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Caso Maestro O, García Moreno V, Justo Alonso I, Marcacuzco Quinto A, Aguado JM, Loinaz Segurola C, Jiménez Romero C. Outcomes of liver transplantation with donors older than 80 years in HCV patients treated with direct-action antivirals vs. non-HCV patients. Med Clin (Barc) 2025; 164:161-167. [PMID: 39580269 DOI: 10.1016/j.medcli.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 09/05/2024] [Accepted: 09/08/2024] [Indexed: 11/25/2024]
Abstract
BACKGROUND Multiple studies have shown good results with the use of octogenarian donors in non-HCV recipients and its use is universally accepted worldwide. There are no studies analyzing differences between hepatitis C virus (HCV) and non-HCV recipients transplanted with donors≥80 years in the direct-action antivirals (DAA) period. The rate of liver transplantation (LT) using old donors is still low, and a change in the acceptance of these grafts could increase the liver pool available for LT. MATERIAL AND METHODS Since the introduction of DAA therapy in our hospital in January 2014 to May 2022, 457 LT were performed, and 74 (16.2%) of these patients underwent LT with donors≥80 years. A cohort study was carried-out comparing 15 HCV-positive recipients vs. 59 HCV-negative patients during the period of the study. RESULTS Recipients were younger in the non-HCV group. MELD and subsequently DMELD were higher in non-HCV group. Nevertheless, the association of hepatocellular carcinoma (HCC) with HCV cirrhosis was higher than with non-HCV cirrhosis (86.7% vs. 28.8%; p<0.001), but there were no recurrences within HCV group and only 1 case in the non-HCV group. The 1-, 3-, and 5-years patient and graft survival were similar in both groups. Recipient age and intraoperative transfusion requirements were predictors of graft survival [(HR 1.10, 95CI 1.01-1.21; p=0.03) and (HR 1.03, 95CI 1.01-1.05; p<0.001), respectively]. CONCLUSIONS In conclusion, the use of octogenarian donors was a safe alternative to younger donors in HCV recipients requiring LT in the era of DAA with similar results to those obtained in non-HCV patients.
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Affiliation(s)
- Oscar Caso Maestro
- Unit of HPB Surgery and Abdominal Organs Transplantation, '12th October' University Hospital, Madrid, Spain; Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain.
| | - Virginia García Moreno
- Unit of HPB Surgery and Abdominal Organs Transplantation, '12th October' University Hospital, Madrid, Spain; Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Iago Justo Alonso
- Unit of HPB Surgery and Abdominal Organs Transplantation, '12th October' University Hospital, Madrid, Spain; Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Alberto Marcacuzco Quinto
- Unit of HPB Surgery and Abdominal Organs Transplantation, '12th October' University Hospital, Madrid, Spain; Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Jose María Aguado
- Unit of Infectious Diseases, '12th October' University Hospital, Madrid, Spain
| | - Carmelo Loinaz Segurola
- Unit of HPB Surgery and Abdominal Organs Transplantation, '12th October' University Hospital, Madrid, Spain; Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
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Moein M, Fioramonti P, Lieb K, Golkarieh A, Forouzan A, Leipman J, Bahreini A, Moallem Shahri M, Jamshidi A, Saidi R. Improved Outcomes of Liver Transplantation in Patients With Hepatitis C, Following the Introduction of Innovative Antiviral Therapies. J Clin Exp Hepatol 2025; 15:102428. [PMID: 39564427 PMCID: PMC11570942 DOI: 10.1016/j.jceh.2024.102428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 10/10/2024] [Indexed: 11/21/2024] Open
Abstract
Background The treatment landscape for hepatitis C virus (HCV) underwent a significant shift with the introduction of direct-acting antiviral (DAA) medications in late 2013. This study aimed to evaluate the impact of DAAs on liver transplantation outcomes, examining both the benefits and any potential drawbacks associated with their use. Methods and materials A retrospective registry analysis of the United Network for Organ Sharing database was done for liver transplants in patients diagnosed with hepatitis C, that were performed in the United States from January 2000 to May 2020. Results The study was divided into two subgroups, based on the timing of the new DAA medication that FDA approved. The only significant difference between the two cohorts is the recipient's age. The data analysis showed a significant overall 5-year graft survival improvement in the 2014-2020 group compared with the 2000-2013 group, from a mean of 64.8% in 2000-2013 to a mean of 76% in 2014-2020 (P < 0.001). Interestingly, when we compared the 5-year graft survivals with recipients who had a donor above age 50, the graft survival rate difference was even more significant (74% vs. 56%, P < 0.001) as some studies have shown a suboptimal graft outcome when the donor age is above 40 years old. Not only has the utilization of donation after circulatory death livers increased significantly after 2014 but the graft survival in this cohort has also been significantly higher (P < 0.001). Conclusion The emergence of DAAs in 2013 marked a watershed moment in the management of HCV offering high cure rates, minimal side effects, and shorter treatment durations to a point that the short- and long-term outcomes of liver transplantation for HCV is almost equal to the other causes of liver transplantation.
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Affiliation(s)
- Mahmoudreza Moein
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
| | - Peter Fioramonti
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
| | - Kayla Lieb
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
| | - Alireza Golkarieh
- University of Michigan, Department of Mechanical Engineering and Data Science, Ann Arbor, MI, USA
| | - Artin Forouzan
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
| | - Jessica Leipman
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
| | - Amin Bahreini
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
| | - Matin Moallem Shahri
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
| | - Abolfazl Jamshidi
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
| | - Reza Saidi
- SUNY Upstate Medical University, Division of Transplant Services, Department of Surgery, Syracuse, NY, USA
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Caso Maestro O, Justo Alonso I, Marcacuzco Quinto A, Manrique Municio A, Calvo Pulido J, García‐Sesma A, Jiménez‐Romero C. Expanding donor age in liver transplantation using liver grafts from nonagenarian donors. Clin Transplant 2022; 36:e14684. [DOI: 10.1111/ctr.14684] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/18/2022] [Accepted: 04/09/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Oscar Caso Maestro
- Unit of HPB Surgery and Abdominal Organ Transplantation `Doce de Octubre´ Hospital. Instituto de Investigación (imas12) Department of Surgery Faculty of Medicine Complutense University Madrid Spain
| | - Iago Justo Alonso
- Unit of HPB Surgery and Abdominal Organ Transplantation `Doce de Octubre´ Hospital. Instituto de Investigación (imas12) Department of Surgery Faculty of Medicine Complutense University Madrid Spain
| | - Alberto Marcacuzco Quinto
- Unit of HPB Surgery and Abdominal Organ Transplantation `Doce de Octubre´ Hospital. Instituto de Investigación (imas12) Department of Surgery Faculty of Medicine Complutense University Madrid Spain
| | - Alejandro Manrique Municio
- Unit of HPB Surgery and Abdominal Organ Transplantation `Doce de Octubre´ Hospital. Instituto de Investigación (imas12) Department of Surgery Faculty of Medicine Complutense University Madrid Spain
| | - Jorge Calvo Pulido
- Unit of HPB Surgery and Abdominal Organ Transplantation `Doce de Octubre´ Hospital. Instituto de Investigación (imas12) Department of Surgery Faculty of Medicine Complutense University Madrid Spain
| | - Alvaro García‐Sesma
- Unit of HPB Surgery and Abdominal Organ Transplantation `Doce de Octubre´ Hospital. Instituto de Investigación (imas12) Department of Surgery Faculty of Medicine Complutense University Madrid Spain
| | - Carlos Jiménez‐Romero
- Unit of HPB Surgery and Abdominal Organ Transplantation `Doce de Octubre´ Hospital. Instituto de Investigación (imas12) Department of Surgery Faculty of Medicine Complutense University Madrid Spain
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Nakamura T, Shirouzu T. Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants. J Clin Med 2021; 10:5417. [PMID: 34830699 PMCID: PMC8619797 DOI: 10.3390/jcm10225417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 02/08/2023] Open
Abstract
The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.
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Affiliation(s)
- Tsukasa Nakamura
- Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Takayuki Shirouzu
- Molecular Diagnositcs Division, Wakunaga Pharmaceutical Co., Ltd., 13-4 Arakicho, shinjyuku-ku, Tokyo 160-0007, Japan;
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Safe use of livers from deceased donors older than 70 years in recipients with HCV cirrhosis treated with direct-action antivirals. Retrospective cohort study. Int J Surg 2021; 91:105981. [PMID: 34098075 DOI: 10.1016/j.ijsu.2021.105981] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/28/2021] [Accepted: 05/25/2021] [Indexed: 01/05/2023]
Abstract
INTRODUCTION There is controversy regarding the use of older grafts for liver transplantation (LT) in HCV-infected patients, but the introduction of direct-acting antivirals (DAA) can radically change that debate. METHODS The aim of this retrospective cohort study was to evaluate outcomes of the use of liver grafts from donors older than 70 years in recipients with HCV infection who underwent pre- or post-LT treatment with DAA. We compared two groups of patients who underwent LT using livers >70 years; the groups were defined according to antiviral therapy: non-DAA therapy group (n = 62; LT between May 1996 and December 2013), and DAA therapy group (n = 31; LT between January 2014 and December 2019). RESULTS Thirty (96.8%) patients of DAA therapy and nine (14.5%) of non-DAA therapy (21 patients underwent complete therapy with interferon-ribavirin) achieved sustained viral response (SVR). One, 3-, and 5-year patient survival were 83.9%, 67.7%, and 56.5% in the non-DAA group vs 93.5%, 88.4%, and 88.4% in the DAA group (P = 0.04); the 1-, 3-, and 5-year graft survival were 77.4%, 62.9%, and 51.6% in the non-DAA group vs. 88.6%, 83.7%, and 83.7% in the DAA group (P = 0.03). Multivariate analysis demonstrated donor female sex and DAA therapy as protective factors of graft survival. CONCLUSIONS Pre- or post-LT therapy with DAA in HCV-infected patients has achieved an almost overall SVR. The use of liver grafts >70 years in these patients treated with DAA was associated with significantly higher 5-year patient and graft survival in DAA group compared to non-DAA group. Thus, the introduction of DAA therapy has allowed the safe use of livers >70 years in HCV-positive recipients.
