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Alyamany R, Alnughmush A, Albaiz F, Aversa M, Law A. Treatment of Late-onset Acute Graft-versus-host Disease Following Double Lung Transplantation Using a JAK2 Inhibitor. Transplantation 2025; 109:e248-e252. [PMID: 39375898 DOI: 10.1097/tp.0000000000005226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/09/2024]
Abstract
Acute graft-versus-host disease (aGVHD) is a rare but potentially life-threatening complication that can occur after solid organ transplantation, particularly in organs with abundant lymphoid tissue like the liver and intestines. While less common in lung transplants, the rising numbers of these procedures have brought more attention to aGVHD, usually appearing within the first 3-mo posttransplant. Given its relative rarity, a clear understanding of the pathophysiology, risk factors, diagnostic, and management strategies remain elusive. These knowledge gaps can lead to delays in diagnosis and the initiation of appropriate treatment leading to predictably inferior outcomes. Managing aGVHD following solid organ transplantation is challenging, and there is no standard approach. Current management involves high-dose steroids and other immunosuppressive drugs. However, these interventions are associated with serious complications, including potentially fatal infections, underscoring the urgent need for more research to refine both diagnostic methods and treatment approaches and ultimately improving patient outcomes. In this report, we aim to deepen our understanding of aGVHD following lung transplants and share our experience with a unique case of aGVHD occurring almost a year after lung transplantation that was successfully managed using ruxolitinib, describing a potential treatment approach modeled on the contemporary management of stem cell transplant associated aGVHD.
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Affiliation(s)
- Ruah Alyamany
- Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Department of Hematology, Stem Cell Transplant and Cellular Therapy, Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Ahmed Alnughmush
- Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Department of Hematology, Stem Cell Transplant and Cellular Therapy, Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Faisal Albaiz
- Division of Respirology, Toronto Lung Transplant Program, University Health Network, Toronto, ON, Canada
- Lung Heath Centre, Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Meghan Aversa
- Division of Respirology, Toronto Lung Transplant Program, University Health Network, Toronto, ON, Canada
| | - Arjun Law
- Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
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Pang L, Wu WR, Xu LB, Liu C. Fatal graft-versus-host disease in recipient with pretransplant exposure to immune checkpoint inhibitors and donor-dominant one-way HLA matching after liver transplantation: A case report. Int J Surg Case Rep 2024; 123:110267. [PMID: 39265369 PMCID: PMC11415855 DOI: 10.1016/j.ijscr.2024.110267] [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: 08/03/2024] [Revised: 09/03/2024] [Accepted: 09/06/2024] [Indexed: 09/14/2024] Open
Abstract
INTRODUCTION AND IMPORTANCE Graft-versus-host disease (GvHD) is a rare but severe complication following liver transplantation (LT), occurring in 1-2 % of cases with a mortality rate exceeding 80 %. Immune checkpoint inhibitors (ICIs) used pretransplant are associated with increased allograft rejection risk, but their impact on GvHD in LT remains unclear. Dominant one-way donor-recipient human leukocyte antigen (HLA) matching is a known risk factor for GvHD. This report presents a rare case of fatal GvHD in a hepatocellular carcinoma (HCC) patient treated with PD-1 inhibitors before LT and transplanted with a liver graft from a deceased donor with donor-dominant one-way HLA matching. CASE PRESENTATION A 59-year-old male with a 30-year history of hepatitis B and unresectable HCC underwent LT after receiving the last dose of PD-1 inhibitors 7 days prior to the transplant. On post-operative day (POD) 12, the patient developed a skin rash, fever, and vomiting, and was diagnosed with GvHD. Despite aggressive treatment, including high-dose corticosteroids and extracorporeal membrane oxygenation (ECMO), the patient succumbed to gastrointestinal bleeding and multi-organ failure on POD 30. HLA genotyping revealed typical donor-dominant one-way HLA matching. CLINICAL DISCUSSION This case highlights a potential link between pretransplant exposure to ICIs and GvHD, particularly with donor-dominant one-way HLA matching. Residual anti-PD-1 antibodies may activate graft-resident immune cells, precipitating GvHD. Further research with larger cohorts and animal models is required to clarify this relationship and understand the underlying mechanisms. CONCLUSION Besides allograft rejection, caution should also be exercised regarding GvHD in patients with prior exposure to ICIs before LT.
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Affiliation(s)
- Li Pang
- Liver Transplantation Center, Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
| | - Wen-Rui Wu
- Liver Transplantation Center, Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
| | - Lei-Bo Xu
- Liver Transplantation Center, Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
| | - Chao Liu
- Liver Transplantation Center, Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
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Ercan LD, Durmaz Ö, Kaymakoğlu S, Önal Z, Büyükbabani N, Güllüoğlu M, Alper A, İbiş C, Cantez S, Yavru HA, Oğuz FS, Özden İ. The Consequences of HLA Screening in the Prevention of Graft-Versus-Host Disease in Living Donor Liver Transplantation. Pediatr Transplant 2024; 28:e14846. [PMID: 39177044 DOI: 10.1111/petr.14846] [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: 04/24/2024] [Revised: 07/16/2024] [Accepted: 08/08/2024] [Indexed: 08/24/2024]
Abstract
AIMS To study the effects of routine HLA screening and the policy of avoiding donor-dominant one-way HLA match to prevent graft-versus-host disease (GVHD) after living donor liver transplantation (LDLT). PATIENTS AND METHODS The records of potential living liver donors and recipients who attended our center between 2007 and 2018 were reviewed retrospectively. RESULTS Of the 149 patients who underwent LDLT and survived longer than 3 months, two developed GVHD despite our strict policy. The first patient presented with grade II GVHD limited to the skin. She was treated successfully by briefly discontinuing immunosuppression and switching to everolimus. In the second case, the policy had been relaxed due to the availability of a single donor for ABO-incompatible transplantation without any intervention to decrease anti-A antibody levels (special case: A2 to O). Nevertheless, the patient presented with grade I GVHD limited to skin and was treated successfully by adding oral methylprednisolone to tacrolimus and mycophenolate mofetil. To the best of our information, this is the second reported case who recovered from GVHD after LDLT from a donor, homozygous at HLA A, B and DR and a recipient, heterozygous for all. Sixteen potential donors (1.2% of all candidates) of 14 recipients were disqualified solely on the basis of the HLA results; five of these patients died due to unavailability of another donor. CONCLUSION The results support the policy of avoiding HLA combinations that preclude immune recognition of graft lymphocytes as foreign to decrease the risk of GVHD after LDLT.
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Affiliation(s)
- Leman Damla Ercan
- Department of General Surgery, İstanbul Faculty of Medicine, İstanbul, Turkey
| | - Özlem Durmaz
- Department of Pediatrics (Gastroenterology), İstanbul Faculty of Medicine, İstanbul, Turkey
| | - Sabahattin Kaymakoğlu
- Department of Internal Medicine (Gastroenterology), İstanbul Faculty of Medicine, İstanbul, Turkey
| | - Zerrin Önal
- Department of Pediatrics (Gastroenterology), İstanbul Faculty of Medicine, İstanbul, Turkey
| | | | - Mine Güllüoğlu
- Department of Pathology, İstanbul Faculty of Medicine, İstanbul, Turkey
| | - Aydın Alper
- Department of General Surgery, İstanbul Faculty of Medicine, İstanbul, Turkey
| | - Cem İbiş
- Department of General Surgery, İstanbul Faculty of Medicine, İstanbul, Turkey
| | - Serdar Cantez
- Department of Pediatrics (Gastroenterology), İstanbul Faculty of Medicine, İstanbul, Turkey
| | - Hacer Ayşen Yavru
- Department of Anesthesiology, İstanbul Faculty of Medicine, İstanbul, Turkey
| | - Fatma Savran Oğuz
- Department of Medical Biology, İstanbul Faculty of Medicine, İstanbul, Turkey
| | - İlgin Özden
- Department of General Surgery, İstanbul Faculty of Medicine, İstanbul, Turkey
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Yim SH, Kim DG, Lee JG, Joo DJ, Kim MS. One-way donor-to-recipient human leukocyte antigen mismatch and graft-versus-host disease in liver transplantation: an observational study of a single-center experience in Korea. KOREAN JOURNAL OF TRANSPLANTATION 2023; 37:269-276. [PMID: 37994082 PMCID: PMC10772268 DOI: 10.4285/kjt.23.0053] [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: 09/14/2023] [Revised: 10/26/2023] [Accepted: 10/26/2023] [Indexed: 11/24/2023] Open
Abstract
Background Graft-versus-host disease (GVHD) is a rare, but potentially fatal complication of liver transplantation. One-way human leukocyte antigens (HLA) mismatch has emerged as a risk factor for GVHD. However, the risk of mortality associated with HLA-one-way mismatch (OWMM) remains uncertain. We investigated the incidence and characteristics of GVHD. Methods In total, 899 patients who underwent liver transplantation at a single center were retrospectively reviewed. The incidence of GVHD and 1- and 5-year survival rates were compared according to whether HLA-OWMM developed. Results In the HLA-OWMM group, GVHD developed in two patients (14.3%). Notably, GVHD was only observed in living donor liver transplant (LDLT) recipients in the HLA-OWMM group. The HLA-OWMM group exhibited a lower 1-year patient survival rate than the control (i.e., non-HLA-OWMM) group (78.6% vs. 90.7%, P=0.120). However, the 5-year survival rate in the HLA-OWMM group was similar to that in the control group (78.6% vs. 78.2%, P=0.821). When the HLA-OWMM group was further stratified by the number of mismatched loci, the 5-year survival rate was 83.3% in patients with HLA-OWMM at one to two loci and 75.0% in those with HLA-OWMM at three loci. Conclusions Despite the higher incidence of GVHD in LDLT recipients with HLA-OWMM, the 5-year patient survival rates were comparable to those in recipients without HLA-OWMM. The decision to perform LDLT in patients with HLA-OWMM depends on the patient's status and the organ supply of a specific region.
