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1
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Odenwald MA, Roth HF, Reticker A, Segovia M, Pillai A. Evolving challenges with long-term care of liver transplant recipients. Clin Transplant 2023; 37:e15085. [PMID: 37545440 DOI: 10.1111/ctr.15085] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/17/2023] [Accepted: 07/23/2023] [Indexed: 08/08/2023]
Abstract
The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long-term post-LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.
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Affiliation(s)
- Matthew A Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Hannah F Roth
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Anesia Reticker
- Department of Pharmacy, University of Chicago Medicine, Chicago, USA
| | - Maria Segovia
- Department of Medicine, Section of Gastroenterology, Duke University School of Medicine, Durham, USA
| | - Anjana Pillai
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
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2
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Rastogi A, Nigam N, Gayatri R, Bihari C, Pamecha V. Biliary Epithelial Senescence in Cellular Rejection Following Live Donor Liver Transplantation. J Clin Exp Hepatol 2022; 12:1420-1427. [PMID: 36340312 PMCID: PMC9630016 DOI: 10.1016/j.jceh.2022.08.004] [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: 05/06/2022] [Accepted: 08/11/2022] [Indexed: 12/12/2022] Open
Abstract
Background As with the hepatocytes, cholangiocyte senescence can also easily be detected in damaged small bile ducts and bile ductules during liver disease affecting the biliary system and cholangiocytes. Despite cellular senescence being a feature of chronic progressive cholangiopathies in adults, only a few studies have investigated its role in liver transplant rejection. Method Transplant biopsies displaying features of rejection were reviewed and classified based on the type of rejection and the time since transplantation. An immunohistochemistry panel has been applied for 3 senescent cell markers (p53, p21, p16). Results Immunohistochemical expression analysis for the biliary senescence markers (53 biopsies) was done in the post-transplantation periods (Group 1-4) for the cases with the histologically proven diagnosis of rejection. In post-transplant group 1 (<3 months), group 2 (3-6 months), group 3 (6-12 months) and group 4 (>12 months), any 2 senescent markers' positivity was noted in 5/14 (35.7%), 8/13 (61.5%), 16/17 (94.1%) and 9/9 (100%) biopsies respectively and were comparable in all four groups (P = 0.001). A comparison of early biopsies (Group1; 3 months) and late biopsies (Group 2,3&4; >3 months) revealed significantly higher expression in late biopsies (>3 months) (P = 0.001 for any two markers). In ACR, LAR, ECR, and CR/DR any two senescent markers were positive in 14/28 (50%), 12/13 (92.3%) cases, 9/9 (100%), and 3/3cases (100%). Senescent markers (any two) were comparable in all four histological groups (P < 0.001).LAR group had increased expression (P = 0.009 for any two markers and 0.001 for all three markers) and has increased progression to CR (P = 0.019) as compared to ACR. Conclusion This study on a large number of LDLT allograft biopsies demonstrates the role of biliary senescence in rejection and suggests a pathobiological role for senescence in the poor prognosis seen in late acute cellular rejection and chronic rejection.
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Affiliation(s)
- Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Neha Nigam
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Ramakrishna Gayatri
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Viniyendra Pamecha
- Department of Hepato-Pancreato-Biliary Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
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3
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Levitsky J, Kandpal M, Guo K, Zhao L, Kurian S, Whisenant T, Abecassis M. Prediction of Liver Transplant Rejection With a Biologically Relevant Gene Expression Signature. Transplantation 2022; 106:1004-1011. [PMID: 34342962 PMCID: PMC9301991 DOI: 10.1097/tp.0000000000003895] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/21/2021] [Accepted: 05/31/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Noninvasive biomarkers distinguishing early immune activation before acute rejection (AR) could more objectively inform immunosuppression management in liver transplant recipients (LTRs). We previously reported a genomic profile distinguishing LTR with AR versus stable graft function. This current study includes key phenotypes with other causes of graft dysfunction and uses a novel random forest approach to augment the specificity of predicting and diagnosing AR. METHODS Gene expression results in LTRs with AR versus non-AR (combination of other causes of graft dysfunction and normal function) were analyzed from single and multicenter cohorts. A 70:30 approach (61 ARs; 162 non-ARs) was used for training and testing sets. Microarray data were normalized using a LT-specific vector. RESULTS Random forest modeling on the training set generated a 59-probe classifier distinguishing AR versus non-AR (area under the curve 0.83; accuracy 0.78, sensitivity 0.70, specificity 0.81, positive predictive value 0.54, negative predictive value [NPV] 0.89; F-score 0.61). Using a locked threshold, the classifier performed well on the testing set (accuracy 0.72, sensitivity 0.67, specificity 0.73, positive predictive value 0.48, NPV 0.86; F-score 0.56). Probability scores increased in samples preceding AR versus non-AR, when liver function tests were normal, and decreased following AR treatment (P < 0.001). Ingenuity pathway analysis of the genes revealed a high percentage related to immune responses and liver injury. CONCLUSIONS We have developed a blood-based biologically relevant biomarker that can be detected before AR-associated graft injury distinct from LTR never developing AR. Given its high NPV ("rule out AR"), the biomarker has the potential to inform precision-guided immunosuppression minimization in LTRs.
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Affiliation(s)
- Josh Levitsky
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Manoj Kandpal
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
- Department of Preventive Medicine, Biostatistics Collaboration Center, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Kexin Guo
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
- Department of Preventive Medicine, Biostatistics Collaboration Center, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Lihui Zhao
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
- Department of Preventive Medicine, Biostatistics Collaboration Center, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Sunil Kurian
- Scripps Clinic Bio-Repository and Bio-Informatics Core, Scripps Green Hospital, La Jolla, CA
| | - Thomas Whisenant
- Center for Computational Biology and Bioinformatics, School of Medicine, University of California San Diego, San Diego, CA
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4
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Levitsky J, Kandpal M, Guo K, Kleiboeker S, Sinha R, Abecassis M. Donor-derived cell-free DNA levels predict graft injury in liver transplant recipients. Am J Transplant 2022; 22:532-540. [PMID: 34510731 DOI: 10.1111/ajt.16835] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 08/15/2021] [Accepted: 09/02/2021] [Indexed: 01/25/2023]
Abstract
Donor-derived cell-free DNA (dd-cfDNA) has been evaluated as a rejection marker in organ transplantation. This study sought to assess the utility of dd-cfDNA to diagnose graft injury in liver transplant recipients (LTR) and as a predictive biomarker prior to different causes of graft dysfunction. Plasma from single and multicenter LTR cohorts was analyzed for dd-cfDNA. Phenotypes of treated biopsy-proven acute rejection (AR, N = 57), normal function (TX, N = 94), and acute dysfunction no rejection (ADNR; N = 68) were divided into training and test sets. In the training set, dd-cfDNA was significantly different between AR versus TX (AUC 0.95, 5.3% cutoff) and AR versus ADNR (AUC 0.71, 20.4% cutoff). Using these cutoffs in the test set, the accuracy and NPV were 87% and 100% (AR vs. TX) and 66.7% and 87.8% (AR vs. ADNR). Blood samples collected serially from LTR demonstrated incremental elevations in dd-cfDNA prior to the onset of graft dysfunction (AR > ADNR), but not in TX. Dd-cfDNA also decreased following treatment of rejection. In conclusion, the serial elevation of dd-cfDNA identifies pre-clinical graft injury in the context of normal liver function tests and is greatest in rejection. This biomarker may help detect early signs of graft injury and rejection to inform LTR management strategies.
