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1
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Vutien P, Nguyen MH. HBV Reactivation in Immunosuppressed Patients: Screening, Prevention, and Management Including Solid Organ Transplant Recipients. Viruses 2025; 17:388. [PMID: 40143316 PMCID: PMC11945625 DOI: 10.3390/v17030388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Hepatitis B virus (HBV) infection remains a global health challenge, affecting over 254 million individuals chronically and contributing significantly to cirrhosis, liver failure, and hepatocellular carcinoma. Despite advancements in antiviral therapy, HBV reactivation remains a critical concern, particularly in immunosuppressed individuals, including non-transplant patients undergoing immunosuppressive therapy and solid organ transplant recipients. This review provides screening and management strategies for HBV reactivation in these populations.
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Affiliation(s)
- Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356175, Seattle, WA 98195, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA 94305, USA;
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA 94305, USA
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2
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Samuel D, De Martin E, Berg T, Berenguer M, Burra P, Fondevila C, Heimbach JK, Pageaux GP, Sanchez-Fueyo A, Toso C. EASL Clinical Practice Guidelines on liver transplantation. J Hepatol 2024; 81:1040-1086. [PMID: 39487043 DOI: 10.1016/j.jhep.2024.07.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 07/30/2024] [Indexed: 11/04/2024]
Abstract
Liver transplantation (LT) is an established life-saving procedure. The field of LT has changed in the past 10 years from several perspectives, with the expansion of indications, transplantation of patients with acute-on-chronic liver failure, evolution of transplant oncology, the use of donations after cardiac death, new surgical techniques, and prioritisation of recipients on the waiting list. In addition, the advent of organ perfusion machines, the recognition of new forms of rejection, and the attention paid to the transition from paediatric to adult patients, have all improved the management of LT recipients. The purpose of the EASL guidelines presented here is not to cover all aspects of LT but to focus on developments since the previous EASL guidelines published in 2016.
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3
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Grossi PA, Wolfe C, Peghin M. Non-Standard Risk Donors and Risk of Donor-Derived Infections: From Evaluation to Therapeutic Management. Transpl Int 2024; 37:12803. [PMID: 39416809 PMCID: PMC11479921 DOI: 10.3389/ti.2024.12803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 07/02/2024] [Indexed: 10/19/2024]
Abstract
Expected and unexpected donor-derived infections are a rare complication of solid organ transplantation, but can result in significant morbidity and mortality. Over the last years, the growing gap existing between patients on the waiting list and available organs has favored the use of organs from donors with suspected or confirmed infections, thanks to the improvement of risk mitigation strategies against transmission of well recognized and emerging infections. Given the recent developments, the particular interest of this review is to summarize data on how to maximize utilization of HIV+ donors in HIV+ recipients, the use of HCV-viremic donors and HBV positive donors. This article also covers the implications for recipient of organs from donors with bacteremia and the challenge of multidrug resistant (MDR) infections. Lastly this review describes emerging risks associated with recent Coronavirus Disease-2019 (COVID-19) pandemics.
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Affiliation(s)
- Paolo A. Grossi
- Infectious and Tropical Diseases Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Cameron Wolfe
- Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, United States
| | - Maddalena Peghin
- Infectious and Tropical Diseases Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Vutien P, Nguyen MH. Expanding the Donor Pool for Liver Transplantation: Assessing the Potential Use of HBV-Positive Allografts. CURRENT HEPATOLOGY REPORTS 2024; 23:227-240. [DOI: 10.1007/s11901-024-00653-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/24/2024] [Indexed: 01/02/2025]
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Ali SE, Vutien P, Bonham CA, Landis C, Kwo P, Esquivel C, Nguyen MH. Use and outcomes of hepatitis B virus-positive grafts in orthotopic liver transplantation in the United States from 1999 to 2021. Liver Transpl 2023; 29:80-90. [PMID: 35844046 PMCID: PMC9839464 DOI: 10.1002/lt.26543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 06/13/2022] [Accepted: 06/28/2022] [Indexed: 01/16/2023]
Abstract
The demand for orthotopic liver transplantation (OLT) is projected to increase, which indicates a need to expand the liver donor pool. We aimed to investigate the use of hepatitis B virus (HBV)-positive grafts and the outcomes of recipients undergoing OLT with HBV-positive grafts. We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if hepatitis B surface antigen was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient sex, donation after circulatory death, recipient location, and Model for End-Stage Liver Disease score at transplant. Among the 185,212 potential donors, 422 (0.2%) were HBV positive, and 265 (63%) of the HBV-positive grafts were transplanted (14 of 265 [5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period ( p < 0.001). Recipients of HBV-positive ( n = 209) grafts had similar mortality (log-rank, p = 0.47) and graft loss (log-rank, p = 0.72) rates to the matched recipients of HBV-negative allografts ( n = 1045). The 3-year graft survival rate was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group. Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. One strategy that may help expand the donor pool and lower the waitlist mortality rate is using HBV-positive allografts.
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Affiliation(s)
- Saad Emhmed Ali
- Division of Gastroenterology and Hepatology, Stanford University Medical Center
| | - Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington Medical Center
| | | | - Charles Landis
- Division of Gastroenterology and Hepatology, University of Washington Medical Center
| | - Paul Kwo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center
| | | | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center
- Department of Epidemiology and Population Health, Stanford University Medical Center
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Gang S, Choi Y, Lee B, Yoon KC, Hong SY, Suh S, Han ES, Hong SK, Lee HW, Cho JY, Yi NJ, Lee KW, Suh KS. Long-term outcomes of liver transplantation using grafts from donors with active hepatitis B virus replication: a multicenter cohort study. Ann Surg Treat Res 2023; 104:183-194. [PMID: 37051154 PMCID: PMC10083344 DOI: 10.4174/astr.2023.104.4.183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 03/06/2023] [Accepted: 03/08/2023] [Indexed: 04/07/2023] Open
Abstract
Purpose Liver grafts from donors with HBV infection contributed to expanding the donor pool under the hepatitis B immunoglobulin and antiviral agents (nucleos(t)ide analogues) in the HBV-endemic area. We report long-term outcomes of liver transplantations (LTs) using grafts from donors with active or chronic HBV infection. Methods Overall, 2,260 LTs performed in 3 major hospitals in Seoul from January 2000 to April 2019 were assessed for inclusion. Twenty-six grafts (1.2%) were obtained from HBsAg (+), HBeAb (+), or HBcAb (+) donors, and recipient outcomes were retrospectively reviewed. Donor and recipient demographics and transplantation outcomes were analyzed. Results Sixteen deceased donor LTs were performed using active HBsAg (+) grafts. Ten other LTs were sourced from 10 living donors. There was no significant difference in survival in patients who received deceased donor LTs compared with that in those who underwent LT with non-hepatitis virus-infected grafts. Fourteen patients who were followed up for >5 years were stable, and no difference in hepatocellular carcinoma recurrence rate was observed 5 years after transplantation between transplants from donors with and those without HBV. Conclusion Considering long-term outcomes, liver grafts from donors with active HBV replication can be safely used for LT.
