-A mismatching was associated with increased graft loss and mortality. The poorer outcome for the HLA-mismatched group was due to hepatic artery thrombosis and sepsis, and these complications occurred exclusively with HLA-A-mismatched transplants. These data suggest that HLA-A mismatching is important for outcomes following liver transplant. Therefore, knowledge of HLA-A matching status may potentially allow for enhanced surveillance, clinical interventions in high-risk transplants or stratified HLA-A matching in high-risk recipients.
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Affiliation(s)
- Christopher Bricogne
- Sheila Sherlock Liver UnitRoyal Free London NHS Foundation Trust and Institute for Liver and Digestive HealthUniversity College LondonLondonUK
| | - Neil Halliday
- Sheila Sherlock Liver UnitRoyal Free London NHS Foundation Trust and Institute for Liver and Digestive HealthUniversity College LondonLondonUK
| | - Raymond Fernando
- The Anthony Nolan Research InstituteRoyal Free London NHS Foundation TrustLondonUK
| | - Emmanuel A. Tsochatzis
- Sheila Sherlock Liver UnitRoyal Free London NHS Foundation Trust and Institute for Liver and Digestive HealthUniversity College LondonLondonUK
| | - Brian R. Davidson
- UCL Division of Surgery and Interventional SciencesRoyal Free HospitalLondonUK
| | - Mark Harber
- Kidney UnitRoyal Free London NHS Foundation TrustLondonUK
| | - Rachel H. Westbrook
- Sheila Sherlock Liver UnitRoyal Free London NHS Foundation Trust and Institute for Liver and Digestive HealthUniversity College LondonLondonUK
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Jeong J, Tanaka M, Iwakiri Y. Hepatic lymphatic vascular system in health and disease. J Hepatol 2022; 77:206-218. [PMID: 35157960 PMCID: PMC9870070 DOI: 10.1016/j.jhep.2022.01.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/13/2022] [Accepted: 01/31/2022] [Indexed: 02/07/2023]
Abstract
In recent years, significant advances have been made in the study of lymphatic vessels with the identification of their specific markers and the development of research tools that have accelerated our understanding of their role in tissue homeostasis and disease pathogenesis in many organs. Compared to other organs, the lymphatic system in the liver is understudied despite its obvious importance for hepatic physiology and pathophysiology. In this review, we describe fundamental aspects of the hepatic lymphatic system and its role in a range of liver-related pathological conditions such as portal hypertension, ascites formation, malignant tumours, liver transplantation, congenital liver diseases, non-alcoholic fatty liver disease, and hepatic encephalopathy. The article concludes with a discussion regarding the modulation of lymphangiogenesis as a potential therapeutic strategy for liver diseases.
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Affiliation(s)
- Jain Jeong
- Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Masatake Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuko Iwakiri
- Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.
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Liu Y, Chan CK. The oxidative potential of fresh and aged elemental carbon-containing airborne particles: a review. ENVIRONMENTAL SCIENCE. PROCESSES & IMPACTS 2022; 24:525-546. [PMID: 35333266 DOI: 10.1039/d1em00497b] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Elemental carbon is often found in ambient particulate matter (PM), and it contributes to the PM's oxidative potential (OP) and thus poses great health concerns. Previous review articles mainly focused on the methodologies in evaluating OP in PM and its relationship with selected chemical constituents, including metal ions, PAHs, and inorganic species. In recent years, growing attention has been paid to the effect of atmospheric aging processes on the OP of EC-containing airborne particles (ECCAPs). This review investigates more than 150 studies concerning the OP measurements and physico-chemical properties of both fresh and aged ECCAPs such as laboratory-generated elemental carbon (LGEC), carbon black (CB), soot (black carbon), and engineered carbon-containing nanomaterials (ECCBNs). Specifically, we summarize the characteristics of water-soluble and insoluble organic species, PAHs, quinone, and oxygen-containing functional groups (OFGs), and EC crystallinity. Both water-soluble organic carbon (WSOC) and water-insoluble organic carbon (WIOC) contribute to the OP. Low molecular weight (MW) PAHs show a higher correlation with OP than high MW PAHs. Furthermore, oxidative aging processes introduce OFGs, where quinone (CO) and epoxide (O-C-O) increase the OP of ECCAPs. In contrast, carboxyl (-COOH) and hydroxyl (-OH) slightly change the OP. The low crystallinity of EC favors the oxygen addition and forms active OFG quinone, thus increasing the OP. More detailed analyses for the EC microstructures and the organic coatings are needed to predict the OP of ECCAPs.
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Affiliation(s)
- Yangyang Liu
- School of Energy and Environment, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
| | - Chak K Chan
- School of Energy and Environment, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
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Ono K, Ide K, Tanaka Y, Ohira M, Tahara H, Tanimine N, Yamane H, Ohdan H. Molecular Mismatch Predicts T Cell-Mediated Rejection and De Novo Donor-Specific Antibody Formation After Living Donor Liver Transplantation. Liver Transpl 2021; 27:1592-1602. [PMID: 34310028 DOI: 10.1002/lt.26238] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/24/2021] [Accepted: 07/19/2021] [Indexed: 02/06/2023]
Abstract
Human leukocyte antigen (HLA) molecular mismatch (MM) analysis improves the prediction of clinical outcomes in kidney transplantation compared with prediction via traditional antigen MM. However, it remains unclear whether the level of MM can be used for risk stratification among liver transplantation (LT) recipients. A retrospective observational study of 45 living donor LTs was performed to evaluate eplet MM as a risk factor for both T cell-mediated rejection (TCMR) in the first month and de novo donor-specific antibody (dnDSA) formation. A total of 9 (20%) patients displayed TCMR. HLA-A, HLA-B, HLA-C, and HLA-DRB1 eplet MM numbers were not associated with TCMR. By contrast, HLA-DQB1 eplet MM (DQB1-EpMM) number was significantly high in patients with TCMR. The predicted indirectly recognizable HLA epitopes (PIRCHE-II) score for the HLA-DQB1 locus (DQB1-PIRCHE-II) was also significantly higher in the TCMR group than in the no-TCMR group. There was a high probability for TCMR to occur with either a DQB1-EpMM ≥7 or a DQB1-PIRCHE-II ≥13. Pretransplant mixed lymphocyte response analyses indicated that there were no significant differences between the antidonor T cell proliferation activities of patients with low-number (<7) and high-number (≥7) DQB1-EpMMs. However, the proportion of CD25 expression on proliferating antidonor CD8+ T cells, used as a cytotoxic activity marker, was high in DQB1-EpMMs ≥7. Moreover, both DQB1-EpMMs ≥9 and DQB1-PIRCHE-II ≥3 were predictors of dnDSA formation. Thus, MM analysis may be applied toward tailored immunosuppression based on individual risks.
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Affiliation(s)
- Kosuke Ono
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuka Tanaka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naoki Tanimine
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroaki Yamane
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Féray C, Taupin JL, Sebagh M, Allain V, Demir Z, Allard MA, Desterke C, Coilly A, Saliba F, Vibert E, Azoulay D, Guettier C, Chatton A, Debray D, Caillat-Zucman S, Samuel D. Donor HLA Class 1 Evolutionary Divergence Is a Major Predictor of Liver Allograft Rejection : A Retrospective Cohort Study. Ann Intern Med 2021; 174:1385-1394. [PMID: 34424731 DOI: 10.7326/m20-7957] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The HLA evolutionary divergence (HED), a continuous metric quantifying the peptidic differences between 2 homologous HLA alleles, reflects the breadth of the immunopeptidome presented to T lymphocytes. OBJECTIVE To assess the potential effect of donor or recipient HED on liver transplant rejection. DESIGN Retrospective cohort study. SETTING Liver transplant units. PATIENTS 1154 adults and 113 children who had a liver transplant between 2004 and 2018. MEASUREMENTS Liver biopsies were done 1, 2, 5, and 10 years after the transplant and in case of liver dysfunction. Donor-specific anti-HLA antibodies (DSAs) were measured in children at the time of biopsy. The HED was calculated using the physicochemical Grantham distance for class I (HLA-A or HLA-B) and class II (HLA-DRB1 or HLA-DQB1) alleles. The influence of HED on the incidence of liver lesions was analyzed through the inverse probability weighting approach based on covariate balancing, generalized propensity scores. RESULTS In adults, class I HED of the donor was associated with acute rejection (hazard ratio [HR], 1.09 [95% CI, 1.03 to 1.16]), chronic rejection (HR, 1.20 [CI, 1.10 to 1.31]), and ductopenia of 50% or more (HR, 1.33 [CI, 1.09 to 1.62]) but not with other histologic lesions. In children, class I HED of the donor was also associated with acute rejection (HR, 1.16 [CI, 1.03 to 1.30]) independent of the presence of DSAs. There was no effect of either donor class II HED or recipient class I or class II HED on the incidence of liver lesions in adults and children. LIMITATION The DSAs were measured only in children. CONCLUSION Class I HED of the donor predicts acute or chronic rejection of liver transplant. This novel and accessible prognostic marker could orientate donor selection and guide immunosuppression. PRIMARY FUNDING SOURCE Institut National de la Santé et de la Recherche Médicale.
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Affiliation(s)
- Cyrille Féray
- Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.)
| | - Jean-Luc Taupin
- Laboratoire d'Immunologie et Histocompatibilité, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université de Paris, and unité Institut National de la Santé et de la Recherche Médicale 976, Université de Paris, Paris, France (J.T., S.C.)
| | - Mylène Sebagh
- Laboratoire d'Anatomopathologie, Assistance Publique-Hôpitaux de Paris, Hôpital Paul-Brousse, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale, Physiopathogénèse et traitement des maladies du Foie, and FHU Hepatinov, Villejuif, France (M.S., C.G.)
| | - Vincent Allain
- Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université de Paris, Laboratoire d'Immunologie et Histocompatibilité, and Institut National de la Santé et de la Recherche Médicale, Paris, France (V.A.)
| | - Zeynep Demir
- Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, and Unité d'Hépatologie pédiatrique, Paris, France (Z.D., D.D.)
| | - Marc-Antoine Allard
- Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.)
| | - Christophe Desterke
- Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.)
| | - Audrey Coilly
- Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.)
| | - Faouzi Saliba
- Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.)
| | - Eric Vibert
- Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.)
| | - Daniel Azoulay
- Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.)
| | - Catherine Guettier
- Laboratoire d'Anatomopathologie, Assistance Publique-Hôpitaux de Paris, Hôpital Paul-Brousse, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale, Physiopathogénèse et traitement des maladies du Foie, and FHU Hepatinov, Villejuif, France (M.S., C.G.)
| | - Arthur Chatton
- Institut National de la Santé et de la Recherche Médicale UMR 1246-SPHERE, Nantes University, Tours University, Nantes, and IDBC, Pacé, France (A.C.)
| | - Dominique Debray
- Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, and Unité d'Hépatologie pédiatrique, Paris, France (Z.D., D.D.)
| | - Sophie Caillat-Zucman
- Laboratoire d'Immunologie et Histocompatibilité, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université de Paris, and unité Institut National de la Santé et de la Recherche Médicale 976, Université de Paris, Paris, France (J.T., S.C.)
| | - Didier Samuel
- Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.)