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Affiliation(s)
- Josh Levitsky
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Manoj Kandpal
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Kexin Guo
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Biostatistics Collaboration Center, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | - Rohita Sinha
- Eurofins Viracor Clinical Diagnostics, Lee's Summit, Missouri
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5
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Melani RD, Gerbasi VR, Anderson LC, Sikora JW, Toby TK, Hutton JE, Butcher DS, Negrão F, Seckler HS, Srzentić K, Fornelli L, Camarillo JM, LeDuc RD, Cesnik AJ, Lundberg E, Greer JB, Fellers RT, Robey MT, DeHart CJ, Forte E, Hendrickson CL, Abbatiello SE, Thomas PM, Kokaji AI, Levitsky J, Kelleher NL. The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells. Science 2022; 375:411-418. [PMID: 35084980 PMCID: PMC9097315 DOI: 10.1126/science.aaz5284] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Human biology is tightly linked to proteins, yet most measurements do not precisely determine alternatively spliced sequences or posttranslational modifications. Here, we present the primary structures of ~30,000 unique proteoforms, nearly 10 times more than in previous studies, expressed from 1690 human genes across 21 cell types and plasma from human blood and bone marrow. The results, compiled in the Blood Proteoform Atlas (BPA), indicate that proteoforms better describe protein-level biology and are more specific indicators of differentiation than their corresponding proteins, which are more broadly expressed across cell types. We demonstrate the potential for clinical application, by interrogating the BPA in the context of liver transplantation and identifying cell and proteoform signatures that distinguish normal graft function from acute rejection and other causes of graft dysfunction.
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Affiliation(s)
- Rafael D. Melani
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Vincent R. Gerbasi
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Lissa C. Anderson
- National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, USA
| | - Jacek W. Sikora
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Timothy K. Toby
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Josiah E. Hutton
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - David S. Butcher
- National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, USA
| | - Fernanda Negrão
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Henrique S. Seckler
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Kristina Srzentić
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Luca Fornelli
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Jeannie M. Camarillo
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Richard D. LeDuc
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Anthony J. Cesnik
- Department of Genetics, Stanford University, Stanford, CA, USA
- Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH-Royal Institute of Technology, Stockholm, Sweden
| | - Emma Lundberg
- Department of Genetics, Stanford University, Stanford, CA, USA
- Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH-Royal Institute of Technology, Stockholm, Sweden
| | - Joseph B. Greer
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Ryan T. Fellers
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Matthew T. Robey
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Caroline J. DeHart
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Eleonora Forte
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, USA
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | | | | | - Paul M. Thomas
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | | | - Josh Levitsky
- Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Neil L. Kelleher
- Department of Molecular Biosciences, Department of Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
- Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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6
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Razafindrazoto CI, Trystram N, Martins GM, Stern C, Charlotte F, Lebray P. Late acute cellular rejection after switch to everolimus monotherapy at 11 months following liver transplantation. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00170-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Acute cellular rejection beyond the 6th month posttransplant is an uncommon complication after liver transplantation. The inadequate immunosuppression (IS) remains the main risk factor. We report a case of acute cellular rejection after a switch to everolimus monotherapy at 11 months following liver transplantation.
Case presentation
This was a 69-year-old man who underwent liver transplantation after hepatocellular carcinoma. The initial immunosuppression was a combination of three immunosuppressive drugs (corticosteroids + tacrolimus + mycophenolate mofetil). The corticosteroid therapy was stopped at the 4th month posttransplant. Serious side effects of the immunosuppressive drugs (agranulocytosis and renal dysfunction), which occurred 4 months after transplantation, required a reduction and then a discontinuation of tacrolimus and mycophenolate mofetil. Everolimus was introduced as a replacement. The patient was consulted at 11 months after liver transplantation, 1 month after stopping the two immunosuppressive drugs, for liver function test abnormalities such as cytolysis and anicteric cholestasis. A moderate late acute cellular rejection was confirmed by a liver biopsy. A satisfactory biological evolution was observed following corticosteroid boluses and optimization of basic immunosuppressive drugs.
Conclusion
Late acute cellular rejection remains an uncommon complication, observed mostly in the first year after liver transplantation. The main risk factor is usually the decrease of immunosuppression.
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7
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D’AMBROSIO D, TAVANO D, LATTANZI B, FRAMARINO DEI MALATESTA M, DE VILLE DE GOYET J, CORSI A, MITTERHOFER AP, GINANNI CORRADINI S, MENNINI G, ROSSI M, MERLI M. Acute rejection on immune-mediated chronic rejection after liver transplantation. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2021. [DOI: 10.23736/s0393-3660.19.04240-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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8
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Harrington CR, Yang GY, Levitsky J. Advances in Rejection Management: Prevention and Treatment. Clin Liver Dis 2021; 25:53-72. [PMID: 33978583 DOI: 10.1016/j.cld.2020.08.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Extended survival of liver transplant recipients has brought rejection management to the forefront of liver transplant research. This article discusses T-cell-mediated rejection, antibody-mediated rejection, and chronic rejection. We focus on the prevention and then discuss treatment options. Future directions of rejection management include biomarkers of rejection, which may allow for monitoring of patients who are considered high risk for rejection and detection of rejection before there is any clinical evidence to improve graft and patient survival. With improved graft life and survival of liver transplant recipients, the new frontier of rejection management focuses on immunosuppression minimization, withdrawal, and personalization.
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Affiliation(s)
- Claire R Harrington
- Department of Medicine, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 2330, Chicago, IL 60611, USA
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University Feinberg School of Medicine, 251 E Huron St. Chicago, IL 60611, USA
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1400, Chicago, IL 60611, USA; Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1900, Chicago, IL 60611, USA.
