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1
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Safi K, Pawlicka AJ, Pradhan B, Sobieraj J, Zhylko A, Struga M, Grąt M, Chrzanowska A. Perspectives and Tools in Liver Graft Assessment: A Transformative Era in Liver Transplantation. Biomedicines 2025; 13:494. [PMID: 40002907 PMCID: PMC11852418 DOI: 10.3390/biomedicines13020494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 02/07/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain-such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease-technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation.
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Affiliation(s)
- Kawthar Safi
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland; (K.S.)
| | | | - Bhaskar Pradhan
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland; (K.S.)
| | - Jan Sobieraj
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Andriy Zhylko
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland
| | - Marta Struga
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland; (K.S.)
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland
| | - Alicja Chrzanowska
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland; (K.S.)
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2
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Zingg SCW, Lemon K. Donor Viral Hepatitis and Liver Transplantation. Surg Clin North Am 2024; 104:67-77. [PMID: 37953041 DOI: 10.1016/j.suc.2023.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Despite increasing numbers of organ transplants completed each year, there continues to be an organ shortage in liver transplantation. This has led to the utilization of previously discarded or "marginal" allografts, such as those from donors with hepatitis C virus (HCV) or hepatitis B virus (HBV). The advent of direct acting antivirals and nucleos(t)ide analogs has allowed these allografts to be safely transplanted regardless of the recipients' hepatitis status with comparable graft and patient survival. Recent advances have even allowed usage of actively viremic donors with similar graft and patient outcomes. This article presents an overview of the use of HCV positive and HBV positive allografts.
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Affiliation(s)
- Sara-Catherine Whitney Zingg
- Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA. https://twitter.com/transplant_u
| | - Kristina Lemon
- Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA; Division of Transplantation, University of Cincinnati School of Mediicne, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA.
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3
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Puri P, Kumar A, Qaleem M. Donor Evaluation Protocol for Live and Deceased Donors. J Clin Exp Hepatol 2024; 14:101217. [PMID: 38076356 PMCID: PMC10709134 DOI: 10.1016/j.jceh.2023.07.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 07/09/2023] [Indexed: 01/05/2025] Open
Abstract
Donor evaluation is a critical step before proceeding with liver transplantation (LT) in both deceased donor LT (DDLT) and living donor LT (LDLT). A good, healthy graft is necessary for the success of the transplantation. Other issues in selecting a donor include the transmission of infections and malignancies from the donor. Because of the scarcity of cadaver organs, an increasing number of extended-criteria donors, or 'marginal donors', are being utilized. LDLT also has potential risks to the donor, and donor safety needs to be kept in mind before proceeding with LT. The current review highlights the factors to be considered during donor evaluation for living and deceased donors before LT.
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, Fortis Escorts Hospital, New Delhi-110025, India
| | - Abhinav Kumar
- Fortis Escorts Liver and Digestive Diseases Institute, Fortis Escorts Hospital, New Delhi-110025, India
| | - Mohd Qaleem
- Department of Liver Transplantation, Minimal Access & GI Surgery, Fortis Escorts Hospital, New Delhi-110025, India
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4
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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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5
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Frye CC, Gauthier JM, Bery A, Gerull WD, Morkan DB, Liu J, Harrison MS, Terada Y, Van Zanden JE, Marklin G, Pasque MK, Nava RG, Meyers BF, Patterson GA, Kozower BD, Hachem RR, Byers DE, Witt CA, Kulkarni H, Kreisel D, Puri V. Donor management using a specialized donor care facility is associated with higher organ utilization from drug overdose donors. Clin Transplant 2021; 35:e14178. [PMID: 33274521 PMCID: PMC8248520 DOI: 10.1111/ctr.14178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 11/19/2020] [Accepted: 11/20/2020] [Indexed: 12/27/2022]
Abstract
Drug overdoses have tripled in the United States over the last two decades. With the increasing demand for donor organs, one potential consequence of the opioid epidemic may be an increase in suitable donor organs. Unfortunately, organs from donors dying of drug overdose have poorer utilization rates than other groups of brain-dead donors, largely due to physician and recipient concerns about viral disease transmission. During the study period of 2011 to 2016, drug overdose donors (DODs) account for an increasingly greater proportion of the national donor pool. We show that a novel model of donor care, known as specialized donor care facility (SDCF), is associated with an increase in organ utilization from DODs compared to the conventional model of hospital-based donor care. This is likely related to the close relationship of the SDCF with the transplant centers, leading to improved communication and highly efficient donor care.
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Affiliation(s)
- CC Frye
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - JM Gauthier
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - A Bery
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, Saint Louis, MO
| | - WD Gerull
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - DB Morkan
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - J Liu
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, MO
| | - MS Harrison
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - Y Terada
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - JE Van Zanden
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - G Marklin
- Mid-America Transplant, Washington University School of Medicine, Saint Louis, MO
| | - MK Pasque
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - RG Nava
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - BF Meyers
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - GA Patterson
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - BD Kozower
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
| | - RR Hachem
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, MO
| | - DE Byers
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, MO
| | - CA Witt
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, MO
| | - H Kulkarni
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, MO
| | - D Kreisel
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
- Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO
| | - V Puri
- Division of Cardiothoracic Surgery, Washington University School of Medicine, Saint Louis, MO
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6
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Paradigm Shift in Utilization of Livers from Hepatitis C-Viremic Donors into Hepatitis C Virus-Negative Patients. Clin Liver Dis 2021; 25:195-207. [PMID: 33978579 DOI: 10.1016/j.cld.2020.08.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Despite record-breaking numbers of liver transplants (LTs) performed in the United States in each of the last 7 years, many patients remain on the wait list as the demand for LT continues to exceed the supply of available donors. The emergence of highly effective and well-tolerated direct-acting antiviral therapy has transformed the clinical course and management of hepatitis C virus (HCV) in both the pretransplant and posttransplant setting. Historically, donor livers infected with HCV were either transplanted into patients already infected with HCV or discarded.
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7
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Bethea E, Arvind A, Gustafson J, Andersson K, Pratt D, Bhan I, Thiim M, Corey K, Bloom P, Markmann J, Yeh H, Elias N, Kimura S, Dageforde LA, Cuenca A, Kawai T, Safa K, Williams W, Gilligan H, Sise M, Fishman J, Kotton C, Kim A, Marks C, Shao S, Cote M, Irwin L, Myoung P, Chung RT. Immediate administration of antiviral therapy after transplantation of hepatitis C-infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant 2020; 20:1619-1628. [PMID: 31887236 PMCID: PMC8005111 DOI: 10.1111/ajt.15768] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 12/04/2019] [Accepted: 12/22/2019] [Indexed: 01/25/2023]
Abstract
The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which 14 HCV-negative patients underwent successful liver transplantation from HCV-positive donors. Nine patients received viremic (nucleic acid testing [NAT]-positive) livers and started a 12-week course of oral glecaprevir-pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody-positive nonviremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.