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Affiliation(s)
- Seung Hyuk Yim
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Deok-Gie Kim
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Geun Lee
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Jin Joo
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Myoung Soo Kim
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
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Park S, Choi YR, Joo DJ, You YK, Kim BW, Nah YW, Cho JY, Kim TS, Hong G, Ju MK, Suh SW, Yang JD, Park PJ, Jeong J, Moon JI, Kim DS, Rhu J. The effect of donor against recipient one-way HLA mismatch on liver transplantation outcomes from a multicenter registry analysis. Sci Rep 2023; 13:22296. [PMID: 38102167 PMCID: PMC10724161 DOI: 10.1038/s41598-023-49178-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 12/05/2023] [Indexed: 12/17/2023] Open
Abstract
Donor against recipient one-way Human leukocyte antigen (HLA) mismatch (D → R one-way HLA MM) seemed strongly associated with graft-versus-host disease (GVHD). The aim of this study is to investigate the relevance of D → R one-way HLA MM in outcome of liver transplantation (LT). We retrospectively analyzed 2670 patients in Korean Organ Transplantation Registry database between April 2014 and December 2020. The patients were categorized into two groups whether D → R one-way HLA MM or not and evaluated the outcomes of LT between the two groups. 18 patients were found to be D → R one-way HLA MM. The incidence of GVHD (0.3% vs. 22.2%, p < 0.001) and mortality rate (11.6% vs. 38.9%, p = 0.003) was much higher in D → R one-way HLA MM group. D → R one-way HLA MM at 3 loci was seemed to be strongly associated with the incidence of GVHD (OR 163.3, p < 0.001), and found to be the strongest risk factor for patient death (HR 12.75, p < 0.001). Patients with D → R one-way HLA MM at 3 loci showed significantly lower overall survival (p < 0.001) but there were no significant differences in rejection-free survival and death-censored graft survival. D → R one-way HLA MM at 3 loci not only affects the overall survival of LT patients but also the incidence of GVHD.
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Affiliation(s)
- Sunghae Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea
| | - Young Rok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Tae-Seok Kim
- Department of Surgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Geun Hong
- Department of Surgery, Ewha Womans University Medical College, Seoul, Korea
| | - Man Ki Ju
- Department of Surgery, Yonsei University Gangnam Severance Hospital, Seoul, Korea
| | - Suk-Won Suh
- Department of Surgery, College of Medicine, Chung-Ang University, Seoul, Korea
| | - Jae Do Yang
- Department of Surgery, Jeonbuk National University Hospital, Jeonju, Korea
| | - Pyoung Jae Park
- Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Jaehong Jeong
- Department of Surgery, School of Medicine, Soonchunhyang University, Bucheon, Korea
| | - Ju Ik Moon
- Department of Surgery, Konyang University Hospital, Daejeon, Korea
| | - Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea.
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea.
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Izzo A, Pellegrino RA, Locci G, Cesaretti M. Acute graft versus host disease after liver transplantation: where do we stand? Minerva Surg 2023; 78:537-544. [PMID: 36883938 DOI: 10.23736/s2724-5691.23.09868-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
Graft-versus-host disease (GVHD) is a rare complication after liver transplantation (LT), with an estimated incidence rate of 0.5% to 2% and a mortality rate as high as 75%. The classical target organs of GVHD include the intestines, liver, and skin. The damage of these organs is not easy to detect for the clinician as there is no widely accepted clinical or laboratory diagnostic tests; as a result, diagnosis and initiation of therapy are often delayed. Moreover, without prospective clinical trials to reference, evidence guiding therapy is limited. This review summarized the current knowledge, the potential applications and the clinical relevance of GVHD after LT, highlighting novel approaches in grading and management of GVHD.
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Affiliation(s)
- Alessandro Izzo
- Department of HPB and Liver Transplantation, Brotzu Hospital, Cagliari, Italy
| | | | - Giorgia Locci
- Department of Pathology, Brotzu Hospital, Cagliari, Italy
| | - Manuela Cesaretti
- Department of HPB and Liver Transplantation, Brotzu Hospital, Cagliari, Italy -
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Kasahara M, Hong JC, Dhawan A. Evaluation of living donors for hereditary liver disease (siblings, heterozygotes). J Hepatol 2023; 78:1147-1156. [PMID: 37208102 DOI: 10.1016/j.jhep.2022.10.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/11/2022] [Accepted: 10/12/2022] [Indexed: 05/21/2023]
Abstract
Living donor liver transplantation (LDLT) is recognised as an alternative treatment modality to reduce waiting list mortality and expand the donor pool. Over recent decades, there have been an increasing number of reports on the use of LT and specifically LDLT for familial hereditary liver diseases. There are marginal indications and contraindications that should be considered for a living donor in paediatric parental LDLT. No mortality or morbidity related to recurrence of metabolic diseases has been observed with heterozygous donors, except for certain relevant cases, such as ornithine transcarbamylase deficiency, protein C deficiency, hypercholesterolemia, protoporphyria, and Alagille syndrome, while donor human leukocyte antigen homozygosity also poses a risk. It is not always essential to perform preoperative genetic assays for possible heterozygous carriers; however, genetic and enzymatic assays must hereafter be included in the parental donor selection criteria in the aforementioned circumstances.
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Affiliation(s)
- Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
| | - Johnny C Hong
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, USA
| | - Anil Dhawan
- Paediatric Liver GI and Nutrition Center and MowatLabs, King's College Hospital, London, UK
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Valencia J, Kaza V, Kim JK, Oliver D, Vandergriff T, Wysocki C, Dominguez AR. Acute graft-versus-host disease after double lung transplant confirmed by short tandem repeat analysis to identify donor chimerism in the skin. JAAD Case Rep 2023; 36:24-27. [PMID: 37361400 PMCID: PMC10285118 DOI: 10.1016/j.jdcr.2023.03.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2023] Open
Affiliation(s)
- Jesus Valencia
- University of Texas Southwestern Medical School, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Vaidehi Kaza
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | | | - Dwight Oliver
- Molecular Diagnostics Laboratory, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Travis Vandergriff
- Departments of Dermatology and Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Christian Wysocki
- Division of Allergy and Immunology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Arturo R. Dominguez
- Departments of Dermatology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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Cooper JP, Abkowitz JL. How I diagnose and treat acute graft-versus-host disease after solid organ transplantation. Blood 2023; 141:1136-1146. [PMID: 36395067 DOI: 10.1182/blood.2022015954] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 11/18/2022] Open
Abstract
Acute graft-versus-host disease (GVHD) is a rare complication after solid organ transplantation (SOT) that carries high mortality. Caused by immunocompetent donor leukocytes within the transplanted organ, which become activated against recipient tissues, GVHD typically develops 2 to 12 weeks after SOT and can affect the skin, gastrointestinal tract, liver, and bone marrow. Signs and symptoms are nonspecific and include a rash, nausea, appetite loss, diarrhea, and cytopenias. Pancytopenia from marrow-directed GVHD is the primary driver of mortality. The diagnosis of GVHD is often delayed but should be confirmed by biopsy of an affected organ. Evidence of donor chimerism in blood or marrow supports the diagnosis. When GVHD is diagnosed we initiate treatment with systemic corticosteroids. At that time, if GVHD only involves skin or oral mucosa we also decrease maintenance immunosuppression levels to allow the recipient to reject the donor immune cells. For GVHD involving the marrow we initiate an allogeneic hematopoietic cell donor search early. In this article, we describe 3 cases of GVHD after SOT, outline our approach to diagnosis and management, and then provide analysis of the 3 instructive cases.
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Affiliation(s)
- Jason P Cooper
- Division of Hematology, Department of Medicine, University of Washington, Seattle, WA
| | - Janis L Abkowitz
- Division of Hematology, Department of Medicine, University of Washington, Seattle, WA
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Ghandorah S, Alsawaf B, Alrefai W, Ghazwani A, Almusabi S. Role of HLA typing and chimerism analysis in post-liver transplantation GVHD in pediatrics: A systematic review. Pediatr Transplant 2022; 26:e14381. [PMID: 35979882 DOI: 10.1111/petr.14381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 07/30/2022] [Accepted: 08/06/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND GVHD is a well-documented complication after liver transplantation. GVHD occurs when donor immune cells mount a destructive immune response against host cells. The rarity of the GVHD complication and the nonspecific presentation of symptoms and histopathological features provide a diagnostic challenge. Therefore, diagnosis and initiation of treatment are often delayed. AIM In this systematic review, we assessed relevant literature to better understand the utilization of HLA typing and chimerism analysis in liver transplantation. We mainly focused on their importance in diagnosing GVHD incidence after liver transplantation. RESULTS A total of 18 articles reported 21 cases of GVHD after liver transplantation in pediatrics. Generally, there is a consensus on the advantage of HLA typing and chimerism analysis in confirming the diagnosis of GVHD after liver transplantation. However, there is an inconsistency in the timing and the application of the accurate HLA typing and chimerism analysis. CONCLUSION Further studies are required to assess the incidence of GVHD post-LT and to determine the impact of HLA typing and chimerism analysis in assessing the risk, early determination of GVHD incidence, and improving outcomes. This systematic review highlights the gap in the field of liver transplantation and calls for revisiting the guidelines to consider HLA typing and chimerism analysis in predicting GVHD before transplantation and diagnosing GVHD incidence after liver transplantation.