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Wang W, Liu Z, Qian J, Xu J, Que S, Zhuang L, Geng L, Zhou L, Zheng S. Systematic Assessment of Safety Threshold for Donor Age in Cadaveric Liver Transplantation. Front Med (Lausanne) 2021; 8:596552. [PMID: 33748155 PMCID: PMC7969668 DOI: 10.3389/fmed.2021.596552] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 02/08/2021] [Indexed: 12/27/2022] Open
Abstract
Background: Donor age affects allograft quality and the prognosis of recipients after liver transplantation (LT). Clinicians have assessed the quality of grafts from older donors based on their appearance and texture, with no reliable quantitative evidence. Our study aimed to assess the quantitative impact of donor age on post-transplant outcomes and its safety threshold for LT, based on the published literature. Methods: Relevant studies were retrieved from the Embase, PubMed, and ISI Web of Science databases. Pooled dichotomous relative risks (RRs) were calculated using metan. Continuous RRs were calculated using a two-stage random-effects model. Results: Eleven studies including 30,691 LT cases were included for further analysis. For categorical comparison, the RR of death within the first post-transplant year was significantly higher among patients who received grafts from older donors. Similarly, the RR of graft failure (GF) was increased within the 3 years after transplantation. For continuous comparison, advanced donor age affected transplant outcomes in a linear manner (P > 0.05). A 10-year increment in donor age was associated with RRs 1.10, 1.12, 1.15, 1.10, and 1.08 for 90-day, 180-day, 1-year, 3-year, and 5-year patient mortality and 1.08, 1.06, 1.10, 1.11, and 1.12, for 90-day, 180-day, 1-year, 2-year, and 3-year GF, respectively (all P < 0.05). A spline model showed that transplants using grafts from donors <43 years old were not associated with age-related risks (P > 0.05). The risk of GF was increased in subgroups with fewer LT cases, longer cold ischemic time, fewer male donors, and recipients with viral hepatitis (P < 0.05). Conclusion: Donor age might affect post-LT outcomes in a dose-dependent manner. The safety threshold for donor age in terms of GF should be lowered to 43 years as an early warning for the guarantee of satisfactory outcomes. Clinicians should weigh the benefits against the risks carefully for patients receiving grafts from older donors. Further studies are warranted to investigate the mechanisms responsible for the relationship between donor age and graft quality.
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Affiliation(s)
- Wenchao Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhengtao Liu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Junjie Qian
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jun Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shuping Que
- Science for Life Laboratory, Kungliga Tekniska Högskolan - Royal Institute of Technology, Stockholm, Sweden.,DingXiang Clinics, Hangzhou, China
| | - Li Zhuang
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
| | - Lei Geng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Lin Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
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Increased Surgical Complications but Improved Overall Survival with Adult Living Donor Compared to Deceased Donor Liver Transplantation: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1320830. [PMID: 32908865 PMCID: PMC7468609 DOI: 10.1155/2020/1320830] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/19/2020] [Accepted: 08/07/2020] [Indexed: 12/23/2022]
Abstract
Background Living donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial. Method A systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed. Results Thirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 − 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 − 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 − 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 − 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 − 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 − 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself. Conclusions LDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.
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Lerut J, Karam V, Cailliez V, Bismuth H, Polak WG, Gunson B, Adam R. What did the European Liver Transplant Registry bring to liver transplantation? Transpl Int 2020; 33:1369-1383. [PMID: 32767799 DOI: 10.1111/tri.13716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/06/2020] [Accepted: 08/04/2020] [Indexed: 11/30/2022]
Abstract
Since its foundation in 1985, the European Liver Transplant Registry has evolved to become an important tool to monitor the liver transplantation activity in Europe. The vast amount of data collected on 169 473 liver transplantations performed in 153 238 recipients has also resulted in scientific publications. Without doubt, several of these have influenced the daily practice of liver transplantation. This paper gives an overview of the development, the functioning, and the scientific activity of the European Liver Transplant Registry during more than three decades. Indeed, it can be said that the registry helped to advance the practice of liver transplantation not only in Europe but also worldwide.
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Affiliation(s)
- Jan Lerut
- Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium
| | - Vincent Karam
- European Liver Transplant Registry, INSERM U 935, APHP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Valérie Cailliez
- European Liver Transplant Registry, INSERM U 935, APHP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Henri Bismuth
- European Liver Transplant Registry, INSERM U 935, APHP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Wojciech G Polak
- Division of Hepatopancreatobiliary and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bridget Gunson
- Liver Unit and National Institute of Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK
| | - Rene Adam
- European Liver Transplant Registry, INSERM U 935, APHP Hôpital Paul Brousse, Université Paris-Saclay, Villejuif, France
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Improvement in Liver Transplant Outcomes From Older Donors: A US National Analysis. Ann Surg 2020; 270:333-339. [PMID: 29958229 DOI: 10.1097/sla.0000000000002876] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To investigate trends in long-term graft and patient outcomes following liver transplantation using grafts from donors ≥60 years old. SUMMARY BACKGROUND DATA The scarcity of donor livers has led to increased utilization of organs from donors ≥60 years old. However, few studies have examined how long-term transplant outcomes from older donors have evolved over time. METHODS The OPTN/UNOS database was queried for all first-time isolated adult liver transplants. We identified 14,796 adult liver transplant using donors ≧60-year-old suitable for analysis from 1990 to 2014. Cohorts were then developed based on 5-year intervals of transplant date. Kaplan-Meier analysis was used to compare graft and patient survival for recipients from older donor across each 5-year era. RESULTS Utilization of donor grafts ≥60 years old increased steadily for the first 15 years of the study, but has leveled off over the last 10 years. Comparison of the earliest and latest eras in the study was notable for an increase in median recipient age (51 vs. 59, P < 0.001) and reduction in median cold ischemic time (10 vs. 6 h, P = 0.001). Unadjusted 5-year graft and patient survival has improved significantly over time (P < 0.0001). More importantly, the discrepancy in survival between older and younger grafts has narrowed substantially over time (P < 0.0001). CONCLUSIONS This study demonstrates significant improvement in transplant outcomes with donor grafts ≥60-years old and supports increased but judicious use of extended criteria donors liver grafts. Improved patient selection and reduction in cold ischemia time appear to be contributing factors.
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Impact of Donor Age on Recipient Survival in Adult-to-Adult Living-donor Liver Transplantation. Ann Surg 2019; 267:1126-1133. [PMID: 28288061 DOI: 10.1097/sla.0000000000002194] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To investigate the influence of donor age on recipient outcome after living-donor partial liver transplantation (LDLT). BACKGROUND Donor age is a well-known prognostic factor in deceased donor liver transplantation; however, its role in LDLT remains unclear. METHODS We retrospectively analyzed 315 consecutive cases of primary adult-to-adult LDLT in our center between April 2006 and March 2014. Recipients were divided into 5 groups according to the donor age: D-20s (n = 60); D-30s (n = 72); D-40s (n = 57); D-50s (n = 94); and D-60s (n = 32). The recipient survival and the association with various clinical factors were investigated. RESULTS Recipient survival proportions were significantly higher in D-20s compared with all the other groups (P = 0.008, < 0.001, < 0.001, and = 0.006, vs D-30s, -40s, -50s, and -60s, respectively), whereas there was no association between recipient survival and their own age. There are 3 typical relationships between donors and recipients in adult-to-adult LDLT: from child-to-parent, between spouses/siblings, and from parent-to-child. The overall survival in child-to-parent was significantly higher than in spouses/siblings (P = 0.002) and in parent-to-child (P = 0.005), despite significantly higher recipient age in child-to-parent [59 (42-69) years, P < 0.001]. Contrastingly, parent-to-child exhibited the lowest survival, despite the youngest recipient age [26 (20-43) years, P < 0.001]. In addition, younger donor age exhibited significantly better recipient survival both in hepatitis C virus-related and in non-hepatitis C virus diseases. Univariate and multivariate analyses both demonstrated that donor age and graft-type (right-sided livers) are independent prognostic factors for recipient survival. CONCLUSIONS Donor age is an independent, strong prognostic factor in adult-to-adult LDLT.
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Donor Age Predicts Calcineurin Inhibitor Induced Neurotoxicity After Liver Transplantation. Transplantation 2019; 103:e211-e215. [DOI: 10.1097/tp.0000000000002750] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Adam R, Karam V, Cailliez V, O Grady JG, Mirza D, Cherqui D, Klempnauer J, Salizzoni M, Pratschke J, Jamieson N, Hidalgo E, Paul A, Andujar RL, Lerut J, Fisher L, Boudjema K, Fondevila C, Soubrane O, Bachellier P, Pinna AD, Berlakovich G, Bennet W, Pinzani M, Schemmer P, Zieniewicz K, Romero CJ, De Simone P, Ericzon BG, Schneeberger S, Wigmore SJ, Prous JF, Colledan M, Porte RJ, Yilmaz S, Azoulay D, Pirenne J, Line PD, Trunecka P, Navarro F, Lopez AV, De Carlis L, Pena SR, Kochs E, Duvoux C. 2018 Annual Report of the European Liver Transplant Registry (ELTR) - 50-year evolution of liver transplantation. Transpl Int 2019; 31:1293-1317. [PMID: 30259574 DOI: 10.1111/tri.13358] [Citation(s) in RCA: 318] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 06/19/2018] [Accepted: 09/22/2018] [Indexed: 02/07/2023]
Abstract
The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience.