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Affiliation(s)
- Emily Bethea
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Ashwini Arvind
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Jenna Gustafson
- Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Karin Andersson
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Daniel Pratt
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Irun Bhan
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Michael Thiim
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Kathleen Corey
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Patricia Bloom
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Jim Markmann
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Heidi Yeh
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Nahel Elias
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Shoko Kimura
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Leigh Anne Dageforde
- Harvard Medical School, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Alex Cuenca
- Harvard Medical School, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Tatsuo Kawai
- Harvard Medical School, Boston, Massachusetts,Transplant Surgery Division, Massachusetts General Hospital, Boston Massachusetts
| | - Kassem Safa
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Winfred Williams
- Harvard Medical School, Boston, Massachusetts,Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Hannah Gilligan
- Harvard Medical School, Boston, Massachusetts,Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Meghan Sise
- Harvard Medical School, Boston, Massachusetts,Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Jay Fishman
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Camille Kotton
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Arthur Kim
- Harvard Medical School, Boston, Massachusetts,Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Christin Marks
- Harvard Medical School, Boston, Massachusetts,Massachusetts General Hospital Division of Pharmacy, Boston Massachusetts
| | - Sarah Shao
- Massachusetts General Hospital Transplant Center, Boston, Massachusetts,Massachusetts General Hospital Division of Pharmacy, Boston Massachusetts
| | - Mariesa Cote
- Massachusetts General Hospital Division of Pharmacy, Boston Massachusetts
| | - Linda Irwin
- Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Paul Myoung
- Massachusetts General Hospital Transplant Center, Boston, Massachusetts
| | - Raymond T. Chung
- Harvard Medical School, Boston, Massachusetts,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts,Massachusetts General Hospital Transplant Center, Boston, Massachusetts
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8
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Abstract
INTRODUCTION The recent availability of highly effective hepatitis C medications, with a cure rate approaching 100%, has created a wide range of questions and uncertainties. AREAS COVERED The most recent data around hepatitis C virus (HCV) elimination will be reviewed. In addition, the impact of HCV cure or sustained virologic response (SVR) on the risk for hepatocellular carcinoma (HCC) development will be discussed. Although the terms 'SVR' and 'cure' are used interchangeably, there are little data to support that they are actually the same. In this review, we will shed some light on the status of HCV vaccine development, obstacles, and published experience. Finally, in the face of decreasing HCV patients needing transplantation, and increasing available organs from donors infected with HCV, the question is that, is it possible to transplant an organ infected with HCV to a patient who is not infected? The pros and cons of transplanting HCV-positive organs to HCV-negative recipients will be discussed. EXPERT OPINION Although the new advances in HCV treatment have solved many problems, it created several new issues which the medical community has to deal with and which will likely remain in the near future.
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Affiliation(s)
- Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, AL, USA
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9
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Ting PS, Hamilton JP, Gurakar A, Urrunaga NH, Ma M, Glorioso J, King E, Toman LP, Wesson R, Garonzik-Wang J, Ottmann S, Philosophe B, Sulkowski M, Cameron AM, Durand CM, Chen PH. Hepatitis C-positive donor liver transplantation for hepatitis C seronegative recipients. Transpl Infect Dis 2019; 21:e13194. [PMID: 31609520 DOI: 10.1111/tid.13194] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 10/06/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The opioid crisis has led to an increase in hepatitis C virus-positive donors in the past decade. Whereas historically hepatitis C seropositive organs were routinely discarded, the advent of direct-acting antiviral agents has notably expanded the utilization of organs from donors with hepatitis C. There has been growing experience with liver transplantation (LT) from hepatitis C seropositive donors to hepatitis C seropositive recipients. However, data remain limited on LT from hepatitis C seropositive or hepatitis C ribonucleic acid positive donors to hepatitis C seronegative recipients. METHODS We performed a retrospective study of 26 hepatitis C seronegative recipients who received hepatitis C seropositive donor livers followed by preemptive antiviral therapy with direct-acting antiviral treatment at the Johns Hopkins Hospital Comprehensive Transplant Center from January 1, 2017, to August 31, 2019. RESULTS Twenty-five of the 26 recipients are alive with proper graft function; 20 of them received livers from hepatitis C nucleic acid testing positive donors. All 12 recipients who completed their direct-acting antiviral courses and have reached sufficient follow-up for sustained virologic response have achieved sustained virologic response. Nine of our recipients have either completed direct-acting antiviral treatment without sufficient follow-up time for sustained virologic response or are undergoing direct-acting antiviral treatment. One patient is awaiting antiviral treatment initiation pending insurance approval. Of note, 11 of 12 patients with sustained virologic response received a hepatitis C nucleic acid testing positive donor liver. CONCLUSION Hepatitis C seronegative patients who receive a hepatitis C seropositive or hepatitis C nucleic acid testing positive liver allograft can enjoy good short-term outcomes with hepatitis C cure following direct-acting antiviral treatment.
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Affiliation(s)
- Peng-Sheng Ting
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - James Peter Hamilton
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Nathalie H Urrunaga
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Michelle Ma
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jaime Glorioso
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elizabeth King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lindsey P Toman
- Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Russell Wesson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Shane Ottmann
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Benjamin Philosophe
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mark Sulkowski
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Andrew M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Christine M Durand
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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10
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Recent advances in liver transplantation for cancer: The future of transplant oncology. JHEP Rep 2019; 1:377-391. [PMID: 32039389 PMCID: PMC7005652 DOI: 10.1016/j.jhepr.2019.07.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 07/15/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is widely indicated as a curative treatment for selected patients with hepatocellular carcinoma. However, with recent therapeutic advances, as well as efforts to increase the donor pool, liver transplantation has been carefully expanded to patients with other primary or secondary malignancies in the liver. Cholangiocarcinoma, colorectal and neuroendocrine liver metastases, and hepatic epithelioid haemangioendothelioma are amongst the most relevant new indications. In this review we discuss the fundamental concepts of this ambitious undertaking, as well as the newest indications for liver transplantation, with a special focus on future perspectives within the recently established concept of transplant oncology.
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11
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Kwong AJ, Wall A, Melcher M, Wang U, Ahmed A, Subramanian A, Kwo PY. Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors. Am J Transplant 2019; 19:1380-1387. [PMID: 30378723 PMCID: PMC6663314 DOI: 10.1111/ajt.15162] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 10/15/2018] [Accepted: 10/17/2018] [Indexed: 01/25/2023]
Abstract
In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.
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Affiliation(s)
- Allison J. Kwong
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
- Division of Gastroenterology, University of California, San Francisco, CA
| | - Anji Wall
- Department of Surgery, Stanford University, Stanford, CA
- Division of Transplant Surgery, Baylor University Medical Center, Dallas, TX
| | - Marc Melcher
- Department of Surgery, Stanford University, Stanford, CA
| | - Uerica Wang
- Department of Pharmacy, Stanford Hospital and Clinics, Stanford, CA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| | | | - Paul Y. Kwo
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
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12
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Use of Hepatitis C-Positive Liver Grafts in Hepatitis C-Negative Recipients. Dig Dis Sci 2019; 64:1110-1118. [PMID: 30560331 DOI: 10.1007/s10620-018-5404-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 11/27/2018] [Indexed: 12/18/2022]
Abstract
As the demand for liver transplantation continues to rise, the scarcity of liver donor grafts has led to the use of extended criteria grafts for liver transplantation in select group of patients. Hepatitis C-seropositive liver grafts have been used primarily in hepatitis C-positive recipients, with studies showing non-inferior outcomes when compared to hepatitis C-negative grafts. Studies suggest that hepatitis C serology status of the donor liver does not influence the patient or graft outcomes in the recipient. These results advocate for offering hepatitis C-positive grafts to all patients awaiting liver transplantation regardless of their hepatitis C status. However, some concerns persist regarding the ethics of potentially introducing a new infection into a patient that could progress to chronic liver disease following liver transplantation. The recent approval of direct-acting antiviral therapy offers a solution to this dilemma, as it has changed the landscape of hepatitis C management by making it a curable disease. In this review, we shall discuss the current evidence regarding the use of hepatitis C-seropositive donor grafts in hepatitis C-positive and hepatitis C-negative patients.