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11
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Bartling T, Oedingen C, Schrem H, Kohlmann T, Krauth C. 'As a surgeon, I am obliged to every single patient': evaluation of focus group discussions with transplantation physicians on the allocation of donor organs. Curr Opin Organ Transplant 2021; 26:459-467. [PMID: 34343155 DOI: 10.1097/mot.0000000000000908] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Organ transplantation is the last resort for many patients. The ubiquitous shortage of suitable donor organs raises the question of best-justifiable allocation worldwide. This study investigates how physicians would allocate donor organs. METHODS Focus group discussions with a total of 12 transplant surgeons and 2 other transplant-related physicians were held at the annual conference of the German Transplantation Society (Oct 2019). Three groups discussed aspects of 'egalitarianism', 'effectiveness/benefit', 'medical urgency', 'own fault', 'medical background' and 'socio-demographic status'. RESULTS AND DISCUSSION It was observed that physicians often find themselves confronted with conflicts between (a) trying to advocate for their individual patients versus (b) seeing the systemic perspective and understanding the global impact of their decisions at the same time. The groups agreed that due to the current shortage of donor organs in the German allocation system, transplanted patients are often too sick at the point of transplantation and that a better balance between urgency and effectiveness is needed. The aspects of 'effectiveness' and 'urgency' were identified as the most challenging issues and thus were the main focus of debate. The dilemmas physicians find themselves in become increasingly severe, the larger the shortage of suitable donor organs is.
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Affiliation(s)
- Tim Bartling
- Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School
- Center for Health Economic Research Hannover (CHERH), Hannover, Germany
| | - Carina Oedingen
- Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School
- Center for Health Economic Research Hannover (CHERH), Hannover, Germany
| | - Harald Schrem
- Center for Health Economic Research Hannover (CHERH), Hannover, Germany
- Transplant Center Graz
- Department of Transplant Surgery, Medical University Graz, Graz, Austria
| | - Thomas Kohlmann
- Department for Methods of Community Medicine, Institute for Community Medicine, University of Greifswald, Greifswald, Germany
| | - Christian Krauth
- Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School
- Center for Health Economic Research Hannover (CHERH), Hannover, Germany
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12
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Mittal S, Sinha P, Sarin S, Rastogi A, Gupta E, Bajpai M, Pamecha V, Trehanpati N. Impact of human leukocyte antigen compatibility on outcomes of living donor liver transplantation: Experience from a tertiary care center. Transpl Infect Dis 2021; 23:e13644. [PMID: 33999511 DOI: 10.1111/tid.13644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 04/19/2021] [Accepted: 05/06/2021] [Indexed: 11/29/2022]
Abstract
INTRODUCTION The role of HLA compatibility in kidney, heart, and stem cell transplantation is well known, but with regard to living donor liver transplantation (LDLT), there is a different scenario. In the present study, we aim to examine the effects of donor-recipient HLA mismatches at A, B, and DR loci on various outcomes of LDLT-like graft survival, early allograft dysfunction (EAD), acute rejection, length of hospital (LOH) stay, sepsis, and cytomegalovirus (CMV) reactivation. METHODS This is a retrospective single center study of a cohort of adult patients who underwent first time ABO-compatible (ABOc) LDLT between January 2010 and December 2018. Transplants with incomplete records or without HLA typing data were excluded. Donor-recipient HLA-A, B, and DR mismatches were assessed in the host versus graft (HVG) direction and were correlated with various post-transplant outcomes. RESULTS Among 140 transplants being evaluated, approximately two third had total HLA mismatches between 2 and 3. HLA mismatches at each locus as well as cumulative HLA mismatches did not show any association with overall graft survival, EAD, acute rejection episodes, and LOH stay. However, the presence of minimum one mismatch at HLA-A and DR loci was associated with the development of CMV reactivation (P = .03) and sepsis (P = .02) post-LDLT respectively. CONCLUSION HLA mismatch is not associated with acute rejection, early graft dysfunction, and overall survival in LDLT. Its impact on CMV reactivation and sepsis needs further evaluation.
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Affiliation(s)
- Siddharth Mittal
- Department of Clinical and Cellular Transplant Immunology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Piyush Sinha
- Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shashwat Sarin
- Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ekta Gupta
- Department of Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Meenu Bajpai
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Viniyendra Pamecha
- Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nirupma Trehanpati
- Department of Clinical and Cellular Transplant Immunology, Institute of Liver and Biliary Sciences, New Delhi, India
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13
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Thomson AW, Vionnet J, Sanchez-Fueyo A. Understanding, predicting and achieving liver transplant tolerance: from bench to bedside. Nat Rev Gastroenterol Hepatol 2020; 17:719-739. [PMID: 32759983 DOI: 10.1038/s41575-020-0334-4] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/11/2020] [Indexed: 02/07/2023]
Abstract
In the past 40 years, liver transplantation has evolved from a high-risk procedure to one that offers high success rates for reversal of liver dysfunction and excellent patient and graft survival. The liver is the most tolerogenic of transplanted organs; indeed, immunosuppressive therapy can be completely withdrawn without rejection of the graft in carefully selected, stable long-term liver recipients. However, in other recipients, chronic allograft injury, late graft failure and the adverse effects of anti-rejection therapy remain important obstacles to improved success. The liver has a unique composition of parenchymal and immune cells that regulate innate and adaptive immunity and that can promote antigen-specific tolerance. Although the mechanisms underlying liver transplant tolerance are not well understood, important insights have been gained into how the local microenvironment, hepatic immune cells and specific molecular pathways can promote donor-specific tolerance. These insights provide a basis for the identification of potential clinical biomarkers that might correlate with tolerance or rejection and for the development of novel therapeutic targets. Innovative approaches aimed at promoting immunosuppressive drug minimization or withdrawal include the adoptive transfer of donor-derived or recipient-derived regulatory immune cells to promote liver transplant tolerance. In this Review, we summarize and discuss these developments and their implications for liver transplantation.
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Affiliation(s)
- Angus W Thomson
- Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. .,Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
| | - Julien Vionnet
- Institute of Liver Studies, Medical Research Council (MRC) Centre for Transplantation, School of Immunology and Infectious Diseases, King's College London University, King's College Hospital, London, UK.,Transplantation Center, University Hospital of Lausanne, Lausanne, Switzerland.,Service of Gastroenterology and Hepatology, University Hospital of Lausanne, Lausanne, Switzerland
| | - Alberto Sanchez-Fueyo
- Institute of Liver Studies, Medical Research Council (MRC) Centre for Transplantation, School of Immunology and Infectious Diseases, King's College London University, King's College Hospital, London, UK
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14
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Evidence of the Prognostic Value of Pretreatment Systemic Inflammation Response Index in Cancer Patients: A Pooled Analysis of 19 Cohort Studies. DISEASE MARKERS 2020; 2020:8854267. [PMID: 32934755 PMCID: PMC7479458 DOI: 10.1155/2020/8854267] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/24/2020] [Accepted: 08/04/2020] [Indexed: 12/13/2022]
Abstract
Objective Systemic inflammation response index (SIRI) is a new inflammation-based evaluation system that has been reported for predicting survival in multiple tumors, but the prognostic significance of SIRI in cancers has not been evinced. Methods Eligible studies updated on December 31, 2019, were selected according to inclusion criteria, the literature searching was performed in PubMed, Web of Science, Google Scholar, and Cochrane. Hazard ratios (HRs), and 95% confidence intervals (CIs) were extracted and pooled by using Stata/SE 14.1. Results 11 publications involving 19 cohort studies with a total of 5,605 subjects were included. Meta-analysis results evinced that high SIRI was associated with worse OS (HR = 2.30, 95% CI: 1.87-2.83, p ≤ 0.001), poor CSS/DSS (HR = 2.83, 95% CI: 1.98-4.04, p ≤ 0.001), and inferior MFS/DFS/PFS/RFS/TTP (HR = 1.88, 95% CI: 1.65-2.15, p ≤ 0.001). The association of SIRI with OS was not significantly affected when stratified by diverse confounding factors. It was suggested that tumor patients with high pretreatment SIRI levels would suffer from adverse outcomes. Conclusion High SIRI is associated with unfavorable clinical outcomes in human malignancies; pretreatment SIRI level might be a useful and promising predictive indicator of prognosis in cancers.
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15
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Number of Antibody-verified Eplet in HLA-C Locus as an Independent Factor of T-cell–Mediated Rejection After Liver Transplantation. Transplantation 2020; 104:562-567. [DOI: 10.1097/tp.0000000000002921] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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16
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Meszaros M, Niemann M, Ursic-Bedoya J, Faure S, Meunier L, Rivière B, Costes-Martineau V, Thevenin C, Pageaux GP. Exploring predicted indirectly recognizable HLA epitopes (PIRCHE-II) in liver transplant recipients on calcineurin inhibitor-free maintenance immunosuppression. A retrospective single center study. Transpl Immunol 2020; 59:101272. [PMID: 32061667 DOI: 10.1016/j.trim.2020.101272] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 02/09/2020] [Accepted: 02/11/2020] [Indexed: 12/12/2022]
Abstract
The PIRCHE (Predicted Indirectly ReCognizable HLA Epitopes) score is an HLA epitope matching algorithm. PIRCHE algorithm estimates the level of presence of T-cell epitopes in mismatched HLA. The PIRCHE-II numbers associate with de novo donor-specific antibody (dnDSA) formation following liver transplantation and kidney allograft survival following renal transplantation. The aim of our study was to assess the PIRCHE-II score in calcineurin inhibitor (CNI)-free maintenance immunosuppression recipients. This was a retrospective study of forty-one liver transplant recipients on CNI-free immunosuppression and with available liver allograft biopsies. Donors and recipients were HLA typed. The HLA-derived mismatched peptide epitopes that could be presented by the recipient's HLA-DRB1 molecules were calculated using PIRCHE-II algorithm. The associations between PIRCHE-II scores and graft immune-mediated events were assessed using receiver operating characteristics curves and subsequent univariate and multivariate analyses. CNI-free patients with cellular rejection, humoral rejection, or severe portal inflammation had higher mean PIRCHE-II scores compared to patients with normal liver allografts. PIRCHE-II score and donor age were independent risk factors for liver graft survival in CNI-free patients (HR: 8.0, 95% CI: 1.3-49, p = .02; and HR: 0.88, 95% CI: 0.00-0.96, p = .007, respectively). PIRCHE-II scores could be predictive of liver allograft survival in CNI-free patients following liver transplantation. Larger studies are needed to confirm these results.