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9
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Levitsky J, Asrani SK, Schiano T, Moss A, Chavin K, Miller C, Guo K, Zhao L, Kandpal M, Bridges N, Brown M, Armstrong B, Kurian S, Demetris AJ, Abecassis M. Discovery and validation of a novel blood-based molecular biomarker of rejection following liver transplantation. Am J Transplant 2020; 20:2173-2183. [PMID: 32356368 PMCID: PMC7496674 DOI: 10.1111/ajt.15953] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 02/28/2020] [Accepted: 04/13/2020] [Indexed: 02/06/2023]
Abstract
Noninvasive biomarker profiles of acute rejection (AR) could affect the management of liver transplant (LT) recipients. Peripheral blood was collected following LT for discovery (Northwestern University [NU]) and validation (National Institute of Allergy and Infectious Diseases Clinical Trials in Organ Transplantation [CTOT]-14 study). Blood gene profiling was paired with biopsies showing AR or ADNR (acute dysfunction no rejection) as well as stable graft function samples (Transplant eXcellent-TX). CTOT-14 subjects had serial collections prior to AR, ADNR, TX, and after AR treatment. NU cohort gene expression (46 AR, 45 TX) was analyzed using random forest models to generate a classifier training set (36 gene probe) distinguishing AR vs TX (area under the curve 0.92). The algorithm and threshold were locked and tested on the CTOT-14 validation cohort (14 AR, 50 TX), yielding an accuracy of 0.77, sensitivity 0.57, specificity 0.82, positive predictive value (PPV) 0.47, and negative predictive value (NPV) 0.87 for AR vs TX. The probability score line slopes were positive preceding AR, and negative preceding TX and non-AR (TX + ADNR) (P ≤ .001) and following AR treatment. In conclusion, we have developed a blood biomarker diagnostic for AR that can be detected prior to AR-associated graft injury as well a normal graft function (non-AR). Further studies are needed to evaluate its utility in precision-guided immunosuppression optimization following LT.
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Affiliation(s)
- Josh Levitsky
- Comprehensive Transplant CenterNorthwestern University Feinberg School of MedicineChicagoIllinois,Division of Gastroenterology and HepatologyDepartment of MedicineNorthwestern University Feinberg School of MedicineChicagoIllinois
| | - Sumeet K. Asrani
- Annette C. and Harold C. Simmons Transplant InstituteBaylor University Medical CenterDallasTexas
| | | | | | | | | | - Kexin Guo
- Comprehensive Transplant CenterNorthwestern University Feinberg School of MedicineChicagoIllinois,Biostatistics Collaboration CenterDepartment of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoIllinois
| | - Lihui Zhao
- Comprehensive Transplant CenterNorthwestern University Feinberg School of MedicineChicagoIllinois,Biostatistics Collaboration CenterDepartment of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoIllinois
| | - Manoj Kandpal
- Comprehensive Transplant CenterNorthwestern University Feinberg School of MedicineChicagoIllinois,Biostatistics Collaboration CenterDepartment of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoIllinois
| | - Nancy Bridges
- Division of Allergy, Immunology, and TransplantationNational Institute of Allergy and Infectious DiseasesBethesdaMaryland
| | - Merideth Brown
- Division of Allergy, Immunology, and TransplantationNational Institute of Allergy and Infectious DiseasesBethesdaMaryland
| | | | - Sunil Kurian
- The Scripps Research InstituteLa JollaCalifornia
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10
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Takeda M, Sakamoto S, Irie R, Uchida H, Shimizu S, Yanagi Y, Abdelwahed MS, Fukuda A, Kasahara M. Late T cell-mediated rejection may contribute to poor outcomes in adolescents and young adults with liver transplantation. Pediatr Transplant 2020; 24:e13708. [PMID: 32333637 DOI: 10.1111/petr.13708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 01/31/2020] [Accepted: 03/10/2020] [Indexed: 12/23/2022]
Abstract
Although poor long-term graft survival in LT in AYA is recognized, detailed epidemiological data are still lacking. L-TCMR may have poor outcomes. This study aimed to provide a detailed, epidemiological assessment of the association between AYA age and rejection. L-TCMR was defined in this study as TCMR with central vein or perivenular inflammation occurring later than 3 months after LT. A total of 342 patients who survived for at least 3 months after LT between 2005 and 2015 were enrolled. The AYA group (10-24 years) was compared with the C group (less than 10 years), and the incidence and outcomes of L-TCMR were analyzed. In total, 342 patients had LT; 38 of these were AYA with the mean follow-up period of 6.7 years. A total of 304 patients in C group had a mean follow-up period of 6.3 years (P = .28). The incidence of L-TCMR in AYA group was significantly higher than in C group (15.8% vs 4.6%, P = .006). The time to L-TCMR after LT was significantly shorter in AYA group (P = .01). Neither patient survival nor the incidence of non-adherence differed significantly between the groups (P = .18 and P = .89). The number of additional immunosuppressants after L-TCMR was significantly higher in the AYA group (P = .04). A high incidence of L-TCMR was observed in AYA group irrespective of non-adherence. AYA patients with L-TCMR should be followed carefully due to the poor results of post-treatment biopsy and the need for intensive immunosuppressive therapy.
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Affiliation(s)
- Masahiro Takeda
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Seisuke Sakamoto
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Rie Irie
- Department of Pathology, National Center for Child Health and Development, Tokyo, Japan
| | - Hajime Uchida
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Seiichi Shimizu
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Yusuke Yanagi
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Mohamed Sami Abdelwahed
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Akinari Fukuda
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
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11
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Jadlowiec CC, Morgan PE, Nehra AK, Hathcock MA, Kremers WK, Heimbach JK, Wiesner RH, Taner T. Not All Cellular Rejections Are the Same: Differences in Early and Late Hepatic Allograft Rejection. Liver Transpl 2019; 25:425-435. [PMID: 30615251 DOI: 10.1002/lt.25411] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 12/19/2018] [Indexed: 12/13/2022]
Abstract
T cell-mediated rejection (TCMR) is common after liver transplantation (LT), and it is often thought to have a minimum impact on outcomes. Because alloimmune response changes over time, we investigated the role of the timing of TCMR on patient and allograft survival and examined the risk factors for early and late TCMR. We reviewed protocol liver biopsies for 787 consecutive LT recipients with an 8.6-year follow-up. The incidence of early TCMR (≤6 weeks after LT) was 33.5% with nonalcoholic steatohepatitis patients having the lowest incidence. Younger recipient age (P < 0.01), number of human leukocyte antigen mismatches (P < 0.01), and use of deceased donor allografts (P = 0.01) were associated with increased risk of early TCMR, which had no impact on allograft (hazard ratio [HR], 1.02; 95% CI, 0.79-1.32; P = 0.89) or overall survival (HR, 1.03; 95% CI, 0.78-1.34; P = 0.86). Late TCMR (>6 weeks after LT) was less common (17.7%) and was associated with different risk factors. The majority of late TCMR (56.2%) episodes had no antecedent early TCMR, although moderate-to-severe early TCMR (HR, 2.85; 95% CI, 1.55-5.23; P < 0.01) and steroid resistance (HR, 3.62; 95% CI, 1.87-6.99; P < 0.01) were associated with late TCMR. Late TCMR increased risk of mortality (HR, 1.89; 95% CI, 1.35-2.65; P = 0.001) and graft loss (HR, 1.71; 95% CI, 1.23-2.37; P = 0.001). Thus, these data suggest that the timing and histologic grade of TCMR determine its impact on patient and allograft survival. Early mild TCMR episodes after LT do not adversely impact patient or allograft survival provided that they are adequately treated. The occurrence of late TCMR carries deleterious effects with increased longterm risk of graft loss and decreased survival. Patients with moderate-to-severe early TCMR are at an increased risk for late TCMR and warrant closer clinical follow-up.