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Affiliation(s)
- Salim Ghandorah
- Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital - Dammam, Dammam, Saudi Arabia
| | | | - Weaam Alrefai
- Royal Commission Medical Center, Yanbu, Saudi Arabia
| | - Aisha Ghazwani
- Prince Sultan Military College of Health Sciences, Dhahran, Saudi Arabia
| | - Saleh Almusabi
- Prince Sultan Military College of Health Sciences, Dhahran, Saudi Arabia
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11
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The clinical impact of donor against recipient HLA one way mismatch on the occurrence of graft versus host disease in liver transplantation. Sci Rep 2022; 12:20337. [PMID: 36434131 PMCID: PMC9700759 DOI: 10.1038/s41598-022-24778-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 11/21/2022] [Indexed: 11/27/2022] Open
Abstract
Graft versus host disease (GVHD) after liver transplantation (LT) is a rare, fatal disease. This study aimed to evaluate the risk factors of GVHD after LT including the human leukocyte antigen (HLA) donor-recipient relationship after LT. LT recipients, who underwent HLA typing together with donors, were included in the study. The donor against recipient (D → R) one-way mismatch of HLA loci was evaluated. HLA relationships, along with basic characteristics, were analyzed as variable factors of GVHD, graft survival, and patient survival. A total of 994 living donor LT (LDLT) and 393 deceased donor LT (DDLT) patients were included. Nine patients had suffered GVHD, four LDLT with D → R one-way at three loci, one LDLT without D → R one-way at three loci, and four DDLT without D → R one-way at three loci. Four (57.1%) of seven LDLT patients, with D → R one-way mismatch at three loci, developed GVHD. D → R one-way mismatch at three loci was related to high GVHD incidence (HR 787, p < 0.001, multivariate). D → R one-way mismatch at three loci was related to graft failure and patient death (HR 9.90, p = 0.020 and HR 12.8, p < 0.001, respectively, multivariate). Only one GVHD without D → R one-way mismatch at three loci, survived despite receiving multiple modalities including tumor necrosis factor-alpha inhibitors. D → R one-way mismatch at three loci was significantly related to GVHD incidence after LT.
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12
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Xu Z, Otrock ZK. Extracorporeal photopheresis: A case of graft-versus-host-disease and hemophagocytic lymphohistiocytosis following liver transplantation. Transfusion 2022; 62:2409-2413. [PMID: 36082758 DOI: 10.1111/trf.17096] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 08/15/2022] [Accepted: 08/16/2022] [Indexed: 12/01/2022]
Abstract
BACKGROUND Graft-versus-host-disease (GVHD) is one of the rare complications following liver transplantation. We report on the efficacy and safety of extracorporeal photopheresis (ECP) in managing GVHD and hemophagocytic lymphohistiocytosis (HLH) after liver transplantation. CASE REPORT The patient is a 63-year-old male with hepatitis B cirrhosis who underwent liver transplantation. Three weeks after transplant, he presented with fever, diarrhea, and poor appetite. The patient also had bilateral blanchable erythematous patches on his palms, biopsy of which was suggestive of GVHD. The patient continued to have high-grade fever with altered mental status. CBC showed pancytopenia. Liver function examination was normal. Patient was started on methylprednisolone. Additional laboratory analysis showed high ferritin (>15000 ug/L), triglycerides (280 mg/dl), and low fibrinogen (80 mg/dl). Chimerism analysis using short tandem repeat (STR) PCR confirmed the diagnosis of GVHD. Marrow biopsy showed hemophagocytosis. The patient fulfilled the HLH-2004 diagnostic criteria. He was kept on tacrolimus and steroids and was started on etanercept and ECP. After the first two cycles of ECP (one cycle defined as the weekly two procedures of ECP), the patient reported improvement of symptoms. He tolerated ECP well. His labs improved during the course of treatment, until his peripheral blood STR showed 100% recipient DNA. He was discharged after the fourth cycle of ECP to receive the remaining treatments as outpatient. At one year follow-up, the patient is asymptomatic with no evidence of GVHD or HLH. DISCUSSION ECP in combination with immunosuppressive therapy and etanercept was safe and efficient in managing GVHD and HLH following liver transplantation.
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Affiliation(s)
- Zhengfan Xu
- Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan, USA
| | - Zaher K Otrock
- Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan, USA
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13
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Abstract
PURPOSE OF REVIEW Living donor liver transplantation (LT) has been increasingly recognized as an effective treatment modality with excellent patient survival. Indications for LT have evolved not only for cholestatic liver disease, but also metabolic liver diseases. Living donor selection, particularly for pediatric inherited disease, is essential to prevent morbidity, both in the donor and recipient. RECENT FINDINGS Based on 30 years of experience in pediatric living donor LT in Japan, we could identify marginal parental living donors who have potential risks following LT, including heterozygous mothers with ornithine transcarbamylase deficiency, heterozygous protein C deficiency, heterozygous hypercholesterolemia, heterozygous protoporphyria, asymptomatic parental donors with paucity of intrahepatic bile duct, and human leukocyte antigen-homozygous parental donors. SUMMARY Although these situations seem rare due to infrequency of the condition, careful living donor evaluation is required to optimize the outcomes for pediatric recipients. In the setting of an appropriate selection of a living donor, we should avoid any additional hazards, given that the procedure itself has risks for a healthy individual.
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14
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Attas RAA, Bader RM, Mashhour M, AlQahtani ZA, Mohammed A, Qahtani M, Arain ZB, Faraidy N, Awaji M, Mohammed G, Alharbi HA, AlZahrani M, Aqool A, Salim G. Graft-versus-host disease after pediatric liver transplantation: A diagnostic challenge. Pediatr Transplant 2022; 26:e14205. [PMID: 34931754 DOI: 10.1111/petr.14205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 11/14/2021] [Accepted: 11/26/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Graft-versus-host disease (GVHD) is a rare but serious complication after pediatric liver transplantation (LTx). Early diagnosis is difficult due to nonspecific presenting symptoms and non-pathognomonic skin histopathological features. The aim of this article was to describe a case of pediatric GVHD after LTx and to review available data on pediatric GVHD highlighting the diagnostic difficulty. We also propose a diagnostic algorithm to improve the diagnostic capability and increase clinical awareness about this potentially fatal condition. METHODS We did a comprehensive literatures review on studies on GvHD following pediatric LTx between 1990 and February 2021, chimerism study by short tandem repeat (STR), HLA typing by sequence-specific oligonucleotide (SSO) method, and flowcytometry crossmatch. RESULTS Our search yielded 23 case reports. The most common clinical manifestations were fever and rash (91%) followed by diarrhea. Mortality rate was 36.8% mainly due to sepsis and organ failure. Diagnosis was challenging and chimerism study to confirm donor engraftment was performed on only half of the cases. Prevalence of "donor dominant HLA one-way matching" typically occurs in homozygous parents-to-child transplantation was 75% in cases with HLA testing. CONCLUSION So far, there are no available standard diagnostic criteria for GVHD following pediatric LTx. Recognition of multiple risk factors through proper laboratory assessment can predict the occurrence, and early chimerism study can confirm suggestive clinical manifestation. The strong likelihood of developing GVHD in "donor one-way HLA match" and the severe problems imposed by this complication may justify avoidance of HLA homozygous parent's donation.