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13
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Abstract
Donor-derived infections are defined as any infection present in the donor that is transmitted to 1 or more recipients. Donor-derived infections can be categorized into 2 groups: "expected" and "unexpected" infections. Expected transmissions occur when the donor is known to have an infection, such as positive serology for cytomegalovirus, Epstein Barr virus, or hepatitis B core antibody, at the time of donation. Unexpected transmissions occur when a donor has no known infection before donation, but 1 or more transplant recipients develop an infection derived from the common donor. Unexpected infections are estimated to occur in far less than 1% of solid organ transplant recipients. We will review the epidemiology, risk factors, and approaches to prevention and management of donor-derived viral infectious disease transmission in liver transplantation.
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14
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Te H, Doucette K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant 2019; 33:e13514. [DOI: 10.1111/ctr.13514] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 02/12/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Helen Te
- Center for Liver Diseases, Section of Gastroenterology, Hepatology and Nutrition University of Chicago Medicine Chicago Illinois
| | - Karen Doucette
- Division of Infectious Diseases University of Alberta Edmonton Alberta Canada
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15
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Saab S, Kardashian A, Saggi S, Choi G, Agopian V, Tong MJ. Use of hepatitis C-positive grafts in hepatitis C-negative liver transplant recipients is cost effective. Clin Transplant 2018; 32:e13383. [PMID: 30129981 DOI: 10.1111/ctr.13383] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 07/02/2018] [Accepted: 08/16/2018] [Indexed: 01/18/2023]
Abstract
BACKGROUND The number of patients needing liver transplantation (LT) exceeds the number of available allografts. The current opioid epidemic in this country has increased the number of potential donors infected with hepatitis C (HCV). METHODS We assessed the incremental cost-effectiveness ratio (ICER) by comparing the costs and number of liver transplants performed using HCV-positive and HCV-negative grafts into patients without HCV infection in a decision analysis model with a 1-year time horizon. RESULTS The use of HCV-positive grafts was found to have an ICER below $50 000 across all MELD scores. Using our baseline cohort with a model for end-stage liver disease (MELD) score of 15-22, the ICER was $21 233/additional LT performed. As the MELD scores increased, the ICER decreased. Above a MELD score of 23, the use of HCV-positive grafts became cost saving (-$115 419). Our model was robust to all variables tested in the sensitivity analyses, except drug costs. CONCLUSION The results of our decision analysis model highlight the potential pharmacoeconomic benefit of utilizing HCV-positive grafts in LT candidates who are not infected with HCV. The use of HCV-positive grafts is at least cost effective and even cost saving in patients with MELD scores above 23.
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Affiliation(s)
- Sammy Saab
- Department of Medicine, University of California, Los Angeles, California.,Department of Surgery, University of California, Los Angeles, California
| | - Ani Kardashian
- Department of Medicine, University of California, Los Angeles, California
| | - Satvir Saggi
- Department of Surgery, University of California, Los Angeles, California
| | - Gina Choi
- Department of Medicine, University of California, Los Angeles, California.,Department of Surgery, University of California, Los Angeles, California
| | - Vatche Agopian
- Department of Surgery, University of California, Los Angeles, California
| | - Myron J Tong
- Department of Surgery, University of California, Los Angeles, California
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16
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Somerville L, Doucette K. Hepatitis C: Current Controversies and Future Potential in Solid Organ Transplantation. Curr Infect Dis Rep 2018; 20:18. [PMID: 29789956 DOI: 10.1007/s11908-018-0625-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE OF REVIEW To highlight the changing landscape of hepatitis C virus (HCV) infection in the context of organ transplantation. This focuses on areas of controversy and future potential in the era of highly effective direct-acting antiviral (DAA) agents. RECENT FINDINGS Since the advent of safe and highly effective DAA therapy, HCV infection is now curable in virtually all cases, including organ transplant recipients. Excellent drug tolerability and safety combined with high cure rates across all organ groups means that HCV is no longer a barrier to transplantation or its outcomes. Mounting data demonstrate the safety of using organs from HCV-infected donors with subsequent treatment of HCV in the recipient and a potential to expand the donor pool. Historical data demonstrating inferior survival in transplant recipients with HCV is of limited relevance in the DAA era. Virtually all transplant recipients with HCV infection can be cured, while early data also suggest excellent outcomes in recipients of organs from HCV viremic donors. The optimal timing of HCV therapy in relation to transplantation and the optimal use of organs from HCV viremic donors remain areas of controversy and ongoing research efforts.
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Affiliation(s)
- Lucy Somerville
- Department of Medicine, Division of Infectious Diseases, University of Alberta, CSB 1-139, 11350 83 Avenue, Edmonton, AB, T6G 2G3, Canada
| | - Karen Doucette
- Department of Medicine, Division of Infectious Diseases, University of Alberta, CSB 1-139, 11350 83 Avenue, Edmonton, AB, T6G 2G3, Canada.
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17
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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18
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Levitsky J, Formica RN, Bloom RD, Charlton M, Curry M, Friedewald J, Friedman J, Goldberg D, Hall S, Ison M, Kaiser T, Klassen D, Klintmalm G, Kobashigawa J, Liapakis A, O'Conner K, Reese P, Stewart D, Terrault N, Theodoropoulos N, Trotter J, Verna E, Volk M. The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation. Am J Transplant 2017; 17:2790-2802. [PMID: 28556422 DOI: 10.1111/ajt.14381] [Citation(s) in RCA: 254] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 05/12/2017] [Accepted: 05/18/2017] [Indexed: 01/25/2023]
Abstract
The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.