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Affiliation(s)
| | - Paige E Morgan
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Avinash K Nehra
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Matthew A Hathcock
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Walter K Kremers
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Julie K Heimbach
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Russell H Wiesner
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Timucin Taner
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
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12
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Koo J, Wang HL. Acute, Chronic, and Humoral Rejection: Pathologic Features Under Current Immunosuppressive Regimes. Surg Pathol Clin 2018; 11:431-452. [PMID: 29751884 DOI: 10.1016/j.path.2018.02.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Under current immunosuppressive regimes, T-cell-mediated acute and chronic rejection remain common and important posttransplant complications. The definition of humoral (antibody-mediated) rejection has been greatly expanded in recent years. The histopathologic assessment of allograft biopsies continues to serve an important role in the diagnosis of rejection and to facilitate patient management. The diagnosis of both acute and chronic antibody-mediated rejection requires integration of the results of donor-specific antibody testing and C4d immunostaining, as well as exclusion of other potential etiologies of allograft dysfunction. Chronic antibody-mediated rejection should also be included in the differential diagnosis for unexplained allograft fibrosis.
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Affiliation(s)
- Jamie Koo
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 8707, Los Angeles, CA 90048, USA
| | - Hanlin L Wang
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 27-061-C8 CHS, Los Angeles, CA 90095, USA.
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13
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Choudhary NS, Saigal S, Bansal RK, Saraf N, Gautam D, Soin AS. Acute and Chronic Rejection After Liver Transplantation: What A Clinician Needs to Know. J Clin Exp Hepatol 2017; 7:358-366. [PMID: 29234201 PMCID: PMC5715482 DOI: 10.1016/j.jceh.2017.10.003] [Citation(s) in RCA: 102] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 10/30/2017] [Indexed: 02/07/2023] Open
Abstract
While antibody mediated hyper-acute vasculitic rejection is rare in liver transplant recipients, acute and chronic rejection have clinical significance. The liver allograft behaves differently to other solid organ transplants as acute rejection generally does not impair graft survival and chronic rejection (CR) is uncommon. The incidence of acute and chronic rejection has declined in current era due to improved immunosuppressive regimens. Acute rejection generally improves with steroid boluses and steroid resistant rejection is uncommon. CR may improve with escalation of immunosuppression or may result in irreversible loss of graft function leading to retransplantation or death. The current review discusses diagnosis and management of acute and chronic liver allograft rejection.
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India
| | - Sanjiv Saigal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India,Address for correspondence: Sanjiv Saigal, Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Sector 38, Gurgaon, Haryana 122001, India. Tel.: +91 9811552928.Sanjiv Saigal, Institute of Liver Transplantation and Regenerative Medicine, Medanta The MedicitySector 38GurgaonHaryana122001India
| | - Rinkesh K. Bansal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India
| | - Dheeraj Gautam
- Department of Pathology, Medanta The Medicity, Gurugram, India
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India
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14
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Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients. Clin Gastroenterol Hepatol 2017; 15:584-593.e2. [PMID: 27567694 PMCID: PMC5326609 DOI: 10.1016/j.cgh.2016.07.035] [Citation(s) in RCA: 161] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 07/25/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors. METHODS We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors. RESULTS At least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes. CONCLUSIONS Contrary to previous data, acute rejection after liver transplant is associated with significantly increased risk of graft failure, all-cause mortality, and graft failure-related death, regardless of primary liver disease etiology. Living donor liver transplantation from a biologically related donor is associated with decreased risk of rejection.
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15
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Long B, Koyfman A. The emergency medicine approach to transplant complications. Am J Emerg Med 2016; 34:2200-2208. [DOI: 10.1016/j.ajem.2016.08.049] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 08/18/2016] [Accepted: 08/20/2016] [Indexed: 02/07/2023] Open
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16
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Nacif LS, Pinheiro RS, Pécora RADA, Ducatti L, Rocha-Santos V, Andraus W, D'Albuquerque LC. Late acute rejection in liver transplant: a systematic review. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2016; 28:212-5. [PMID: 26537150 PMCID: PMC4737366 DOI: 10.1590/s0102-67202015000300017] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2014] [Accepted: 01/06/2015] [Indexed: 02/07/2023]
Abstract
Introduction: Late acute rejection leads to worse patient and graft survival after liver
transplantation. Aim: To analyze the reported results published in recent years by leading transplant
centers in evaluating late acute rejection and update the clinical manifestations,
diagnosis and treatment of liver transplantation. Method: Systematic literature review through Medline-PubMed database with headings related
to late acute rejection in articles published until November 2013 was done. Were
analyzed demographics, immunosuppression, rejection, infection and graft and
patient survival rates. Results: Late acute rejection in liver transplantation showed poor results mainly regarding
patient and graft survival. Almost all of these cohort studies were retrospective
and descriptive. The incidence of late acute rejection varied from 7-40% in these
studies. Late acute rejection was one cause for graft loss and resulted in
different outcomes with worse patient and graft survival after liver transplant.
Late acute rejection has been variably defined and may be a cause of chronic
rejection with worse prognosis. Late acute rejection occurs during a period in
which the goal is to maintain lower immunosuppression after liver transplantation.
Conclusion: The current articles show the importance of late acute rejection. The real benefit
is based on early diagnosis and adequate treatment at the onset until late follow
up after liver transplantation.
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Affiliation(s)
| | | | | | - Liliana Ducatti
- School of Medicine, University of São Paulo, São Paulo, SP, Brazil
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17
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Ozbilgin M, Egeli T, Unek T, Ozkardesler S, Avkan-Oguz V, Sagol O, Ozbilgin S, Bacakoglu A, Astarcıoglu I. Incidence of Late Acute Rejection in Living Donor Liver Transplant Patients, Risk Factors, and the Role of Immunosuppressive Drugs. Transplant Proc 2016; 47:1474-7. [PMID: 26093746 DOI: 10.1016/j.transproceed.2015.04.076] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Late acute rejection (LAR) is a clinical manifestation that occurs 6 months after liver transplantation, shows histopathologic features different from those of acute rejection, and is the cause of a high prevalence of morbidity and mortality. METHODS In this study, hospital records of 211 living donor liver transplantation (LDLT) patients who underwent surgery in our clinic between June 2000 and February 2014 were reviewed retrospectively. The patients were ≥ 18 years old and were followed for ≥ 6 months. RESULTS Of the 211 patients, 21 (9.9%; 16 males, 5 females) developed LAR. The mean age of the patients was 46 years (range, 33-58). The mean follow-up period was 61.2 months (range, 6-152) and the median time to development of LAR was 26.4 months (range, 7-77). In our study, patients who received cyclosporine and mycophenolate mofetil (MMF) treatment developed more LAR than did patients who received tacrolimus and MMF therapy (P = .05). In addition, the incidence of LAR in patients who underwent LDLT was significantly greater in the ABO-matched groups than in the ABO identical group (P = .028). CONCLUSIONS Development of LAR and serious complications related to it can be avoided if liver transplant recipients are followed regularly and closely in outpatient clinics after transplantation.