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Affiliation(s)
- René Adam
- Paul Brousse Hospital, Univ Paris-Sud, Inserm U935, Villejuif, France
| | - Vincent Karam
- Paul Brousse Hospital, Univ Paris-Sud, Inserm U935, Villejuif, France
| | - Valérie Cailliez
- Paul Brousse Hospital, Univ Paris-Sud, Inserm U935, Villejuif, France
| | | | | | - Daniel Cherqui
- Paul Brousse Hospital, Univ Paris-Sud, Inserm U935, Villejuif, France
| | | | | | | | | | | | | | | | - Jan Lerut
- Cliniques Universitaires Saint Luc, Brussels, Belgium
| | - Lutz Fisher
- Universitatsklinikum Hamburg Eppendorf, Hamburg, Germany
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Robert J Porte
- University Medical Center Groningen, Groningen, The Netherlands
| | | | | | | | | | - Pavel Trunecka
- Transplant Center, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
| | | | | | | | | | - Eberhard Kochs
- Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Munich, Germany
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13
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Caso-Maestro O, Jiménez-Romero C, Justo-Alonso I, Calvo-Pulido J, Lora-Pablos D, Marcacuzco-Quinto A, Cambra-Molero F, García-Sesma A, Pérez-Flecha M, Muñoz-Arce C, Loinaz-Segurola C, Manrique-Municio A. Analyzing predictors of graft survival in patients undergoing liver transplantation with donors aged 70 years and over. World J Gastroenterol 2018; 24:5391-5402. [PMID: 30598583 PMCID: PMC6305532 DOI: 10.3748/wjg.v24.i47.5391] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 11/24/2018] [Accepted: 12/01/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To increase the number of available grafts.
METHODS This is a single-center comparative analysis performed between April 1986 and May 2016. Two hundred and twelve liver transplantation (LT) were performed with donors ≥ 70 years old (study group). Then, we selected the first cases that were performed with donors < 70 years old immediately after the ones that were performed with donors ≥ 70 years old (control group).
RESULTS Graft and patient survivals were similar between both groups without increasing the risk of complications, especially primary non-function, vascular complications and biliary complications. We identified 5 risk factors as independent predictors of graft survival: recipient hepatitis C virus (HCV)-positivity [hazard ratio (HR) = 2.35; 95% confidence interval (CI): 1.55-3.56; P = 0.00]; recipient age (HR = 1.04; 95%CI: 1.02-1.06; P = 0.00); donor age X model for end-stage liver disease (D-MELD) (HR = 1.00; 95%CI: 1.00-1.00; P = 0.00); donor value of serum glutamic-pyruvic transaminase (HR = 1.00; 95%CI: 1.00-1.00; P = 0.00); and donor value of serum sodium (HR = 0.96; 95%CI: 0.94-0.99; P = 0.00). After combining D-MELD and recipient age we obtained a new scoring system that we called DR-MELD (donor age X recipient age X MELD). Graft survival significantly decreased in patients with a DR-MELD score ≥ 75000, especially in HCV patients (77% vs 63% at 5 years in HCV-negative patients, P = 0.00; and 61% vs 25% at 5 years in HCV-positive patients; P = 0.00).
CONCLUSION A DR-MELD ≥ 75000 must be avoided in order to obtain the best results in LT with donors ≥ 70 years old.
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Affiliation(s)
- Oscar Caso-Maestro
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Carlos Jiménez-Romero
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Iago Justo-Alonso
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Jorge Calvo-Pulido
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - David Lora-Pablos
- Clinical Research Department, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Alberto Marcacuzco-Quinto
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Félix Cambra-Molero
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Alvaro García-Sesma
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Marina Pérez-Flecha
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Carlos Muñoz-Arce
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Carmelo Loinaz-Segurola
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
| | - Alejandro Manrique-Municio
- Unit of HBP Surgery and Abdominal Organs Transplantation, Department of General Surgery, “12 de octubre” University Hospital, Madrid 28041, Spain
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14
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Zhuang X, Lai AG, McKeating JA, Rowe I, Balfe P. Daytime variation in hepatitis C virus replication kinetics following liver transplant. Wellcome Open Res 2018; 3:96. [PMID: 30175249 PMCID: PMC6107978 DOI: 10.12688/wellcomeopenres.14696.2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2018] [Indexed: 12/26/2022] Open
Abstract
Background: There is a growing interest in the role of circadian regulated pathways in disease pathogenesis. Methods: In a cohort of hepatitis C virus (HCV) infected patients undergoing liver transplantation, we observed differences in early viral infection kinetics of the allograft that associated with the time of liver transplant. Results: A higher frequency of subjects transplanted in the morning showed a rebound in viral RNA levels (n=4/6) during the first week post-surgery. In contrast, no viral rebound was observed in seven subjects transplanted in the afternoon. None of the other parameters previously reported to influence viral replication in the post-transplant setting, such as donor age, cold-ischemia time and length of surgery associated with viral rebound. Conclusions: These observation highlights a role for circadian processes to regulate HCV infection of the liver and warrants further investigation.
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Affiliation(s)
- Xiaodong Zhuang
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Alvina G. Lai
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Jane A. McKeating
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Ian Rowe
- Institute for Data Analytics, University of Leeds, Leeds, Yorkshire, UK
| | - Peter Balfe
- Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK
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15
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Zhuang X, Lai AG, McKeating JA, Rowe I, Balfe P. Daytime variation in hepatitis C virus replication kinetics following liver transplant. Wellcome Open Res 2018; 3:96. [PMID: 30175249 PMCID: PMC6107978 DOI: 10.12688/wellcomeopenres.14696.1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2018] [Indexed: 09/29/2023] Open
Abstract
Background: There is a growing interest in the role of circadian regulated pathways in disease pathogenesis. Methods: In a cohort of hepatitis C virus (HCV) infected patients undergoing liver transplantation, we observed differences in early viral infection kinetics of the allograft that associated with the time of liver transplant. Results: A higher frequency of subjects transplanted in the morning showed a rebound in viral RNA levels (n=4/6) during the first week post-surgery. In contrast, no viral rebound was observed in seven subjects transplanted in the afternoon. None of the other parameters previously reported to influence viral replication in the post-transplant setting, such as donor age, cold-ischemia time and length of surgery associated with viral rebound. Conclusions: These observation highlights a role for circadian processes to regulate HCV infection of the liver and warrants further investigation.
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Affiliation(s)
- Xiaodong Zhuang
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Alvina G. Lai
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Jane A. McKeating
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX3 7AZ, UK
| | - Ian Rowe
- Institute for Data Analytics, University of Leeds, Leeds, Yorkshire, UK
| | - Peter Balfe
- Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK
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16
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Bodro M, Sanclemente G, Crespo G, Linares L, Marcos MA, Marco F, Miquel R, Forns X, Navasa M, Moreno A. Severe Hepatitis C Recurrence as a Risk Factor for Opportunistic Infections in Liver Transplant Recipients. Transplant Proc 2018; 50:1437-1443. [PMID: 29880367 DOI: 10.1016/j.transproceed.2018.02.081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 12/13/2017] [Accepted: 02/17/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The aim of the study was to determine the clinical characteristics, frequency of opportunistic infections (OI), and the outcomes for liver transplant recipients with severe hepatitis C virus (HCV) recurrence. In addition, the objective was to evaluate HCV recurrence as a risk factor for developing an OI. METHODS We conducted a retrospective observational study recording all liver transplant recipients from July 1, 2003, to December 31, 2012. Patients with liver disease due to HCV were selected. Active surveillance of infections was conducted periodically, and patients were classified according to presence of severe HCV recurrence. RESULTS Three hundred seventy patients underwent liver transplantation because of chronic HCV. One hundred forty-seven patients presented severe recurrence (SR) (49%) and 50 (17%) of them had post-liver transplant cholestatic hepatitis C. Patients with SR presented OI, especially cytomegalovirus (CMV) infections and invasive fungal infections, more frequently than patients without SR (33% vs 13%; P < .001). From the diagnosis of SR to the presentation of OI, the median number of days was 169 (6-2083). Acute allograft rejection (OR 1.8 95% confidence interval [CI] 1.1-3.3) donor age ≥60 years (OR 2.9 95% CI 1.3-6.8), and SR (OR 2.8, 95% CI 1.6-5.1) were independently associated with the development of OI in liver transplant recipients. CONCLUSION A high index of suspicion of opportunistic infections must be maintained when faced with severe HCV recurrence in liver transplant recipients. Moreover, active surveillance against CMV infection and other prophylactic strategies against opportunistic infections should be considered.
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Affiliation(s)
- M Bodro
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain.
| | - G Sanclemente
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - G Crespo
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - L Linares
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - M A Marcos
- Microbiology Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - F Marco
- Microbiology Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - R Miquel
- Pathology Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - X Forns
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - M Navasa
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - A Moreno
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
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17
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Elnaggar AS, Guarrera JV. The Marginal Liver Donor and Organ Preservation Strategies. LIVER ANESTHESIOLOGY AND CRITICAL CARE MEDICINE 2018:207-220. [DOI: 10.1007/978-3-319-64298-7_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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18
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Abstract
Mortality rates on the liver transplant waiting list are increasing. The shortage of organs has resulted in higher utilization of extended criteria donors (ECDs), with centers pushing the limits of what is acceptable for transplantation. Donor quality is more appropriately represented as a continuum of risk, and careful selection and matching of ECD grafts with recipients may lead to excellent outcomes. Although there is no precise definition for what constitutes an ECD liver, this review focuses on frequently cited characteristics, including donor age, steatosis, donation after cardiac death, and donors with increased risk of disease transmission.