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Affiliation(s)
- Sujin Gang
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Kyung Chul Yoon
- Department of Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Su young Hong
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sanggyun Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Eui Soo Han
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Nam-joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Russo FP, Viganò M, Stock P, Ferrarese A, Pugliese N, Burra P, Aghemo A. HBV-positive and HIV-positive organs in transplantation: A clinical guide for the hepatologist. J Hepatol 2022; 77:503-515. [PMID: 35398460 DOI: 10.1016/j.jhep.2022.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 02/08/2022] [Accepted: 03/02/2022] [Indexed: 12/04/2022]
Abstract
Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation.
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Affiliation(s)
- Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy
| | - Mauro Viganò
- Division of Hepatology, San Giuseppe Hospital, MultiMedica IRCCS, Milan, Italy
| | - Peter Stock
- Department of Surgery, University of California at San Francisco, San Francisco, California, USA
| | - Alberto Ferrarese
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, Verona, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy.
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
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Yu S, Cen C, Zhang X, Cheng L, Xia W, Jia J, Ye Y, Yu J, Zhang M, Shen Y, Zheng S. Utilization of hepatitis B virus surface antigen positive grafts in liver transplantation: A matched study based on a national registry cohort. J Gastroenterol Hepatol 2022; 37:1052-1059. [PMID: 35249229 DOI: 10.1111/jgh.15821] [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: 10/08/2021] [Revised: 12/25/2021] [Accepted: 02/08/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Donor shortage has become worldwide limitation in liver transplantation (LT). Use of hepatitis B virus surface antigen positive (HBsAg+) donors could be an alternative source of donor organs. This study aims to investigate the safety and efficacy of LT using HBsAg+ liver grafts and associated long-term outcome. METHODS This was a retrospective study of adults LT registered in the database of the China Liver Transplant Registry between January 2015 and September 2018. By propensity score matching (1:1), 503 eligible patients who received HBsAg+ liver grafts were compared with 503 matched patients who received HBsAg- liver grafts. RESULTS The 1-, 3-, and 5-year patient survival rates were 81.52%, 72.04%, and 66.65% in HBsAg+ donor group, which were comparable with 83.93%, 77.27%, and 65.73% in HBsAg- donor group (P = 0.222). The 1-, 3-, and 5-year graft survival rates were also comparable between the two groups (81.49%, 71.45%, and 67.26% vs 83.62%, 77.11%, and 65.81%, respectively, P = 0.243). Most main complications were not increased in HBsAg+ donor group except for the retaining of HBsAg positivity after LT. Furthermore, transplanting HBsAg+ liver grafts did not result in inferior outcomes either in HBsAg+ or HBsAg- recipients. The risk of tumor recurrence after LT was not increased in hepatocellular carcinoma patients. CONCLUSIONS The outcomes of using HBsAg+ liver grafts were comparable with those of HBsAg- liver grafts. Our study provided strong evidence for the safe use of HBsAg+ grafts in LT to expand the donor liver pool.
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Affiliation(s)
- Songfeng Yu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Chao Cen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Xuanyu Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Longyu Cheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Weiliang Xia
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Junjun Jia
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Yufu Ye
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Jun Yu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Min Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Yan Shen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
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McCain JD, Chascsa DM. Special Considerations in the Management of HIV and Viral Hepatitis Coinfections in Liver Transplantation. Hepat Med 2022; 14:27-36. [PMID: 35514530 PMCID: PMC9063796 DOI: 10.2147/hmer.s282662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 04/07/2022] [Indexed: 11/26/2022] Open
Abstract
Modern therapies for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus have become so effective that patients treated for these conditions can have normal life-expectancies. Suitable livers for transplantation remain a scarce and valuable resource. As such, significant efforts have been made to expand donation criteria at many centers. This constant pressure, coupled with the increasing effectiveness of antiviral therapies, has meant that more and more patients infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) may be considered appropriate donors in the right circumstances. Patients with these infections are also more likely to be considered appropriate transplantation recipients than in the past. The treatment of HBV, HCV, and HIV after liver transplantation (LT) can be challenging and complicated by viral coinfections. The various pharmaceutical agents used to treat these infections, as well as the immunosuppressants used post-LT must be carefully balanced for maximum efficacy, and to avoid resistance and drug–drug interactions.
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Affiliation(s)
- Josiah D McCain
- Department of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, AZ, USA
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11
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An Update on Usage of High-Risk Donors in Liver Transplantation. J Clin Med 2021; 11:jcm11010215. [PMID: 35011956 PMCID: PMC8746244 DOI: 10.3390/jcm11010215] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/01/2021] [Accepted: 12/28/2021] [Indexed: 12/13/2022] Open
Abstract
The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use.
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Ferrando-Martinez S, Snell Bennett A, Lino E, Gehring AJ, Feld J, Janssen HLA, Robbins SH. Functional Exhaustion of HBV-Specific CD8 T Cells Impedes PD-L1 Blockade Efficacy in Chronic HBV Infection. Front Immunol 2021; 12:648420. [PMID: 34589081 PMCID: PMC8473828 DOI: 10.3389/fimmu.2021.648420] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 08/24/2021] [Indexed: 01/12/2023] Open
Abstract
Background A functional cure for chronic HBV could be achieved by boosting HBV-specific immunity. In vitro studies show that immunotherapy could be an effective strategy. However, these studies include strategies to enrich HBV-specific CD8 T cells, which could alter the expression of the anti-PD-1/anti-PD-L1 antibody targets. Our aim was to determine the efficacy of PD-L1 blockade ex vivo. Methods HBV-specific CD8 T cells were characterized ex vivo by flow cytometry for the simultaneous analysis of six immune populations and 14 activating and inhibitory receptors. Ex vivo functionality was quantified by ELISpot and by combining peptide pool stimulation, dextramers and intracellular flow cytometry staining. Results The functionality of HBV-specific CD8 T cells is associated with a higher frequency of cells with low exhaustion phenotype (LAG3-TIM3-PD-1+), independently of the clinical parameters. The accumulation of HBV-specific CD8 T cells with a functionally exhausted phenotype (LAG3+TIM3+PD-1+) is associated with lack of ex vivo functionality. PD-L1 blockade enhanced the HBV-specific CD8 T cell response only in patients with lower exhaustion levels, while response to PD-L1 blockade was abrogated in patients with higher frequencies of exhausted HBV-specific CD8 T cells. Conclusion Higher levels of functionally exhausted HBV-specific CD8 T cells are associated with a lack of response that cannot be restored by blocking the PD-1:PD-L1 axis. This suggests that the clinical effectiveness of blocking the PD-1:PD-L1 axis as a monotherapy may be restricted. Combination strategies, potentially including the combination of anti-LAG-3 with other anti-iR antibodies, will likely be required to elicit a functional cure for patients with high levels of functionally exhausted HBV-specific CD8 T cells.