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Affiliation(s)
- M Ozbilgin
- Department of General Surgery, Hepatopancreatobiliary Surgery and Liver Transplantation Unit, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey.
| | - T Egeli
- Department of General Surgery, Hepatopancreatobiliary Surgery and Liver Transplantation Unit, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey
| | - T Unek
- Department of General Surgery, Hepatopancreatobiliary Surgery and Liver Transplantation Unit, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey
| | - S Ozkardesler
- Deparment of Anesthesiology, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey
| | - V Avkan-Oguz
- Department of Infectious Diseases and Clinical Microbiology, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey
| | - O Sagol
- Department of Pathology, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey
| | - S Ozbilgin
- Deparment of Anesthesiology, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey
| | - A Bacakoglu
- Department of General Surgery, Hepatopancreatobiliary Surgery and Liver Transplantation Unit, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey
| | - I Astarcıoglu
- Department of General Surgery, Hepatopancreatobiliary Surgery and Liver Transplantation Unit, Inciralti Dokuz Eylul University Medical Faculty, Inciralti, Izmir, Turkey
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18
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Late liver function test abnormalities post-adult liver transplantation: a review of the etiology, investigation, and management. Hepatol Int 2015; 10:106-14. [PMID: 26603541 DOI: 10.1007/s12072-015-9685-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 11/06/2015] [Indexed: 12/14/2022]
Abstract
Approximately 24,000 liver transplants are performed annually worldwide, almost 7000 of which are performed in the USA. Survival is excellent and continues to improve, with 1-year survival currently exceeding 85 %, but effective management of patients after liver transplantation is critical to achieve optimal results. A plethora of diseases can affect the transplanted allograft, ranging from recurrence of the original disease to de novo liver pathology, and diagnosis can be complicated by nonclassical presentation, de novo disease, or inconclusive histology. Patients can remain asymptomatic despite significant damage to the transplanted liver, so prompt identification and treatment of liver disease after transplantation is crucial to preserve allograft function. Liver function tests are routinely taken throughout the postoperative period to monitor the graft. Although nonspecific, they are inexpensive, noninvasive, and sensitive for allograft disease and can quickly alert physicians to the presence of asymptomatic pathology. This review will outline possible causes of liver function test abnormalities in the late posttransplant period and provide guidance for investigation, diagnosis, and management.
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19
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Ramanathan R, Sharma A, Kaspar M, Behnke M, Song S, Stravitz RT, Cotterell A, Posner M, Fisher RA. Local allograft irradiation as an adjunct for treating severe resistant rejection after liver transplantation in adults. Liver Transpl 2015; 21:47-56. [PMID: 25287272 DOI: 10.1002/lt.24016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 09/10/2014] [Accepted: 09/11/2014] [Indexed: 02/07/2023]
Abstract
Acute rejection after liver transplantation occurs in one-third of all recipients and can be managed with conventional rejection therapy in the majority of cases. In rare instances, patients with severe acute rejection may be refractory to or have contraindications for conventional therapies. This case series evaluates the role of local allograft irradiation (LAI) as an adjunct for patients with rejection that is refractory to or contraindicated for conventional therapies. Additionally, the literature on the use of radiation therapy for reversing rejection in solid organ transplantation is reviewed. Five patients underwent 9 LAI treatments: 2 had refractory rejection, and 1 each had a malignancy, a concurrent life-threatening infection, and serum sickness with antibody therapy. Conventional rejection therapies included steroids, calcineurin inhibitors, and antithymocyte globulin. LAI consisted of 3 cycles of 1.5 Gy directed toward the liver allograft. Two of the 5 patients remained alive with excellent graft function. Six of the 9 treatments were successful in rescuing the liver allograft (reversing the rejection episode). Treatment success was associated with lower pretreatment serum bilirubin levels and higher pretreatment alanine aminotransferase levels. Compared with patients with immunosuppression-responsive severe acute rejection, those requiring LAI trended toward a later onset of first rejection. In conclusion, local irradiation of liver allografts can be a useful adjunct in patients for whom conventional options have been exhausted or cannot be used. The ability of LAI to reverse allograft dysfunction and promote patient survival appears to be greatest before the onset of severe cholestatic injury.
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Affiliation(s)
- Rajesh Ramanathan
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, VA
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20
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Pre-transplant left ventricular diastolic dysfunction is associated with post transplant acute graft rejection and graft failure. Dig Dis Sci 2014; 59:674-80. [PMID: 24323177 DOI: 10.1007/s10620-013-2955-8] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Accepted: 11/13/2013] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Acute cellular rejection (ACR) is a significant cause of morbidity and graft failure in liver transplant recipients (LTR). Diastolic dysfunction (DD) is frequently present in patients with cirrhosis undergoing liver transplantation. However, it is unclear if DD leads to ACR. METHODS Data was collected retrospectively for consecutive LTR between January 2000 and December 2010. Demographic data and mortality related data was obtained from social security index. Primary outcome was biopsy proven ACR. Graft failure and all-cause mortality were also evaluated. DD was evaluated as a predictor of these outcomes. Other echocardiographic indices were also assessed as predictors of ACR by using Cox proportional hazard modeling adjusted for covariates. RESULTS A total of 970 LTR (mean age 53.2 ± 10 years, women 34.6 % and white 64.5 %) were followed for 5.3 ± 3.4 years. Patients with DD (n = 145, 14.9 %) were significantly more likely to develop ACRs (HR 10.56; 95 % CI 6.78-16.45, p value = 0.0001) as well as graft failure (HR 2.09; 95 % CI 1.22-3.59, p value = 0.007) and all-cause mortality (HR 1.52; 95 % CI 1.08-2.13, p = 0.01). There was an increase in the risk of these outcomes with worsening of DD, when adjusted for various risk factors such as donor and recipient age, gender, race, Framingham risk score, pre-transplant MELD, transplant etiology and cold ischemia time. CONCLUSION Pre-transplant DD is significantly associated with increased risk of allograft rejection, graft failure and mortality. This signifies the importance of cardiac evaluation during the pre-transplant period.