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Affiliation(s)
- Irine Vodkin
- Division of Gastroenterology and Hepatology, University of California, San Diego, 200 West Arbor Drive M/C 8413, San Diego, CA, USA.
| | - Alexander Kuo
- Division of Gastroenterology and Hepatology, University of California, San Diego, 200 West Arbor Drive M/C 8413, San Diego, CA, USA
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19
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Soin AS, Goja S, Yadav SK, Tamang TY, Rastogi A, Bhangui P, Thiagrajan S, Raut V, Babu RY, Saigal S, Saraf N, Choudhary NS, Vohara V. (D+10) MELD as a novel predictor of patient and graft survival after adult to adult living donor liver transplantation. Clin Transplant 2017; 31. [DOI: 10.1111/ctr.12939] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/19/2017] [Indexed: 12/22/2022]
Affiliation(s)
- Arvinder Singh Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Sanjay Goja
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Sanjay Kumar Yadav
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Tseten Yonjen Tamang
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Amit Rastogi
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Srinivasan Thiagrajan
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Vikram Raut
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Raghvendra Y. Babu
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Sanjiv Saigal
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Neeraj Saraf
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Narendra Singh Choudhary
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
| | - Vijay Vohara
- Medanta Institute of Liver Transplantation and Regenerative Medicine; Medanta-The Medicity; Gurgaon India
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20
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Dimou FM, Mehta HB, Adhikari D, Harland RC, Riall TS, Kuo YF. The role of extended criteria donors in liver transplantation for nonalcoholic steatohepatitis. Surgery 2016; 160:1533-1543. [PMID: 27554622 DOI: 10.1016/j.surg.2016.06.051] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 06/14/2016] [Accepted: 06/23/2016] [Indexed: 01/04/2023]
Abstract
BACKGROUND Nonalcoholic steatohepatitis is expected to become the leading indication for liver transplantation. Use of extended criteria donors (ECD) may help with donor allocation in these patients. The objective of this study was to determine the use of ECDs in patients with nonalcoholic steatohepatitis undergoing liver transplantation to stimulate a liver-specific predictive model for ECD use. METHODS The United Network for Organ Sharing database was used to identify patients undergoing liver transplantation for nonalcoholic steatohepatitis (2002-2014). Cox hazards models were created using (1) United Network for Organ Sharing ECD criteria (based on kidney allocation), (2) individual donor characteristics (age, sex, race, cause of death, body mass index, cold ischemic time), and (3) the Kidney Donor Profile Index (KDPI) to examine the effect of ECDs on mortality and graft failure. RESULTS A total of 4,387 patients underwent liver transplantation for nonalcoholic steatohepatitis; 1,359 (30.9%) patients received an ECD. Transplantation with ECD livers had comparable patient survival (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.91-1.23) between donor types but an increased risk of graft failure (HR 1.18, 95% CI 1.03-1.36) compared to standard donors. Individual characteristics did not affect patient survival or graft failure. A 10% increase in KDPI was associated with a 28% increase in patient mortality (HR 1.28, 95% CI 1.02-1.60) and 45% increase in graft failure (HR 1.45, 95% CI 1.18-1.80). CONCLUSION Based on the current United Network for Organ Sharing definition, ECDs in nonalcoholic steatohepatitis were associated with similar overall survival but increased risk of graft failure. Given the shortage of organs, creation of an easily calculated, liver-specific model similar to the KDPI may help risk stratify patients and improve organ allocation.
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Affiliation(s)
- Francesca M Dimou
- Department of Surgery, The University of Texas Medical Branch, Galveston, TX; Department of Surgery, University of South Florida, Tampa, FL.
| | - Hemalkumar B Mehta
- Department of Surgery, The University of Texas Medical Branch, Galveston, TX
| | - Deepak Adhikari
- Department of Surgery, The University of Texas Medical Branch, Galveston, TX
| | | | - Taylor S Riall
- Department of Surgery, University of Arizona, Tucson, AZ
| | - Yong-Fang Kuo
- Department of Surgery, The University of Texas Medical Branch, Galveston, TX
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21
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Results of the TOP Study: Prospectively Randomized Multicenter Trial of an Ex Vivo Tacrolimus Rinse Before Transplantation in EDC Livers. Transplant Direct 2016; 2:e76. [PMID: 27500266 PMCID: PMC4946517 DOI: 10.1097/txd.0000000000000588] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 03/30/2016] [Indexed: 12/29/2022] Open
Abstract
Background Organ shortage results in the transplantation of extended donor criteria (EDC) livers which is associated with increased ischemia-reperfusion injury (IRI). Experimental studies indicate that an organ rinse with the calcineurin inhibitor tacrolimus before implantation protects against IRI. The tacrolimus organ perfusion study was initiated to examine the effects of ex vivo tacrolimus perfusion on IRI in transplantation of EDC livers. Methods A prospective randomized multicenter trial comparing ex vivo perfusion of marginal liver grafts (≥2 EDC according to Eurotransplant manual) with tacrolimus (20 ng/mL) or histidine-tryptophane-ketoglutarate solution (control) was carried out at 5 German liver transplant centers (Munich Ludwig-Maximilians University, Berlin, Heidelberg, Mainz, Regensburg) between October 2011 and July 2013. Primary endpoint was the maximum alanine transaminase (ALT) level within 48 hours after transplantation. Secondary endpoints were aspartate transaminase (AST), prothrombine ratio, and graft-patient survival within an observation period of 1 week. After an interim analysis, the study was terminated by the scientific committee after the treatment of 24 patients (tacrolimus n = 11, Control n = 13). Results Tacrolimus rinse did not reduce postoperative ALT peaks compared with control (P = 0.207; tacrolimus: median, 812; range, 362-3403 vs control: median, 652; range, 147-2034). Moreover, ALT (P = 0.100), prothrombine ratio (P = 0.553), and bilirubin (P = 0.815) did not differ between the groups. AST was higher in patients treated with tacrolimus (P = 0.011). Survival was comparable in both groups (P > 0.05). Conclusions Contrary to experimental findings, tacrolimus rinse failed to improve the primary endpoint of the study (ALT). Because 1 secondary endpoint (AST) was even higher in the intervention group, the study was terminated prematurely. Thus, tacrolimus rinse cannot be recommended in transplantation of EDC livers.
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22
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Impact of Cytomegalovirus Infection on Severe Hepatitis C Recurrence in Patients Undergoing Liver Transplantation. Transplantation 2016; 100:593-9. [PMID: 26371595 DOI: 10.1097/tp.0000000000000912] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The influence of cytomegalovirus (CMV) on recurrent hepatitis C virus (HCV) in liver grafts is controversial. Our aim was to investigate the association between CMV infection and disease and severe HCV recurrence (composite variable of presence of stage 3 to 4 fibrosis, need for retransplantation or death due to liver disease) in the first year after transplantation. METHODS An observational, prospective, multicenter study was performed. The CMV replication was monitored by determining CMV viral load weekly during hospitalization after transplantation, twice monthly in the first 3 months after discharge, and at each follow-up visit until month 12. Liver fibrosis was assessed histologically by liver biopsy or transient elastometry. Pretransplant, intraoperative, and posttransplant variables were recorded. Multiple logistic regression was performed to study the impact of CMV on severe HCV recurrence. RESULTS Ninety-eight patients were included. The CMV infection was detected in 48 patients (49%) in the first year posttransplant, of which 11 patients (22.9%) had CMV disease. Twenty-three patients (23.5%) had severe HCV recurrence. Of these, 17 (73.9%) developed stage 3 to 4 fibrosis, 4 (17.4%) died, and 2 (8.7%) underwent retransplantation. Only 7 of 12 (58.3%) seronegative recipients of a seropositive donor (positive donor/negative recipient [D+/R-]) received universal prophylaxis, and 10 of 12 (83.3%) D+/R- patients developed CMV replication. In the multivariate analysis, the presence of CMV D+/R- serodiscordance (odds ratio, 6.87; 95% confidence interval, 1.89-24.99; P = 0.003), and detection of a higher peak HCV viral load (odds ratio, 3.85; 95% confidence interval, 1.49-9.94; P = 0.005) were associated with severe HCV recurrence. CONCLUSIONS Our results support an association between CMV D+/R- serodiscordance and severe HCV recurrence in patients undergoing liver transplantation for HCV liver disease.
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23
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Lué A, Solanas E, Baptista P, Lorente S, Araiz JJ, Garcia-Gil A, Serrano MT. How important is donor age in liver transplantation? World J Gastroenterol 2016; 22:4966-4976. [PMID: 27275089 PMCID: PMC4886372 DOI: 10.3748/wjg.v22.i21.4966] [Citation(s) in RCA: 79] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Revised: 04/15/2016] [Accepted: 05/04/2016] [Indexed: 02/06/2023] Open
Abstract
The age of liver donors has been increasing in the past several years because of a donor shortage. In the United States, 33% of donors are age 50 years or older, as are more than 50% in some European countries. The impact of donor age on liver transplantation (LT) has been analyzed in several studies with contradictory conclusions. Nevertheless, recent analyses of the largest databases demonstrate that having an older donor is a risk factor for graft failure. Donor age is included as a risk factor in the more relevant graft survival scores, such as the Donor Risk Index, donor age and Model for End-stage Liver Disease, Survival Outcomes Following Liver Transplantation, and the Balance of Risk. The use of old donors is related to an increased rate of biliary complications and hepatitis C virus-related graft failure. Although liver function does not seem to be significantly affected by age, the incidence of several liver diseases increases with age, and the capacity of the liver to manage or overcome liver diseases or external injuries decreases. In this paper, the importance of age in LT outcomes, the role of donor age as a risk factor, and the influence of aging on liver regeneration are reviewed.