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Affiliation(s)
- Sara Ferrando-Martinez
- Microbial Sciences, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States
| | - Angie Snell Bennett
- Microbial Sciences, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States
| | - Elisabete Lino
- Microbial Sciences, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States
| | - Adam J Gehring
- Toronto Center for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.,Department of Immunology, University of Toronto, Toronto, ON, Canada
| | - Jordan Feld
- Toronto Center for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Harry L A Janssen
- Toronto Center for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Scott H Robbins
- Late Stage Oncology Development, Oncology R&D, AstraZeneca, Gaithersburg, MD, United States
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Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients. Ann Surg 2021; 274:556-564. [PMID: 34506310 DOI: 10.1097/sla.0000000000005071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.
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Duvoux C, Belli LS, Fung J, Angelico M, Buti M, Coilly A, Cortesi P, Durand F, Féray C, Fondevila C, Lebray P, Martini S, Nevens F, Polak WG, Rizzetto M, Volpes R, Zoulim F, Samuel D, Berenguer M. 2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus-related infection before and after liver transplantation. Aliment Pharmacol Ther 2021; 54:583-605. [PMID: 34287994 DOI: 10.1111/apt.16374] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/25/2020] [Accepted: 04/01/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA). AIM This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence. METHODS Based on a 4-round Delphi process, ELITA investigated 16 research questions and established 50 recommendations. RESULTS Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre-LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low-risk patients, short-term (4 weeks) combination of third-generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high-risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1 year is advised. HBV-HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long-term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen. CONCLUSIONS These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs.
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Orfanidou A, Papatheodoridis GV, Cholongitas E. Antiviral prophylaxis against hepatitis B recurrence after liver transplantation: Current concepts. Liver Int 2021; 41:1448-1461. [PMID: 33656809 DOI: 10.1111/liv.14860] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 01/20/2021] [Accepted: 02/13/2021] [Indexed: 12/14/2022]
Abstract
The advance in treatment against hepatitis B virus (HBV) infection with the development of nucleos(t)ide analogues (NAs) with high genetic barrier to resistance, including entecavir and tenofovir, has improved clinical outcomes of patients transplanted for HBV infection, by preventing HBV recurrence after liver transplantation (LT) effectively. Currently, after LT, the combination of hepatitis B immunoglobulin (HBIG) and a high-barrier NA is considered as the standard of care for prophylaxis against HBV recurrence. However, because of the high cost of intravenous high-dose HBIG, other routes of HBIG administration, such as intramuscular or subcutaneous, have come to the foreground. In addition, several transplant centres tend to use a NA as monoprophylaxis, following a short post-LT period of HBIG and NA combination. Lately, studies using HBIG-free prophylactic regimens with entecavir or tenofovir have shown promising outcomes in preventing HBV recurrence, mostly regarding patients with undetectable HBV DNA at the time of LT. Although vaccination against HBV has been an attractive prophylactic approach, its efficacy has been controversial. Moreover, further studies are needed regarding long-term outcomes of complete withdrawal anti-HBV prophylaxis. For patients transplanted for HBV/HDV co-infection, combined regimen should be administered for a longer period post-LT. Finally, the use of grafts from hepatitis B core antibody-positive donors is safe for HBV-negative recipients, with the administration of lifelong antiviral prophylaxis.
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Affiliation(s)
- Afroditi Orfanidou
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - George V Papatheodoridis
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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Cost-Effectiveness of Utilization of Hepatitis B Virus-Positive Liver Donors for HBV-Negative Transplant Recipients. J Gastrointest Surg 2021; 25:1760-1769. [PMID: 32728822 DOI: 10.1007/s11605-020-04759-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 07/19/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Utilization of hepatitis B virus (HBV)-infected donors represents an opportunity to expand the liver transplantation (LT) donor pool. However, benefits of accepting HBV-positive donors for HBV-negative candidates, potentially expanding the donor pool resulting in earlier transplantation, must be balanced with costs of lifelong antiviral therapy. The aim of this study was to evaluate cost-effectiveness of this strategy. METHODS We developed a Markov model with two strategies, transplant with (1) a HBV-positive donor versus and (2) a HBV-negative donor for a HBV-negative LT candidate. A healthcare system perspective was utilized, effectiveness measured in quality-adjusted life-years, and costs in 2018 USD. RESULTS In the base-case, the HBV-positive donor strategy is more effective (gain of 0.46 QALYs), but $26,159 more expensive, yielding an incremental cost-effectiveness ratio (ICER) of $57,389/QALY. However, increasing the candidate's Model for End-Stage Liver Disease score resulted in increasing cost-effectiveness, ICER of $69,507/QALY (MELD 6-10) to $47,385/QALY (MELD > 30). Results were most sensitive to antiviral cost and cost after first year of LT. In probabilistic sensitivity analysis, the HBV-positive strategy was always more effective but more expensive, with average ICER of $64,883/QALY. This strategy was highly cost-effective (ICER < $50,000/QALY) 21% of the time and cost < $100/000/QALY 94% of the time. CONCLUSIONS Consideration of these donors must be individualized to each candidate's severity of liver disease, associated costs, and personal preferences that impact quality of life. Expansion of the donor pool to include HBV-positive donors for appropriate recipients may be a cost-effective policy and may provide significant benefit for individual patients.
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Risk of disease transmission in an expanded donor population: the potential of hepatitis B virus donors. Curr Opin Organ Transplant 2021; 25:631-639. [PMID: 33027191 DOI: 10.1097/mot.0000000000000810] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW Lack of availability of donor organs is a constant challenge that patients and providers face in transplantation. To address this shortage, donors that test positive for hepatitis B, in particular those with resolved infection, have been increasingly utilized in clinical practice. We review here the potential risks for the recipient and the advances in hepatitis B management that have made use of these donors a well tolerated and advisable proposition. RECENT FINDINGS As routine administration of antiviral prophylaxis in the posttransplant setting among those deemed high risk for transmission, outcomes for recipients of hepatitis B donors, including liver transplant recipients, have been comparable to uninfected donors. Universal hepatitis B nucleic acid testing of donors has also enhanced our ability to accurately inform recipients regarding transmission risk. Appropriate use of prophylaxis and careful monitoring for transmission posttransplant is key to ensuring no adverse outcomes occur. SUMMARY Treatment of hepatitis B has evolved over the past two decades. Expanding the donor pool with hepatitis B donors is now well tolerated, ethical, and advantageous to the transplant community at large. A clear discussion with recipients on the substantial benefit and low harm of using hepatitis B donors will lead to greater acceptance and utilization of these organs.
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Delman AM, Ammann AM, Shah SA. The current status of virus-positive liver transplantation. Curr Opin Organ Transplant 2021; 26:160-167. [PMID: 33595981 DOI: 10.1097/mot.0000000000000850] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW The last 2 years have seen significant developments in virus-positive liver transplantation. This review provides an updated account of the transplantation of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV-positive livers, with a specific focus on studies published in the last 18 months. RECENT FINDINGS The advent of highly efficacious direct acting antiviral agents, nucleos(t)ide analogues and a continued organ shortage have led to the well tolerated utilization of HCV, HBV and HIV-positive organs. There has been a significant increase in the transplantation of HCV seropositive and NAT+ organs into HCV-negative recipients, without compromising patient or graft survival. Early reports of HBV core antibody (HBVcAb), HBV surface antigen (HBVsAg) positive and NAT+ donors are growing in the USA with promising results. Similarly, small studies have described the use of HIV-positive to HIV-positive liver transplantation without concerns for superinfection. SUMMARY HCV, HBV and HIV-positive liver transplantations can be accomplished safely and are associated with equivalent outcomes when paired with appropriate recipients. The practice of virus positive liver transplantation should be encouraged to combat the ongoing organ shortage.