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Affiliation(s)
- Rabab Ali Al Attas
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia.,Saudi Society of Bone Marrow Transplantation (SSBM), Riyadh, Saudi Arabia
| | - Razan M Bader
- Pediatric Liver Transplant, Liver Transplant Department, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia
| | - Miral Mashhour
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
| | - Zuhoor A AlQahtani
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
| | - Amani Mohammed
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
| | - Masood Qahtani
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
| | - Zahid B Arain
- Liver Transplant, Liver Transplant Department, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia
| | - Nadya Faraidy
- Dermatology, Medicine Department, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia
| | - Mohammad Awaji
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
| | - Gamil Mohammed
- Dermatology, Medicine Department, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia
| | - Hassan A Alharbi
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
| | - Mariam AlZahrani
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
| | - Amal Aqool
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
| | - Ghandorah Salim
- Histocompatibility and Immunogenetic Lab, Department of pathology and Laboratory Medicine, King Fahad Specialist Hospital- Dammam, Dammam, Saudi Arabia
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15
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Sato N, Marubashi S. How is transfusion-associated graft-versus-host disease similar to, yet different from, organ transplantation-associated graft-versus-host disease? Transfus Apher Sci 2022; 61:103406. [DOI: 10.1016/j.transci.2022.103406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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16
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Cooper JP, Perkins JD, Warner PR, Shingina A, Biggins SW, Abkowitz JL, Reyes JD. Acute Graft-Versus-Host Disease After Orthotopic Liver Transplantation: Predicting This Rare Complication Using Machine Learning. Liver Transpl 2022; 28:407-421. [PMID: 34587357 PMCID: PMC9297869 DOI: 10.1002/lt.26318] [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: 06/07/2021] [Revised: 09/13/2021] [Accepted: 09/22/2021] [Indexed: 01/13/2023]
Abstract
Acute graft-versus-host disease (GVHD) is a rare complication after orthotopic liver transplantation (OLT) that carries high mortality. We hypothesized that machine-learning algorithms to predict rare events would identify patients at high risk for developing GVHD. To develop a predictive model, we retrospectively evaluated the clinical features of 1938 donor-recipient pairs at the time they underwent OLT at our center; 19 (1.0%) of these recipients developed GVHD. This population was divided into training (70%) and test (30%) sets. A total of 7 machine-learning classification algorithms were built based on the training data set to identify patients at high risk for GVHD. The C5.0, heterogeneous ensemble, and generalized gradient boosting machine (GGBM) algorithms predicted that 21% to 28% of the recipients in the test data set were at high risk for developing GVHD, with an area under the receiver operating characteristic curve (AUROC) of 0.83 to 0.86. The 7 algorithms were then evaluated in a validation data set of 75 more recent donor-recipient pairs who underwent OLT at our center; 2 of these recipients developed GVHD. The logistic regression, heterogeneous ensemble, and GGBM algorithms predicted that 9% to 11% of the validation recipients were at high risk for developing GVHD, with an AUROC of 0.93 to 0.96 that included the 2 recipients who developed GVHD. In conclusion, we present a practical model that can identify patients at high risk for GVHD who may warrant additional monitoring with peripheral blood chimerism testing.
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Affiliation(s)
- Jason P. Cooper
- Division of HematologyDepartment of MedicineUniversity of WashingtonSeattleWA
| | - James D. Perkins
- Division of Transplant SurgeryUniversity of WashingtonSeattleWA,Clinical and Bio‐Analytics Transplant Laboratory in the Department of Surgery at the University of Washington School of MedicineSeattleWA
| | | | - Alexandra Shingina
- Division of GastroenterologyDepartment of MedicineUniversity of WashingtonSeattleWA,Present address:
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical CenterNashvilleTN
| | - Scott W. Biggins
- Clinical and Bio‐Analytics Transplant Laboratory in the Department of Surgery at the University of Washington School of MedicineSeattleWA,Division of GastroenterologyDepartment of MedicineUniversity of WashingtonSeattleWA
| | - Janis L. Abkowitz
- Division of HematologyDepartment of MedicineUniversity of WashingtonSeattleWA
| | - Jorge D. Reyes
- Division of Transplant SurgeryUniversity of WashingtonSeattleWA,Clinical and Bio‐Analytics Transplant Laboratory in the Department of Surgery at the University of Washington School of MedicineSeattleWA
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17
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OHTO H. Editorial: Two hits and four factors affecting the development of, or resistance to, transfusion-associated graft-versus-host disease. Transfus Apher Sci 2022; 61:103401. [DOI: 10.1016/j.transci.2022.103401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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18
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Complementary Roles of Cadaveric and Living Donor Liver Transplantation in Acute Liver Failure. J Gastrointest Surg 2021; 25:2516-2523. [PMID: 33565013 DOI: 10.1007/s11605-021-04932-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 01/16/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Living donor liver transplantation may complement cadaveric transplantation in acute liver failure (ALF) patients. METHODS Between 2008 and 2017, 89 patients were treated for ALF; 15 patients (17%) recovered with intensive care treatment; 31 (35%) died without transplant. The records of the remaining 43 patients (median (range) age: 14 (1-62)) who underwent transplantation were evaluated. RESULTS The etiologic factors were toxic agents (10; mushrooms: 8; herbs: 2), hepatitis viruses (7; A: 1; B: 6), Wilson's disease (7), autoimmune hepatitis (4), and Budd-Chiari syndrome (2); 13 cases were idiopathic. Cadaveric organs (whole, split, reduced) were transplanted to 32 patients; 11 patients underwent living donor transplantation. One patient (2%) died of septic shock on the second postoperative day. Bacterial infection was the most common early (< 3 months) complication in the remaining patients (31/42; 74%), followed by delirium (5/42; 12%) and acute rejection requiring steroid pulse (5/42; 12%). Seven other patients died during median (range) follow-up of 94 (14-142) months: various infections (5), leukemia (1), and acute myocardial infarction (1). The 1-, 5-, and 10-year survival rates were 100%, 96%, and 92% in children and 94%, 82%, and 65% in adults respectively. CONCLUSIONS Cadaveric organ sharing and transplantation from living donors when appropriate yield a high survival rate, despite high early morbidity, in ALF patients whose conditions deteriorate despite intensive care treatment. Efforts to eliminate preventable causes of acute liver failure will lead to more efficient use of health care resources.
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19
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Ghandorah SS, Alwosaibai K. Post-liver transplantation GVHD: time to consider histocompatibility testing. JOURNAL OF LIVER TRANSPLANTATION 2021. [DOI: 10.1016/j.liver.2021.100021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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20
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Cotter TG, Minhem M, Wang J, Peeraphatdit T, Ayoub F, Pillai A, Hernandez-Alejandro R, di Sabato D, Charlton M. Living Donor Liver Transplantation in the United States: Evolution of Frequency, Outcomes, Center Volumes, and Factors Associated With Outcomes. Liver Transpl 2021; 27:1019-1031. [PMID: 33619854 PMCID: PMC9257956 DOI: 10.1002/lt.26029] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 01/31/2021] [Accepted: 02/17/2021] [Indexed: 12/13/2022]
Abstract
Recent modifications in organ allocation policies and increases in chronic liver diseases may have resulted in important changes in living donor liver transplantation (LDLT) in the United States. We examined the trends, outcomes, and factors associated with outcomes in adult LDLT. United Network for Organ Sharing data on 2566 adult LDLT recipients who received transplants from January 1, 2010, through December 31, 2019, were analyzed. LDLT graft and patient survival rates were compared with propensity score-matched deceased donor liver transplantation recipients by the Kaplan-Meier curve estimator. The association between preceding LDLT frequency and subsequent outcomes were assessed by Cox proportional hazards mixed effects modeling. After a stable annual frequency of LDLTs from 2010 to 2014 (~200 per year), the number of LDLTs doubled to 440 in 2019. The 1-year and 5-year graft survival rates for LDLT recipients were 88.4% and 78.1%, respectively, compared with 92.5% and 80.7% in the propensity score-matched donation after brain death recipients (P = 0.005), respectively. Older donor age and recipient diabetes mellitus and life support requirement were significantly associated with graft failure among LDLT recipients (P values <0.05). Average preceding LDLT frequencies of <3 per year, 3 to 20 per year, and >20 per year resulted in 1-year graft survival rates of 82%, 88% to 89%, and 93%, respectively (P values <0.05). There were 3 living donor deaths (0.12%). The frequency of LDLTs has doubled during the past decade, with good outcomes and acceptable donor safety profiles. However, there appear to be varying threshold transplant frequencies (volume/unit time) associated with acceptable (88%-89%) and aspirational (93%) 1-year graft survival rates. These data should be reassuring and encourage LDLT practice as efforts continue to expand the donor pool.
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Affiliation(s)
- Thomas G. Cotter
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL, USA
| | - Mohamad Minhem
- Department of Medicine, Loyola University Medical Center at Trinity Mercy Chicago, Chicago, IL, USA
| | - Jennifer Wang
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL, USA
| | | | - Fares Ayoub
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL, USA
| | - Anjana Pillai
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL, USA
| | | | - Diego di Sabato
- Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA
| | - Michael Charlton
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL, USA
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21
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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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22
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Incidence and Risk Factors for Fatal Graft-versus-host Disease After Liver Transplantation. Transplantation 2021; 105:2571-2578. [PMID: 33449608 DOI: 10.1097/tp.0000000000003607] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but serious complication. The aim of this study is to identify risk factors, including immunosuppressive regimens, for mortality due to GVHD (fatal GVHD). METHODS Using data from the OPTN/UNOS registry, 77,416 adult patients who underwent LT between 2003 and 2018 were assessed. Risk factors for fatal GVHD were analyzed by focusing on induction and maintenance immunosuppression regimens. RESULTS The incidence of fatal GVHD was 0.2% (121/77,416), of whom 105 (87%) died within 180 days and 13 (11%) died between 181 days and 1 year. Median survival after LT was 68.0 (49.5-125.5) days. Recipient age minus donor age greater than 20 years (HR 2.57, P<0.001) and basiliximab induction (HR 1.69, P=0.018) were independent risk factors for fatal GVHD. Maintenance therapy with mycophenolate mofetil (MMF) was associated with a decrease in fatal GVHD (HR 0.51, P=0.001). In an increased risk cohort of patients with recipient-donor age discrepancy greater than 20 years, MMF use was associated with a 50% decline in fatal GVHD (HR 0.50, P<0.001). CONCLUSIONS Recipient age minus donor age greater than 20 years remains a significant risk factor for fatal GVHD. The risk of fatal GVHD significantly increases in association with basiliximab induction and decreases with MMF maintenance. These associations were pronounced in patients with recipient minus donor age greater than 20 years. These results emphasize the importance of donor age and individualized immunosuppression regimens on the risk of fatal GVHD.