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Affiliation(s)
- Magdalena Meszaros
- CHU Saint Eloi, Hepatology and Liver transplantation unit, Montpellier, France.
| | | | - José Ursic-Bedoya
- CHU Saint Eloi, Hepatology and Liver transplantation unit, Montpellier, France
| | - Stéphanie Faure
- CHU Saint Eloi, Hepatology and Liver transplantation unit, Montpellier, France
| | - Lucy Meunier
- CHU Saint Eloi, Hepatology and Liver transplantation unit, Montpellier, France
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17
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Gao Y, Twigg AR, Hirose R, Roll GR, Nowacki AS, Maytin EV, Vidimos AT, Rajalingam R, Arron ST. Association of HLA Antigen Mismatch With Risk of Developing Skin Cancer After Solid-Organ Transplant. JAMA Dermatol 2020; 155:307-314. [PMID: 30673077 DOI: 10.1001/jamadermatol.2018.4983] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Importance Risk factors for the development of skin cancer after solid-organ transplant can inform clinical care, but data on these risk factors are limited. Objective To study the association between HLA antigen mismatch and skin cancer incidence after solid-organ transplant. Design, Setting, and Participants This retrospective cohort study is a secondary analysis of the multicenter Transplant Skin Cancer Network study of 10 649 adults who underwent a primary solid-organ transplant between January 1, 2003, and December 31, 2003, or between January 1, 2008, and December 31, 2008. These participants were identified through the Scientific Registry of Transplant Recipients standard analysis files, which contain data collected mostly by the Organ Procurement and Transplantation Network. Participants were matched to skin cancer outcomes by medical record review. This study was conducted from August 1, 2016, to July 31, 2017. Main Outcomes and Measures The primary outcome was time to diagnosis of posttransplant skin cancer, including squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The HLA antigen mismatch was calculated based on the 2016 Organ Procurement and Transplantation Network guidelines. Risk of skin cancer was analyzed using a multivariate Cox proportional hazards regression model. Results In total, 10 649 organ transplant recipients (6776 men [63.6%], with a mean [SD] age of 51 [12] years) contributed 59 923 years of follow-up. For each additional mismatched allele, a 7% to 8% reduction in skin cancer risk was found (adjusted hazard ratio [HR], 0.93; 95% CI, 0.87-0.99; P = .01). Subgroup analysis found the protective effect of HLA antigen mismatch to be statistically significant in lung (adjusted HR, 0.70; 95% CI, 0.56-0.87; P = .001) and heart (adjusted HR, 0.75; 95% CI, 0.60-0.93; P = .008) transplant recipients but not for recipients of liver, kidney, or pancreas. The degree of HLA-DR mismatch, but not HLA-A or HLA-B mismatch, was the most statistically significant for skin cancer risk (adjusted HR, 0.85; 95% CI, 0.74-0.97; P = .01). Conclusions and Relevance The HLA antigen mismatch appears to be associated with reductions in the risk of skin cancer after solid-organ transplant among heart and lung transplant recipients; this finding suggests that HLA antigen mismatch activates the tumor surveillance mechanisms that protect against skin cancer in transplant recipients and that skin cancer risk may be higher in patients who received a well-matched organ.
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Affiliation(s)
- Yi Gao
- Department of Medicine, Banner University Medical Center, Phoenix, Arizona
| | - Amanda R Twigg
- Department of Dermatology, University of California, San Francisco, San Francisco
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco
| | - Garrett R Roll
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco
| | - Amy S Nowacki
- Department of Quantitative Health Sciences, The Cleveland Clinic Foundation, Cleveland, Ohio
| | - Edward V Maytin
- Department of Dermatology, The Cleveland Clinic Foundation, Cleveland, Ohio
| | - Allison T Vidimos
- Department of Dermatology, The Cleveland Clinic Foundation, Cleveland, Ohio
| | - Raja Rajalingam
- Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California, San Francisco, San Francisco
| | - Sarah T Arron
- Department of Dermatology, University of California, San Francisco, San Francisco
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Best LMJ, Leung J, Freeman SC, Sutton AJ, Cooper NJ, Milne EJ, Cowlin M, Payne A, Walshaw D, Thorburn D, Pavlov CS, Davidson BR, Tsochatzis E, Williams NR, Gurusamy KS, Cochrane Hepato‐Biliary Group. Induction immunosuppression in adults undergoing liver transplantation: a network meta-analysis. Cochrane Database Syst Rev 2020; 1:CD013203. [PMID: 31978255 PMCID: PMC6984652 DOI: 10.1002/14651858.cd013203.pub2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Liver transplantation is considered the definitive treatment for people with liver failure. As part of post-liver transplantation management, immunosuppression (suppressing the host immunity) is given to prevent graft rejections. Immunosuppressive drugs can be classified into those that are used for a short period during the beginning phase of immunosuppression (induction immunosuppression) and those that are used over the entire lifetime of the individual (maintenance immunosuppression), because it is widely believed that graft rejections are more common during the first few months after liver transplantation. Some drugs such as glucocorticosteroids may be used for both induction and maintenance immunosuppression because of their multiple modalities of action. There is considerable uncertainty as to whether induction immunosuppression is necessary and if so, the relative efficacy of different immunosuppressive agents. OBJECTIVES To assess the comparative benefits and harms of different induction immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different induction immunosuppressive regimens according to their safety and efficacy. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until July 2019 to identify randomised clinical trials in adults undergoing liver transplantation. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) in adults undergoing liver transplantation. We excluded randomised clinical trials in which participants had multivisceral transplantation and those who already had graft rejections. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, and hazard ratio (HR) with 95% credible intervals (CrIs) based on an available case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included a total of 25 trials (3271 participants; 8 treatments) in the review. Twenty-three trials (3017 participants) were included in one or more outcomes in the review. The trials that provided the information included people undergoing primary liver transplantation for various indications and excluded those with HIV and those with renal impairment. The follow-up in the trials ranged from three to 76 months, with a median follow-up of 12 months among trials. All except one trial were at high risk of bias, and the overall certainty of evidence was very low. Overall, approximately 7.4% of people who received the standard regimen of glucocorticosteroid induction died and 12.2% developed graft failure. All-cause mortality and graft failure was lower with basiliximab compared with glucocorticosteroid induction: all-cause mortality (HR 0.53, 95% CrI 0.31 to 0.93; network estimate, based on 2 direct comparison trials (131 participants; low-certainty evidence)); and graft failure (HR 0.44, 95% CrI 0.28 to 0.70; direct estimate, based on 1 trial (47 participants; low-certainty evidence)). There was no evidence of differences in all-cause mortality and graft failure between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). There was also no evidence of differences in serious adverse events (proportion), serious adverse events (number), renal failure, any adverse events (proportion), any adverse events (number), liver retransplantation, graft rejections (any), or graft rejections (requiring treatment) between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the studies reported health-related quality of life. FUNDING the source of funding for 14 trials was drug companies who would benefit from the results of the study; two trials were funded by neutral organisations who have no vested interests in the results of the study; and the source of funding for the remaining nine trials was unclear. AUTHORS' CONCLUSIONS Based on low-certainty evidence, basiliximab induction may decrease mortality and graft failure compared to glucocorticosteroids induction in people undergoing liver transplantation. However, there is considerable uncertainty about this finding because this information is based on small trials at high risk of bias. The evidence is uncertain about the effects of different induction immunosuppressants on other clinical outcomes, including graft rejections. Future randomised clinical trials should be adequately powered, employ blinding, avoid post-randomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, graft failure, and health-related quality of life.