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Affiliation(s)
- Aaron M Delman
- The Department of Surgery, University of Cincinnati
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS) Research Group, The Department of Surgery at The University of Cincinnati, Cincinnati, Ohio, USA
| | - Allison M Ammann
- The Department of Surgery, University of Cincinnati
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS) Research Group, The Department of Surgery at The University of Cincinnati, Cincinnati, Ohio, USA
| | - Shimul A Shah
- The Department of Surgery, University of Cincinnati
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS) Research Group, The Department of Surgery at The University of Cincinnati, Cincinnati, Ohio, USA
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Abstract
Hepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.
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Affiliation(s)
- Yu Shi
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, China
| | - Min Zheng
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, China
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Crismale JF, Ahmad J. Expanding the donor pool: Hepatitis C, hepatitis B and human immunodeficiency virus-positive donors in liver transplantation. World J Gastroenterol 2019; 25:6799-6812. [PMID: 31885421 PMCID: PMC6931007 DOI: 10.3748/wjg.v25.i47.6799] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 11/26/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply. The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C (HCV) and hepatitis B (HBV) related liver disease and yet the number of patients waiting for LT continues to increase, driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcohol-related liver disease. In addition, human immunodeficiency virus (HIV) infection, which was previously a contra-indication for LT, is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT. The rising demand for LT is projected to increase further in the future, thus driving the need to investigate potential means of expanding the pool of potential donors. One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive, HBV-positive, and HIV-positive donors. The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV, HBV or HIV infected recipients and in some cases uninfected recipients.
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Affiliation(s)
- James F Crismale
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| | - Jawad Ahmad
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
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21
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Chen Y, Tian Z. HBV-Induced Immune Imbalance in the Development of HCC. Front Immunol 2019; 10:2048. [PMID: 31507621 PMCID: PMC6718466 DOI: 10.3389/fimmu.2019.02048] [Citation(s) in RCA: 180] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 08/13/2019] [Indexed: 12/12/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection is one of the high-risk factors for human HCC. Despite the integration of virus DNA and the oncoprotein HBx, chronic necroinflammation and hepatocellular regeneration account for hepatocarcinogenesis. As a non-cytopathic virus, HBV is extensively recognized to mediate chronic liver damage through abnormal immune attack. However, the mechanisms driving HBV infection to HCC are poorly understood. During chronic HBV infection in humans, the adaptive immunity changes from immune tolerance to progressive immune activation, inactivation, reactivation and exhaustion, all of which may be the immune pathogenic factors for the development of HCC. Recently, the immunopathogenic mechanisms were described in mouse HBV-induced HCC models, which is absolutely dependent on the presence of HBV-specific T cell response and NK cell-derived IFN-γ, findings which are consistent with the observations from CHB and HCC patients. In this review, we summarize recent research progression on the HBV-specific CD8+ T cells, and also CD4+ T cells, B cells and non-specific immune cells and molecules underlying chronic HBV infection and eventual HCC development to demonstrate the pathogenesis of HBV-induced immune imbalance. Based on the progression, we discussed the potential of immune-based therapies and their challenges in the treatment of HBV-related HCC, including the checkpoint inhibition, genetically modified T cell transfer, therapeutic vaccines and metabolic modulation.
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Affiliation(s)
- Yongyan Chen
- Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Molecular Medicine, School of Life Sciences, University of Science and Technology of China, Hefei, China.,Institute of Immunology, University of Science and Technology of China, Hefei, China
| | - Zhigang Tian
- Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Molecular Medicine, School of Life Sciences, University of Science and Technology of China, Hefei, China.,Institute of Immunology, University of Science and Technology of China, Hefei, China
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22
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Chien RN, Kao JH, Peng CY, Chen CH, Liu CJ, Huang YH, Hu TH, Yang HI, Lu SN, Ni YH, Chuang WL, Lee CM, Wu JC, Chen PJ, Liaw YF. Taiwan consensus statement on the management of chronic hepatitis B. J Formos Med Assoc 2019; 118:7-38. [PMID: 30527436 DOI: 10.1016/j.jfma.2018.11.008] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Revised: 11/06/2018] [Accepted: 11/15/2018] [Indexed: 01/10/2023] Open
Abstract
The experts of Taiwan Association for the Study of Liver (TASL) have actively participated and led the guidelines on hepatitis B virus (HBV) management by Asian Pacific Association for the Study of Liver (APASL) which is the first international association for the study of liver to publish the statement on HBV management before. However, there are more and more new data on the natural history and treatment of HBV infection in the past decade. These include new application of an old biomarker (quantitative HBsAg), clinical significance of HBV genotype and naturally occurring mutations, the role of non-invasive examination in evaluating severity of hepatic fibrosis, clinical significance of outcome calculators, new drug or new combination strategies towards more effective therapy and organ transplantation including liver and non-liver transplantation. It is time to publish the guidelines on HBV management of Taiwan. Hence, TASL have conducted an expert meeting to review, to discuss and to debate the relevant literatures, followed by draft the manuscript of HBV management guidelines and recommendations. The guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patient receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.
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Affiliation(s)
- Rong-Nan Chien
- Liver Research Unit, Linkou Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan.
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, Department of Internal Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hwa-I Yang
- Department of Genomic Research Center, Sinica Academia, Taipei, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
| | - Won-Long Chuang
- Division of Hepatobiliary and Pancreas, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chuan-Mo Lee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jaw-Chin Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yun-Fan Liaw
- Liver Research Unit, Linkou Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan
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Gehring AJ, Protzer U. Targeting Innate and Adaptive Immune Responses to Cure Chronic HBV Infection. Gastroenterology 2019; 156:325-337. [PMID: 30367834 DOI: 10.1053/j.gastro.2018.10.032] [Citation(s) in RCA: 137] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 10/18/2018] [Accepted: 10/19/2018] [Indexed: 12/11/2022]
Abstract
Fewer than 1% of chronic hepatitis B virus infections per year are cured with antiviral treatment. This creates a need for long-term treatment, which poses challenges for patients and health systems. Because cure is accompanied by recovery of antiviral immunity, a combination of direct-acting antiviral agents and immunotherapy are likely to be required. Extensive efforts have been made to identify determinants of the failed immune response to hepatitis B virus in patients with chronic infection. We review mechanisms of immune dysfunction in patients with chronic hepatitis B virus infection, immunotherapy strategies in development, and the challenges associated with successful implementation of immunotherapy.
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Affiliation(s)
- Adam J Gehring
- Toronto Centre for Liver Disease and Toronto General Hospital Research Institute, University Health Network, Toronto, Canada; Department of Immunology, University of Toronto, Toronto, Canada.
| | - Ulrike Protzer
- Institute of Virology, Technical University of Munich/Helmholtz Zentrum München, Munich, Germany; German Center for Infection Research (DZIF), Munich partner site, Munich, Germany.