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23
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Hirata M, Yagi S, Shindo T, Yoshizawa A, Kiguchi G, Kaneshiro M, Yurugi K, Miyachi Y, Iwamura S, Yao S, Uemoto S. Donor-dominant one-way matching of human leukocyte antigen-A/B/DR alleles predicts graft-versus-host disease following living donor liver transplantation. Hepatol Res 2021; 51:135-148. [PMID: 33034106 DOI: 10.1111/hepr.13579] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 08/31/2020] [Accepted: 09/18/2020] [Indexed: 12/12/2022]
Abstract
AIM Graft-versus-host disease (GVHD) following liver transplantation is rare but fatal. Therefore, it is important to identify possible risk factors before transplantation. Although it has been suggested that donor-dominant one-way human leukocyte antigen (HLA) matching of three loci (HLA-A/B/DR) is associated with the occurrence of GVHD, the precise significance of HLA matching including HLA-C/DQ/DP remains unclear. METHODS We retrospectively analyzed the impact of donor-dominant one-way HLA matching at six HLA loci at the allele level on GVHD using clinical registry data from 1759 cases who underwent living donor liver transplantation between June 1990 and June 2019. We extracted cases with donor-dominant one-way HLA matching at the antigen level and reconfirmed them at the allele level using preserved DNA samples. RESULTS Three of four cases (75%) who developed GVHD showed donor-dominant one-way HLA matching at three HLA-A/B/DR loci. These cases also showed donor-dominant one-way HLA matching at HLA-C/DQ/DP. Three of six cases (50%) with donor-dominant one-way HLA matching at three loci of HLA-A/B/DR developed GVHD. Notably, none of the cases with donor-dominant one-way HLA matching at one or two HLA-A/B/DR loci developed GVHD, irrespective of matching status at HLA-C/DQ/DP. The HLA matching status at the antigen level was revised in 22 of 56 cases, following reconfirmation at the allele level. CONCLUSIONS Pairing of donors and recipients with donor-dominant one-way HLA matching at three HLA-A/B/DR loci should be avoided to prevent GVHD. No impact of HLA-C/DQ/DP on GVHD was identified. For liver transplantation, HLA genotypes should be determined at the allele level.
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Affiliation(s)
- Masaaki Hirata
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shintaro Yagi
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takero Shindo
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Atsushi Yoshizawa
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Gozo Kiguchi
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masakatsu Kaneshiro
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kimiko Yurugi
- Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan
| | - Yosuke Miyachi
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Sena Iwamura
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Siyuan Yao
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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24
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Kim KJ, Lee TB, Yang KH, Ryu JH, Choi BH, Lee HJ, Lee SM, Kim IS. Temporary Cessation of Immunosuppression for Infection May Contribute to the Development of Graft-vs-Host Disease After ABO-Incompatible Living Donor Liver Transplantation: A Case Report. Transplant Proc 2019; 51:3136-3139. [PMID: 31611115 DOI: 10.1016/j.transproceed.2019.07.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 07/28/2019] [Indexed: 11/27/2022]
Abstract
Graft-vs-host disease (GVHD) after liver transplantation is a rare complication with a high mortality rate. A complex interplay between donor and recipient immunity plays a role in the development of GVHD. Infection following liver transplantation is one of the most common complications in a recipient of an organ transplant who is immunosuppressed. On clinical signs of infection, the immune reaction of the recipient can be reconstituted by withdrawal of immunosuppression in order to help combat infection. However, the discontinuation of immunosuppression could restore the donor's immune activity rather than that of the recipient. There is little information available as to whether the discontinuation of immunosuppression for severe infection could contribute to the development of GVHD in a patient who underwent ABO-incompatible (ABO-I) living donor liver transplantation (LDLT). Herein, we present a unique case of GVHD following ABO-I LDLT, for which the cessation of immunosuppression could be responsible.
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Affiliation(s)
- Keun Ju Kim
- Department of Laboratory Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Tae Beom Lee
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Kwang Ho Yang
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Je Ho Ryu
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Byung Hyun Choi
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Hyun-Ji Lee
- Department of Laboratory Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
| | - Sun-Min Lee
- Department of Laboratory Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - In-Suk Kim
- Department of Laboratory Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
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25
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Minnee RC, Fieuws S, Jochmans I, Aerts R, Sainz Barriga M, Debaveye Y, Maertens J, Vandenberghe P, Laleman W, van der Merwe S, Verslype C, Cassiman D, Ferdinande P, Nevens F, Pirenne J, Monbaliu D. Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review. Am J Transplant 2018; 18:3007-3020. [PMID: 29734503 DOI: 10.1111/ajt.14923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 04/25/2018] [Accepted: 04/26/2018] [Indexed: 01/25/2023]
Abstract
Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.
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Affiliation(s)
- R C Minnee
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - S Fieuws
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, KU Leuven-University of Leuven, Leuven, Belgium.,University Hasselt, Hasselt, Belgium
| | - I Jochmans
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - R Aerts
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - M Sainz Barriga
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - Y Debaveye
- Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
| | - J Maertens
- Department of Hematology, University Hospitals Leuven, Leuven, Belgium
| | - P Vandenberghe
- Department of Hematology, University Hospitals Leuven, Leuven, Belgium.,Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
| | - W Laleman
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - S van der Merwe
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - C Verslype
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - D Cassiman
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - P Ferdinande
- Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
| | - F Nevens
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - J Pirenne
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - D Monbaliu
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
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26
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Iemura T, Itoh M, Mano C, Oba A, Kawabata N, Horisawa Y, Matsui M, Miyahara Y, Kanda J. Successful engraftment after cord blood transplantation from an HLA-homozygous donor (homo-to-hetero cord blood transplantation) in a primary myelofibrosis patient with broad HLA antibodies. Transfusion 2018; 58:2773-2776. [DOI: 10.1111/trf.14885] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 06/12/2018] [Accepted: 06/12/2018] [Indexed: 11/30/2022]
Affiliation(s)
- Tomoki Iemura
- Department of Hematology; Kyoto City Hospital; Kyoto Japan
| | - Mitsuru Itoh
- Department of Hematology; Kyoto City Hospital; Kyoto Japan
| | - Chihiro Mano
- Department of Hematology; Kyoto City Hospital; Kyoto Japan
| | - Akifumi Oba
- Department of Hematology; Kyoto City Hospital; Kyoto Japan
| | | | | | - Masashi Matsui
- Department of Hematology; Kyoto City Hospital; Kyoto Japan
| | | | - Junya Kanda
- Department of Hematology, Graduate School of Medicine; Kyoto University; Kyoto Japan
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27
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Shimata K, Sakamoto R, Anan T, Uchida K, Honda M, Kouroki M, Urabe T, Hayashida S, Yamamoto H, Sugawara Y, Inomata Y. Fatal graft-versus-host disease after living-donor liver transplantation from an HLA-DR-mismatched donor. Pediatr Transplant 2017; 21. [PMID: 28834141 DOI: 10.1111/petr.13039] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/27/2017] [Indexed: 11/30/2022]
Abstract
Acute GVHD is a rare complication after liver transplantation that has a high mortality rate. We experienced an infant case complicated with acute GVHD. An 8-month-old infant with biliary atresia underwent LDLT with a graft obtained from his mother. Their HLAs showed a donor-dominant one-way match, not at HLA-DR but at HLA-A, HLA-B, and HLA-C (recipient; A 31/33, B 51/54, C 1/14, DR 9/11, donor; A 31/-, B 51/-, C 14/-, DR 8/11). The patient exhibited a high fever, skin rash, and diarrhea, and was diagnosed with acute GVHD based on the blood chimerism test. Despite immunosuppression treatment with prednisolone and tacrolimus, plasma exchange, blood transfusion including cord blood transplantation, and antibiotics, the child died on postoperative day 126. Donor-dominant one-way matching at HLA class 1 can be a high-risk factor for acute GVHD despite HLA class 2 mismatching.
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Affiliation(s)
- Keita Shimata
- Department of Transplantation and Pediatric Surgery, Kumamoto University Hospital, Kumamoto, Japan
| | - Rieko Sakamoto
- Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan
| | - Tadashi Anan
- Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan
| | - Koushi Uchida
- Department of Transplantation and Pediatric Surgery, Kumamoto University Hospital, Kumamoto, Japan
| | - Masaki Honda
- Department of Transplantation and Pediatric Surgery, Kumamoto University Hospital, Kumamoto, Japan
| | - Masahiko Kouroki
- Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan
| | - Tomonari Urabe
- Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan
| | - Shintaro Hayashida
- Department of Transplantation and Pediatric Surgery, Kumamoto University Hospital, Kumamoto, Japan
| | - Hidekazu Yamamoto
- Department of Transplantation and Pediatric Surgery, Kumamoto University Hospital, Kumamoto, Japan
| | - Yasuhiko Sugawara
- Department of Transplantation and Pediatric Surgery, Kumamoto University Hospital, Kumamoto, Japan
| | - Yukihiro Inomata
- Department of Transplantation and Pediatric Surgery, Kumamoto University Hospital, Kumamoto, Japan
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28
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Abstract
Living-donor liver transplantation is an important component of all liver transplant programs especially in those that care for the pediatric population. Over the last 30 years, innovations in surgical technique have converted living donation from an experimental procedure to a standard of care. Many of these innovations occurred in countries where culturally, deceased donation is limited leaving no alternatives but living donation. The Organ Transplantation Center at the National Center for Child Health and Development (NCCHD) in Tokyo, Japan, was established in 2005 where we have generated some of those innovations and in so doing, have performed living-donor liver transplantation in over 400 children. Here we review the indications, technical details, and outcomes of that cohort.