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Affiliation(s)
- Lawrence MJ Best
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
| | - Jeffrey Leung
- University College LondonMedical SchoolGower StreetLondonUKWC1H6BT
| | - Suzanne C Freeman
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Alex J Sutton
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Nicola J Cooper
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | | | | | - Anna Payne
- Royal Free London NHS Foundation TrustHPB and Liver Transplant SurgeryPond StreetLondonGreater LondonUKNW3 2QG
| | - Dana Walshaw
- Barts and The London NHS TrustAcute MedicineLondonUK
| | - Douglas Thorburn
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentrePond StreetLondonUKNW3 2QG
| | - Chavdar S Pavlov
- 'Sechenov' First Moscow State Medical UniversityCenter for Evidence‐Based MedicinePogodinskja st. 1\1MoscowRussian Federation119881
| | - Brian R Davidson
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
| | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentrePond StreetLondonUKNW3 2QG
| | - Norman R Williams
- UCL Division of Surgery & Interventional ScienceSurgical & Interventional Trials Unit (SITU)3rd Floor, Charles Bell House 43 – 45Foley StreetLondonUKW1W 7TY
| | - Kurinchi Selvan Gurusamy
- University College LondonDivision of Surgery and Interventional ScienceRowland Hill StreetLondonUKNW32PF
- 'Sechenov' First Moscow State Medical UniversityCenter for Evidence‐Based MedicinePogodinskja st. 1\1MoscowRussian Federation119881
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Bartling T, Oedingen C, Kohlmann T, Schrem H, Krauth C. Comparing preferences of physicians and patients regarding the allocation of donor organs: A systematic review. Transplant Rev (Orlando) 2020; 34:100515. [DOI: 10.1016/j.trre.2019.100515] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 10/23/2019] [Accepted: 10/24/2019] [Indexed: 12/13/2022]
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Choudhary NS, Saha SK, Saigal S, Gautam D, Saraf N, Rastogi A, Bhangui P, Thiagrajan S, Soin AS. Do Recipients of Genetically Related Donors Have Better Outcomes After Living Donor Liver Transplantation? J Clin Exp Hepatol 2020; 10:334-338. [PMID: 32655237 PMCID: PMC7335709 DOI: 10.1016/j.jceh.2019.12.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 12/16/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND There are few data on genetic relation of the donor and outcomes in living donor liver transplantation (LDLT) recipients. We compared outcomes of LDLT between recipients of genetically related and unrelated donors in a large single-center series. METHODS The study included 1372 adult, ABO-compatible, primary LDLT recipients, who received a graft from either a first-degree relative (parent, sibling, son, or daughter; n = 756) or unrelated donor (spouse or relative of the spouse; n = 616). RESULTS The mean age of the recipients with a related donor was 50.2 ± 10.8 years compared with 47.3 ± 9.3 years for recipients with unrelated donors (P = 0.000). Chronic rejection was significantly more common in the genetically unrelated donor group than in the genetically related donor group (28 [4.5%] versus 9 [1.1%]; P = 0.000) at a mean follow-up of 37 months (15-95 months). There were no significant differences in other outcomes between the 2 groups. The 12-month and 36-month survival between the unrelated and related groups was 87.6% versus 90%, and 86.3% versus 89.7% respectively (P = 0.115). The multivariate analysis revealed genetically unrelated donors (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.80-8.34, P = 0.001) and history of acute cellular rejection (OR: 3.39, 95% CI: 1.68-6.81, P = 0.001) as predictors of chronic rejection. CONCLUSION Although chronic rejection was found to be more common in genetically unrelated donors, the patient survival after LDLT was similar.
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, the Medicity, India
| | - Sujeet K. Saha
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, the Medicity, India
| | - Sanjiv Saigal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, the Medicity, India,Address for correspondence: Dr. Sanjiv Saigal Director, Transplant Hepatology Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, 122001, India.
| | - Dheeraj Gautam
- Department of Histopathology, Medanta, the Medicity, Gurgaon, India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, the Medicity, India
| | - Amit Rastogi
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, the Medicity, India
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, the Medicity, India
| | - Srinivasan Thiagrajan
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, the Medicity, India
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, the Medicity, India
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21
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The clinicopathological and prognostic value of PD-L1 in urothelial carcinoma: a meta-analysis. Clin Exp Med 2019; 19:407-416. [DOI: 10.1007/s10238-019-00572-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 07/22/2019] [Indexed: 11/25/2022]
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22
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Lu X, Guo W, Xu W, Zhang X, Shi Z, Zheng L, Zhao W. Prognostic value of the Glasgow prognostic score in colorectal cancer: a meta-analysis of 9,839 patients. Cancer Manag Res 2018; 11:229-249. [PMID: 30636896 PMCID: PMC6307678 DOI: 10.2147/cmar.s185350] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Purpose The aim of this study was to perform a systematic review and meta-analysis to evaluate the value of the Glasgow prognostic score (GPS) or modified Glasgow prognostic score (mGPS) in patients with colorectal cancer (CRC). Methods A comprehensive medical literature search was performed using the online databases PubMed, Embase, Web of Science, and the Cochrane Library. After extracting basic characteristics and prognostic data from the included studies, overall survival (OS) and cancer-specific survival (CSS) were pooled as primary outcomes. Subgroup analyses were performed according to therapeutic strategies, models, cutoff values, regions, tumor, node, metastasis stages, sample size, and ages. Results Forty-three independent cohorts from 41 studies with 9,839 CRC patients were included in the present study. Correlation between GPS or mGPS and OS was analyzed in 32 cohorts of 7,714 patients, and 23 independent cohorts of 5,375 patients focused on the correlation between GPS or mGPS and CSS. The overall outcomes showed that patients with elevated GPS or mGPS were associated with poor OS (HR: 2.20, 95% CI: 1.88–2.57, P<0.001). Elevated GPS or mGPS also resulted in worse CSS (HR: 1.86, 95% CI: 1.59–2.17, P<0.001). The results of the subgroup analyses confirmed the overall outcomes. Conclusion GPS or mGPS is an accurate prognostic predictor in patients with CRC. Patients with elevated pretreatment GPS or mGPS have a poor prognosis. Subgroup analyses confirmed the overall outcomes. Pretreatment GPS is a useful biomarker in the management of CRC.
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Affiliation(s)
- Xin Lu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Wanying Guo
- Department of Breast Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Wei Xu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Xuelei Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Zhijie Shi
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Leizhen Zheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Wenzhao Zhao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
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23
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Gurusamy KS, Tsochatzis E. Induction immunosuppression in adults undergoing liver transplantation: a network meta-analysis. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2018. [DOI: 10.1002/14651858.cd013203] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Affiliation(s)
- Kurinchi Selvan Gurusamy
- University College London; Division of Surgery and Interventional Science; 9th Floor, Royal Free Hospital Rowland Hill Street London UK NW3 2PF
| | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive Health; Sheila Sherlock Liver Centre; Pond Street London UK NW3 2QG
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24
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Feng J, Gu X, Liu L, Lu M, Ma X, Cao Y, Jiang R, Wang B, Zhao Q. Prognostic Role of MicroRNA-497 In Cancer Patients: A Meta-analysis. J Cancer 2018; 9:3334-3342. [PMID: 30271494 PMCID: PMC6160686 DOI: 10.7150/jca.25514] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 07/16/2018] [Indexed: 01/08/2023] Open
Abstract
Background: MicroRNA-497(miR-497) has been studied for its irreplaceable role of predicting the prognosis of various cancers, but there has been no systematic study to summarize the data. Consequently, we performed this meta-analysis to reveal the association between the expression level of miR-497 and cancer prognosis systematically. Materials and Methods: PubMed was searched for appropriate studies and a total of 12 eligible publications with 989 cancer patients were recruited into our analysis to assess the strength of the association. Hazard ratios (HRs) and odds ratios (ORs) were analyzed to finish this work. Results: The cancer patients who have high expressing level of miR-497 are less possible to have lymph node metastasis (OR = 0.25, 95% CI: 0.16-0.40, P < 0.001) and more likely to have favourable tumor-node-metastasis stage (OR = 0.29, 95% CI: 0.17-0.49, P < 0.001). Also, high miR-497 expression level was notably connected to better overall survival (pooled HR = 0.41, 95% CI: 0.32-0.53, P < 0.001). Conclusions: High expressing levels of miR-497 might be a potential biomarker which can be used to predict the better prognosis of different cancer types.
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Affiliation(s)
- Jiaxi Feng
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xi Gu
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Liyang Liu
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ming Lu
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiang Ma
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yang Cao
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Rongjiang Jiang
- Department of Urology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Baolin Wang
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qinghong Zhao
- Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Wen Y, Shu F, Chen Y, Chen Y, Lan Y, Duan X, Zhao SC, Zeng G. The prognostic value of HOXA13 in solid tumors: A meta-analysis. Clin Chim Acta 2018; 483:64-68. [DOI: 10.1016/j.cca.2018.04.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 04/14/2018] [Accepted: 04/16/2018] [Indexed: 11/30/2022]
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26
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Cillo U, Bechstein WO, Berlakovich G, Dutkowski P, Lehner F, Nadalin S, Saliba F, Schlitt HJ, Pratschke J. Identifying risk profiles in liver transplant candidates and implications for induction immunosuppression. Transplant Rev (Orlando) 2018; 32:142-150. [DOI: 10.1016/j.trre.2018.04.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 04/03/2018] [Accepted: 04/05/2018] [Indexed: 12/16/2022]
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27
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Badawy A, Kaido T, Yoshizawa A, Yagi S, Fukumitsu K, Okajima H, Uemoto S. Human leukocyte antigen compatibility and lymphocyte cross-matching play no significant role in the current adult-to-adult living donor liver transplantation. Clin Transplant 2018; 32:e13234. [DOI: 10.1111/ctr.13234] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Amr Badawy
- Hepato-Biliary-Pancreatic Surgery and Transplantation department; Kyoto University; Kyoto Japan
- General Surgery department; Alexandria University; Alexandria Egypt
| | - Toshimi Kaido
- Hepato-Biliary-Pancreatic Surgery and Transplantation department; Kyoto University; Kyoto Japan
| | - Atsushi Yoshizawa
- Hepato-Biliary-Pancreatic Surgery and Transplantation department; Kyoto University; Kyoto Japan
| | - Shintaro Yagi
- Hepato-Biliary-Pancreatic Surgery and Transplantation department; Kyoto University; Kyoto Japan
| | - Ken Fukumitsu
- Hepato-Biliary-Pancreatic Surgery and Transplantation department; Kyoto University; Kyoto Japan
| | - Hideaki Okajima
- Hepato-Biliary-Pancreatic Surgery and Transplantation department; Kyoto University; Kyoto Japan
| | - Shinji Uemoto
- Hepato-Biliary-Pancreatic Surgery and Transplantation department; Kyoto University; Kyoto Japan
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Human leukocyte antigen, allele, and eplet mismatches in liver transplantation; observations from a small, single center cohort. Hum Immunol 2017; 79:154-159. [PMID: 29289739 DOI: 10.1016/j.humimm.2017.12.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 11/08/2017] [Accepted: 12/13/2017] [Indexed: 11/21/2022]
Abstract
BACKGROUND The impact of human leukocyte antigen (HLA) matching on outcomes in liver transplantation is controversial. Varying levels of HLA matching resolutions were examined in a uniform patient population with no pre-transplant DSA from a small, single center cohort. METHODS Retrospective chart review from a single center yielded 131 patients, 67 of which were confirmed to be DSA negative, all of which received induction immunotherapy and post-operative immunosuppression. HLA typing was achieved by sequence specific oligonucleotide probe (SSOP) method using LABType® kits. Eplet mismatch analysis was conducted using HLAMatchMaker software. RESULTS The mean number of HLA-A antigen mismatches was significantly higher in patients experiencing acute rejection (1.8 vs 1.6, p = 0.006). Rejection patients more frequently possessed two HLA-A mismatches compared to their non-rejection counterparts (77% vs 43%, p = 0.071). Patient survival was found to be non-significantly decreased in patients with a higher eplet mismatch load at the HLA-A locus (p = 0.155). No other loci were found to be predictive. CONCLUSION In conclusion, HLA mismatches were found to increase acute rejection and be associated with decreased patient survival. The outcomes of this study suggest an involvement of HLA-A locus mismatches in predicting liver transplant rejection and patient survival.