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Affiliation(s)
| | | | - R D Bloom
- University of Pennsylvania, Philadelphia, PA
| | - M Charlton
- Intermountain Medical Center, Salt Lake City, UT
| | - M Curry
- Beth Israel Deaconess Medical Center, Boston, MA
| | | | - J Friedman
- Optum Population Health Solutions, Minneapolis, MN
| | - D Goldberg
- University of Pennsylvania, Philadelphia, PA
| | - S Hall
- Baylor University Medical Center, Dallas, TX
| | - M Ison
- Northwestern University, Chicago, IL
| | - T Kaiser
- University of Cincinnati, Cincinnati, OH
| | - D Klassen
- United Network of Organ Sharing, Richmond, VA
| | - G Klintmalm
- Baylor University Medical Center, Dallas, TX
| | | | | | | | - P Reese
- University of Pennsylvania, Philadelphia, PA
| | - D Stewart
- United Network of Organ Sharing, Richmond, VA
| | - N Terrault
- University of California San Francisco, San Francisco, CA
| | | | - J Trotter
- Baylor University Medical Center, Dallas, TX
| | - E Verna
- Columbia University, New York, NY
| | - M Volk
- Loma Linda University, San Diego, CA
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19
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ELITA consensus statements on the use of DAAs in liver transplant candidates and recipients. J Hepatol 2017; 67:585-602. [PMID: 28323126 DOI: 10.1016/j.jhep.2017.03.006] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 03/01/2017] [Accepted: 03/09/2017] [Indexed: 02/07/2023]
Abstract
The advent of safe and highly effective direct-acting antiviral agents (DAAs) has had huge implications for the hepatitis C virus (HCV) transplant field, and changed our management of both patients on the waiting list and those with HCV graft re-infection after liver transplantation (LT). When treating HCV infection before LT, HCV re-infection of the graft can be prevented in nearly all patients. In addition, some candidates show a remarkable clinical improvement and may be delisted. Alternatively, HCV infection can be treated post-LT either soon after the transplant, taking advantage of the removal of the infected native liver, or at the time of disease recurrence, as was carried out in the past. In either case, some DAAs have a limited use because of their drug to drug interactions with various immunosuppressants as well as the many other drugs liver transplant recipients are often prescribed. In addition, some DAAs should be avoided in case of severe renal failure, which is not an unusual complication after LT. The present document provides a series of consensus statements on the LT issues that have not been extensively addressed previously. These statements have been developed to support physicians and other stakeholders in charge of LT candidates and recipients when deciding to treat HCV, especially in difficult situations.
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20
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Salazar J, Saxena V, Kahn JG, Roberts JP, Mehta N, Volk M, Lai JC. Cost-Effectiveness of Direct-Acting Antiviral Treatment in Hepatitis C-Infected Liver Transplant Candidates With Compensated Cirrhosis and Hepatocellular Carcinoma. Transplantation 2017; 101:1001-1008. [PMID: 27926593 PMCID: PMC5403544 DOI: 10.1097/tp.0000000000001605] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV)(+) donors represent an effective strategy to increase liver donor availability to HCV-infected recipients. However, many HCV(+) transplant candidates are now receiving treatment with direct-acting anti-viral (DAA) agents that lower the risk of posttransplant HCV recurrence but could make the patient ineligible for HCV(+) livers. METHODS We compared pretransplant DAA treatment versus deferred DAA treatment using a cost-effectiveness decision analysis model to estimate incremental cost-effectiveness ratios (cost per quality-adjusted life year gained) from the societal perspective across a range of HCV(+) liver availability rates. For practical considerations, the population modeled was restricted to well-compensated HCV(+) cirrhotics listed for liver transplantation with hepatocellular carcinoma MELD exception points. RESULTS Under base case conditions, the deferred DAA treatment strategy was found to be the "dominant" strategy. That is, it provided superior health outcomes at cost savings compared to the pretransplant DAA treatment strategy. The pretransplant DAA treatment strategy trended towards cost-effectiveness as HCV(+) donor liver availability declined. However, only in 1 scenario that was highly optimized for favorable outcomes in the pretransplant DAA treatment arm (low availability of HCV(+) organs, low cost of DAA treatment, high cost of HCV recurrence) was the incremental cost-effectiveness ratio associated with HCV DAA treatment before transplant less than US $150 000/quality-adjusted life-year gained. CONCLUSIONS Deferring HCV treatment until after liver transplant and maintaining access to the expanded pool of HCV(+) donors appears to be the most cost-effective strategy for well-compensated HCV-infected cirrhotics listed for liver transplantation with hepatocellular carcinoma, even in geographic areas of relatively low HCV(+) donor availability.
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Affiliation(s)
- James Salazar
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
| | - Varun Saxena
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
| | - James G. Kahn
- Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, San Francisco, California, United States of America
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, California, United States of America
| | - Neil Mehta
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
| | - Michael Volk
- Division of Gastroenterology and Hepatology, Transplantation Institute, Loma Linda University Health, Loma Linda, California, United States of America
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
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21
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Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol 2017; 14:203-217. [PMID: 28053342 DOI: 10.1038/nrgastro.2016.193] [Citation(s) in RCA: 322] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver transplantation for hepatocellular carcinoma (HCC) is the best treatment option for patients with early-stage tumours and accounts for ∼20-40% of all liver transplantations performed at most centres worldwide. The Milan criteria are the most common criteria to select patients with HCC for transplantation but they can be seen as too restrictive. Several proposals have been made for a moderate expansion of the criteria, which result in good outcomes but with an increase in the risk of tumour recurrence. In this Review, we provide a comprehensive overview of the outcomes after liver transplantation for HCC, focusing on tumour recurrence in terms of surveillance, prevention and treatment. Additionally, novel surgical techniques have been developed to increase the available pool of organs for liver transplantation (such as living donor liver transplantation, donation after circulatory death and split livers), but the effect of these techniques on patients with HCC is still under debate. Thus, we will describe these techniques and expose the benefits and disadvantages of each surgical approach. Finally, we will comment on the limitations of the current priority policies for liver transplantation and the need to further refine them to better serve the population.
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22
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Toniutto P, Zanetto A, Ferrarese A, Burra P. Current challenges and future directions for liver transplantation. Liver Int 2017; 37:317-327. [PMID: 27634369 DOI: 10.1111/liv.13255] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Accepted: 09/08/2016] [Indexed: 12/14/2022]
Abstract
Liver transplantation is an effective and widely used therapy for several patients with acute and chronic liver diseases. The discrepancy between the number of patients on the waiting list and available donors remains the key issue and is responsible for the high rate of waiting list mortality. The recent news is that the majority of patients with hepatitis C virus related liver disease will be cured by new antivirals therefore we should expect soon a reduction in the need of liver transplantation for these recipients. This review aims to highlight, in two different sections, the main open issues of liver transplantation concerning the current and future strategies to the best use of limited number of organs. The first section cover the strategies to increase the donor pool, discussing the use of older donors, split grafts, living donation and donation after cardiac death and mechanical perfusion systems to improve the preservation of organs before liver transplantation. Challenges in immunosuppressive therapy and operational tolerance induction will be evaluated as potential tools to increase the survival in liver transplant recipients and to reducing the need of re-transplantation. The second section is devoted to the evaluation of possible new indications to liver transplantation, where the availability of organs by implementing the strategies mentioned in the first section and the reduction in the number of waiting transplants for HCV disease is realized. Among these new potential indications for transplantation, the expansion of the Milan criteria for hepatocellular cancer is certainly the most open to question.