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24
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Sclair SN, Fiel MI, Wu HS, Doucette J, Aloman C, Schiano TD. Increased hepatic progenitor cell response and ductular reaction in patients with severe recurrent HCV post-liver transplantation. Clin Transplant 2016; 30:722-30. [PMID: 27027987 DOI: 10.1111/ctr.12740] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2016] [Indexed: 01/05/2023]
Abstract
OBJECTIVES Post-liver transplant (LT) hepatitis C virus (HCV) patients may develop allograft cirrhosis and rarely fibrosing cholestatic hepatitis (FCH), while others have a stable course. Hepatic progenitor cells (HPC) may be implicated in liver injury and fibrogenesis through ductular reaction (DR). We studied HPC response and DR in three distinct post-LT patterns of HCV: stable recurrence, allograft cirrhosis, and FCH. METHODS We identified 52 patients with untreated recurrent HCV and longitudinal liver biopsies (20 stable/23 cirrhosis/9 FCH) and eight healthy controls. Archived liver biopsy specimens for three time points (LT; initial recurrence; and clinical outcome) were stained for cytokeratin-7. Manual HPC counts and DR quantification using image analysis were performed. RESULTS HCV counts and DR at LT did not differ across groups. At initial recurrence, HPC expansion occurred only in patients who developed cirrhosis, while prominent DR was present in those who developed FCH vs. stable and controls (p < 0.05). At outcome biopsies, HPC response and DR were increased in cirrhosis and FCH vs. stable and controls (p < 0.05). HPC response and DR did not differ in stable vs. CONCLUSIONS These findings suggest that an altered HPC response assessed by cytokeratin-7 stain after LT may predict severity of HCV recurrence.
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Affiliation(s)
- Seth N Sclair
- Division of Hepatology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.,Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Maria Isabel Fiel
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Hai-Shan Wu
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - John Doucette
- Department of Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Costica Aloman
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois, Chicago, IL, USA.,Division of Transplant Surgery, Department of Surgery, University of Illinois, Chicago, IL, USA
| | - Thomas D Schiano
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Recanati-Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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25
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Ghinolfi D, De Simone P, Lai Q, Pezzati D, Coletti L, Balzano E, Arenga G, Carrai P, Grande G, Pollina L, Campani D, Biancofiore G, Filipponi F. Risk analysis of ischemic-type biliary lesions after liver transplant using octogenarian donors. Liver Transpl 2016; 22:588-98. [PMID: 26784011 DOI: 10.1002/lt.24401] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 11/23/2015] [Accepted: 12/31/2015] [Indexed: 12/22/2022]
Abstract
The use of octogenarian donors to increase the donor pool in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk of ischemic-type biliary lesions (ITBL). The aim of this study was to investigate retrospectively the role of a number of different pre-LT risk factors for ITBL in a selected population of recipients of octogenarian donor grafts. Between January 2003 and December 2013, 123 patients underwent transplantation at our institution with deceased donor grafts from donors of age ≥80 years. Patients were divided into 2 groups based on the presence of ITBL in the posttransplant course. Exclusion criteria were retransplantations, presence of vascular complications, and no availability of procurement liver biopsy. A total of 88 primary LTs were included, 73 (83.0%) with no posttransplant ITBLs and 15 (17.0%) with ITBLs. The median follow-up after LT was 2.1 years (range, 0.7-5.4 years). At multivariate analysis, donor hemodynamic instability (hazard ratio [HR], 7.6; P = 0.005), donor diabetes mellitus (HR, 9.5; P = 0.009), and donor age-Model for End-Stage Liver Disease (HR, 1.0; P = 0.04) were risk factors for ITBL. Transplantation of liver grafts from donors of age ≥80 years is associated with a higher risk for ITBL. However, favorable results can be achieved with accurate donor selection. Donor hemodynamic instability, a donor history of diabetes mellitus, and allocation to higher Model for End-Stage Liver Disease score recipient all increase the risk of ITBL and are associated with worse graft survival when octogenarian donors are used. Liver Transplantation 22 588-598 2016 AASLD.
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Affiliation(s)
- Davide Ghinolfi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Quirino Lai
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Daniele Pezzati
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Laura Coletti
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Emanuele Balzano
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Giuseppe Arenga
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Paola Carrai
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Gennaro Grande
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Luca Pollina
- Department of Pathology, University of Pisa Medical School Hospital, Pisa, Italy
| | - Daniela Campani
- Department of Pathology, University of Pisa Medical School Hospital, Pisa, Italy
| | - Gianni Biancofiore
- Post-transplant Intensive Care Unit, University of Pisa Medical School Hospital, Pisa, Italy
| | - Franco Filipponi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
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26
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Murthy V, Murray D, Hebballi S, Bramhall S, Lester W, Mutimer D, Wilde J. Outcome of liver transplantation in patients with hereditary bleeding disorders: a single centre UK experience. Haemophilia 2016; 22:e139-44. [PMID: 26931744 DOI: 10.1111/hae.12877] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/22/2015] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Patients with hereditary bleeding disorders who have developed end-stage liver disease as a consequence of hepatitis C infection (HCV) acquired from factor concentrates prior to the introduction of viral inactivation continue to be referred for liver transplantation. METHODS A retrospective review of case notes and electronic records was performed on all patients with bleeding disorders who have undergone liver transplantation at the University Hospital Birmingham (UHB). RESULTS Between 1990 and 2014, 35 liver transplants have been performed in 33 patients with hereditary bleeding disorders. The indication for transplantation was mainly end-stage liver disease secondary to HCV. Five patients had human immunodeficiency virus (HIV) co-infection. No excess mortality due to bleeding occurred in the peri or postoperative period. Median overall survival post transplant is 9.7 years. Overall survival rates at 1, 3 and 5 years are 90%, 72% and 64% respectively. The predominant cause of mortality was liver failure secondary to either recurrent HCV or recurrent hepatocellular carcinoma (HCC). The median overall survival in patients with HIV co-infection is shorter than in those with mono-infection but this is not statistically significant. Patients with a pre-existing HCC had a statistically significant shorter survival (2.4 years vs. 13.6 years, P = 0.007). CONCLUSION Liver transplantation has become an accepted treatment option for patients with hereditary bleeding disorders and HCV associated end-stage liver disease with survival rates similar to non-bleeding disorder patients.
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Affiliation(s)
- V Murthy
- West Midlands Adult Haemophilia Comprehensive Care Centre and Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - D Murray
- West Midlands Adult Haemophilia Comprehensive Care Centre and Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - S Hebballi
- West Midlands Adult Haemophilia Comprehensive Care Centre and Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - S Bramhall
- West Midlands Adult Haemophilia Comprehensive Care Centre and Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - W Lester
- West Midlands Adult Haemophilia Comprehensive Care Centre and Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - D Mutimer
- West Midlands Adult Haemophilia Comprehensive Care Centre and Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - J Wilde
- West Midlands Adult Haemophilia Comprehensive Care Centre and Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
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27
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Rowe IA, Tully DC, Armstrong MJ, Parker R, Guo K, Barton D, Morse GD, Venuto CS, Ogilvie CB, Hedegaard DL, McKelvy JF, Wong-Staal F, Allen TM, Balfe P, McKeating JA, Mutimer. DJ. Effect of scavenger receptor class B type I antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation. Liver Transpl 2016; 22:287-97. [PMID: 26437376 PMCID: PMC4901184 DOI: 10.1002/lt.24349] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 08/26/2015] [Accepted: 09/08/2015] [Indexed: 12/14/2022]
Abstract
Hepatitis C virus (HCV) entry inhibitors have been hypothesized to prevent infection of the liver after transplantation. ITX5061 is a scavenger receptor class B type I antagonist that blocks HCV entry and infection in vitro. We assessed the safety and efficacy of ITX5061 to limit HCV infection of the graft. The study included 23 HCV-infected patients undergoing liver transplantation. The first 13 "control" patients did not receive drug. The subsequent 10 patients received 150 mg of ITX5061 immediately before and after transplant and daily for 1 week thereafter. ITX5061 pharmacokinetics and plasma HCV RNA were quantified. Viral genetic diversity was measured by ultradeep pyrosequencing (UDPS). ITX5061 was well tolerated with measurable plasma concentrations during therapy. Although the median HCV RNA reduction was greater in ITX-treated patients at all time points in the first week after transplantation, there was no difference in the overall change in the area over the HCV RNA curve in the 7-day treatment period. However, in genotype (GT) 1-infected patients, treatment was associated with a sustained reduction in HCV RNA levels compared to the control group (area over the HCV RNA curve analysis, P = 0.004). UDPS revealed a complex and evolving pattern of HCV variants infecting the graft during the first week. ITX5061 significantly limited viral evolution where the median divergence between day 0 and day 7 was 3.5% in the control group compared to 0.1% in the treated group. In conclusion, ITX5061 reduces plasma HCV RNA after transplant notably in GT 1-infected patients and slows viral evolution. Following liver transplantation, the likely contribution of extrahepatic reservoirs of HCV necessitates combining entry inhibitors such as ITX5061 with inhibitors of replication in future studies.
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Affiliation(s)
- Ian A Rowe
- Viral Hepatitis Laboratory, Centre for Human Virology, University of Birmingham, UK,NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, UK,Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | | | - Matthew J Armstrong
- NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, UK,Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Richard Parker
- NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, UK,Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Kathy Guo
- NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, UK
| | - Darren Barton
- NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, UK,Cancer Research UK Clinical Trials Unit, University of Birmingham, UK
| | - Gene D Morse
- School of Pharmacy and Pharmaceutical Sciences and NYS Centre of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, NY, US
| | - Charles S Venuto
- Center for Human Experimental Therapeutics, University of Rochester School of Medicine, Rochester, NY, US
| | | | - Ditte L Hedegaard
- Viral Hepatitis Laboratory, Centre for Human Virology, University of Birmingham, UK
| | | | | | - Todd M Allen
- Ragon Institute of MGH, MIT and Harvard, Harvard, US
| | - Peter Balfe
- Viral Hepatitis Laboratory, Centre for Human Virology, University of Birmingham, UK
| | - Jane A McKeating
- Viral Hepatitis Laboratory, Centre for Human Virology, University of Birmingham, UK,NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, UK
| | - David J Mutimer.
- NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, UK,Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
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29
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Dirchwolf M, Dodge JL, Gralla J, Bambha KM, Nydam T, Hung KW, Rosen HR, Feng S, Terrault NA, Biggins SW. The corrected donor age for hepatitis C virus-infected liver transplant recipients. Liver Transpl 2015; 21:1022-30. [PMID: 26074140 PMCID: PMC4809736 DOI: 10.1002/lt.24194] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Revised: 05/13/2015] [Accepted: 05/21/2015] [Indexed: 12/11/2022]
Abstract
Donor age has become the dominant donor factor used to predict graft failure (GF) after liver transplantation (LT) in hepatitis C virus (HCV) recipients. The purpose of this study was to develop and validate a model of corrected donor age (CDA) for HCV LT recipients that transforms the risk of other donor factors into the scale of donor age. We analyzed all first LT recipients with HCV in the United Network for Organ Sharing (UNOS) registry from January 1998 to December 2007 (development cohort, n = 14,538) and January 2008 to December 2011 (validation cohort, n = 7502) using Cox regression, excluding early GF (<90 days from LT). Accuracy in predicting 1 year GF (death or repeat LT) was assessed with the net reclassification index (NRI). In the development cohort, after controlling for pre-LT recipient factors and geotemporal trends (UNOS region, LT year), the following donor factors were independent predictors of GF, all P < 0.05: donor age (hazard ratio [HR], 1.02/year), donation after cardiac death (DCD; HR, 1.31), diabetes (HR, 1.23), height < 160 cm (HR, 1.13), aspartate aminotransferase (AST) ≥ 120 U/L (HR, 1.10), female (HR, 0.94), cold ischemia time (CIT; HR, 1.02/hour), and non-African American (non-AA) donor-African American (AA) recipient (HR, 1.65). Transforming these risk factors into the donor age scale yielded the following: DCD = +16 years; diabetes = +12 years; height < 160 cm = +7 years; AST ≥ 120 U/L = +5 years; female = -4 years; and CIT = +1 year/hour > 8 hours and -1 year/hour < 8 hours. There was a large effect of donor-recipient race combinations: +29 years for non-AA donor and an AA recipient but only +5 years for an AA donor and an AA recipient, and -2 years for an AA donor and a non-AA recipient. In a validation cohort, CDA better classified risk of 1-year GF versus actual age (NRI, 4.9%; P = 0.009) and versus the donor risk index (9.0%, P < 0.001). The CDA, compared to actual donor age, provides an intuitive and superior estimation of graft quality for HCV-positive LT recipients because it incorporates additional factors that impact LT GF rates.
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Affiliation(s)
- Melisa Dirchwolf
- Hepatopatías Infecciosas, Hospital Francisco J. Muñiz, Buenos Aires, Argentina
| | | | | | | | | | | | | | - Sandy Feng
- University of California, San Francisco, CA
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30
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Diwan TS, Paterno F, Shah SA. Use of Extended Criteria Deceased Donors in Adult Liver Transplantation. CURRENT SURGERY REPORTS 2015. [DOI: 10.1007/s40137-015-0103-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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31
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Chapman WC, Vachharajani N, Collins KM, Garonzik-Wang J, Park Y, Wellen JR, Lin Y, Shenoy S, Lowell JA, Doyle MM. Donor Age-Based Analysis of Liver Transplantation Outcomes: Short- and Long-Term Outcomes Are Similar Regardless of Donor Age. J Am Coll Surg 2015; 221:59-69. [DOI: 10.1016/j.jamcollsurg.2015.01.061] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 01/27/2015] [Indexed: 01/09/2023]
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Abstract
Chronic HCV infection is the leading indication for liver transplantation. However, as a result of HCV recurrence, patient and graft survival after liver transplantation are inferior compared with other indications for transplantation. HCV recurrence after liver transplantation is associated with considerable mortality and morbidity. The development of HCV-related fibrosis is accelerated after liver transplantation, which is influenced by a combination of factors related to the virus, donor, recipient, surgery and immunosuppression. Successful antiviral therapy is the only treatment that can attenuate fibrosis. The advent of direct-acting antiviral agents (DAAs) has changed the therapeutic landscape for the treatment of patients with HCV. DAAs have improved tolerability, and can potentially be used without PEG-IFN for a shorter time than previous therapies, which should result in better outcomes. In this Review, we describe the important risk factors that influence HCV recurrence after liver transplantation, highlighting the mechanisms of fibrosis and the integral role of hepatic stellate cells. Indirect and direct assessment of fibrosis, in addition to new antiviral therapies, are also discussed.
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33
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Flemming JA, Vagefi PA, Freise CE, Yao FY, Terrault NA. Restricting liver transplant recipients to younger donors does not increase the wait-list time or the dropout rate: the hepatitis C experience. Liver Transpl 2014; 20:1202-10. [PMID: 24961679 PMCID: PMC4803440 DOI: 10.1002/lt.23937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Accepted: 06/06/2014] [Indexed: 01/12/2023]
Abstract
Older donor age is associated with lower graft and patient survival among all recipients of liver transplantation (LT). Among patients with hepatitis C virus (HCV), donor age is one of the strongest predictors of fibrosis severity and graft loss. We evaluated the implementation of a donor age restriction policy for LT patients with HCV at a single center and the effects that this policy had on wait-list (WL) and post-LT outcomes for HCV and non-HCV patients. This was a cohort study of 2388 WL patients and 1015 LT recipients between March 2002 and January 2013 and reflected 3 different eras of donor age policies. With the donor age restriction, the median donor age was reduced in LT recipients with HCV versus LT recipients without HCV (30 versus 48 years, P < 0.001) without differences in the WL time (10.6 versus 8.0 months, P = 0.23). According to a competing risks regression, those with HCV and those without HCV had lower subhazard ratios (SHRs) of dropout or death on the WL during the donor age restriction era versus the era without donor age restriction [SHR = 0.68 (P < 0.01) and SHR = 0.64 (P = 0.01), respectively]. No differences were seen in early post-LT survival for patients with or without HCV between eras (P = 0.7 and P = 0.88, respectively). In conclusion, we show that donor age restriction for HCV results in a lower donor age for HCV recipients without obvious adverse WL consequences. Although additional studies are needed, our results demonstrate the feasibility of donor age restriction for LT recipients with HCV, and such information may be relevant to programs with limited access to new antiviral therapies for which modifying the risk of severe disease remains of paramount importance.
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Affiliation(s)
- Jennifer A. Flemming
- Department of Medicine, Queen’s University, Kingston, Canada,Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Canada
| | - Parsia A. Vagefi
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Chris E. Freise
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Francis Y. Yao
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Norah A. Terrault
- Department of Medicine, University of California San Francisco, San Francisco, CA
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34
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Halldorson JB, Jr RLC, Bhattacharya R, Bakthavatsalam R, Liou IW, Dick AA, Reyes JD, Perkins JD. D-MELD risk capping improves post-transplant and overall mortality under markov microsimulation. World J Transplant 2014; 4:206-215. [PMID: 25346894 PMCID: PMC4208084 DOI: 10.5500/wjt.v4.i3.206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 07/08/2014] [Accepted: 07/18/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To hypothesize that the product of calculated Model for End-Stage Liver Disease score excluding exception points and donor age (D-MELD) risk capping ± Rule 14 could improve post liver transplant and overall survival after listing.
METHODS: Probabilities derived from the United Network for Organ Sharing database between 2002 and 2004 were used to simulate potential outcomes for all patients listed for transplantation. The Markov simulation was then modified by screening matches using a 1200 or 1600 D-MELD risk cap ± allowing transplants for Model for End-Stage Liver Disease (MELD) ≤ 14 (Rule 14). The differential impact of the rule changes was assessed.
RESULTS: The Markov simulation accurately reproduced overall and post transplant survival. A 1200 D-MELD risk cap improved post-transplant survival. Both the 1200 and 1600 risk caps improved overall survival for waitlisted patients. The addition of Rule 14 further improved post transplant and overall survival by redistribution of donor livers to recipients in higher MELD subgroups. The mechanism for improved overall and post-transplant survival after listing was due to shifting a larger percentage of transplants to the moderate MELD score subgroup (MELD 15-29) while also ensuring that high MELD recipients have livers of high quality to achieve excellent post transplant survival.
CONCLUSION: A 1200 D-MELD risk cap + Rule 14 provided the greatest overall benefit primarily by focusing liver transplantation towards the moderate MELD recipient.
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35
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Kakati B, Seetharam A. Hepatitis C Recurrence after Orthotopic Liver Transplantation: Mechanisms and Management. J Clin Transl Hepatol 2014; 2:189-96. [PMID: 26355427 PMCID: PMC4521242 DOI: 10.14218/jcth.2014.00016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 06/06/2014] [Accepted: 07/07/2014] [Indexed: 12/04/2022] Open
Abstract
Chronic Hepatitis C (HCV) infection is the leading indication for orthotopic liver transplantation and recurrence is nearly universal. Chronic HCV infection is frequently established through evasion of the innate immune system. Priming of adaptive immune responses modulate the severity and rate of fibrosis progression. Those with demonstrable viremia entering the transplant period uniformly suffer recurrence post-transplant. Progression to cirrhosis is accelerated post-transplant secondary to systemic immunosuppression. In addition, a number of factors, including donor, host, and viral characteristics, influence severity and rate of fibrosis progression. Interferon-based therapy, the previous standard of care, in those with advanced cirrhosis or post-transplant has been limited by a number of issues. These include a relative lack of efficacy and poor tolerability with higher incidence of infection and anemia. Recently, approval of direct acting antivirals have ushered in a new era in HCV therapeutics and have applicability in these special populations. Their use immediately prior to or post-transplant is expected to improve both morbidity and mortality.