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29
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Baas M, Gouw ASH, van den Heuvel MC, Hepkema BG, Peeters PMGJ, Verkade H, Scheenstra R. Unique clinical conditions associated with different acinar regions of fibrosis in long-term surviving pediatric liver grafts. Pediatr Transplant 2017. [PMID: 28627016 DOI: 10.1111/petr.12988] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
In the majority of long-term survivors after PLTx, graft fibrosis has been identified. Recently, subtypes of graft fibrosis have been described based on their predominant acinar localization. We aimed to evaluate whether the development of portal, perisinusoidal, and centrilobular distribution of graft fibrosis is related to patient or transplantation-related parameters. We reviewed the histological features in protocol liver biopsies taken at 1 and 5 years after PLTx of 47 children on a tacrolimus-based immunosuppressive regimen. Fibrosis was assessed according to the LAFSc. The prevalence of portal fibrosis increased from 31% to 62%, sinusoidal from 68% to 79%, and centrilobular from 76% to 85%. The presence of portal fibrosis was associated with total bilirubin and γGT levels (each P<.02) and tended to be associated with biliary complications (P=.06). Sinusoidal fibrosis was associated with prior rejection episodes (P<.02) and centrilobular fibrosis with the presence of HLA mismatches (P=.02). In conclusion, using the LAFSc, we found a high incidence of progressive fibrosis in the 1-year and 5-year protocol biopsies after PLTx. Progression of fibrosis was observed in all acinar compartments, and each of the three locations is associated with different clinical conditions.
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Affiliation(s)
- Marjolein Baas
- Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Annette S H Gouw
- Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Marius C van den Heuvel
- Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Bouke G Hepkema
- Laboratory of Transplant Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Paul M G J Peeters
- Department of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - HenkJan Verkade
- Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - René Scheenstra
- Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Liu L, Wen J, Gu X, Wu D, Lu M, Zhao Q. Prognostic role of long non-coding RNA LINC00152 in Chinese cancer patients: a meta-analysis. Oncotarget 2017; 8:93227-93235. [PMID: 29190992 PMCID: PMC5696258 DOI: 10.18632/oncotarget.21838] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 09/21/2017] [Indexed: 12/24/2022] Open
Abstract
The role of long intergenic non-coding RNA 152 (LINC00152) in predicting the prognosis of cancer has been investigated but results remain inconclusive and inconsistent. A meta-analysis was performed to explore the effect of LINC00152 on cancer prognosis. PubMed and ScienceDirect were searched for suitable studies and the results of 10 studies with a total of 775 patients were pooled. Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated to assess the prognostic value of LINC00152. The results revealed that tumour patients with high LINC00152 expression were more likely to have lymph node metastasis (OR = 2.94, 95% CI 1.97–4.40, P < 0.001) and unfavourable tumour–node–metastasis stage (grade III/IV vs. I/II: OR = 3.07, 95% CI 1.69–5.59, P < 0.001). In addition, high LINC00152 expression levels were significantly associated with poor overall survival (pooled HR = 1.99, 95% CI 1.54–2.56, P < 0.001). The results suggest that high LINC00152 expression may serve as a predictive biomarker for the poor prognosis of various cancers in the Chinese population.
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Affiliation(s)
- Liyang Liu
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jianfei Wen
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xi Gu
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Dongdong Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ming Lu
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qinghong Zhao
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Wei L, Xue T, Tao KS, Zhang G, Zhao GY, Yu SQ, Cheng L, Yang ZX, Zheng MJ, Li F, Wang Q, Han Y, Shi YQ, Dong HL, Lu ZH, Wang Y, Yang H, Ma XD, Liu SJ, Liu HX, Xiong LZ, Chen BL. Modified human uterus transplantation using ovarian veins for venous drainage: the first report of surgically successful robotic-assisted uterus procurement and follow-up for 12 months. Fertil Steril 2017; 108:346-356.e1. [PMID: 28778283 DOI: 10.1016/j.fertnstert.2017.05.039] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 05/31/2017] [Accepted: 05/31/2017] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To report the 12-month results of the first human uterus transplantation case using robot-assisted uterine retrieval. This type of transplantation may become a treatment for permanent uterine factor infertility. DESIGN Case study. SETTING University hospital. PATIENT(S) A 22-year-old woman with complete müllerian agenesis who underwent a previous surgery for vaginal reconstruction. The live uterine donor was her mother. INTERVENTION(S) The uterus transplantation procedure consisted of robot-assisted uterine procurement, orthotopic replacement and fixation of the retrieved uterus, revascularization, and end-to-side anastomoses of bilateral hypogastric arteries and ovarian-uterine vein to the bilateral external iliac arteries and veins. MAIN OUTCOME MEASURE(S) Data from preoperative investigations, surgery, and follow-up (12 months). RESULT(S) The duration of the donor and recipient surgeries were 6 and 8 hours, 50 minutes, respectively. No immediate perioperative complications occurred in the recipient or donor. The recipient experienced menarche 40 days after transplant surgery, and she has had 12 menstrual cycles since the surgery. No rejection episodes occurred in the recipient. CONCLUSION(S) These results demonstrate the feasibility of live-donor uterine transplantation with a low-dose immunosuppressive protocol and the role of DaVinci robotic assistance during human uterine procurement. CLINICAL TRIAL REGISTRATION NUMBER XJZT12Z06.
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Affiliation(s)
- Li Wei
- Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Tao Xue
- Department of Otorhinolaryngology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Kai-Shan Tao
- Department of Hepatic and Splenic Surgery, Department of Organ Transplant Centers, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Geng Zhang
- Department of Urinary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Guang-Yue Zhao
- Department of Osteology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Shi-Qiang Yu
- Department of Cardiac Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Liang Cheng
- Department of Cardiac Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Zhao-Xu Yang
- Department of Hepatic and Splenic Surgery, Department of Organ Transplant Centers, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Min-Juan Zheng
- Department of Ultrasound Diagnosis, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Fei Li
- Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Qiong Wang
- Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Ying Han
- Department of Gastroenterology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Yong-Quan Shi
- Department of Gastroenterology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Hai-Long Dong
- Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Zhi-Hong Lu
- Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Yun Wang
- Department of Ultrasound Diagnosis, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Hong Yang
- Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Xiang-Dong Ma
- Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Shu-Juan Liu
- Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Hai-Xia Liu
- Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Li-Ze Xiong
- Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Bi-Liang Chen
- Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China.
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Rodríguez‐Perálvarez M, Guerrero‐Misas M, Thorburn D, Davidson BR, Tsochatzis E, Gurusamy KS, Cochrane Hepato‐Biliary Group. Maintenance immunosuppression for adults undergoing liver transplantation: a network meta-analysis. Cochrane Database Syst Rev 2017; 3:CD011639. [PMID: 28362060 PMCID: PMC6464256 DOI: 10.1002/14651858.cd011639.pub2] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND As part of liver transplantation, immunosuppression (suppressing the host immunity) is given to prevent graft rejections resulting from the immune response of the body against transplanted organ or tissues from a different person whose tissue antigens are not compatible with those of the recipient. The optimal maintenance immunosuppressive regimen after liver transplantation remains uncertain. OBJECTIVES To assess the comparative benefits and harms of different maintenance immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until October 2016 to identify randomised clinical trials on immunosuppression for liver transplantation. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adult participants undergoing liver transplantation (or liver retransplantation) for any reason. We excluded trials in which participants had undergone multivisceral transplantation or participants with established graft rejections. We considered any of the various maintenance immunosuppressive regimens compared with each other. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included a total of 26 trials (3842 participants) in the review, and 23 trials (3693 participants) were included in one or more outcomes in the review. The vast majority of the participants underwent primary liver transplantation. All of the trials were at high risk of bias, and all of the evidence was of low or very low quality. In addition, because of sparse data involving trials at high risk of bias, it is not possible to entirely rely on the results of the network meta-analysis. The trials included mainly participants undergoing primary liver transplantation of varied aetiologies. The follow-up in the trials ranged from 3 to 144 months. The most common maintenance immunosuppression used as a control was tacrolimus. There was no evidence of difference in mortality (21 trials; 3492 participants) or graft loss (15 trials; 2961 participants) at maximal follow-up between the different maintenance immunosuppressive regimens based on the network meta-analysis. In the direct comparison, based on a single trial including 222 participants, tacrolimus plus sirolimus had increased mortality (HR 2.76, 95% CrI 1.30 to 6.69) and graft loss (HR 2.34, 95% CrI 1.28 to 4.61) at maximal follow-up compared with tacrolimus. There was no evidence of differences in the proportion of people with serious adverse events (1 trial; 719 participants), proportion of people with any adverse events (2 trials; 940 participants), renal impairment (8 trials; 2233 participants), chronic kidney disease (1 trial; 100 participants), graft rejections (any) (16 trials; 2726 participants), and graft rejections requiring treatment (5 trials; 1025 participants) between the different immunosuppressive regimens. The network meta-analysis showed that the number of adverse events was lower with cyclosporine A than with many other immunosuppressive regimens (12 trials; 1748 participants), and the risk of retransplantation (13 trials; 1994 participants) was higher with cyclosporine A than with tacrolimus (HR 3.08, 95% CrI 1.13 to 9.90). None of the trials reported number of serious adverse events, health-related quality of life, or costs. FUNDING 14 trials were funded by pharmaceutical companies who would benefit from the results of the trial; two trials were funded by parties who had no vested interest in the results of the trial; and 10 trials did not report the source of funding. AUTHORS' CONCLUSIONS Based on low-quality evidence from a single small trial from direct comparison, tacrolimus plus sirolimus increases mortality and graft loss at maximal follow-up compared with tacrolimus. Based on very low-quality evidence from network meta-analysis, we found no evidence of difference between different immunosuppressive regimens. We found very low-quality evidence from network meta-analysis and low-quality evidence from direct comparison that cyclosporine A causes more retransplantation compared with tacrolimus. Future randomised clinical trials should be adequately powered; performed in people who are generally seen in the clinic rather than in highly selected participants; employ blinding; avoid postrandomisation dropouts or planned cross-overs; and use clinically important outcomes such as mortality, graft loss, renal impairment, chronic kidney disease, and retransplantation. Such trials should use tacrolimus as one of the control groups. Moreover, such trials ought to be designed in such a way as to ensure low risk of bias and low risks of random errors.