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Affiliation(s)
- Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, Japan.
| | - Seisuke Sakamoto
- Organ Transplantation Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, Japan
| | - Akinari Fukuda
- Organ Transplantation Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, Japan
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29
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Nugroho A, Kim OK, Lee KW, Song S, Kim H, Hong SK, Yoon KC, Kim HS, Choi Y, Lee HW, Yi NJ, Suh KS. Evaluation of donor workups and exclusions in a single-center experience of living donor liver transplantation. Liver Transpl 2017; 23:614-624. [PMID: 28294533 DOI: 10.1002/lt.24762] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 01/27/2017] [Indexed: 02/07/2023]
Abstract
The process of evaluating potential donors in liver transplantation is important to ensure donor safety and provide optimal recipient outcomes. However, there has been no report about donor exclusion rates and reasons for such exclusion in Korea. In this study, we aimed to elucidate the outcomes of potential living liver donor evaluation in a major living donor liver transplantation center. From July 2011 to June 2015, prospectively collected data of 726 potential donors for 588 matched recipients were subsequently evaluated. Among 726 potential donors, 374 potential donors (51.5%) finally reached donation; 352 potential donors (48.5%) were excluded for various reasons. Donor reasons were 29.8%, including medical problems, withdrawal of consent, graft volume issues, and identification of a better suitable donor. Recipient reasons were 20.7%, including recipient death or recovery, allocation to deceased donor, and progressions of hepatocellular carcinoma. A total of 38 (5.2%) potential donors had a fatty liver. Among them, 15 (39.5%) potential donors tried short-term weight reduction and eventually were able to donate. In conclusion, the main reasons for donor exclusion were medical problems and withdrawal of consent. Therefore, thorough medical screening and careful examination for donor voluntarism are important in the donor evaluation process. Liver Transplantation 23 614-624 2017 AASLD.
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Affiliation(s)
- Adianto Nugroho
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Ok-Kyung Kim
- Organ Transplant Center, Seoul National University Hospital, Seoul, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.,Organ Transplant Center, Seoul National University Hospital, Seoul, South Korea
| | - Sanghee Song
- Organ Transplant Center, Seoul National University Hospital, Seoul, South Korea
| | - Hyeyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.,Organ Transplant Center, Seoul National University Hospital, Seoul, South Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyung Chul Yoon
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyo-Sin Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.,Organ Transplant Center, Seoul National University Hospital, Seoul, South Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.,Organ Transplant Center, Seoul National University Hospital, Seoul, South Korea
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30
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Yu E, Ueta H, Kimura H, Kitazawa Y, Sawanobori Y, Matsuno K. Graft-Versus-Host Disease Following Liver Transplantation: Development of a High-Incidence Rat Model and a Selective Prevention Method. Am J Transplant 2017; 17:979-991. [PMID: 27732765 DOI: 10.1111/ajt.14077] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 10/03/2016] [Accepted: 10/04/2016] [Indexed: 01/25/2023]
Abstract
Graft-versus-host disease (GvHD) following liver transplantation (LT) is a rare but serious complication with no presently available animal model and no preventive measures. To develop a rat model of GvHD after LT (LT-GvHD), we preconditioned hosts with sublethal irradiation plus reduction of natural killer (NK) cells with anti-CD8α mAb treatment, which invariably resulted in acute LT-GvHD. Compared with those in the peripheral counterpart, graft CD4+ CD25- passenger T cells showed lower alloreactivities in mixed leukocyte culture. Immunohistology revealed that donor CD4+ T cells migrated and formed clusters with host dendritic cells in secondary lymphoid organs, with early expansion and subsequent accumulation in target organs. For selectively preventing GvHD, donor livers were perfused ex vivo with organ preservation media containing anti-TCRαβ mAb. T cell-depleted livers almost completely suppressed clinical GvHD such that host rats survived for >100 days. Our results showed that passenger T cells could develop typical LT-GvHD if resistant cells such as host radiosensitive cells and host radioresistant NK cells were suppressed. Selective ex vivo T cell depletion prevented LT-GvHD without affecting host immunity or graft function. This method might be applicable to clinical LT in prediagnosed high-risk donor-recipient combinations and for analyzing immunoregulatory mechanisms of the liver.
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Affiliation(s)
- E Yu
- Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan.,Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - H Ueta
- Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan
| | - H Kimura
- Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan
| | - Y Kitazawa
- Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan
| | - Y Sawanobori
- Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan
| | - K Matsuno
- Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan
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31
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Yu YD, Kim DS, Ha N, Jung SW, Han JH, Kim JY, Park SH, Cho YJ. Fatal Graft-Versus-Host Disease Following Adult-To-Adult Living Donor Liver Transplantation From an HLA Nonhomozygous Donor. Prog Transplant 2016; 26:394-396. [PMID: 27555077 DOI: 10.1177/1526924816664087] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The use of a human leukocyte antigen (HLA) homozygous donor to a haploidentical recipient is a well-documented cause of transfusion-associated graft-versus-host disease (GVHD). Several authors have reported that use of a graft from an HLA-homozygous donor with 1-way donor-recipient HLA matching led to an extremely high risk of developing GVHD in LDLT. We have experienced a fatal case of acute GVHD following adult-to-adult LDLT from a donor who was heterozygous at a single HLA locus. A 53-year-old female underwent LDLT for chronic hepatitis B and recurrent hepatocellular carcinoma. The donor was her 23-year-old son. The HLA phenotype of the donor was not homozygous (A24, -; B54, -; DR4, 9) and revealed one-way donor-dominant HLA matching at two loci with the recipient (A2, 24; B48, 54; DR4, 12). On the fortieth postoperative day, the patient showed erythematous skin lesions. Skin biopsy revealed typical findings of GVHD. Donor-derived chimerism was demonstrated by performing fluorescent in situ hybridization (FISH) using the recipient's skin tissue. As the clinical course deteriorated, etanercept was started in addition to broad-spectrum antibiotics but there was no improvement. As multi-organ failure progressed, the patient succumbed to death on the 54th postoperative day, which was 2 weeks after onset of GVHD. The prevention of GVHD is more important since the results of treatment have been disappointing. We have experienced a fatal case of acute GVHD following adult-to-adult LDLT from a HLA non-homozygous donor. HLA heterozygosity at a single locus does not preclude the possibility of developing GVHD following adult-to-adult LDLT.
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Affiliation(s)
- Young-Dong Yu
- 1 Division of HBP surgery and Liver transplantation, Department of Surgery, Korea University Medical Center, Korea University Medical College, Seoul, Korea
| | - Dong-Sik Kim
- 1 Division of HBP surgery and Liver transplantation, Department of Surgery, Korea University Medical Center, Korea University Medical College, Seoul, Korea
| | - Neul Ha
- 1 Division of HBP surgery and Liver transplantation, Department of Surgery, Korea University Medical Center, Korea University Medical College, Seoul, Korea
| | - Sung-Won Jung
- 1 Division of HBP surgery and Liver transplantation, Department of Surgery, Korea University Medical Center, Korea University Medical College, Seoul, Korea
| | - Jae-Hyun Han
- 1 Division of HBP surgery and Liver transplantation, Department of Surgery, Korea University Medical Center, Korea University Medical College, Seoul, Korea
| | - Joo-Young Kim
- 2 Department of Pathology, Korea University Medical Center, Seoul, Korea
| | - Sung-Hwan Park
- 3 Department of Forensic Medicine, Korea University Medical Center, Seoul, Korea
| | - Yun-Jung Cho
- 4 Department of Laboratory Medicine, Korea University Medical Center, Seoul, Korea
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32
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Green T, Hind J. Graft-versus-host disease in paediatric solid organ transplantation: A review of the literature. Pediatr Transplant 2016; 20:607-18. [PMID: 27198497 DOI: 10.1111/petr.12721] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/24/2016] [Indexed: 12/23/2022]
Abstract
GvHD is a rare and serious complication of organ transplantation. The literature is sparse following solid organ transplantation. The aim of this report was to review the literature of GvHD in paediatric solid organ transplantation. We searched PubMed for English-language full-text manuscripts between 1990 and 2015 for eligible studies. A total of 28 publications were found pertaining to paediatric GvHD following solid organ transplantation. GvHD had a mean incidence of 11% (range 8.3-13.4%) following SBTx and 1.5% following liver transplantation. Where described, the most common sites for presentation of GvHD were the skin (87%), the native GI tract (43%), the lungs (7%), the eyes (4%), HA (4%), and the kidneys (1%). Diagnosis was confirmed with biopsy (93%) and/or chimerism (41%). Treatments used include steroids (80%), of which 75% showed partial or complete resolution. Mortality was 33.3% (range 0-100%). Novel therapies include ECP and MSC therapy. GvHD is a rare but serious disease with high mortality. Novel therapies may offer hope in the future, but currently there is limited evidence for their efficacy in the context of intestinal or liver transplantation.