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21
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Late acute liver allograft rejection; a study of its natural history and graft survival in the current era. Transplantation 2013; 95:955-9. [PMID: 23442806 DOI: 10.1097/tp.0b013e3182845f6c] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Late acute rejection (LAR) after liver transplantation is often associated with poor clinical outcomes. We reviewed our experience of managing LAR in the current era to determine its natural history. METHODS A database of 970 consecutive adult liver transplants was reviewed retrospectively. LAR was defined as histologically proven acute cellular rejection occurring more than 90 days after transplantation. RESULTS The incidence of LAR was 11%, with a mean time of 565 days (median, 311 days; range, 90-2922 days) after transplantation. The highest rates for LAR were in seronegative hepatitis (17%), primary biliary cirrhosis (16%), and primary sclerosing cholangitis (13%) with an odds ratio of 2.3, 2.1, and 1.8, respectively. Logistic regression showed that younger recipients, primary biliary cirrhosis, and previous graft loss were independent predictors of LAR (P<0.001). Mean trough whole blood tacrolimus levels were at their lowest levels 1 week before the diagnosis of rejection (5.5 ng/mL; SD, 2.6) compared with levels of 7.7 ng/mL 4 weeks before rejection, showing a clear temporal relation. Graft survival was worse in those with LAR (P<0.01), whereas the best graft survival was among early acute rejection cases (85% 10-year survival; P<0.01). Poor response to treatment correlated with the development of ductopenic rejection (r=0.3; P<0.01). Approximately half with early ductopenic rejection eventually died (n=15). CONCLUSION LAR continues to provide a risk to patient and graft survival: understanding risk factors may allow an improvement in monitoring and early intervention and so prevent early graft loss.
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22
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Cheng L, Tian F, Tang L, Wang S, Chen G, Duan G, Yan X. Local distribution analysis of cytotoxic molecules in liver allograft is helpful for the diagnosis of acute cellular rejection after orthotopic liver transplantation. Diagn Pathol 2012; 7:148. [PMID: 23111143 PMCID: PMC3523046 DOI: 10.1186/1746-1596-7-148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Accepted: 10/24/2012] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND As it is often difficult for a transplant pathologist to make a definite diagnosis of acute cellular rejection (ACR) by routine morphological analysis of liver allograft biopsy, supplementary methods and objective markers are needed to facilitate this determination. METHODS To evaluate the diagnostic value of cytotoxic molecules in ACR episodes, immunohistochemical staining for perforin, granzyme B and T-cell intracellular antigen-1 (TIA-1) were performed in liver allograft biopsies. The positive cells in the portal tract area and lobules were counted separately to investigate the distribution of the cytotoxic molecules. RESULTS The immunohistochemical study showed that the overall positive rates for the three markers were not significantly different between the ACR and non-ACR groups. However, in the portal tract area, perforin-, granzyme B- and TIA-1-positive cells in the ACR group were significantly more than those in the non-ACR groups. In the lobules, perforin- and granzyme B-positive cells in the ACR group were significantly more than those in the biliary complication and opportunistic infection groups, while TIA-1-positive cells was significantly fewer than those in non-ACR groups. The numbers of positive cells in the portal tract area correlated with the rejection activity index of ACR. CONCLUSIONS These results indicate that, though the overall positive rates have nonsense in ACR diagnosis, the quantification and local distribution analysis of cytotoxic molecule positive cells in liver tissue is helpful for differential diagnosis and severity evaluation of ACR following liver transplantation. VIRTUAL SLIDES The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2292255038100487.
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Affiliation(s)
- Long Cheng
- Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
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23
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Fosby B, Karlsen TH, Melum E. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis. World J Gastroenterol 2012; 18:1-15. [PMID: 22228965 PMCID: PMC3251800 DOI: 10.3748/wjg.v18.i1.1] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2011] [Revised: 06/15/2011] [Accepted: 06/22/2011] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to fibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can influence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible influence of rejection on the risk of recurrent disease in the allograft.
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24
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Zahn A, Schott N, Hinz U, Stremmel W, Schmidt J, Ganten T, Gotthardt D, Meuer S, Zeier M, Giese T, Sommerer C. Immunomonitoring of nuclear factor of activated T cells-regulated gene expression: the first clinical trial in liver allograft recipients. Liver Transpl 2011; 17:466-73. [PMID: 21445930 DOI: 10.1002/lt.22254] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Long-term calcineurin inhibitor (CNI) treatment can cause serious side effects in liver allograft recipients. An optimal risk-to-benefit ratio for CNI blood levels has not been established. Pharmacodynamic drug monitoring through the measurement of the CNI biological activity, that is, the expression of nuclear factor of activated T cells (NFAT)-regulated genes, seems to be a promising approach. The residual gene expression (RGE) of NFAT-regulated genes 2 and 1.5 hours after cyclosporine A (CsA) and tacrolimus (FK-506) intake was measured in 100 liver allograft recipients with 1 or more years of follow-up post-transplantation. The mean RGE in all patients was 62% ± 33%. A significant negative correlation between the CsA (P < 0.0001, r = -0.8026) and FK-506 peak levels (P < 0.0001, r = -0.6982) and the RGE of all NFAT-regulated genes was observed. Clinical reliability was proven too. In conclusion, the data presented in this pilot study reveal the applicability of the pharmacodynamic monitoring of CNI efficacy in liver allograft recipients. To confirm the advantage of individualized pharmacodynamic drug monitoring over pharmacokinetic drug monitoring with respect to clinical outcomes, controlled, prospective studies are needed.
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Affiliation(s)
- Alexandra Zahn
- Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany.