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Affiliation(s)
- Manuel Rodríguez‐Perálvarez
- Reina Sofía University Hospital, IMIBIC, CIBERehdHepatology and Liver TransplantationAvenida Menéndez Pidal s/nCórdobaSpain14004
| | - Marta Guerrero‐Misas
- Reina Sofía University Hospital, IMIBIC, CIBERehdHepatology and Liver TransplantationAvenida Menéndez Pidal s/nCórdobaSpain14004
| | - Douglas Thorburn
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentrePond StreetLondonUKNW3 2QG
| | - Brian R Davidson
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryPond StreetLondonUKNW3 2QG
| | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentrePond StreetLondonUKNW3 2QG
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AlncRNA HULC as an effective biomarker for surveillance of the outcome of cancer: A meta-analysis. PLoS One 2017; 12:e0171210. [PMID: 28146578 PMCID: PMC5287472 DOI: 10.1371/journal.pone.0171210] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Accepted: 01/18/2017] [Indexed: 01/07/2023] Open
Abstract
PURPOSE High expression of highly upregulated in iver cancer (HULC) has been found associated with increased metastasis and poor prognosis with cancer. This meta-analysis aimed to determine the pooled effect of HULC on metastasis and prognosis of cancers. METHOD The studies were accessed using multiple databases. RevMan5.3 and STATA14.0 were used to estimate pooled effects, the heterogeneity among studies, and publication bias for the association of HULC and overall survival (OS). RESULTS A total of 9 studies of 966 cancer patients were included. Risk of lymph node metastasis was increased with high versus low HULC expression (pooled odds ratio [OR] = 4.83, 95% confidence interval [CI] 1.59-14.63) as was distant metastasis (pooled OR = 5.44, 95% CI 2.33-12.74). Furthermore, OS time was shortened with high HULC expression (pooled hazard ratio [HR] = 1.48, 95% CI 1.03-2.12), especially in Chinese patients (pooled HR = 2.04, 95% CI 1.55-2.68), and risk of recurrence was increased (pooled OR = 6.68, 95% CI 2.77-16.13). CONCLUSION HULC might be a potential biomarker for therapy and prognosis surveillance in cancers.
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Role of Human Leukocyte Antigen Compatibility in Graft Outcomes After Living Donor Liver Transplantation. Transplant Proc 2017; 48:1123-9. [PMID: 27320571 DOI: 10.1016/j.transproceed.2016.01.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 01/08/2016] [Accepted: 01/21/2016] [Indexed: 11/21/2022]
Abstract
PURPOSE The influence of human leukocyte antigen (HLA) mismatch on liver transplantation has been widely studied, but is still controversial. The aim of this large single-center study was to analyze the role of HLA compatibility between donor and recipient in the graft outcomes of living donor liver transplantation (LDLT). MATERIALS AND METHODS A total of 925 recipients who had undergone LDLT between March 2001 and April 2012 were retrospectively analyzed. HLA typing was performed using a standard complement-dependent cytotoxicity technique. The degree and type of HLA-A, HLA-B, and HLA-DR mismatch were assessed. We also investigated the posttransplantation laboratory data, incidence of rejection, recurrence of hepatitis B virus (HBV), and graft survival as outcome parameters. RESULTS The type of HLA-A, HLA-B, and HLA-DR mismatch had no effect on rejection episodes, whereas the beneficial effect of a much lower degree (0-2) of HLA mismatch was notable. Recipients with 2 HLA-B mismatches or recipients with a higher degree of mismatch were associated with elevated bilirubin level, a higher recurrence rate of HBV, and inferior graft survival. A complete mismatch of 2 at the DR locus also decreased graft survival in LDLT recipients. CONCLUSIONS This study confirmed that the degree of HLA mismatch, as well as the locus-specific type of HLA mismatch, namely B and DR, play a major role in graft outcomes after LDLT. To obtain an improved graft outcome, HLA compatibility should be considered in the setting of LDLT, which provides sufficient time to select a more favorable donor-recipient combination.
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Zachary AA, Leffell MS. HLA Mismatching Strategies for Solid Organ Transplantation - A Balancing Act. Front Immunol 2016; 7:575. [PMID: 28003816 PMCID: PMC5141243 DOI: 10.3389/fimmu.2016.00575] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Accepted: 11/23/2016] [Indexed: 12/24/2022] Open
Abstract
HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching. Furthermore, finding a well-matched donor may not be possible for all patients and usually prolongs waiting time. Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches: what are the least immunogenic mismatches considering the patient’s HLA phenotype; should repeated mismatches be avoided; is the patient sensitized to HLA and, if so, what are the strengths of the patient’s antibodies? This information can then be used to define the HLA type of an immunologically optimal donor and the probability of such a donor occurring. A probability that is considered to be too low may require expanding the donor population through paired donation or modifying what is acceptable, which may require employing treatment to overcome immunologic barriers such as increased immunosuppression or desensitization. Thus, transplantation must strike a balance between the risk associated with waiting for the optimal donor and the risk associated with a less than optimal donor.
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Affiliation(s)
- Andrea A Zachary
- Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, MD , USA
| | - Mary S Leffell
- Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, MD , USA
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Zou Z, An MM, Xie Q, Chen XY, Zhang H, Liu GJ, Shi XY. Single dose intra-articular morphine for pain control after knee arthroscopy. Cochrane Database Syst Rev 2016; 2016:CD008918. [PMID: 27140500 PMCID: PMC6517216 DOI: 10.1002/14651858.cd008918.pub2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Knee arthroscopy is a common procedure and is associated with postoperative pain. Intra-articular (IA) injection of morphine for pain control has been widely studied, but its analgesic effect after knee arthroscopy is uncertain. OBJECTIVES To evaluate the relative effects on pain relief and adverse events of IA morphine given for pain control after knee arthroscopy compared with placebo, other analgesics (local anaesthetics, non-steroidal anti-inflammatory drugs (NSAIDs), other opioids) and other routes of morphine administration. SEARCH METHODS We searched CENTRAL (The Cochrane Library Issue 4, 2015), MEDLINE via Ovid (January 1966 to May 2015), EMBASE via Ovid (January 1988 to May 2015), and the reference lists of included articles. We also searched the metaRegister of controlled trials, clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials. SELECTION CRITERIA We identified all the randomised, double-blind controlled trials that compared single dose IA morphine with other interventions for the treatment of postoperative pain after knee arthroscopy. We excluded studies with fewer than 10 participants in each group, using spinal or epidural anaesthesia, or assessing the analgesic effect of IA morphine on chronic pain. DATA COLLECTION AND ANALYSIS Two authors independently assessed the quality of each trial and extracted information on pain intensity, supplementary analgesics consumption and adverse events. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. MAIN RESULTS We included 28 small, low quality studies (29 reports) involving 2564 participants. Of 20 studies (21 reports) comparing morphine with placebo, nine studies with adequate data were included in the meta-analysis. Overall, the risk of bias was unclear. Overall, the quality of the evidence assessed using GRADE was low to very low, downgraded primarily due to risk of bias, small study size, and imprecision.No statistical difference was found between 1 mg IA morphine and placebo in pain intensity (visual analogue scale (VAS)) at early phase (zero to two hours) (mean difference (MD) -0.50, 95% CI -1.15 to 0.14; participants = 297; studies = 7; low quality evidence), medium phase (two to six hours) (MD -0.47, 95% CI -1.09 to 0.14; participants = 297; studies = 7; low quality evidence) and late phase (six to 30 hours) (MD -0.88, 95% CI -1.81 to 0.04; participants = 297; studies = 7; low quality evidence). No significant difference was found between 1 mg and 2 mg morphine for pain intensity at early phase (MD -0.56, 95% CI -1.93 to 0.81; participants = 105; studies = 2; low quality evidence), while 4 mg/5 mg morphine provided better analgesia than 1 mg morphine at late phase (MD 0.67, 95% CI 0.08 to 1.25; participants = 97; studies = 3; low quality evidence). IA morphine was not better than local anaesthetic agents at early phase (MD 1.43, 95% CI 0.49 to 2.37; participants = 248; studies = 5; low quality evidence), NSAIDs at early phase (MD 0.95, 95% CI -0.95 to 2.85; participants = 80; studies = 2; very low quality evidence), sufentanil, fentanyl or pethidine for pain intensity. IA morphine was similar to intramuscular (IM) morphine for pain intensity at early phase (MD 0.21, 95% CI -0.48 to 0.90; participants = 72; studies = 2; very low quality evidence).Meta-analysis indicated that there was no difference between IA morphine and placebo or bupivacaine in time to first analgesic request. Eleven out of 20 studies comparing morphine with placebo reported adverse events and no statistical difference was obtained regarding the incidence of adverse events (risk ratio (RR) 1.09, 95% CI 0.51 to 2.36; participants = 314; studies = 8; low quality evidence). Seven of 28 studies reported participants' withdrawal. There were not enough data for withdrawals to be able to perform meta-analysis. AUTHORS' CONCLUSIONS We have not found high quality evidence that 1 mg IA morphine is better than placebo at reducing pain intensity at early, medium or late phases. No statistical difference was reported between IA morphine and placebo regarding the incidence of adverse events. The relative effects of 1 mg morphine when compared with IA bupivacaine, NSAIDs, sufentanil, fentanyl and pethidine are uncertain. The quality of the evidence is limited by high risk of bias and small size of the included studies, which might bias the results. More high quality studies are needed to get more conclusive results.