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Affiliation(s)
- Thomas Green
- King's College London - GKT School of Medical Education, London, UK
| | - Jonathan Hind
- King's College Hospital - Paediatric Liver, GI and Nutrition Centre, London, UK
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33
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Rai V, Dietz NE, Agrawal DK. Immunological basis for treatment of graft versus host disease after liver transplant. Expert Rev Clin Immunol 2016; 12:583-93. [PMID: 26795873 DOI: 10.1586/1744666x.2016.1145056] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Graft versus host disease (GVHD) after liver transplant, although a rare disease, has a very high mortality rate. GVHD occurs due to immunoreactions caused by donor T lymphocytes and host cell surface antigens resulting in proliferation and clonal expansion of T lymphocyte. Migration of effector cells, including macrophages, NK cells and cytotoxic T lymphocyte, to the target organs such as skin, intestine and bone marrow results in skin rashes, diarrhea and bone marrow depression. GVHD is diagnosed by clinical symptoms, histopathological findings and by the presence of chimerism. The delayed diagnosis, opportunistic infections and lack of definitive treatment of post orthotopic liver transplant (OLT)-GVHD results in sepsis and multi-organ failure leading to very low survival rates. In this review, we have focused on early diagnosis and critically discuss novel treatment modalities to decrease the incidence of GVHD.
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Affiliation(s)
- Vikrant Rai
- a Department of Clinical and Translational Science , Creighton University School of Medicine , Omaha , NE , USA
| | - Nicholas Edward Dietz
- b Department of Pathology , Creighton University School of Medicine , Omaha , NE , USA
| | - Devendra K Agrawal
- a Department of Clinical and Translational Science , Creighton University School of Medicine , Omaha , NE , USA
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34
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Cheung CYM, Leung AYH, Chan SC, Trendell-Smith NJ, So CC, Kwong YL. Fatal graft-versus-host disease after unrelated cadaveric liver transplantation due to donor/recipient human leucocyte antigen matching. Intern Med J 2015; 44:425-6. [PMID: 24754694 DOI: 10.1111/imj.12389] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Accepted: 02/03/2014] [Indexed: 11/28/2022]
Affiliation(s)
- C Y M Cheung
- Department of Medicine, Queen Mary Hospital, Hong Kong
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35
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Acute graft-versus-host disease following simultaneous pancreas-kidney transplantation: report of a case. Surg Today 2014; 45:1567-71. [DOI: 10.1007/s00595-014-1069-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Accepted: 10/05/2014] [Indexed: 12/13/2022]
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36
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Reddy MS, Varghese J, Venkataraman J, Rela M. Matching donor to recipient in liver transplantation: Relevance in clinical practice. World J Hepatol 2013; 5:603-611. [PMID: 24303088 PMCID: PMC3847943 DOI: 10.4254/wjh.v5.i11.603] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Revised: 10/23/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor, graft and recipient factors. Within the cohort of patients waiting for a transplant, better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation. A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age, gender, ethnicity, viral serology; graft factors such as size and quality, recipient factors such as age, size, gender and transplant factors such as major or minor blood group incompatibility and immunological factors. We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’ clinical experience. Multiple donor and recipient factors impact graft survival after liver transplantation. Appropriate matching based on donor-organ-recipient variables, modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.
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37
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Lee HJ, Lee SM, Kim BC, Chu CW, Yang KH, Ryu JH, Moon KM, Choi KU, Kim HH. A Case of Acute Graft versus Host Disease after Liver Transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2013. [DOI: 10.4285/jkstn.2013.27.1.15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Hyun Ji Lee
- Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Sun Min Lee
- Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Byung Chang Kim
- Department of Laboratory Medicine, Maryknoll Medical Center, Busan, Korea
| | - Chong Woo Chu
- Department of Surgery, Pusan National University School of Medicine, Busan, Korea
| | - Kwang Ho Yang
- Department of Surgery, Pusan National University School of Medicine, Busan, Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University School of Medicine, Busan, Korea
| | - Ki Myung Moon
- Department of Surgery, Pusan National University School of Medicine, Busan, Korea
| | - Kyung-Un Choi
- Department of Pathology, Pusan National University School of Medicine, Busan, Korea
| | - Hyung Hoi Kim
- Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea
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38
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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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39
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Rogulj IM, Deeg J, Lee SJ. Acute graft versus host disease after orthotopic liver transplantation. J Hematol Oncol 2012; 5:50. [PMID: 22889203 PMCID: PMC3445845 DOI: 10.1186/1756-8722-5-50] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Accepted: 07/27/2012] [Indexed: 11/25/2022] Open
Abstract
Graft versus host disease (GVHD) is an uncommon complication after orthotopic liver transplantation (OLT) with an incidence of 0.1–2%, but an 80–100% mortality rate. Patients can present with skin rashes, diarrhea, and bone marrow aplasia between two to eight weeks after OLT. Diagnosis of GVHD is made based on clinical and histologic evidence, supported by chimerism studies showing donor HLA alleles in the recipient bone marrow or blood. Several therapeutic approaches have been used for the management of GVHD after OLT including increased immunosuppression, decreased immunosuppression, and cellular therapies. However, success rates have been low, and new approaches are needed.
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Affiliation(s)
- Inga Mandac Rogulj
- University of Zagreb School of Medicine, University Hospital Merkur, Zagreb, Croatia
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40
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Yuksekkaya HA, Arikan C, Tumgor G, Aksoylar S, Kilic M, Aydogdu S. Late-onset graft-versus-host disease after pediatric living-related liver transplantation for Langerhans cell histiocytosis. Pediatr Transplant 2011; 15:E105-E109. [PMID: 21884342 DOI: 10.1111/j.1399-3046.2008.00899.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
GVHD is the most common and well-known cause of morbidity and mortality following allogeneic BM transplantation. The GVHD following OLT is an uncommon complication but has a high mortality and poses a major diagnostic and therapeutic challenge. We herein discussed a 12-month-old girl with multi-system LCH, who developed end-stage liver disease despite intensive chemotherapy. She underwent ABO-compatible liver transplantation at 28 months while in remission from LCH. The donor was her 26-yr-old father. Post-operative course was uneventful. The GVHD manifested with skin rash and BM suppression on post-transplant day 94 and confirmed by both microchimerism and skin biopsy. Prednisolone, basiliximab, and ATG were administered immediately but the bone marrow suppression was not improved and the patient died because of Candida sepsis at six-month post-transplant. GVHD after OLT should be keep in mind in patients with rash and BM suppression after liver transplantation. In LDLT, a patient who carries risk factors should investigated for optimal HLA matching.
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Affiliation(s)
- Hasan Ali Yuksekkaya
- Department of Pediatric Gastroenterology, Ege University School of Medicine, Izmir, Turkey
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41
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HLA mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood unit selection. Blood 2011; 118:3969-78. [PMID: 21750317 DOI: 10.1182/blood-2010-11-317271] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Donor-recipient human leukocyte antigen mismatch level affects the outcome of unrelated cord blood (CB) transplantation. To identify possible "permissive" mismatches, we examined the relationship between direction of human leukocyte antigen mismatch ("vector") and transplantation outcomes in 1202 recipients of single CB units from the New York Blood Center National Cord Blood Program treated in United States Centers from 1993-2006. Altogether, 98 donor/patient pairs had only unidirectional mismatches: 58 in the graft-versus-host (GVH) direction only (GVH-O) and 40 in the host-versus-graft or rejection direction only (R-O). Engraftment was faster in patients with GVH-O mismatches compared with those with 1 bidirectional mismatch (hazard ratio [HR] = 1.6, P = .003). In addition, patients with hematologic malignancies given GVH-O grafts had lower transplantation-related mortality (HR = 0.5, P = .062), overall mortality (HR = 0.5, P = .019), and treatment failure (HR = 0.5, P = .016), resulting in outcomes similar to those of matched CB grafts. In contrast, R-O mismatches had slower engraftment, higher graft failure, and higher relapse rates (HR = 2.4, P = .010). Based on our findings, CB search algorithms should be modified to identify unidirectional mismatches. We recommend that transplant centers give priority to GVH-O-mismatched units over other mismatches and avoid selecting R-O mismatches, if possible.
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Xue F, Chen W, Bai XL, Xu GD, Liang L, Liang TB. Correlation of Chimerism with Acute Graft-versus-Host Disease in Rats following Liver Transplantation. Int J Hepatol 2011; 2011:947150. [PMID: 21994878 PMCID: PMC3170856 DOI: 10.4061/2011/947150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2010] [Accepted: 03/05/2011] [Indexed: 12/04/2022] Open
Abstract
The accurate diagnosis of acute graft-versus-host disease following liver transplantation (LTx-aGVHD) has been hampered. Chimerism appears in the majority of recipients after LT and its significance in the diagnosis of LTx-aGVHD has not been clearly established. To demonstrate the significance of chimerism on the diagnosis of LTx-aGVHD, we compared the change of chimerism in syngeneic LT recipients, semiallogeneic LT recipients, and LTx-aGVHD induced recipients. Chimerism in PBMCs following sex-mismatched LT was identified by real-time PCR based on a rat Y-chromosome-specific primer. All recipients in semiallogeneic group grew in a normal pattern. However, when 4 × 10(8) donor splenocytes were transferred simultaneously during LT, the morbidity of lethal aGVHD was 100%. The chimerism appeared slightly higher in the semiallogeneic group than in the syngeneic LT group, but the difference was not significant. However, when the recipients developed lethal aGVHD after LT, chimerism in the PBMCs increased progressively, and even at an early time, a significant increase in chimerism was observed. In conclusion, high level chimerism correlated well with LTx-aGVHD, and detection of chimerism soon after transplantation may be of value in the diagnosis of LTx-aGVHD prior to the onset of symptoms.