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Affiliation(s)
- Pierluigi Toniutto
- Department of Clinical Sciences Experimental and Clinical, Medical Liver Transplant Section, University of Udine, Udine, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padova, Italy
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padova, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padova, Italy
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23
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Burra P, De Martin E, Zanetto A, Senzolo M, Russo FP, Zanus G, Fagiuoli S. Hepatitis C virus and liver transplantation: where do we stand? Transpl Int 2016; 29:135-152. [PMID: 26199060 DOI: 10.1111/tri.12642] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 03/06/2015] [Accepted: 07/15/2015] [Indexed: 12/14/2022]
Abstract
The hepatitis C virus (HCV) infects more than 180 million people globally, with increasing incidence, especially in developing countries. HCV infection frequently progresses to liver cirrhosis leading to liver transplantation or death, and HCV recurrence still constitutes a major challenge for the transplant team. Antiviral therapy is the only available instrument to slow down this process, although its actual impact on liver histology, in responders and nonresponders, is still controversial. We are now facing a "new era" of direct antiviral agents that is already changing the approach to HCV burden both in the pre- and in the post-liver transplantation settings. Available data on sofosbuvir/ledipasvir and sofosbuvir/simeprevir in patients with decompensated cirrhosis sustain a SVR12 of 89% , but one-third of patients do not clinically improved. The sofosbuvir/ribavirin treatment in stable cirrhotic patients with HCC before liver transplantation is associated with 2% recurrence rate if liver transplantation is performed at least one month after undetectable HCV-RNA is achieved. The treatment of recurrence with the new antiviral drugs is associated with a SVR that ranges between 60 and 90%. In this review, we have focused on the evolution of antiviral therapy for HCV recurrence from the "old" interferon-based therapy to the "new" interferon-free regimens, highlighting useful information to aid the transplant hepatologist in the clinical practice.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Eleonora De Martin
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
- Centre Hepato-Biliaire Paul Brousse, Villejuif, France
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Giacomo Zanus
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
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24
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Coilly A, Samuel D. Pros and Cons: Usage of organs from donors infected with hepatitis C virus - Revision in the direct-acting antiviral era. J Hepatol 2016; 64:226-31. [PMID: 26375245 DOI: 10.1016/j.jhep.2015.09.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 08/26/2015] [Accepted: 09/04/2015] [Indexed: 12/12/2022]
Abstract
Should organs from hepatitis C antibody positive donors (HCVD+) be used for transplantation? Organ shortage forces transplant teams to use donors with extended criteria. The decision to transplant a HCVD+ graft is a balance between the risk of transmission of a virus that could lead to end-stage liver diseases and the benefit of access to transplantation, specifically in patients with life-threatening disease. The other issue is the impact of HCV-related liver fibrosis in the donor graft on the long-term outcome in the recipient. Thus, the use of HCVD+ demonstrated a shorter meantime on the waiting list in kidney transplantation. When a HCVD+ graft is transplanted, the risk of HCV transmission depends on; 1) the quality of screening of the donor; 2) the presence of viral replication in the donor at the time of transplantation and the ability to detect it; and 3) the HCV status of the recipient but also the type of transplanted organ. In liver transplantation, the use of HCVD+ graft is usually restricted to recipients with a chronic HCV infection. Several reports showed some competition between HCV donor and recipient strain without deleterious impact on graft and patient survival. Controversies are still pending regarding the quality of the graft and the progression of fibrosis. The recent approval of direct-acting antiviral agents (DAA) dramatically changes the landscape of HCV infection treatment. After transplantation, combinations of DAA show high efficacy and good safety profile. In the near future, extensive use of DAA should reduce the number of HCVD+ with a positive HCV RNA, limiting the risk of transmission but also the number of patients on waiting lists for a disease related to HCV.
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Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Univ. Paris-Sud, UMR-S 1193, Villejuif F-94800, France; Inserm, Unité 1193, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Univ. Paris-Sud, UMR-S 1193, Villejuif F-94800, France; Inserm, Unité 1193, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France.
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25
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Baleriola C, Webster AC, Rawlinson WD. Characterization and risk of blood-borne virus transmission in organ transplantation: what are the priorities? Future Virol 2014. [DOI: 10.2217/fvl.14.94] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
ABSTRACT Blood-borne virus transmission through organ transplantation, although rare, has been associated with severe complications in recipients. There are few data available to ascertain the risk of infection in organ transplantation for known and emerging pathogens, as most information comes from events of transmission, which are rare and not always well characterized. The balance between quality of life through organ transplantation and the risks of donor-derived infection can be improved through advances in donor screening, enhanced monitoring and a multidisciplinary approach to improving donor assessment and recipient biosurveillance. The involvement of investigators with clinical, laboratory, surveillance and policy expertise is critical to bridge research knowledge and clinical practice.
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Affiliation(s)
- Cristina Baleriola
- Department of Virology, South Eastern Area Laboratory Services, Prince of Wales Hospital, Randwick, NSW 2031, Australia
| | - Angela C Webster
- Centre for Transplant & Renal Research, Westmead Hospital, Westmead, NSW 2145, Australia
| | - William D Rawlinson
- South Eastern Area Laboratory Services, Prince of Wales Hospital, Randwick, NSW 2031, Australia
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26
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Pinna AD, Neri F, Ravaioli M. A bridge too far: We have overstepped the line for extended deceased donors. Liver Transpl 2014; 20 Suppl 2:S6-8. [PMID: 25219495 DOI: 10.1002/lt.24003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 09/12/2014] [Indexed: 01/12/2023]
Affiliation(s)
- Antonio D Pinna
- Department of General Surgery and Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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27
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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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Dumortier J, Boillot O, Scoazec JY. Natural history, treatment and prevention of hepatitis C recurrence after liver transplantation: Past, present and future. World J Gastroenterol 2014; 20:11069-11079. [PMID: 25170196 PMCID: PMC4145750 DOI: 10.3748/wjg.v20.i32.11069] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 03/07/2014] [Accepted: 06/23/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV)-related liver disease, including cirrhosis and hepatocellular carcinoma is the main indication for liver transplantation (LT) worldwide. Post-transplant HCV re-infection is almost universal and results in accelerated progression from acute hepatitis to chronic hepatitis, and liver cirrhosis. Comprehension and treatment of recurrent HCV infection after LT have been major issues for all transplant hepatologists and transplant surgeons for the last decades. The aim of this paper is to review the evolution of our knowledge on the natural history of HCV recurrence after LT, including risk factors for disease progression, and antiviral therapy. We will focus our attention on possible ways (present and future) to improve the final long-term results of LT for HCV-related liver disease.
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29
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Burra P, Fagiuoli S. Use of Anti-HCV Positive Grafts in Liver Transplantation. HEPATITIS C VIRUS AND LIVER TRANSPLANTATION 2014:107-116. [DOI: 10.1007/978-1-4614-8438-7_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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30
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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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31
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Takeichi T, Asonuma K, Yamamoto H, Ohya Y, Okumura K, Lee KJ, Inomata Y. Liver Transplant From an ABO-Incompatible and Hepatitis C Antibody-Positive but an HCV-RNA Negative Living Donor in a Familial Amyloid Polyneuropathy Patient. EXP CLIN TRANSPLANT 2013. [DOI: 10.6002/ect.2012.0158] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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32
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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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33
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Álvaro E, Abradelo M, Fuertes A, Manrique A, Colina F, Alegre C, Calvo J, García M, García-Sesma A, Cambra F, Sanabria R, Moreno E, Jimenez C. Liver transplantation from anti-hepatitis C virus-positive donors: our experience. Transplant Proc 2013; 44:1475-8. [PMID: 22841188 DOI: 10.1016/j.transproceed.2012.05.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
BACKGROUND Hepatitis C (HCV) is among the most common causes of end-stage liver disease worldwide. The donor shortage leads us to consider alternative organ sources such as HCV-positive donors. The outcomes of these transplants must be evaluated thoroughly since there is universal recurrence of disease among HCV-positive liver transplant recipients. METHODS From January 2005 to April 2011, we performed 143 liver transplants (OLT) to treat end-stage liver disease secondary to HCV infection. Thirteen patients (9,1%) received livers from HCV-positive donors. A control group consisted of 130 HCV-positive patients who underwent OLT during the same period with organs from HCV-negative donors. Donor HCV status was assessed by 2 tests: HCV antibodies and viral load. Not only recipient and graft survivals were analyzed, but also frequency, timing and severity of hepatitis recurrence. RESULTS Among 143 transplants performed in HCV-positive recipients during a 6-year period from January 1, 2005, to April 30, 2011, 9.1% of patients received an organ from an anti-HCV-positive donor, 72.7% of whom showed a negative viral load. The vast majority (80%) of our patients suffered hepatitis during their follow-up, 22.4% of which were severe cases. CONCLUSIONS No significant difference in patient or graft survival was observed between the 2 groups. A high percentage of grafts with initial positive serology for HCV showed no viral replication. Grafts from HCV-positive donors can be considered to be a safe, effective source for liver donation.