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Affiliation(s)
- Zui Zou
- Department of Anaesthesiology, Changzheng Hospital, The Second Military Medical University, No 415, Feng Yang Road, Shanghai, Shanghai, China, 200003
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Long-term Clinical Relevance of De Novo Donor-Specific Antibodies After Pediatric Liver Transplantation. Transplantation 2015; 99:1876-81. [PMID: 25706279 DOI: 10.1097/tp.0000000000000638] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Anti-HLA antibodies and especially donor-specific antibodies (DSA) play a significant role in graft survival after solid organ transplantation. Their impact on long-term survival in adult liver transplantation (LT) is controversial, but they may be a risk factor. The effects of DSA after pediatric LT are still unclear. METHODS We performed a retrospective evaluation of DSA in sera from 43 children who had received transplants at our tertiary center. Twenty-four patients had good long-term clinical and laboratory graft function (group 1), whereas 19 LT recipients suffered from histologically confirmed and clinically relevant chronic allograft rejection (group 2); 16 of these have already undergone retransplantation due to graft dysfunction. Inclusion criteria were availability of sera before the first LT to identify preformed antibodies in case of DSA positivity after LT and long-term follow-up at our institution. Sera were analyzed for anti-HLA antibodies using Luminex single antigen beads, where a mean fluorescence intensity value of more than 1500 was considered positive. RESULTS The prevalence of DSA was 33% for group 1 and 68% for group 2. Antibodies were predominantly HLA class II. Values of mean fluorescence intensity were comparable in both groups. Only one of the DSA+ ve patients from group 1 exhibited preformed antibodies. In conclusion, pediatric patients with chronic rejection revealed a higher rate of de novo DSA, especially of HLA-class II DSA. Further studies are necessary to confirm these data with a larger pediatric cohort.
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Sun QB, Liu SD, Meng QJ, Qu HZ, Zhang Z. Single administration of intra-articular bupivacaine in arthroscopic knee surgery: a systematic review and meta-analysis. BMC Musculoskelet Disord 2015; 16:21. [PMID: 25887534 PMCID: PMC4328055 DOI: 10.1186/s12891-015-0477-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Accepted: 01/22/2015] [Indexed: 11/10/2022] Open
Abstract
Background Single administration of intra-articular (IA) bupivacaine for pain relief after arthroscopic knee surgery is effective, but its active duration and dose–response relationship is unclear. We conducted this meta-analysis to summarize all published randomized controlled trials (RCTs), thus providing the most recent information on the safety and efficacy of single-administration IA bupivacaine for pain relief after arthroscopic knee surgery, and to determine whether a dose–response relationship exists. Methods A systematic electronic literature search (through April 2014) was conducted to identify those RCTs that addressed the safety and efficacy of a single administration of IA bupivacaine for pain management after arthroscopic knee surgery. Subgroup analysis was conducted to determine changes in visual analog scale (VAS) scores at seven postoperative time points. Meta-regression and subgroup analyses were carried out to assess the effects of various treatment factors on efficacy and to evaluate the dose–response relationship of bupivacaine. Weighted mean differences or relative risks were calculated and pooled using a random-effects model. Results Twenty-eight trials involving 1,560 patients who underwent arthroscopic knee surgery met the inclusion criteria. The trials were subject to medium risk of bias. VAS scores at 2, 4, 6, 12, and 24 h postoperatively were significantly lower, the number of patients requiring supplementary analgesia was smaller, and the time to first request for analgesia was longer in the IA bupivacaine group than in the placebo group. The analgesic effect of single-administration IA bupivacaine may be associated with the effect of concomitant administration of epinephrine and concentration of bupivacaine, and no dose–response relationship was identified. No significant difference in side effects was detected between groups. Conclusions Current evidence shows that the use of single-administration IA bupivacaine is effective for postoperative pain management in patients undergoing arthroscopic knee surgery, with satisfactory short-term safety. Low-dose administration of IA bupivacaine 0.5% combined with epinephrine adjuvant in clinical practice should be performed. Additional high-quality RCTs with longer follow-up periods are required to examine the safety of single-administration IA bupivacaine. Electronic supplementary material The online version of this article (doi:10.1186/s12891-015-0477-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Qi-Bin Sun
- Department of Spine and Joint Surgery, The Third People's Hospital of Jinan, No.1 North Industrial Road, Wangsheren North Street, Jinan, 250101, Shandong, People's Republic of China.
| | - Shi-Dong Liu
- Department of Spine and Joint Surgery, The Third People's Hospital of Jinan, No.1 North Industrial Road, Wangsheren North Street, Jinan, 250101, Shandong, People's Republic of China.
| | - Qin-Jun Meng
- Department of Spine and Joint Surgery, The Third People's Hospital of Jinan, No.1 North Industrial Road, Wangsheren North Street, Jinan, 250101, Shandong, People's Republic of China.
| | - Hua-Zheng Qu
- Department of Spine and Joint Surgery, The Third People's Hospital of Jinan, No.1 North Industrial Road, Wangsheren North Street, Jinan, 250101, Shandong, People's Republic of China.
| | - Zheng Zhang
- Department of Spine and Joint Surgery, The Third People's Hospital of Jinan, No.1 North Industrial Road, Wangsheren North Street, Jinan, 250101, Shandong, People's Republic of China.
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Song SH, Kim MS, Lee JJ, Ju MK, Lee JG, Lee J, Choi JS, Choi GH, Kim SI, Joo DJ. Effect of donor-specific antibodies and panel reactive antibodies in living donor liver transplant recipients. Ann Surg Treat Res 2015; 88:100-5. [PMID: 25692121 PMCID: PMC4325653 DOI: 10.4174/astr.2015.88.2.100] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 08/05/2014] [Accepted: 08/14/2014] [Indexed: 11/30/2022] Open
Abstract
Purpose Preformed circulating donor-specific antibodies (DSAs) immunologically challenge vascular endothelium and the bile duct. However, the liver is an immune-tolerant organ and can avoid immunological challenges. This study was undertaken to analyze the effects of DSAs after adult living donor liver transplantation (LDLT). Methods We retrospectively reviewed 219 LDLT patients' records treated at our center. Results Of the 219 patients, 32 (14.6%) were DSA (+) and 187 (85.4%) were DSA (-). Class I DSAs were present in 18 patients, class II in seven patients, and both in seven patients. Seven patients (3.2%) showed DSA to HLA-A, four (1.8%) to HLA-B, seven (3.2%) to HLA-DR, and 14 (6.4%) to two or more HLAs. More DSAs were observed in female recipients than male recipients in the DSA (+) group. The DSA (+) group showed significantly higher levels of class I and II panel reactive antibody (PRA) than did the DSA (-) group. No significant intergroup differences were found between incidences of primary nonfunction, acute rejection, vascular complication, or biliary complication. There were no significant differences in graft survival rates between the two groups. However, the recipients with multiple DSAs tended to have more acute rejection episodes and events of biliary stricture and lower graft survival rates than did patients in the DSA (-) group. Conclusion In LDLT, the presence of multiple DSAs and high PRA seemed to be associated with poor graft outcomes, although our results did not reach statistical significance. Large cohort studies are necessary to clarify the impact of DSA and PRA in LDLT.
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Affiliation(s)
- Seung Hwan Song
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. ; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Jun Lee
- Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Man Ki Ju
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. ; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. ; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. ; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sub Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. ; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Hong Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. ; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Soon Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. ; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. ; The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
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Lüthold SC, Kaseje N, Jannot AS, Mentha G, Majno P, Toso C, Belli DC, McLin VA, Wildhaber BE. Risk factors for early and late biliary complications in pediatric liver transplantation. Pediatr Transplant 2014; 18:822-30. [PMID: 25263826 DOI: 10.1111/petr.12363] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/14/2014] [Indexed: 12/14/2022]
Abstract
BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990-12/2011, medium follow-up 7.9 yr). One-, five-, and 10-yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26-fold) and early HAT (<30 days post-LT; increase 5.87-fold). Risk factor for primary anastomotic stricture was duct-to-duct choledochal anastomosis (increase 5.96-fold when compared to biliary-enteric anastomosis). Risk factors for intrahepatic strictures were donor age >48 yr (increase 1.09-fold) and MELD score >30 (increase 1.2-fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary-enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.
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Affiliation(s)
- Samuel C Lüthold
- Division of Pediatric Surgery, Geneva University Hospitals, Geneva, Switzerland
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Xu CP, Li X, Wang ZZ, Song JQ, Yu B. Efficacy and safety of single-dose local infiltration of analgesia in total knee arthroplasty: a meta-analysis of randomized controlled trials. Knee 2014; 21:636-46. [PMID: 24704172 DOI: 10.1016/j.knee.2014.02.024] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 01/03/2014] [Accepted: 02/26/2014] [Indexed: 02/02/2023]
Abstract
PURPOSE To examine the efficacy and safety of single-dose local infiltration of analgesia (LIA) for post-operative pain relief in total knee arthroplasty (TKA) patients. METHODS A systematic electronic literature search (up to Aug 2013) was conducted to identify the RCTs that address the efficacy and safety of single-dose LIA in the pain management after TKA. Subgroup analysis was conducted to determine changes of visual analog score (VAS) values at six different postoperative time points. Weighted mean differences or relative risks with accompanying 95% confidence intervals were calculated and pooled using a random effect model. RESULTS Eighteen trials involving 1858 TKA patients met the inclusion criteria. The trials were liable to medium risk of bias. The VAS values at postoperative 2h, 4h, 6h, 12h, 24h, and 48h per patient were significantly lower in the LIA group than in the placebo group, and the former group also had less morphine consumption and better early functional recovery including range of motion, time to straight leg raise and 90° knee flexion than the latter group. No significant difference in length of hospital stay or side effects was detected between the two groups. CONCLUSIONS The current evidence shows that the use of single-dose LIA is effective for postoperative pain management in TKA patients, with satisfactory short-term safety. More high-quality RCTs with long-term follow-ups are required for examining the long-term safety of single-dose LIA. LEVEL OF EVIDENCE I, II.