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25
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26
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Venkat VL, Nick TG, Wang Y, Bucuvalas JC. An objective measure to identify pediatric liver transplant recipients at risk for late allograft rejection related to non-adherence. Pediatr Transplant 2008; 12:67-72. [PMID: 18186891 DOI: 10.1111/j.1399-3046.2007.00794.x] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Non-adherence to a prescribed immunosuppressive regimen increases risk for late allograft rejection (LAR). We implemented a protocol for immunosuppression management which decreased variation in calcineurin inhibitor blood levels in pediatric liver transplant recipients by controlling for confounders such as physician practice variability. We hypothesized that patients with increased variation in tacrolimus blood levels despite implementation of the immunosuppression management protocol were at increased risk for LAR. We conducted a single center retrospective cohort study of 101 pediatric liver transplant recipients who were at least one year post liver transplantation and receiving tacrolimus for immunosuppression. The primary outcome variable was biopsy proven allograft rejection. Primary candidate predictor variables were the standard deviation (SD) of tacrolimus blood levels (a marker of drug level variability), mean tacrolimus blood level, age, and insurance type. SD of tacrolimus blood levels was determined for each patient from a minimum of four outpatient levels during the study period. Unadjusted and adjusted logistic regression models were used to determine the prognostic value of candidate predictors. The median and interquartile range of the SD of tacrolimus blood levels was 1.6 (1.1, 2.1). Eleven episodes of LAR occurred during the study period. Ten of the 11 episodes occurred in patients with tacrolimus blood level SD > 2. Insurance type, mean tacrolimus blood level and SD of tacrolimus blood levels were significantly related to LAR in the unadjusted analyses (p<0.05). A multivariable model including age, insurance type, mean and SD of tacrolimus blood levels was significantly associated with LAR (validated C-statistic = 0.88, p = 0.012). The adjusted odds of rejection for a one unit increase in the SD of tacrolimus blood level was 3.49 (95% CI 1.31 to 9.29). Effects of age and insurance status on LAR did not provide independent prognostic value after controlling for SD. Variation in tacrolimus blood levels is associated with an increased risk of LAR in pediatric liver transplant recipients. Despite standardized management of tacrolimus levels to control for confounders, some patients were found to have significant variability of tacrolimus blood levels. This may be due to non-adherence and amenable to targeted psychosocial and behavioral interventions to prevent LAR.
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Affiliation(s)
- Veena L Venkat
- Department of Pediatrics, the Univerity of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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27
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Uemura T, Ikegami T, Sanchez EQ, Jennings LW, Narasimhan G, McKenna GJ, Randall HB, Chinnakotla S, Levy MF, Goldstein RM, Klintmalm GB. Late acute rejection after liver transplantation impacts patient survival. Clin Transplant 2008; 22:316-23. [PMID: 18190550 DOI: 10.1111/j.1399-0012.2007.00788.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hepatic allograft rejection still remains an important problem following liver transplantation. Early acute rejection, occurring within three months of transplant, is a common event and usually of lesser significance with respect to prognosis than other non-immune-related post-transplant morbidities. However, little is known about late acute rejection (LAR) including factors affecting its occurrence and long-term outcome. In this study, we analyzed LAR including the incidence, clinical risk factors, patient survival, and graft survival. LAR was defined as acute cellular rejection later than six months after liver transplant. Adult patients who had a minimum of 24 months of graft survival were included in this study. A total of 1604 case records of consecutive adult patients (over age 18 yr) who underwent liver transplant between 1985 and 2003 were reviewed. Of the 1604 patients, 305 (19.0%) developed LAR. Patients with primary diagnoses of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis had higher incidences of LAR, while patients with metabolic disease and retransplant had lower incidence of LAR (p = 0.0024). The LAR group had more female and younger recipients than the no LAR group (p = 0.0026, p = 0.0131, respectively). Patient survival as well as graft survival were significantly lower in the LAR group (p = 0.0083, p = 0.0075, respectively). PTLD was the only significant independent predictor of late rejection. The careful management and treatment of PTLD, especially immunosuppressive management, is important to prevent LAR, which is related to poorer patient survival.
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Affiliation(s)
- Tadahiro Uemura
- Transplantation Services, Baylor University Medical Center, Dallas, TX 75246, USA
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Hong Z, Wu J, Smart G, Kaita K, Wen SW, Paton S, Dawood M. Survival analysis of liver transplant patients in Canada 1997-2002. Transplant Proc 2007; 38:2951-6. [PMID: 17112872 DOI: 10.1016/j.transproceed.2006.08.180] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2005] [Indexed: 01/05/2023]
Abstract
UNLABELLED Liver transplantation is an important health care issue for Canadians. Very few studies have assessed survival and determinants of survival in liver transplant patients in Canada. METHODS We carried out an epidemiological analysis of 1 year survival and determinants of 1 year survival in liver transplant patients, using Canadian Organ Replacement Registry data (1997-2002). Survival curves were plotted by the Kaplan-Meier method. Cox proportional hazards analysis was applied to evaluate hazard ratios with different age groups, gender, ethnicity, blood groups, donor type, pretransplantation medical status, and HBV infection status. RESULTS A total of 1164 liver transplant patients were included in the analysis. One-year survival rate was 84.7%. Male recipients had a 21% higher risk of developing organ failure than females. Recipients over 60 years of age had a 5% lower survival probability in comparison with recipients below 20 years of age. Pacific Islanders and Aboriginals had 32% and 9% lower survival probabilities, respectively, in comparison with Caucasians. Type B blood recipients had a 12% higher survival probability, whereas type AB blood recipients had a 7% lower survival probability compared with type O blood recipients. Twenty-six live organ recipients had 40% higher survival probabilities than 1138 cadaveric organ recipients. Patients with fulminant hepatitis (status 3F) had the highest survival, while patients with fulminant failure in ICU with intubation/ventilation (status 4F) had the lowest survival. One hundred sixty-seven recipients with positive HBsAg antigen showed 10% lower survival probability than 997 cases with negative HBsAg antigen. CONCLUSION In Canada, the first year survival rate is about 85%, which is comparable with other industrialized countries. Type of donor organs and recipient gender, ethnicity, ABO blood group, pretransplantation medical status, and HBV infection status had significant affects on the recipient survival.
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Affiliation(s)
- Z Hong
- Blood Safety Surveillance and Health Care Acquired Infection Division, Centre for Infectious Disease Prevention and Control, Public Health Agency of Canada, Ottawa, Ontario.
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Nakanishi C, Kawagishi N, Sekiguchi S, Akamatsu Y, Sato K, Miyagi S, Takeda I, Hukushima K, Aiso T, Sato A, Fujimori K, Satomi S. Steroid-Resistant Late Acute Rejection after a Living Donor Liver Transplantation: Case Report and Review of the Literature. TOHOKU J EXP MED 2007; 211:195-200. [PMID: 17287604 DOI: 10.1620/tjem.211.195] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The majority of acute cellular rejection occurs in the first few months after liver transplantation. It has been, however, reported that some recipients experience late acute rejection, which occurs more than 3 months after transplantation. We herein report a case of late acute rejection that occurred nearly 10 years after liver transplantation. The patient is a 27-year-old male who underwent a living donor liver transplantation when he was 17 years old. At 9 years 6 months after transplantation, the patient presented with the elevated serum levels of liver enzymes and total bilirubin. A liver biopsy showed acute cellular rejection. Steroid bolus therapy was not effective, but we successfully used deoxyspergualin as a rescue therapy. Late acute cellular rejection that occurs nearly 10 years after transplantation has so far been rarely reported. It is generally believed that late acute rejection may be more resistant to treatment and be associated with a higher rate of graft loss, as well being associated with the development of chronic ductopenic rejection. In this report, we have shown that deoxyspergualin is safe and effective for treatment of steroid-resistant late acute rejection, preventing from graft loss of chronic rejection.
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Affiliation(s)
- Chikashi Nakanishi
- Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Japan.