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Affiliation(s)
- E Álvaro
- Department of General and Digestive Surgery, Hospital Universitario 12 de Octubre.
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34
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Bertuzzo VR, Cescon M, Morelli MC, Di Gioia P, Tamè M, Lorenzini S, Andreone P, Ercolani G, Del Gaudio M, Ravaioli M, Cucchetti A, Dazzi A, D'Errico-Grigioni A, Pinna AD. Long-term antiviral treatment for recurrent hepatitis C after liver transplantation. Dig Liver Dis 2012; 44:861-867. [PMID: 22819767 DOI: 10.1016/j.dld.2012.06.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Revised: 06/05/2012] [Accepted: 06/13/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS The management of patients treated for hepatitis C recurrence after liver transplantation and not achieving virological response following treatment with interferon plus ribavirin is controversial. METHODS A retrospective analysis of the outcomes of 70 patients non-responders to antiviral treatment after liver transplantation was performed. Twenty-one patients (30.0%; Group A) were treated for ≤ 12 months and 49 (70.0%; Group B) for more than 12 months. RESULTS The 2 groups were comparable for main demographic, clinical and pathological variables. Median duration of antiviral treatment was 8.2 months in Group A and 33.4 months in Group B. No patient achieved a complete virological response. The 5-year patient hepatitis C-related survival rate was 49.2% in Group A and 88.3% in Group B (P=0.002), while the 5-year graft survival rate was 49.2% in Group A and 85.9% in Group B (P=0.007). The median yearly fibrosis progression rate was 1.21 per year in Group A and 0.40 per year in Group B (P=0.001). CONCLUSIONS Prolonged antiviral treatment showed an overall beneficial effect in transplanted patients with a recurrent hepatitis C infection and not responding to conventional therapy. The treatment should be continued as long as it is permitted, in order to improve clinical and histological outcomes.
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Affiliation(s)
- Valentina Rosa Bertuzzo
- Department of General Surgery and Organ Transplantation, University of Bologna, Bologna, Italy
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35
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Lai JC, O’Leary JG, Trotter JF, Verna EC, Brown RS, Stravitz RT, Duman JD, Forman LM, Terrault NA. Risk of advanced fibrosis with grafts from hepatitis C antibody-positive donors: a multicenter cohort study. Liver Transpl 2012; 18:532-8. [PMID: 22271671 PMCID: PMC3334393 DOI: 10.1002/lt.23396] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Over the last decade, the use of liver grafts from hepatitis C virus antibody-positive donors [HCV(+)Ds] has tripled in the United States. Although previous studies have demonstrated no association between an HCV(+)D status and graft loss, the effects of an HCV(+)D on histological outcomes are not well known. Hepatitis C virus (HCV)-infected recipients at 5 US centers (2002-2007) who survived more than 30 days with 1 or more posttransplant biopsy samples were included. Cox regression was used to examine the association between an HCV(+)D status and advanced fibrosis (stage 3/4 or higher). Ninety-nine of the 1206 patients (8%) received an HCV(+)D graft. Recipients of HCV(+)D grafts were older than recipients of hepatitis C virus antibody-negative donor [HCV(-)D] grafts (P = 0.03), but they were otherwise similar. HCV(+)D grafts were significantly lower in quality according to the donor risk index (P < 0.001). Advanced fibrosis occurred in 32% of HCV(+)D graft recipients and in 28% of HCV(-)D graft recipients (P = 0.39). The unadjusted 1- and 3-year rates of advanced fibrosis were significantly higher for HCV(+)D graft recipients (14% and 48%) versus HCV(-)D graft recipients (7% and 33%, P = 0.01). Transplantation with HCV(+)D grafts was associated with a 58% increased risk of advanced fibrosis [95% confidence interval (CI) = 1.05-2.36, P = 0.03]. However, in an analysis stratified by the mean donor age of 45 years, an HCV(+)D status was associated with advanced fibrosis only with donors >45 years old [hazard ratio (HR) = 1.76, 95% CI = 1.06-2.93, P = 0.03] and not with donors ≤45 years old (HR = 0.94, 95% CI = 0.47-1.87, P = 0.85). In conclusion, a careful consideration of the risks and benefits is needed with HCV(+)D grafts. Recipients of HCV(+)D grafts (especially from older donors) should undergo close monitoring for more rapidly progressive fibrosis. Studies are needed to determine whether early HCV therapy modifies this risk.
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Affiliation(s)
- Jennifer C. Lai
- Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA
| | - Jacqueline G. O’Leary
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - James F. Trotter
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Elizabeth C. Verna
- Division of Gastroenterology and Hepatology, New York Presbyterian Hospital-Columbia, New York, NY
| | - Robert S. Brown
- Division of Gastroenterology and Hepatology, New York Presbyterian Hospital-Columbia, New York, NY
| | - R. Todd Stravitz
- Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA
| | | | - Lisa M. Forman
- Division of Hepatology, University of Colorado, Denver, CO
| | - Norah A. Terrault
- Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA
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36
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Desai CJ. Selection and maintenance of a cadaver donor for liver transplantation. APOLLO MEDICINE 2012. [DOI: 10.1016/s0976-0016(12)60114-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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37
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Abdala E, Azevedo LSFD, Campos SV, Caramori ML, Costa SF, Strabelli TMV, Pierrotti LC, Varkulja GF, Almeida GMDD, Shikanai-Yasuda MA. Use of hepatitis C-positive donors in transplantation. Clinics (Sao Paulo) 2012; 67:517-9. [PMID: 22666799 PMCID: PMC3351258 DOI: 10.6061/clinics/2012(05)19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Affiliation(s)
- Edson Abdala
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Liver transplant Service, Brazil
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38
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Abstract
Several criteria are used to differentiate between standard and extended allograft donors. These criteria include deceased after cardiac death, advanced donor age, steatosis, previous malignancy in the donor, hepatitis C virus-positive allografts, human T-cell lymphotropic virus-positive allografts, active infections in the donor, high-risk donors, split liver transplantations, and living donor liver transplantations. Review of the literature can lead each practitioner to incorporate extended criteria donors into their transplant program, thereby individualizing the use of these allografts, increasing the donor pool, and decreasing overall waitlist mortality.