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Affiliation(s)
- Chang-Peng Xu
- Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Xue Li
- Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Zhi-Zhong Wang
- Department of Orthopaedics and Traumatology, People's Hospital of Sanshui District of Foshan, Foshan, Guangdong, People's Republic of China
| | - Jin-Qi Song
- Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Bin Yu
- Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
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Ansari D, Bućin D, Nilsson J. Human leukocyte antigen matching in heart transplantation: systematic review and meta-analysis. Transpl Int 2014; 27:793-804. [PMID: 24725030 DOI: 10.1111/tri.12335] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 03/16/2014] [Accepted: 04/07/2014] [Indexed: 11/29/2022]
Abstract
Allocation of donors with regard to human leukocyte antigen (HLA) is controversial in heart transplantation. This paper is a systematic review and meta-analysis of the available evidence. PubMed, Embase, and the Cochrane Library were searched systematically for studies that addressed the effects of HLA matching on outcome after heart transplantation. Fifty-seven studies met the eligibility criteria. 34 studies had graft rejection as outcome, with 26 of the studies reporting a significant reduction in graft rejection with increasing degree of HLA matching. Thirteen of 18 articles that reported on graft failure found that it decreased significantly with increasing HLA match. Two multicenter studies and nine single-center studies provided sufficient data to provide summary estimates at 12 months. Pooled comparisons showed that graft survival increased with fewer HLA-DR mismatches [0-1 vs. 2 mismatches: risk ratio (RR) = 1.09 (95% confidence interval (CI): 1.01-1.19; P = 0.04)]. Having fewer HLA-DR mismatches (0-1 vs. 2) reduced the incidence of acute rejection [(RR = 0.81 (0.66-0.99; P = 0.04)]. Despite the considerable heterogeneity between studies, the short observation time, and older data, HLA matching improves graft survival in heart transplantation. Prospective HLA-DR matching is clinically feasible and should be considered as a major selection criterion.
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Affiliation(s)
- David Ansari
- Division of Cardiothoracic Surgery, Department of Clinical Sciences Lund, Lund University and Skane University Hospital, Lund, Sweden
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Guardia AC, Stucchi RSB, Milan A, Costa SCB, Boin IDFSF. Human herpesvirus-6 and cytomegalovirus DNA in liver donor biopsies and their correlation with HLA matches and acute cellular rejection. Braz J Infect Dis 2013; 18:220-4. [PMID: 24275367 PMCID: PMC9427445 DOI: 10.1016/j.bjid.2013.07.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Revised: 07/23/2013] [Accepted: 07/27/2013] [Indexed: 11/27/2022] Open
Abstract
Herpesvirus reactivation is common after liver transplantation. Objective Analyze the presence of cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA)-A, B and DR, as well as correlations with acute cellular rejection. Methods Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients’ records regarding acute cellular rejection were studied. Results Seven (11.8%) biopsies were positive for HCMV DNA and 29 (49%) were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p = 0.09), 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p = 0.03; χ2 = 4.51), which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p = 0.08). Conclusion HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation.
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Affiliation(s)
- Ana Carolina Guardia
- Faculty of Medical Science, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
| | | | - Arlete Milan
- Faculty of Medical Science, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
| | - Sandra Cecília Botelho Costa
- Internal Medicine Department, Diagnosis of Molecular Infection Disease, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
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Júnior ADPJ, Erdmann TR, Santos TVD, Brunharo GM, Filho CTB, Losso MJ, Filho GRDO. Comparison between continuous thoracic epidural and paravertebral blocks for postoperative analgesia in patients undergoing thoracotomy: Systematic review. Braz J Anesthesiol 2013; 63:433-42. [PMID: 24565302 DOI: 10.1016/j.bjane.2013.10.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 09/10/2012] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Thoracotomy is a procedure associated with postoperative severe pain. Epidural block (EB) is considered the gold standard for its control. Paravertebral block (PVB) is an option for the management of postoperative pain. The aim of this study was to evaluate by meta-analyses the effectiveness of continuous thoracic epidural and paravertebral blocks for pain management after thoracotomy and the incidence of adverse effects. METHOD The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. We analyzed primary (postoperative pain at rest) and secondary outcomes (urinary retention, nausea, vomiting, hypotension). We estimated the weighted mean difference for continuous variables and odds ratios for categorical variables. RESULTS We included eight prospective, randomized, controlled studies. Meta-analysis showed no statistically significant differences between the two techniques regarding the outcomes of postoperative pain at rest at four, eight, 12, 16, 20, 24, 36, and 48 hours. Incidence of urinary retention was higher in EP group (OR = 7.19, CI95 = 1.87 to 27.7). The occurrence of hypotension was higher in PVB group (OR = 10.28, 95 = 2.95 to 35.77). There was no statistically significant difference between both groups regarding the outcome nausea/vomiting (OR = 3.00, CI95 = 0.49 to 18.45). CONCLUSION There were no statistically significant differences in pain relief after thoracotomy between EB and PVB. PVB showed a lower incidence of side effects with reduced frequency of urinary retention and hypotension.
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Affiliation(s)
- Alberto de Pontes Jardim Júnior
- Centro de Ensino e Treinamento da Sociedade Brasileira de Anestesiologia Integrado de Anestesiologia da Secretaria de Estado de Saúde de Santa Catarina, Florianópolis, SC, Brasil
| | - Thomas Rolf Erdmann
- Centro de Ensino e Treinamento da Sociedade Brasileira de Anestesiologia Integrado de Anestesiologia da Secretaria de Estado de Saúde de Santa Catarina, Florianópolis, SC, Brasil
| | - Thiago Viçoso dos Santos
- Centro de Ensino e Treinamento da Sociedade Brasileira de Anestesiologia Integrado de Anestesiologia da Secretaria de Estado de Saúde de Santa Catarina, Florianópolis, SC, Brasil
| | - Guilherme Muriano Brunharo
- Centro de Ensino e Treinamento da Sociedade Brasileira de Anestesiologia Integrado de Anestesiologia da Secretaria de Estado de Saúde de Santa Catarina, Florianópolis, SC, Brasil
| | - Clovis Tadeu Bevilacqua Filho
- Centro de Ensino e Treinamento da Sociedade Brasileira de Anestesiologia Integrado de Anestesiologia da Secretaria de Estado de Saúde de Santa Catarina, Florianópolis, SC, Brasil
| | - Márcio Joaquim Losso
- Centro de Ensino e Treinamento da Sociedade Brasileira de Anestesiologia Integrado de Anestesiologia da Secretaria de Estado de Saúde de Santa Catarina, Florianópolis, SC, Brasil
| | - Getúlio R de Oliveira Filho
- Centro de Ensino e Treinamento da Sociedade Brasileira de Anestesiologia Integrado de Anestesiologia da Secretaria de Estado de Saúde de Santa Catarina, Florianópolis, SC, Brasil.
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Comparação entre Bloqueios Peridural e Paravertebral Torácicos Contínuos para Analgesia Pós-Operatória em Pacientes Submetidos a Toracotomias: Revisão Sistemática. Braz J Anesthesiol 2013. [DOI: 10.1016/j.bjan.2012.09.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Kisu I, Banno K, Mihara M, Suganuma N, Aoki D. Current status of uterus transplantation in primates and issues for clinical application. Fertil Steril 2013; 100:280-94. [DOI: 10.1016/j.fertnstert.2013.03.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2012] [Revised: 03/02/2013] [Accepted: 03/06/2013] [Indexed: 01/14/2023]
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Kisu I, Mihara M, Banno K, Umene K, Araki J, Hara H, Suganuma N, Aoki D. Risks for donors in uterus transplantation. Reprod Sci 2013; 20:1406-15. [PMID: 23793471 DOI: 10.1177/1933719113493517] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Uterus transplantation (UTx) is an alternative to gestational surrogacy and adoption for patients with absolute uterine infertility. Studies have been conducted in animals, and UTx is now within the reach of clinical application in humans. Procedures in humans have been published, but many medical, ethical, and social problems and risks of UTx require discussion prior to widespread clinical application, from the perspectives of donors, recipients, families, and newborns. In this article, we summarize the burdens and risks of UTx, with a focus on donors who provide the uterus.
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Affiliation(s)
- Iori Kisu
- 1Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan
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Ciria R, Pleguezuelo M, Khorsandi SE, Davila D, Suddle A, Vilca-Melendez H, Rufian S, de la Mata M, Briceño J, Cillero PL, Heaton N. Strategies to reduce hepatitis C virus recurrence after liver transplantation. World J Hepatol 2013; 5:237-50. [PMID: 23717735 PMCID: PMC3664282 DOI: 10.4254/wjh.v5.i5.237] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2012] [Revised: 11/16/2012] [Accepted: 12/01/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not re-transplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pre-transplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of post-transplant HCV recurrence and strategies to reduce its impact on our patients.
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Affiliation(s)
- Ruben Ciria
- Ruben Ciria, Shirin Elizabeth Khorsandi, Diego Davila, Abid Suddle, Hector Vilca-Melendez, Nigel Heaton, Institute of Liver Studies, King's College Hospital, London SE5 9RS, United Kingdom
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Uchiyama H, Kayashima H, Matono R, Shirabe K, Yoshizumi T, Ikegami T, Soejima Y, Matsuura T, Taguchi T, Maehara Y. Relevance of HLA compatibility in living donor liver transplantation: the double-edged sword associated with the patient outcome. Clin Transplant 2013; 26:E522-9. [PMID: 23061761 DOI: 10.1111/ctr.12019] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD.
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Affiliation(s)
- Hideaki Uchiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Ozkan O, Akar ME, Ozkan O, Erdogan O, Hadimioglu N, Yilmaz M, Gunseren F, Cincik M, Pestereli E, Kocak H, Mutlu D, Dinckan A, Gecici O, Bektas G, Suleymanlar G. Preliminary results of the first human uterus transplantation from a multiorgan donor. Fertil Steril 2012; 99:470-6. [PMID: 23084266 DOI: 10.1016/j.fertnstert.2012.09.035] [Citation(s) in RCA: 163] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2012] [Revised: 09/18/2012] [Accepted: 09/19/2012] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To describe the first-year results of the first human uterus transplantation case from a multiorgan donor. DESIGN Case study. SETTING University hospital. PATIENT(S) A 21-year-old woman with complete müllerian agenesis who had been previously operated on for vaginal reconstruction. INTERVENTION(S) Uterus transplantation procedure consisting of orthotopic replacement and fixation of the retrieved uterus, revascularization, end to site anastomoses of bilateral hypogastric arteries and veins to bilateral external iliac arteries and veins was performed. MAIN OUTCOME MEASURE(S) Resumption of menstrual cycles. RESULT(S) The patient had menarche 20 days after transplant surgery. She has had 12 menstrual cycles since the operation. CONCLUSION(S) We have described the longest-lived transplanted human uterus to date with acquirement of menstrual cycles.
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Affiliation(s)
- Omer Ozkan
- Department of Plastic Surgery, Akdeniz University, Antalya, Turkey
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