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Toso C, Kneteman N. Does mycophenolate mofetil reduce the risk of late acute rejection after liver transplantation? ACTA ACUST UNITED AC 2006; 3:664-5. [PMID: 17130874 DOI: 10.1038/ncpgasthep0662] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2006] [Accepted: 09/28/2006] [Indexed: 11/09/2022]
Affiliation(s)
- Christian Toso
- Capital Health and the University of Alberta, Edmonton, AB, Canada
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Akamatsu N, Sugawara Y, Tamura S, Keneko J, Matsui Y, Hasegawa K, Makuuchi M. Late-onset acute rejection after living donor liver transplantation. World J Gastroenterol 2006; 12:6674-7. [PMID: 17075982 PMCID: PMC4125674 DOI: 10.3748/wjg.v12.i41.6674] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the incidence and risk factors of late-onset acute rejection (LAR) and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids.
METHODS: Adult living donor liver transplantation recipients (n = 204) who survived more than 6 mo after living donor liver transplantation were enrolled. Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation, tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration. Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median follow-up period was 34 mo.
RESULTS: LAR was observed in 15 cases (7%) and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset post-transplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients (19%). Multivariate analysis revealed that a cyclosporine-based regimen was significantly associated with LAR.
CONCLUSION: Both LAR and drug-induced adverse events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.
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Affiliation(s)
- Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Wiesner RH, Steffen BJ, David KM, Chu AH, Gordon RD, Lake JR. Mycophenolate mofetil use is associated with decreased risk of late acute rejection in adult liver transplant recipients. Am J Transplant 2006; 6:1609-16. [PMID: 16827861 DOI: 10.1111/j.1600-6143.2006.01382.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Mycophenolate mofetil (MMF) used in a triple-drug regimen has been shown to decrease acute rejection rates, compared to a double-drug regimen. The impact of MMF on late acute rejection (LAR) episodes has not been well described. To investigate the risk of LAR (rejection > or = 6 months post-transplantation) data from the Scientific Registry of Transplant Recipients (SRTR) were used. We studied adult primary liver transplant recipients transplanted between June 1, 1995, and April 30, 2004, with hepatitis C virus (HCV) (n = 3356), hepatitis B virus (HBV) (n = 550) or a nonviral (n = 5740) primary cause of liver disease who were recorded as receiving continuous 3-(MMF + Tacro + steroids) versus 2-drug (Tacro + steroids) therapy for at least 6 months immediately post transplantation. Kaplan-Meier analysis showed significantly lower LAR rates 4 years post-transplant in 3- versus 2-drug HCV, HBV and nonviral disease patients. Multivariate regression confirmed 3- versus 2-drug therapy to be associated with a decreased risk of LAR. Late graft survival was significantly lower at 4 years post-transplant for patients with LAR 6-12 months post-transplantation versus patients with early rejection (78.0% vs. 87.0%, p < 0.001) and no rejection (88.1%, p < 0.001). Three-drug versus 2-drug therapy for a minimum of 6 months may offer a better treatment strategy to avoid the consequences and expense of LAR episodes.
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Affiliation(s)
- R H Wiesner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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Abstract
During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection.
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Affiliation(s)
- Ludger Barthelmes
- Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical SchoolDundeeUnited Kingdom
| | - Iain S. Tait
- Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical SchoolDundeeUnited Kingdom
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Saab S, Kalmaz D, Gajjar NA, Hiatt J, Durazo F, Han S, Farmer DG, Ghobrial RM, Yersiz H, Goldstein LI, Lassman CR, Busuttil RW. Outcomes of acute rejection after interferon therapy in liver transplant recipients. Liver Transpl 2004; 10:859-67. [PMID: 15237369 DOI: 10.1002/lt.20157] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Interferon alfa has been increasingly used against recurrent hepatitis C (HCV) disease in post-liver transplant (LT) recipients. A serious potential adverse effect is acute rejection. We reviewed our experience using interferon-based therapy (interferon or pegylated interferon with or without ribavirin) for treating recurrent HCV in LT recipients. Forty-four LT recipients were treated with interferon for recurrent HCV. Five of the 44 patients developed acute rejection during interferon-based therapy. These 5 patients started treatment of 42.4 +/- 33.89 months (mean +/- SD) after LT. Mean (+/- SD) histological activity index and fibrosis scores before initiating antiviral therapy were 8.8 (+/- 1.92) and 2.6 (+/- 0.55), respectively. Patients were treated for 3.3 +/- 2.28 months (mean +/- SD) prior to rejection. At the time of rejection, HCV load was not detectable in 4 of the 5 recipients. All 5 patients had tolerated interferon therapy, and none had stopped therapy because of adverse effects. The rejection was successfully treated in 3 patients. In 2 of those 3 patients, cirrhosis eventually developed. In the 2 patients who did not respond to rejection treatment, immediate graft failure occurred, leading to re-LT in 1 patient and death from sepsis in the other. In conclusion, the results indicate that further studies are needed to assess the safety of interferon in LT recipients. Interferon-based therapy may lead to acute rejection and subsequent graft loss and should therefore be used with caution. Treated recipients may also develop progressive cirrhosis despite achieving a sustained virological response.
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Affiliation(s)
- Sammy Saab
- Department of Medicine, Dumont-UCLA Liver Transplant Center, Los Angeles, CA, USA.
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Yan LN, Wang W, Li B, Lu SC, Wen TF, Lin QY, Zeng Y, Cheng NS, Zhao JC, Dai YM. Single-dose daclizumab induction therapy in patients with liver transplantation. World J Gastroenterol 2003; 9:1881-3. [PMID: 12918145 PMCID: PMC4611568 DOI: 10.3748/wjg.v9.i8.1881] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the efficacy and safety of a single-dose daclizumab induction therapy in orthotopic liver transplantation (OLTx).
METHODS: A retrospective study was made for 54 cases of OLTx in recent three years. The daclizumab group consisted of 23 cases of OLTx who received single-dose of 2 mg/kg intravenously after postoperative 24 hours. The control group consisted of the remaining 31 patients. Additional immunosuppressors included steroids, mycomphenolate mofetil, facrolimus or microemulsion cyclosporine used in all patients. Meta-statistical analysis was made for general data, incidence of acute rejection and infection, postoperative clinical course, complications and prognosis between two groups.
RESULTS: Pretransplant demographies were not significantly different between two groups. In the induction group there were significantly less acute rejection episodes (5 of 23, 21.74%) than those in the control group (12 of 31, 38.71%), which were proved by pathologic diagnosis (P < 0.05). The incidence of infection at the early stage was not significantly different between two groups.
CONCLUSION: Induction therapy with single-dose of daclizumab is safe and effective and appears to be able to reduce the incidence of acute rejection.
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Affiliation(s)
- Lu-Nan Yan
- Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
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