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Affiliation(s)
- Theresa R Harring
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
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39
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Hidaka M, Takatsuki M, Soyama A, Miyaaki H, Ichikawa T, Nakao K, Kanematsu T, Eguchi S. Living donor liver transplantation from a donor previously treated with interferon for hepatitis C virus: a case report. J Med Case Rep 2011; 5:276. [PMID: 21722402 PMCID: PMC3143103 DOI: 10.1186/1752-1947-5-276] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2010] [Accepted: 07/03/2011] [Indexed: 11/12/2022] Open
Abstract
Introduction Selecting a marginal donor in liver transplantation (LT) remains controversial but is necessary because of the small number of available donors. Case presentation A 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV) infection (serotype 2). She had received anti-viral therapy with interferon α-2b three times weekly for 24 weeks and had a sustained viral response (SVR). A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA. Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT. A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation. Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later. Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no de novo malignancy. Neither of the siblings has developed an HCV infection. Conclusions A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient. A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.
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Affiliation(s)
- Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
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40
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Long-term follow-up and outcome of liver transplantation from anti-hepatitis C virus-positive donors: a European multicentric case-control study. Transplantation 2011; 91:1265-72. [PMID: 21478815 DOI: 10.1097/tp.0b013e318219eb8f] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. Given the significant disparity between organ supply and demand for transplantation, it becomes essential to consider whether livers from anti-HCV-positive donors may be considered suitable for transplantation. METHODS Based on a multicenter European database, 694 patients with HCV-related cirrhosis underwent liver transplantation and 11% of them received the graft from anti-HCV-positive donors. Of this group, we selected 63 patients (study group) and, after a 1:1 case-control approach, compared them with 63 patients that received an anti-HCV-negative donor graft (control group). Only grafts with preperfusion liver biopsy results with a fibrosis score of not more than 1 were used for transplantation. RESULTS Patients who received anti-HCV-positive grafts had a cumulative survival rate of 83.6% and 61.7% at 1 and 5 years, respectively, vs. 95.1% and 68.2% for the control group. In comparing overall patient and graft survival, there was no statistically significant difference between the two groups (P=0.22 and 0.11). Recurrence of hepatitis C tended to be more rapid in the group of patients who received anti-HCV-positive grafts, although it did not reach statistical significance (P=0.07). CONCLUSIONS We do not recommend the indiscriminate use of anti-HCV-positive donors, especially if HCV-RNA positive, as the use of this kind of graft could be linked to an advanced stage of fibrosis, the main risk factor we observed for earlier hepatitis C recurrence.
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41
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Northup PG, Argo CK, Nguyen DT, McBride MA, Kumer SC, Schmitt TM, Pruett TL. Liver allografts from hepatitis C positive donors can offer good outcomes in hepatitis C positive recipients: a US National Transplant Registry analysis. Transpl Int 2011; 23:1038-44. [PMID: 20444239 DOI: 10.1111/j.1432-2277.2010.01092.x] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Organ donors are screened for the hepatitis C antibody (anti-HCV) and those with positive tests can be used under extended criteria donation. However, there is still a question of long-term organ viability. The aim of this study was to assess the long-term outcomes of anti-HCV positive (HCV+) liver grafts. The US Organ Procurement and Transplantation Network Scientific Registry was reviewed for the period from April 1994 to February 6, 2008 and 56,275 liver transplantations were analyzed. In total, there were 19,496 HCV+ recipients and 934 HCV+ donors. Patient and graft survival were assessed accounting for both donor and recipient anti-HCV status. Multivariable proportional hazards survival models were developed to adjust for factors known to affect post-transplant survival. With anti-HCV negative (HCV-) recipient/HCV- donor as the reference, the adjusted hazard ratio for death was similar for HCV+ recipient/HCV- donor compared with HCV+ recipient/HCV+ donor (1.176 vs. 1.165, P = 0.91). Our results suggest that HCV+ liver donors do not subject the HCV+ recipient to an increased risk for death over the HCV- donor, keeping in mind that careful donor and recipient selection is critical for the proper use of these extended criteria donors.
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Affiliation(s)
- Patrick G Northup
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA 22908-0708, USA.
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42
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43
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Gordon Burroughs S, Busuttil RW. Optimal utilization of extended hepatic grafts. Surg Today 2009; 39:746-51. [PMID: 19779769 DOI: 10.1007/s00595-008-4022-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2008] [Accepted: 07/09/2008] [Indexed: 12/22/2022]
Abstract
Orthotopic liver transplantation has emerged as the standard treatment for end-stage liver disease. In the United States, the number of listed patients has tripled in the last two decades. Organ availability during the same period has plateaued at approximately 6000 grafts annually, resulting in a fivefold increase in wait-list mortality. The problem is not specific to the United States; European and Asian registries report similar shortages. Donor pool expansion strategies such as the use of living donors, cadaveric split livers, and "extended criteria donors"; (ECD) are being pursued. Used judiciously, ECD grafts provide an opportunity for addressing the shortage. Although there is no universally accepted definition of ECD, the term generally refers to donor factors predisposing recipients to poor initial graft function and/or increased long-term risk. These factors include advanced donor age, hypernatremia, prolonged warm ischemic time, pressor requirement, and donation after cardiac death. The transplant community is scrutinizing all factors to evaluate the degree of risk they impart on the recipient and the extent to which grafts can be "matched"; to maintain acceptable outcomes. We review the importance of selected factors and the impact of a "matching"; strategy to minimize recipient risk while optimizing graft use.
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Affiliation(s)
- Sherilyn Gordon Burroughs
- Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA 90095-7054, USA
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44
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Durand F, Renz JF, Alkofer B, Burra P, Clavien PA, Porte RJ, Freeman RB, Belghiti J. Report of the Paris consensus meeting on expanded criteria donors in liver transplantation. Liver Transpl 2008; 14:1694-707. [PMID: 19025925 DOI: 10.1002/lt.21668] [Citation(s) in RCA: 212] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Because of organ shortage and a constant imbalance between available organs and candidates for liver transplantation, expanded criteria donors are needed. Experience shows that there are wide variations in the definitions, selection criteria, and use of expanded criteria donors according to different geographic areas and different centers. Overall, selection criteria for donors have tended to be relaxed in recent years. Consensus recommendations are needed. This article reports the conclusions of a consensus meeting held in Paris in March 2007 with the contribution of experts from Europe, the United States, and Asia. Definitions of expanded criteria donors with respect to donor variables (including age, liver function tests, steatosis, infections, malignancies, and heart-beating versus non-heart-beating, among others) are proposed. It is emphasized that donor quality represents a continuum of risk rather than "good or bad." A distinction is made between donor factors that generate increased risk of graft failure and factors independent of graft function, such as transmissible infectious disease or donor-derived malignancy, that may preclude a good outcome. Updated data concerning the risks associated with different donor variables in different recipient populations are given. Recommendations on how to safely expand donor selection criteria are proposed.