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Affiliation(s)
- Fei Xue
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation of Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China,Department of Hepatobiliary and Pancreatic Surgery, Organ Transplantation Center, Henan Province People's Hospital, Zhengzhou 450003, Henan Province, China
| | - Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation of Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Xue-Li Bai
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation of Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Guo-Dong Xu
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation of Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Liang Liang
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation of Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Ting-Bo Liang
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation of Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China,*Ting-Bo Liang:
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43
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Acute graft-versus-host disease after living donor liver transplantation with donor-dominant one-way human leukocyte antigen matching at two Loci. Transplantation 2010; 89:1164-6. [PMID: 20440198 DOI: 10.1097/tp.0b013e3181cea646] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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44
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Sharma S, Gurakar A, Camci C, Jabbour N. Avoiding pitfalls: what an endoscopist should know in liver transplantation--part II. Dig Dis Sci 2009; 54:1386-402. [PMID: 19085103 DOI: 10.1007/s10620-008-0520-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2007] [Accepted: 08/27/2008] [Indexed: 02/07/2023]
Abstract
Over the last decade the number of patients undergoing transplantation has increased. At the same time, effective peri- and postoperative care and better surgical techniques have resulted in greater numbers of recipients achieving long-term survival. Identification and effective management in the form of adequate treatment is essential, since any delay in diagnosis or treatment may result in graft loss or serious threat to patient's life. Various aspects of endoscopic findings that can be commonly encountered among liver transplant recipients are discussed herein. Topics include: persistent and/or recurrent esophageal varices, reflux, Candida or cytomegalovirus (CMV) esophagitis, esophageal neoplasms, posttransplant peptic ulcer, biliary complications, posttransplant lymphoproliferative disorder (PTLD), Kaposi's sarcoma, CMV colitis and inflammatory bowel disease, colonic neoplasms, Clostridium difficile infection, and graft versus host disease (GVHD).
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Affiliation(s)
- Sharad Sharma
- Nazih Zuhdi Transplant Institute, 3300 North West Expressway, Oklahoma City, OK 73112, USA.
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45
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Xue F, Chen W, Wang XG, Liang L, Bai XL, Wang LY, Wang HP, Liang TB. Establishment of an acute graft-versus-host disease model following liver transplantation in donor-dominant one-way major histocompatibility complex matching rats. Transplant Proc 2009; 41:1914-1920. [PMID: 19545756 DOI: 10.1016/j.transproceed.2008.11.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2008] [Accepted: 11/14/2008] [Indexed: 01/16/2023]
Abstract
Acute graft-versus-host disease is an uncommon but devastating complication following liver transplantation (LTx-aGVHD). We investigated whether a rat model of LTx-aGVHD could be established using Lewis rat donors and (LewisXBN)F1 rats as recipients, which provides favorable conditions for studies of graft-versus-host reaction or disease. Replacement of (LewisXBN)F1 livers by Lewis livers alone was not sufficient to induce aGVHD; all recipients grew in a normal pattern as the syngeneic liver transplantation (LT) from Lewis to Lewis rat. However, when various numbers of donor splenocytes (1 x 10(8), 2 x 10(8), 3 x 10(8), 4 x 10(8)) were transferred simultaneously with the LT, the morbidities of lethal aGVHD were 16.7%, 50%, 83.3%, and 100%, respectively. The clinical courses as well as histologic analyses of skin and colon showed typical aGVHD characteristics. However, unlike transfusion-associated aGVHD, the liver graft was not involved. These clinical and histologic characteristics of aGVHD were consistent with those in humans who develop aGVHD after LT. Thus, a reproducible rat model of LTx-aGVHD was developed by performing LT from Lewis to (LewisXBN)F1 rats in combination with donor splenocyte transfusion. This model may be useful for further studies on the mechanisms and effective treatment modalities for LTx-aGVHD.
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Affiliation(s)
- F Xue
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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46
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Kanehira K, Riegert-Johnson DL, Chen D, Gibson LE, Grinnell SD, Velgaleti GV. FISH diagnosis of acute graft-versus-host disease following living-related liver transplant. J Mol Diagn 2009; 11:355-8. [PMID: 19460938 DOI: 10.2353/jmoldx.2009.080172] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Acute graft-versus-host disease (GVHD) is an uncommon but often fatal complication following liver transplant. We describe a GVHD case in which a female patient with primary biliary cirrhosis underwent a living-related liver transplant from her son. The human leukocyte antigen typing of the donor was homozygous at all loci. The recipient's human leukocyte antigen type was haplo-identical to that of the donor. A bone marrow aspirate performed for pancytopenia revealed a severely hypoplastic marrow. Fluorescent in situ hybridization (FISH) using X- and Y-chromosome probes demonstrated that 80% of marrow cells were of donor origin. Comparison of Giemsa-stained cell morphology and FISH showed that the erythroid precursor cells were predominantly of male pattern (XY). This report is one of only a few studies that prove the migration of a donor's hematopoietic stem cells to a recipient's bone marrow. We demonstrated that FISH analysis using sex chromosome probes is useful to confirm a diagnosis of GVHD following organ transplantation from a donor of the opposite sex. We also showed that donor hematopoietic stem cells in a liver graft can migrate to the recipient's bone marrow. We suggest that FISH is a rapid and reliable test for confirming the diagnosis of GVHD in a peripheral blood or skin biopsy sample.
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Affiliation(s)
- Kazunori Kanehira
- Departments of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
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47
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Xue F, Chen W, Wang X, Wang L, Xu G, Liang L, Bai X, Liang T. Regulatory T cells contribute to the immunoregulatory effect on graft versus host reaction after liver transplantation in donor-dominant one-way MHC matching rats. Transpl Immunol 2009; 20:232-7. [DOI: 10.1016/j.trim.2008.11.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2008] [Revised: 10/24/2008] [Accepted: 11/03/2008] [Indexed: 11/26/2022]
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48
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Kohler S, Pascher A, Junge G, Sauer IM, Nagy M, Schönemann C, Koch M, Neumann U, Pratschke J, Neuhaus P. Graft versus host disease after liver transplantation - a single center experience and review of literature. Transpl Int 2008; 21:441-51. [PMID: 18266778 DOI: 10.1111/j.1432-2277.2007.00625.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Graft versus host disease (GvHD) after liver transplantation has an incidence of 0.1-1%. It is an infrequent but severe and mostly lethal complication. Approximately, 80 cases have been reported in literature so far. A single center experience is reported retrospectively. We performed a retrospective analysis of 1815 liver transplants in our center, transplanted over a period of 17 years. Five patients (5/1815 = 0.28%) with histologically diagnosed GvHD were included in the analysis. Onset of GvHD was between postoperative day (POD) 20 and 60. All patients developed skin rash, being the first symptom in four cases; one patient had joint pain as initial symptom. Macrochimerism was confirmed in all patients. Treatment consisted of augmentation of baseline immunosuppression (n = 4), methylprednisolone (n = 4), and T-cell depleting antibodies (n = 3). One patient received no specific therapy because of her deleterious condition. All patients died because of either haemorrhage or uncontrollable infections. In our experience, GvHD has been an extremely rare, albeit deleterious clinical condition, which was resistant to classical immunosuppressive rescue regimens.
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Affiliation(s)
- Sven Kohler
- Department of Visceral and Transplant Surgery, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
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49
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50
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Chan EY, Larson AM, Gernsheimer TB, Kowdley KV, Carithers RL, Reyes JD, Perkins JD. Recipient and donor factors influence the incidence of graft-vs.-host disease in liver transplant patients. Liver Transpl 2007; 13:516-22. [PMID: 17394149 DOI: 10.1002/lt.21082] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Acute cellular graft-vs.-host disease (GVHD) following liver transplantation has an incidence of 1 to 2% and a mortality rate of 85%. Our aim was to identify a patient population at high risk for developing GVHD using a large clinical database to study both recipient and donor factors. We compared our liver transplant patients who developed GVHD to those that did not for recipient and donor factors and combinations of factors. For 2003-2004 we had 205 first-time liver transplant patients surviving >30 days. From this group, 4 (1.9%) developed GVHD. Compared to the control group, there were no significant differences in recipient age, recipient gender, donor age, donor gender, total ischemia time, donor-recipient human leukocyte antigen (HLA) mismatch, or donor-recipient age difference. Percentages of liver disease etiologies among the patients who developed GVHD were as follows: 16% (1/6) autoimmune hepatitis (AIH) (P = 0.003), 5.6% (3/54) alcoholic liver disease (ALD) (P = 0.057), and 7.1% (3/42) hepatocellular carcinoma (HCC) (P = 0.026). The incidence of GVHD in patients with glucose intolerance (either Type I or Type II diabetes mellitus [DM]) was significant (P = 0.022). Focusing on patients only with high-risk factors for GVHD during the years 2003-2005, we had 19 such patients. Four of these high-risk patients developed GVHD. Three of these 4 patients had received a donor liver with steatosis of degree >or=mild compared to only 2 of the 15 high-risk patients who did not develop GVHD (P = 0.037). In conclusion, we have identified liver transplant patients with AIH or the combination of ALD, HCC, and glucose intolerance who receive a steatotic donor liver as being at high risk for developing GVHD.
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Affiliation(s)
- Edie Y Chan
- Division of Transplantation, Department of Surgery, University of Washington, Seattle, WA 98195, USA
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