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Affiliation(s)
- Bobby Kakati
- Banner Transplant and Advanced Liver Disease Center, Phoenix, AZ, USA
| | - Anil Seetharam
- Banner Transplant and Advanced Liver Disease Center, Phoenix, AZ, USA
- University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA
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36
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Ghinolfi D, Marti J, De Simone P, Lai Q, Pezzati D, Coletti L, Tartaglia D, Catalano G, Tincani G, Carrai P, Campani D, Miccoli M, Biancofiore G, Filipponi F. Use of octogenarian donors for liver transplantation: a survival analysis. Am J Transplant 2014; 14:2062-71. [PMID: 25307037 DOI: 10.1111/ajt.12843] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Revised: 04/22/2014] [Accepted: 04/23/2014] [Indexed: 01/25/2023]
Abstract
Use of very old donors in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk for graft dysfunction and worse long-term results, especially for hepatitis C virus (HCV)-positive recipients. This was a retrospective, single-center review of primary, ABO-compatible LT performed between 2001 and 2010. Recipients were stratified in four groups based on donor age (<60 years; 60-69 years; 70-79 years and ≥80 years) and their outcomes were compared. A total of 842 patients were included: 348 (41.3%) with donors <60 years; 176 (20.9%) with donors 60-69 years; 233 (27.7%) with donors 70-79 years and 85 (10.1%) with donors ≥80 years. There was no difference across groups in terms of early (≤30 days) graft loss, and graft survival at 1 and 5 years was 90.5% and 78.6% for grafts <60 years; 88.6% and 81.3% for grafts 60-69 years; 87.6% and 75.1% for grafts 70-79 years and 84.7% and 77.1% for grafts ≥80 years (p = 0.065). In the group ≥80 years, the 5-year graft survival was lower for HCV-positive versus HCV-negative recipients (62.4% vs. 85.6%, p = 0.034). Based on our experience, grafts from donors ≥80 years may provide favorable results but require appropriate selection and allocation policies.
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Affiliation(s)
- D Ghinolfi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
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Chedid MF, Rosen CB, Nyberg SL, Heimbach JK. Excellent long-term patient and graft survival are possible with appropriate use of livers from deceased septuagenarian and octogenarian donors. HPB (Oxford) 2014; 16:852-8. [PMID: 24467292 PMCID: PMC4159459 DOI: 10.1111/hpb.12221] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Accepted: 12/17/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although increasing donor age adversely affects survival after liver transplantation, livers have been used from selected deceased donors older than 70 years. Although there are reports of excellent short-term results, long-term results are unknown. Our experience was reviewed with septuagenarian and octogenarian deceased donors to determine long-term outcomes. METHODS All primary deceased donor liver transplants performed at our institution between July 1998 and December 2010 were reviewed. Recipients of livers procured after circulatory arrest, split and reduced-size livers and multiple organ transplants were excluded from the study. Patient and graft survival were calculated using the Kaplan-Meier method, and survival comparisons were made with the log-rank test. RESULTS In total, 780 patients met inclusion criteria, and 109 patients received livers from donors older than 70 years (range = 70-86). There were no differences in long-term patient (P = 0.67) or graft (P = 0.42) survival between hepatitis C negative recipients of livers from older compared with younger donors. In contrast, 7-year survival for HCV-positive recipients of older donor livers was less than half that of HCV-negative recipients. DISCUSSION Transplantation of livers from septua- and octogenarian donors can achieve excellent long-term patient and graft survival for selected HCV-negative patients.
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Affiliation(s)
| | - Charles B Rosen
- Correspondence, Charles B. Rosen, Division of Transplantation Surgery, Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel: +1 507 266 6640. Fax: +1 507 266 2810. E-mail:
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Jiménez-Romero C, Caso Maestro O, Cambra Molero F, Justo Alonso I, Alegre Torrado C, Manrique Municio A, Calvo Pulido J, Loinaz Segurola C, Moreno González E. Using old liver grafts for liver transplantation: Where are the limits? World J Gastroenterol 2014; 20:10691-10702. [PMID: 25152573 PMCID: PMC4138450 DOI: 10.3748/wjg.v20.i31.10691] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 12/16/2013] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.
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39
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Dall’Agata M, Gramenzi A, Biselli M, Bernardi M. Hepatitis C virus reinfection after liver transplantation: Is there a role for direct antiviral agents? World J Gastroenterol 2014; 20:9253-9260. [PMID: 25071318 PMCID: PMC4110555 DOI: 10.3748/wjg.v20.i28.9253] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Revised: 03/27/2014] [Accepted: 06/05/2014] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatitis C virus (HCV) infection following liver transplantation (LT) is almost universal and can accelerate graft cirrhosis in up to 30% of patients. The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge, considering the shortage of donor organs and the accelerated progression of HCV in LT recipients. Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients, even though the combination is not as effective as it is in immunocompetent patients. A sustained virological response in the setting of LT improves patient and graft survival, but this is only achieved in 30%-45% of patients and the treatment is poorly tolerated. To improve the efficacy of pre- and post-transplant antiviral therapy, a new class of potent direct-acting antiviral agents (DAAs) has been developed. The aim of this review is to summarize the use of DAAs in LT HCV patients. PubMed, Cochrane Library, MEDLINE, EMBASE, Web of Science and clinical trial databases were searched for this purpose. To date, only three clinical studies on the topic have been published and most of the available data are in abstract form. Although a moderately successful early virological response has been reported, DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness. Moreover, the ongoing nature of data, the lack of randomized studies, the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable. In conclusion, large well-designed clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.
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Staatz CE, Tett SE, Hollenbeak CS, Khan A, Kadry Z. Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update. Arch Toxicol 2014; 24:640-50. [PMID: 24792322 DOI: 10.1111/j.1432-2277.2011.01250.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
This review aims to provide an update of the literature on the pharmacology and toxicology of mycophenolate in solid organ transplant recipients. Mycophenolate is now the antimetabolite of choice in immunosuppressant regimens in transplant recipients. The active drug moiety mycophenolic acid (MPA) is available as an ester pro-drug and an enteric-coated sodium salt. MPA is a competitive, selective and reversible inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH), an important rate-limiting enzyme in purine synthesis. MPA suppresses T and B lymphocyte proliferation; it also decreases expression of glycoproteins and adhesion molecules responsible for recruiting monocytes and lymphocytes to sites of inflammation and graft rejection; and may destroy activated lymphocytes by induction of a necrotic signal. Improved long-term allograft survival has been demonstrated for MPA and may be due to inhibition of monocyte chemoattractant protein 1 or fibroblast proliferation. Recent research also suggested a differential effect of mycophenolate on the regulatory T cell/helper T cell balance which could potentially encourage immune tolerance. Lower exposure to calcineurin inhibitors (renal sparing) appears to be possible with concomitant use of MPA in renal transplant recipients without undue risk of rejection. MPA displays large between- and within-subject pharmacokinetic variability. At least three studies have now reported that MPA exhibits nonlinear pharmacokinetics, with bioavailability decreasing significantly with increasing doses, perhaps due to saturable absorption processes or saturable enterohepatic recirculation. The role of therapeutic drug monitoring (TDM) is still controversial and the ability of routine MPA TDM to improve long-term graft survival and patient outcomes is largely unknown. MPA monitoring may be more important in high-immunological recipients, those on calcineurin-inhibitor-sparing regimens and in whom unexpected rejection or infections have occurred. The majority of pharmacodynamic data on MPA has been obtained in patients receiving MMF therapy in the first year after kidney transplantation. Low MPA area under the concentration time from 0 to 12 h post-dose (AUC0-12) is associated with increased incidence of biopsy-proven acute rejection although AUC0-12 optimal cut-off values vary across study populations. IMPDH monitoring to identify individuals at increased risk of rejection shows some promise but is still in the experimental stage. A relationship between MPA exposure and adverse events was identified in some but not all studies. Genetic variants within genes involved in MPA metabolism (UGT1A9, UGT1A8, UGT2B7), cellular transportation (SLCOB1, SLCO1B3, ABCC2) and targets (IMPDH) have been reported to effect MPA pharmacokinetics and/or response in some studies; however, larger studies across different ethnic groups that take into account genetic linkage and drug interactions that can alter a patient's phenotype are needed before any clinical recommendations based on patient genotype can be formulated. There is little data on the pharmacology and toxicology of MPA in older and paediatric transplant recipients.
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Affiliation(s)
- Christine E Staatz
- School of Pharmacy, The University of Queensland, Brisbane, QLD, 4072, Australia,
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Detry O, Deroover A, Meurisse N, Hans MF, Delwaide J, Lauwick S, Kaba A, Joris J, Meurisse M, Honoré P. Donor age as a risk factor in donation after circulatory death liver transplantation in a controlled withdrawal protocol programme. Br J Surg 2014; 101:784-92. [PMID: 24771475 DOI: 10.1002/bjs.9488] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in deceased donor liver transplantation, and particularly in DCD liver transplantation. At the authors' institute, age is not an absolute exclusion criterion for discarding DCD liver grafts, DCD donors receive comfort therapy before withdrawal, and cold ischaemia is minimized. METHODS All consecutive DCD liver transplantations performed from 2003 to 2012 were studied retrospectively. Three age groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 h, and results at 1 and 3 years. RESULTS A total of 70 DCD liver transplants were performed, including 32 liver grafts from donors aged 55 years or less, 20 aged 56-69 years, and 18 aged 70 years or more. The overall graft survival rate at 1 month, 1 and 3 years was 99, 91 and 72 per cent respectively, with no graft lost secondary to non-anastomotic stricture. No difference other than age was noted between the three groups for donor or recipient characteristics, or procurement conditions. No primary non-function occurred, but one patient needed retransplantation for artery thrombosis. Biliary complications were similar in the three groups. Graft and patient survival rates were no different at 1 and 3 years between the three groups (P = 0.605). CONCLUSION Results for DCD liver transplantation from younger and older donors were similar. Donor age above 50 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as warm and cold ischaemia time) are minimized.