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Affiliation(s)
- François Durand
- Hepatology and Liver Intensive Care, Hospital Beaujon, University Paris 7, Clichy, France
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45
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Verna EC, Brown RS. Hepatitis C and liver transplantation: enhancing outcomes and should patients be retransplanted. Clin Liver Dis 2008; 12:637-59, ix-x. [PMID: 18625432 DOI: 10.1016/j.cld.2008.03.010] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatitis C (HCV)-related end-stage liver disease is the most common indication for liver transplantation. Safe expansion of the donor pool with improved rates of deceased donation and more widespread use of living and extended criteria donation are likely to decrease wait list mortality. In addition, improved antiviral treatments and a better understanding of the delicate balance between under- and over-immunosuppression in this population are needed. Finally, when recurrent advanced fibrosis occurs, the criteria for patient selection for retransplantation remain widely debated. This article reviews the literature on these topics and the work being done in each area to maximize outcomes in patients receiving transplants for HCV-related cirrhosis.
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Affiliation(s)
- Elizabeth C Verna
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
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46
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Transmission of viral disease to the recipient through the donor liver. Curr Opin Organ Transplant 2007; 12:231-241. [DOI: 10.1097/mot.0b013e32814e6b67] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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47
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Gallegos-Orozco JF, Vargas HE. Should antihepatitis B virus core positive or antihepatitis C virus core positive subjects be accepted as organ donors for liver transplantation? J Clin Gastroenterol 2007; 41:66-74. [PMID: 17198068 DOI: 10.1097/01.mcg.0000225636.60404.bf] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Since the introduction of liver transplantation as a routine surgical procedure for the treatment of end-stage liver disease, there has been an increasing gap between the number of available grafts and the number of patients on the waiting list. This has led transplant centers to expand the donor pool by different means. One of them has been the introduction of living donor liver transplantation. Other strategies include using less than optimal allografts from deceased donors, the so-called marginal donors, which include the use of grafts from older subjects, livers with moderate amounts of steatosis, or from donors with markers of past or current infection with hepatitis viruses who have absent or minimal liver biochemical or histologic injury. In this review, we will focus on the current use of allografts from donors with antihepatitis B core antibody and/or antibodies against hepatitis C virus in cadaveric and living donor liver transplantation.
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Affiliation(s)
- Juan F Gallegos-Orozco
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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48
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Akoad M, Wagener M, Francis F, Ahmed J, Ulizio D, Cacciarelli TV. Outcome of Imported Liver Allografts and Impact on Patient Access to Liver Transplantation. Transplant Proc 2006; 38:3564-6. [PMID: 17175332 DOI: 10.1016/j.transproceed.2006.10.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2006] [Indexed: 01/07/2023]
Abstract
Liver allografts declined by local transplant centers are then offered regionally or nationally as imported grafts. Most of these grafts are declined because of poor donor quality. We retrospectively reviewed the medical records of patients who underwent liver transplantation between January 2004 and December 2005. There were 102 liver transplants in 98 recipients. They were divided into two groups: imported graft recipients (n = 37) and locally procured grafts recipients (n = 61). Eighty-six percent (32 of 37) of imported grafts were obtained from extended criteria donors defined as subjects treated with high doses of ionotropes with elevated liver enzymes, donor age over 70 years, macrosteatosis above 25%, positive hepatitis C or hepatitis B core antibody serology, systemic disease, history of cancer, hypernatremia, or with infection. The remaining grafts were declined due to unavailability of suitable recipients or social history. Recipient age and etiology of liver disease were similar for both groups. The mean MELD score was 22.1 +/- .9 among the imported graft recipients and 26.1 +/- 1 for the locally procured graft recipients (P < .01). There was no difference in blood loss or postoperative complications. Postoperative mean peak total bilirubin was similar in both groups. However, imported graft recipients had significantly higher mean peak AST (2436 +/- 282 vs 1380 +/- 165 U/L, P < .001) and ALT (1098 +/- 114 vs 803 +/- 87 U/L, P < .05). Primary graft nonfunction as well as 30 day and 1-year patient and graft survivals were similar for both groups. In conclusion, imported grafts can be transplanted in selected patients with outcomes comparable to locally procured grafts.
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Affiliation(s)
- M Akoad
- VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania 15237, USA.
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Abstract
Hepatitis C virus (HCV) infection remains the most common cause of hepatic failure requiring orthotopic liver transplantation, and the disparity between the number of patients in need of liver replacement and the number of organs available continues to grow. Unfortunately, without viral eradication before transplantation, HCV recurrence is universal and is associated with poor graft and patient survival. Despite expansion of the donor pool and attempts to suppress HCV activity with various pretransplant and posttransplant antiviral therapies, many questions remain. This article reviews the literature regarding the evaluation of patients for transplantation, the antiviral therapies available in the peritransplant period, the immunosuppressive regimens, used, and the approach to patients with recurrent HCV infection.
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Affiliation(s)
- Elizabeth C Verna
- Department of Medicine, Columbia University Medical Center, 5th Floor, Room 5-006, 177 Fort Washington, New York, NY 10032, USA
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Tector AJ, Mangus RS, Chestovich P, Vianna R, Fridell JA, Milgrom ML, Sanders C, Kwo PY. Use of extended criteria livers decreases wait time for liver transplantation without adversely impacting posttransplant survival. Ann Surg 2006; 244:439-50. [PMID: 16926570 PMCID: PMC1856546 DOI: 10.1097/01.sla.0000234896.18207.fa] [Citation(s) in RCA: 183] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION The use of extended criteria donors (ECDs) could minimize shortage of suitable donor livers for transplantation. In 3 years, the aggressive use of ECD livers has reduced the wait list at our center from 257 to 30 patients with a median wait time of 18 days without using living donors. This study compares the graft/patient survival from standard (SD) and ECD for our transplant population between 2001 and 2005. METHODS Records of all adult liver transplant recipients over 4 years were reviewed (n = 571). ECD criteria included: age >59 years, BMI >34.9, maximum AST/ALT >500, maximum bilirubin >2.0, peak serum sodium >170, HBV/HCV/HTLV reactive, donation after cardiac death, cold ischemia time >12 hours, ICU stay >5 days, 3 or more pressors simultaneously, extensive alcohol abuse, cancer history (nonskin), active meningitis/bacteremia, or significant donor liver trauma. Outcomes included graft and patient survival at 90 days, 1 year, and 2 years. RESULTS Sixty-eight percent of recipients (n = 388) received ECD livers. Primary factors accounting for ECD-liver status included: elevated liver function tests (20%), hypernatremia (12.6%), and extensive alcohol abuse (11.4%). Graft survival was (SD, ECD): 90-day 91%, 88%; 1-year 84%, 80%; 2-year 78%, 77%; patient survival was: 90-day 93%, 90%; 1-year 87%, 82%; 2-year 83%, 79%. Kaplan-Meier survival analysis failed to demonstrate an overall difference in graft or patient survival at any time point. Only donor age >60 years was associated with decreased graft and patient survival. CONCLUSIONS Liver grafts from ECD can be used to dramatically reduce wait list time with outcomes comparable to those for SD without resorting to living donor liver transplantation.
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Affiliation(s)
- A Joseph Tector
- Department of Surgery, Transplantation Section, Gastroenterology Division, Indiana University School of Medicine, Indianapolis, IN 46202-5250, USA.
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