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Wei L, Chen D, Zhang B, Zhao Y, Liu B, Shi H, Zeng F, Ming C, Jiang J, Du D, Chen Z. Long-term outcome and recurrence of hepatitis B virus following liver transplantation from hepatitis B surface antigen-positive donors in a Chinese population. J Viral Hepat 2018; 25:1576-1581. [PMID: 30009520 DOI: 10.1111/jvh.12972] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Accepted: 06/30/2018] [Indexed: 12/19/2022]
Abstract
Due to the severe shortage of the donor pool in China, a large number of patients are waiting for a suitable liver, or even worse lose the opportunity of transplantation. Reasonable use of hepatitis B surface antigen-positive (HBsAg-positive) donors is one possible strategy to increase the donor pool but the long-term outcome in a Chinese population is unknown. To evaluate the safety of using of HBsAg-positive donor for liver transplantation, we set up a multicentric retrospective study from 1 January 2007 to 31 December 2012. A total of 8632 patients underwent liver transplantation during the period and 282 (2.97%) received a liver from a HBsAg-positive donor. A total of 259 cases in both the case and control groups were matched. The incidence of postoperative liver dysfunction, early-stage and long-term complications and the 1-, 3- and 5-year patient survival (78.92% vs 85.65%, 60.41% vs 69.14%, 58.08% vs 69.14%, respectively) showed no difference between the two groups (P value > 0.05). However, the 1-, 3- and 5-year HBV recurrence for patients received the HBsAg-positive donor was higher compared with controls (5.85% vs 1.97%, 11.63% vs 4.46%, 17.94% vs 4.46%, respectively, P value = 0.016). Our results showed the use of HBsAg-positive donors is feasible and postoperative antiviral therapy should be managed.
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Affiliation(s)
- Lai Wei
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Dong Chen
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Bo Zhang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Yuanyuan Zhao
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Bin Liu
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Huibo Shi
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Fanjun Zeng
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Changsheng Ming
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Jipin Jiang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Dunfeng Du
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Zhishui Chen
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.,NHC Key Laboratory of Organ Transplantation, Wuhan, China.,Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
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Gehring AJ. New treatments to reach functional cure: Rationale and challenges for emerging immune-based therapies. Best Pract Res Clin Gastroenterol 2017; 31:337-345. [PMID: 28774416 DOI: 10.1016/j.bpg.2017.05.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Revised: 05/03/2017] [Accepted: 05/13/2017] [Indexed: 01/31/2023]
Abstract
The landscape for chronic HBV therapy is rapidly evolving. The latest generation of antiviral drugs provide robust virus suppression with a high barrier to resistance that facilitates long-term treatment. However, low rates of HBsAg loss demonstrate that additional strategies are needed to consistency achieve a functional cure. The immune system can clear HBV and establish long-term control over the virus. Sufficiently boosting HBV immunity in chronic patients has been very difficult due to immune exhaustion, immune dysregulation, and inhibitory pathways suppressing the immune response. Therapeutic vaccines employing new technology, vectors and new immunomodulatory drugs that can elicit direct antiviral effects and cancel inhibitory mechanism may be able to overcome exhaustion. This review will discuss the justification for immunotherapy, lessons from previous trials and new vaccines/drugs in early stage clinical trials. The challenges of correlating immune responses induced by these drugs to clinical efficacy will also be addressed.
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Affiliation(s)
- Adam J Gehring
- Toronto Centre for Liver Disease and Toronto General Hospital Research Institute, University Health Network, Toronto, Canada; Department of Immunology, University of Toronto, Toronto, Canada.
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Abstract
Mortality rates on the liver transplant waiting list are increasing. The shortage of organs has resulted in higher utilization of extended criteria donors (ECDs), with centers pushing the limits of what is acceptable for transplantation. Donor quality is more appropriately represented as a continuum of risk, and careful selection and matching of ECD grafts with recipients may lead to excellent outcomes. Although there is no precise definition for what constitutes an ECD liver, this review focuses on frequently cited characteristics, including donor age, steatosis, donation after cardiac death, and donors with increased risk of disease transmission.
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Affiliation(s)
- Irine Vodkin
- Division of Gastroenterology and Hepatology, University of California, San Diego, 200 West Arbor Drive M/C 8413, San Diego, CA, USA.
| | - Alexander Kuo
- Division of Gastroenterology and Hepatology, University of California, San Diego, 200 West Arbor Drive M/C 8413, San Diego, CA, USA
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Ballarin R, Cucchetti A, Russo FP, Magistri P, Cescon M, Cillo U, Burra P, Pinna AD, Di Benedetto F. Long term follow-up and outcome of liver transplantation from hepatitis B surface antigen positive donors. World J Gastroenterol 2017; 23:2095-2105. [PMID: 28405138 PMCID: PMC5374122 DOI: 10.3748/wjg.v23.i12.2095] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Revised: 01/30/2017] [Accepted: 03/02/2017] [Indexed: 02/06/2023] Open
Abstract
Liver transplant for hepatitis B virus (HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28 (2%) received the graft from hepatitis B surface antigen positive (HBsAg)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary non-function, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3- and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBsAg-positive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.
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Loggi E, Conti F, Cucchetti A, Ercolani G, Pinna AD, Andreone P. Liver grafts from hepatitis B surface antigen-positive donors: A review of the literature. World J Gastroenterol 2016; 22:8010-8016. [PMID: 27672295 PMCID: PMC5028814 DOI: 10.3748/wjg.v22.i35.8010] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Revised: 06/06/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023] Open
Abstract
The scarcity of available organs and the gap between supply and demand continue to be the main limitations of liver transplantation. To relieve the organ shortage, current transplant strategies have implemented extended criteria, which include the use of liver from patients with signs of past or present hepatitis B virus (HBV) infection. While the use of liver grafts from donors with evidence of past HBV infection is quite limited, some data have been collected regarding the feasibility of transplanting a liver graft from a hepatitis B surface antigen (HBsAg) positive donor. The aim of the present work was to review the literature regarding liver transplants from HBsAg-positive donors. A total of 17 studies were identified by a search in Medline. To date, HBsAg positive grafts have preferentially been allocated to HBsAg positive recipients. The large majority of these patients continue to be HBsAg positive despite the use of immunoglobulin, and infection prevention can only be guaranteed by using antiviral prophylaxis. Although serological persistence is evident, no significant HBV-related disease has been observed, except in patients coinfected with delta virus. Consistently less data are available for HBsAg negative recipients, although they are mostly promising. HBsAg-positive grafts could be an additional organ source for liver transplantation, provided that the risk of reinfection/reactivation is properly prevented.
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Wong TCL, She WH, Cheung TT, Chan SC, Lo CM. Case Report of Relay Liver Transplantation With Graft Infected With Hepatitis B Virus. Transplant Proc 2016; 47:2768-70. [PMID: 26680090 DOI: 10.1016/j.transproceed.2015.09.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 09/24/2015] [Indexed: 01/01/2023]
Abstract
Reuse of liver graft for transplantation is extremely uncommon. We report the 1st case of reuse of liver graft from a recipient who had hepatitis B virus (HBV) infection, 11 years after the 1st transplantation. Our relay liver transplantation challenged conventional thinking because of late reuse of graft in the presence of HBV infection. Moreover, both the 1st and the 2nd donors were of advanced age. The key questions were whether the liver graft could be reused safely, especially in the setting of HBV infection, and technical concerns during organ procurement and implantation. The absence of HBV replication was confirmed with negative hepatitis B surface antigen and undetectable serum HBV DNA in the 2nd donor. Based on our experience in managing HBV infection after liver transplantation, we were confident that the adequately suppressed HBV infection in the donor would not jeopardize graft function and that the graft would be able to withstand another ischemia-perfusion injury to continue to function well in our recipient.
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Affiliation(s)
- T C L Wong
- Department of Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong, People's Republic of China
| | - W H She
- Department of Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong, People's Republic of China
| | - T T Cheung
- Department of Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong, People's Republic of China
| | - S C Chan
- Department of Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong, People's Republic of China
| | - C M Lo
- Department of Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong, People's Republic of China.
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Donor-Derived Infections: Incidence, Prevention, and Management. TRANSPLANT INFECTIONS 2016. [PMCID: PMC7123109 DOI: 10.1007/978-3-319-28797-3_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Organ donors reflect the diverse US population, and there are an increasing number of donors born in, who have resided in, or who have traveled to underdeveloped areas of the world or areas with geographically restricted infections. As such, these donors are exposed to pathogens that can potentially be transmitted to recipients of the donor’s organs. Additionally, there are newer techniques to identify many pathogens that may be transmitted from the donor to the transplant recipients. Finally, high-profile reports of several donor-derived infections have heightened awareness of donor-derived infections and have likely contributed to increased recognition. In this chapter, the incidence, methods of identification and prevention, and management of unexpected donor-derived infections will be reviewed.
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Song ZL, Cui YJ, Zheng WP, Teng DH, Zheng H. Application of nucleoside analogues to liver transplant recipients with hepatitis B. World J Gastroenterol 2015; 21:12091-12100. [PMID: 26576094 PMCID: PMC4641127 DOI: 10.3748/wjg.v21.i42.12091] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/22/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus (HBV) core antibody (HBcAb) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues (NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBcAb-positive liver grafts.
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Diwan TS, Paterno F, Shah SA. Use of Extended Criteria Deceased Donors in Adult Liver Transplantation. CURRENT SURGERY REPORTS 2015. [DOI: 10.1007/s40137-015-0103-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Kornberg A. Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation. World J Hepatol 2015; 7:1494-1508. [PMID: 26085909 PMCID: PMC4462688 DOI: 10.4254/wjh.v7.i11.1494] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Revised: 04/19/2015] [Accepted: 05/08/2015] [Indexed: 02/06/2023] Open
Abstract
Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liver disease (MELD) score helped to reduce waiting list mortality in liver transplantation (LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients’ infectious and immunologic risk profiles. The administration of intravenous immunoglobulins (IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.
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Huprikar S, Danziger-Isakov L, Ahn J, Naugler S, Blumberg E, Avery RK, Koval C, Lease ED, Pillai A, Doucette KE, Levitsky J, Morris MI, Lu K, McDermott JK, Mone T, Orlowski JP, Dadhania DM, Abbott K, Horslen S, Laskin BL, Mougdil A, Venkat VL, Korenblat K, Kumar V, Grossi P, Bloom RD, Brown K, Kotton CN, Kumar D. Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. Am J Transplant 2015; 15:1162-72. [PMID: 25707744 DOI: 10.1111/ajt.13187] [Citation(s) in RCA: 162] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Revised: 12/08/2014] [Accepted: 12/24/2014] [Indexed: 01/25/2023]
Abstract
Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.
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Affiliation(s)
- S Huprikar
- Icahn School of Medicine at Mount Sinai, New York, NY
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Shouval D. Expanding the donor pool for liver transplant recipients using HBsAg positive grafts. J Hepatol 2014; 61:717-9. [PMID: 25038488 DOI: 10.1016/j.jhep.2014.07.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Accepted: 07/10/2014] [Indexed: 12/26/2022]
Affiliation(s)
- Daniel Shouval
- Liver Unit, Institute for Gastroenterology and Hepatology, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
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Yu S, Yu J, Zhang W, Cheng L, Ye Y, Geng L, Yu Z, Yan S, Wu L, Wang W, Zheng S. Safe use of liver grafts from hepatitis B surface antigen positive donors in liver transplantation. J Hepatol 2014; 61:809-15. [PMID: 24824283 DOI: 10.1016/j.jhep.2014.05.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Revised: 05/01/2014] [Accepted: 05/05/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Liver grafts from hepatitis B surface antigen (HBsAg) positive donors could have potential to increase the donor pool. However, knowledge is extremely limited in this setting because currently available data are mostly from case reports. We aimed to assess the outcomes and experiences of liver transplantation from HBsAg positive donors in a single centre study. METHODS From January 2010 to February 2013, 42 adult patients underwent liver transplantation from HBsAg positive donors and 327 patients from HBsAg negative ones. The outcomes including complications and survival of two groups were compared and antiviral therapy retrospectively reviewed. RESULTS HBsAg positive liver grafts were more likely to be allocated to patients with hepatitis B (HBV)-related diseases. Post-transplant evaluation showed similar graft function regaining pace and no differences in complications such as primary non-function, acute rejection and biliary complications. Patient and graft survivals were comparable to that of HBsAg negative grafts. Furthermore, HBsAg persisted after transplant in all patients that received positive grafts. The donor HBV serum status determined the one of the recipient after transplantation. No HBV flare-ups were observed under antiviral therapy of oral nucleotide analogues, regardless of using hepatitis B immunoglobulin combination. CONCLUSIONS Utilization of HBsAg positive liver grafts seems not to increase postoperative morbidity and mortality. Therefore it is a safe way to expand the donor pool when no suitable donor is available. Our experience also suggests that hepatitis B immunoglobulin should be abandoned in recipients of HBsAg positive liver grafts, in whom HBV prophylaxis could be the only oral antiviral therapy.
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Affiliation(s)
- Songfeng Yu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Jun Yu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Wei Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Longyu Cheng
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Yufu Ye
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Lei Geng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Zhiyong Yu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Sheng Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Lihua Wu
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
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Rao W, Xie M, Yang T, Zhang JJ, Gao W, Deng YL, Zheng H, Pan C, Liu YH, Shen ZY. Risk factors for de novo hepatitis B infection in pediatric living donor liver transplantation. World J Gastroenterol 2014; 20:13159-13166. [PMID: 25278711 PMCID: PMC4177496 DOI: 10.3748/wjg.v20.i36.13159] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Revised: 05/12/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection. METHODS The clinical and laboratory data of children who underwent LDLT from June 2010 to September 2012 in First Center Hospital in Tianjin, China, were retrospectively included in the study. Intrahepatic HBV DNA in donors and recipients was quantified by real-time polymerase chain reaction using DNA extracted from formalin-fixed, paraffin-embedded tissues. RESULTS Between June 2010 to September 2012, 32 consecutive pediatric patients underwent LDLT in our institute. Thirty LDLT patients (13 girls and 17 boys) were followed up for a median of 15 mo, of whom 53.3% (16/30) were hepatitis B core antibody (HBcAb) positive and 36.7% (11/30) were hepatitis B surface antibody (HBsAb)/HBcAb positive before transplantation. Sixteen of the children received HBcAb-positive allografts, and 43.7% (7/16) of the grafts were found to be intrahepatic HBV DNA positive. De novo HBV infection developed in 16.1% (5/30) of the children within a median of 11 mo after transplantation. All five of the HBV-infected children had received HBcAb-positive allografts, four of which were intrahepatic HBV DNA positive. Two of the children developed de novo HBV infection despite the preoperative presence of both HBsAb and HBcAb CONCLUSION In pediatric recipients, positive intrahepatic HBV DNA in allografts could be a risk factor for de novo HBV infection from HBcAb-positive allografts. HBsAb/HBcAb positivity in pediatric LDLT patients before transplantation exhibited only weak effectiveness in protecting them against de novo HBV infection from HBcAb-positive allografts.
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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40
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Loggi E, Gamal N, Bihl F, Bernardi M, Andreone P. Adaptive response in hepatitis B virus infection. J Viral Hepat 2014; 21:305-313. [PMID: 24674098 DOI: 10.1111/jvh.12255] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Accepted: 03/06/2014] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) is a major cause of acute and chronic liver inflammation worldwide. The immune response against the virus represents a key factor in determining infection outcome, in terms of both viral clearance and the perpetuation of liver damage. Significant advances have recently been achieved regarding the functions of antiviral CD8+ T cells, leading to a better understanding of their abnormalities during chronic infection as well as the pathways to be manipulated to reverse the immune impairment of chronic infection. In this review, we aimed to analyse the patterns of adaptive immunity that develop during acute infection and the profiles in chronic infection. In addition to CD8+ T cells, which are the best-described subset to date, we reviewed and commented on the direct and indirect roles of CD4+ T cells and B cells.
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Affiliation(s)
- E Loggi
- Institute for Research in Biomedicine, Bellinzona, Switzerland; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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41
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Wang Z, Hisatake G, Yang L. Liver-specific deceased donor risk indices. Hepatol Res 2014; 44:159-64. [PMID: 24033790 DOI: 10.1111/hepr.12228] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Revised: 08/07/2013] [Accepted: 08/19/2013] [Indexed: 12/20/2022]
Abstract
In order to assess the quality of the donor liver, procuring surgeons should accurately evaluate not only general donor risk indices, such as donor age, causes of brain death and cold ischemic time, but also consider the specific donor risk indices. In this review, we focus on liver-specific deceased donor risk indices, including liver steatosis, anti-hepatitis B core (HBc) positive or hepatitis C virus (HCV) positive donors, hypernatremia and anatomical variations. Liver steatosis is strongly associated with poor graft function after liver transplantation. Liver with more than 40-50% macrosteatosis should not be used. However, at present the quantity of fatty livers lack accepted standards. The computerized image analysis programs should be used to automate the determination of fat content in liver biopsy specimens. Liver grafts from anti-HBc positive donors can be safely used, preferentially in hepatitis B surface antigen (HBsAg) positive or anti-HBc/anti-HBs positive recipients. HCV positive allografts free from fibrosis or severe inflammation are a safe option for HCV positive recipients. The procurement team should consider liver biopsy to evaluate these HCV positive allografts. Donor serum sodium over 150 mm may predict a higher rate of graft primary non-functions. Recently, however, some investigators reported the sodium level likely has little clinical impact on post-transplant liver function. The incidence of hepatic artery variations has been reported to be approximately 30%. To avoid injuries, it is very important to know and identify these variations with precision at the time of organ procurement.
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Affiliation(s)
- Zifa Wang
- Department of Transplant, California Pacific Medical Center, San Francisco, California, USA; Department of General Surgery, First Affiliated Hospital, Xinxiang Medical University, Weihui, China
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42
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Li Z, Hu Z, Xiang J, Zhou J, Yan S, Wu J, Zhou L, Zheng S. Use of hepatitis B surface antigen-positive grafts in liver transplantation: a matched analysis of the US National database. Liver Transpl 2014; 20:35-45. [PMID: 24142889 DOI: 10.1002/lt.23774] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2013] [Accepted: 09/30/2013] [Indexed: 12/27/2022]
Abstract
The scarcity of available donor organs is the key challenge in orthotopic liver transplantation (OLT). A viable way of expanding the donor pool is the use of liver grafts from hepatitis B surface antigen (HBsAg)-positive donors. The present study used the US Scientific Registry of Transplant Recipients database (1987-2010), and each of the 78 patients who underwent OLT with HBsAg-positive grafts was matched with 4 patients who received HBsAg-negative grafts by urgent status, donor sex, recipient sex, donor age, recipient age, transplant date, Model for End-Stage Liver Disease score, and warm ischemia time. The overall graft and patient survival rates were similar for recipients of HBsAg-positive grafts and matched controls: the 5-year graft survival rates were 66% and 64%, respectively (P = 0.95), and the 5-year patient survival rates were 71% and 71%, respectively (P = 0.87). A Cox proportional hazards regression analysis that was adjusted for other variables showed no impact of the donor HBsAg status on graft or patient survival. The use of hepatitis B immunoglobulin (HBIG) was independently associated with better posttransplant graft survival [hazard ratio (HR) = 0.23, 95% confidence interval (CI) = 0.06-0.81] and patient survival (HR = 0.16, 95% CI = 0.04-0.75) for recipients of HBsAg-positive grafts. In conclusion, the use of HBsAg-positive liver grafts did not reduce posttransplant graft or patient survival. Moreover, matching these donors to recipients treated with HBIG may improve safety.
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Affiliation(s)
- Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
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43
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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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Abstract
There is an extremely high burden of liver disease owing to viral hepatitis B (HBV); about 2 billion people are infected and 350 million are chronic carriers of HBV worldwide. More effective medical therapy and liver transplantation are available for those with advancing disease. The interaction between the host immune system and the virus influences the rate of development of advanced liver disease or hepatocellular carcinoma (HCC); treatment that successfully reduces viral replication of HBV also reduces the incidence of development of advanced liver disease and HCC. Liver transplantation for HBV has yielded favorable outcomes since the institution of hepatitis B immune globulin and antiviral therapy. The ability to stabilize and rescue some patients with advanced liver disease owing to HBV has resulted in a changing demographic for patients with HBV undergoing liver transplantation. The main indications for transplant owing to HBV are now acute liver failure (both acute and acute reactivation on the background of chronic HBV) and HCC. Use of donor organs exposed to HBV with positive HBV core antibody is now routinely accepted for its good outcomes, and in selected cases with active HBV, HBV surface antigen-positive donors may be utilized to further expand the donor pool. Another indication for antiviral therapy for HBV is to reduce the risk of reactivation of latent virus in some patients previously exposed to HBV who are being treated with chemotherapy. Health care providers with HBV infection have an obligation to appropriately treat or monitor their disease closely to reduce the risk of transmission of disease from provider to patient. In the future, universal vaccination will reduce the overall burden of HBV liver disease, but until then appropriate utilization of available medical and surgical therapeutic options gives excellent clinical outcomes.
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Affiliation(s)
- M L Schilsky
- Department of Medicine and Surgery, Section of Digestive Diseases and Section of Transplantation and Immunology, Yale University School of Medicine, New Haven, Connecticut, USA.
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45
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Choi Y, Choi JY, Yi NJ, Lee K, Mori S, Hong G, Kim H, Park MS, Yoo T, Suh SW, Lee HW, Lee KW, Suh KS. Liver transplantation for HBsAg-positive recipients using grafts from HBsAg-positive deceased donors. Transpl Int 2013; 26:1173-83. [PMID: 24131436 DOI: 10.1111/tri.12177] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Revised: 06/23/2013] [Accepted: 08/11/2013] [Indexed: 12/27/2022]
Abstract
This study reports our experience using deceased donor liver grafts from HBsAg-positive donors. We performed eight cases of liver transplantation (LT) using grafts from deceased HBsAg-positive donors between November 2005 and October 2010. The median age of donors was 48 years (range: 26-64). HBV DNA in the serum of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative. Preoperative laboratory and liver biopsy samples revealed the absence of definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive preoperatively except one patient with HBsAg(-) status post previous LT for HBV related liver cirrhosis. The median age was 60 years (range: 46-76) at LT. Post-LT antiviral management consisted of hepatitis B immunoglobulin and antiviral nucleos(t)ide analogues. The median follow-up period was 25.5 months (range: 14-82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA disappearance postoperatively. Three recipients died of HBV-unrelated causes. The remaining five recipients were stable with normal liver function and no marked pathologic changes on follow-up biopsies. This experience shows that LT using grafts from deceased HBsAg-positive donors is feasible, and may represent a valuable expansion of the pool of organ donors with appropriate antiviral management and monitoring.
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Affiliation(s)
- YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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46
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Freeman RB. Deceased donor risk factors influencing liver transplant outcome. Transpl Int 2013; 26:463-70. [PMID: 23414069 DOI: 10.1111/tri.12071] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2012] [Revised: 11/27/2012] [Accepted: 01/07/2013] [Indexed: 12/14/2022]
Abstract
As the pressure for providing liver transplantation to more and more candidates increases, transplant programs have begun to consider deceased donor characteristics that were previously considered unacceptable. With this trend, attention has focused on better defining those donor factors that can impact the outcome of liver transplantation. This review examines deceased donor factors that have been associated with patient or graft survival as well as delayed graft function and other liver transplant results.
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Affiliation(s)
- Richard B Freeman
- Department of Surgery, Dartmouth Hitchcock Medical Center, Geisel School of Medicine a Dartmouth, 1 Medical Center Drive, Lebanon, NH 03756, USA.
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47
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Hepatitis B-positive donors in renal transplantation: increasing the deceased donor pool. Transplantation 2012; 94:205-10. [PMID: 22430067 DOI: 10.1097/tp.0b013e31824e3db4] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
It is reasonable to transplant HbsAg-positive kidneys into recipients who are themselves hepatitis B surface antigen (HbsAg) positive with appropriate antiviral treatment after transplantation. Although there are limited data regarding the hepatitis B virus (HBV) transmission risk following transplantation of kidneys from HbsAg-positive donors into HBV-immune recipients, current literature suggests that the risk of chronic infection in the recipient can be prevented by using antiviral agents or by boosting protective anti-HBs titers. The risk of chronic HBV infection following transplantation of kidneys from HbsAg-positive donors for HBV-naive recipients is high but can be minimized by administering lifelong antiviral therapy. Such a policy could be considered in an urgent situation. The most cost-effective antiviral prophylaxis strategy is lifelong lamivudine. Kidneys from HBsAg neg/anti-HBcore pos recipients are associated with a low rate of chronic HBV infection in the recipient and therefore can no longer be regarded as marginal donors. Booster vaccination to achieve protective HBV immunity or lifelong lamivudine therapy should prevent posttransplant HBV infection. Hence, we believe that strategies allowing transplantation of kidneys from donors with HBV can be undertaken safely with careful selection and matching of donors and recipients increasing access to kidney transplantation.
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48
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Saidi RF, Jabbour N, Shah SA, Li YF, Bozorgzadeh A. Liver transplantation from hepatitis B surface antigen-positive donors. Transplant Proc 2012; 45:279-80. [PMID: 23267801 DOI: 10.1016/j.transproceed.2012.05.077] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2012] [Accepted: 05/30/2012] [Indexed: 12/16/2022]
Abstract
One possibility to increase the organ pool is to use grafts from hepatitis B virus (HBV) surface antigen (HBsAg)-positive donors, but few data are currently available in this setting. Herein, we reviewed the outcome of 92 liver transplantations using allografts from HBsAg-positive donors in the United States (1990-2009). They had experienced HBV-related (n = 68) or HBV-unrelated disease (n = 24). There was no difference between patients who received HBsAg-positive versus HBsAg-negative allografts based on age, Model for End-stage Liver Disease (MELD) score, length of stay, wait time, and donor risk index. HBsAg-positive allografts were more likely to be imported and used in MELD exceptional cases. Allograft and patient survival were comparable between the two groups. HBsAg-positive allografts deserve consideration when no other organ is available in a suitable waiting time in the present era of highly effective antiviral therapy.
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Affiliation(s)
- R F Saidi
- Division of Organ Transplantation, Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
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49
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Rowe IA, Wilde JT, Mutimer D. Is it justifiable to transplant infected livers into haemophilia recipients? Haemophilia 2012; 18:685-7. [PMID: 22925332 DOI: 10.1111/j.1365-2516.2012.02801.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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50
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Kosieradzki M, Lisik W, Rowiński W, Małkowski P. Progress in abdominal organ transplantation. Med Sci Monit 2012; 17:RA282-91. [PMID: 22129915 PMCID: PMC3628136 DOI: 10.12659/msm.882119] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The excellent results of vascularized organ transplantation have resulted in an increasing number of end-stage organ failure patients seeking such treatment. The results of organ transplantation depend on a number of factors – the quality of the donor (and an organ), living vs. deceased donation, magnitude of ischemic injury (and its prevention), and recipient-dependent factors. Ischemia/reperfusion injury in organ transplantation is a multifactorial process, which may lead to delayed graft function. In addition, surgical and preservation techniques, type of immunosuppressive regimens, complications after transplantation and post-transplant management may also have a significant impact on short- and long-term results of transplantation. In this paper we describe advances in transplantation in recent years, with particular emphasis on kidney, liver, intestines, whole pancreas and pancreatic islets.
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Affiliation(s)
- Maciej Kosieradzki
- Department of General Surgery and Transplantology, Medical University of Warsaw, Warsaw, Poland
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