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Affiliation(s)
- O Detry
- Department of Abdominal Surgery and Transplantation, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium
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Joshi D, Carey I, Foxton M, Al-Freah M, Bruce M, Heaton N, Quaglia A, O'Grady J, Aluvihare V, Agarwal K. CXCL10 levels identify individuals with rapid fibrosis at 12 months post-transplant for hepatitis C virus and predict treatment response. Clin Transplant 2014; 28:569-78. [DOI: 10.1111/ctr.12354] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/26/2014] [Indexed: 01/14/2023]
Affiliation(s)
- Deepak Joshi
- Institute of Liver Studies; King's College Hospital; London UK
| | - Ivana Carey
- Institute of Liver Studies; King's College Hospital; London UK
| | - Matthew Foxton
- Institute of Liver Studies; King's College Hospital; London UK
| | | | - Matthew Bruce
- Institute of Liver Studies; King's College Hospital; London UK
| | - Nigel Heaton
- Institute of Liver Studies; King's College Hospital; London UK
| | - Alberto Quaglia
- Institute of Liver Studies; King's College Hospital; London UK
| | - John O'Grady
- Institute of Liver Studies; King's College Hospital; London UK
| | | | - Kosh Agarwal
- Institute of Liver Studies; King's College Hospital; London UK
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Hibi T, Nishida S, Sageshima J, Levi DM, Ruiz P, Roth D, Martin P, Okabayashi K, Burke GW, Ciancio G, Tzakis AG. Excessive immunosuppression as a potential cause of poor survival in simultaneous liver/kidney transplantation for hepatitis C. Transpl Int 2014; 27:606-16. [PMID: 24606223 DOI: 10.1111/tri.12303] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Revised: 08/26/2013] [Accepted: 03/03/2014] [Indexed: 02/06/2023]
Abstract
Appropriate recipient selection of simultaneous liver/kidney transplantation (SLKT) remains controversial. In particular, data on liver graft survival in hepatitis C virus-infected (HCV+) SLKT recipients are lacking. We conducted a single-center, retrospective study of HCV+ SLKT recipients (N = 25) in comparison with HCV- SLKT (N = 26) and HCV+ liver transplantation alone (LTA, N = 296). Despite backgrounds of HCV+ and HCV- SLKT being similar, HCV+ SLKT demonstrated significantly impaired 5-year liver graft survival of 35% (HCV- SLKT, 79%, P = 0.004). Compared with HCV+ LTA, induction immunosuppression was more frequently used in HCV+ SLKT. Five-year liver graft survival rate for HCV+ SLKT was significantly lower than that for LTA (35% vs. 74%, respectively, P < 0.001). Adjusted hazard ratio of liver graft loss in HCV+ SLKT was 4.9 (95% confidence interval 2.0-12.1, P = 0.001). HCV+ SLKT recipients were more likely to succumb to recurrent HCV and sepsis compared with LTA (32% vs. 8.8%, P < 0.001 and 24% vs. 8.8%, P = 0.030, respectively). Ten HCV+ SLKT recipients underwent anti-HCV therapy for recurrent HCV; only 1 achieved sustained virological response. HCV+ SLKT is associated with significantly decreased long-term prognosis compared with HCV- SLKT and HCV+ LTA.
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Affiliation(s)
- Taizo Hibi
- Miami Transplant Institute, University of Miami Leonard M. Miller School of Medicine and Jackson Memorial Hospital, Miami, Florida, USA; DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine and Jackson Memorial Hospital, Miami, Florida, USA; Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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Han JH, You YK, Na GH, Kim EY, Lee SH, Hong TH, Kim DG. Outcomes of living donor liver transplantation using elderly donors. Ann Surg Treat Res 2014; 86:184-91. [PMID: 24783177 PMCID: PMC3996718 DOI: 10.4174/astr.2014.86.4.184] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 11/05/2013] [Accepted: 11/15/2013] [Indexed: 12/18/2022] Open
Abstract
Purpose Living donor liver transplantation (LDLT) using elderly donors is increasing in frequency in response to organ shortage. However, elderly donor graft has been reported to negatively affect graft patency and patient survival. Methods We retrospectively reviewed the medical records of 604 patients who underwent LDLT at Seoul St. Mary's Hospital, The Catholic University of Korea between May 1999 and September 2012. Elderly donors were defined as those ≥55 years of age. Here, we evaluate the survival differences and causes of death of recipients of elderly donor grafts. Results The overall mortality rate of the recipients was significantly higher in the elderly donor group (group A) than in the younger donor group (group B: 46.2% vs. 18.1%, P = 0.004). The survival length of group A was significantly shorter than that of group B (31.2 ± 31.3 and 51.4 ± 40.8 months, P = 0.014). The significantly common causes of death in group A were biliary (41.7%) and arterial complication (16.7%), and it was higher than those in group B (P = 0.000 and P = 0.043, respectively). Conclusion LDLT using elderly donors could induce more serious complications and higher mortality rates than those at using younger donors. As such, careful donor selection is needed, especially with regard to assessing the condition of potential elderly donor livers. Furthermore, a large-volume and multicenter study of complications and outcomes of LDLT using elderly donor liver is required.
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Affiliation(s)
- Jae Hyun Han
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Young Kyoung You
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Gun Hyung Na
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Eun Young Kim
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Soo Ho Lee
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Tae Ho Hong
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Dong Goo Kim
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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Angelico M, Lenci I. Donor–Recipient Matching in HCV-Infected Patients. HEPATITIS C VIRUS AND LIVER TRANSPLANTATION 2014:15-27. [DOI: 10.1007/978-1-4614-8438-7_2] [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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Shores NJ, Dodge JL, Feng S, Terrault NA. Donor Risk Index for African American liver transplant recipients with hepatitis C virus. Hepatology 2013; 58:1263-9. [PMID: 23696235 PMCID: PMC4561529 DOI: 10.1002/hep.26478] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Revised: 03/17/2013] [Accepted: 04/14/2013] [Indexed: 01/06/2023]
Abstract
UNLABELLED African American (AA) liver transplant (LT) recipients with hepatitis C virus (HCV) have higher rates of graft loss than other racial/ethnic groups. The Donor Risk Index (DRI) predicts graft loss but is neither race- nor disease-specific and may not be optimal for assessing donor risk for AA HCV-positive LT recipients. We developed a DRI for AA with HCV with the goal of enhancing graft loss predictions. All U.S. HCV-positive adult AA first deceased donor LTs surviving ≥30 days from March 2002 to December 2009 were included. A total of 1,766 AA LT recipients were followed for median 2.8 (interquartile range [IQR] 1.3-4.9) years. Independent predictors of graft loss were donor age (40-49 years: hazard ratio [HR] 1.54; 50-59 years: HR 1.80; 60+ years: HR 2.34, P < 0.001), non-AA donor (HR 1.66, P < 0.001), and cold ischemia time (CIT) (HR 1.03 per hour >8 hours, P = 0.03). Importantly, the negative effect of increasing donor age on graft and patient survival among AAs was attenuated by receipt of an AA donor. A new donor risk model for AA (AADRI-C) consisting of donor age, race, and CIT yielded 1-year, 3-year, and 5-year predicted graft survival rates of 91%, 77%, and 68% for AADRI <1.60; 86%, 67%, and 55% for AADRI 1.60-2.44; and 78%, 53%, and 39% for AADRI >2.44. In the validation dataset, AADRI-C correctly reclassified 27% of patients (net reclassification improvement P = 0.04) compared to the original DRI. CONCLUSION AADRI-C identifies grafts at higher risk of failure and this information is useful for risk-benefit discussions with recipients. Use of AA donors allows consideration of older donors.
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Affiliation(s)
| | | | - Sandy Feng
- University of California San Francisco, San Francisco, CA
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Agarwal K, Barnabas A. Treatment of chronic hepatitis C virus infection after liver transplantation. Dig Liver Dis 2013; 45 Suppl 5:S349-54. [PMID: 24091115 DOI: 10.1016/j.dld.2013.07.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Accepted: 07/01/2013] [Indexed: 12/11/2022]
Abstract
Chronic hepatitis C virus infection is a leading cause of end stage liver disease and one of the leading indications for liver transplantation. Furthermore, hepatitis C virus recurrence is universal post-transplant leading to decreased graft and patient survival. Recurrent disease related to hepatitis C virus can lead to between 20 and 30% of patients developing recurrent cirrhosis within 5 years. Treatment options with antiviral therapy are limited and are associated with a significant side-effect profile, suboptimal tolerability and inferior response rates. Attention has therefore turned to strategies that can reduce hepatitis C virus recurrence rates post-transplant. Approximately only 30% of patients will achieve a sustained virologic response with current therapy with pegylated interferon and ribavirin. Successful hepatitis C virus eradication is the only factor associated with improved graft and patient survival post liver transplantation. Here we provide an overview of antiviral treatment in patients in the transplant arena and the potential opportunities and challenges with the introduction of new directly acting antivirals in G1 patients.
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Affiliation(s)
- Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, UK.
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Dumitra S, Alabbad SI, Barkun JS, Dumitra TC, Coutsinos D, Metrakos PP, Hassanain M, Paraskevas S, Chaudhury P, Tchervenkov JI. Hepatitis C infection and hepatocellular carcinoma in liver transplantation: a 20-year experience. HPB (Oxford) 2013; 15:724-31. [PMID: 23490176 PMCID: PMC3948541 DOI: 10.1111/hpb.12041] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2012] [Accepted: 11/28/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatitis C infection (HCV) and hepatocellular carcinoma (HCC), the two main causes of liver transplantation (LT), have reduced survival post-LT. The impact of HCV, HCC and their coexistence on post-LT survival were assessed. METHODOLOGY All 601 LT patients from 1992 to 2011 were reviewed. Those deceased within 30 days (n = 69) and re-transplants (n = 49) were excluded. Recipients were divided into four groups: (a) HCC-/HCV-(n = 252) (b) HCC+/HCV- (n = 58), (c) HCC-/HCV+ (n = 106) and (d) HCC+/HCV+ (n = 67). Demographics, the donor risk index (DRI), Model for End-Stage Liver Disease (MELD) score, survival, complications and tumour characteristics were collected. Statistical analysis included anova, chi-square, Fisher's exact tests and Cox and Kaplan-Meier for overall survival. RESULTS Groups were comparable with regards to baseline characteristics, but HCC patients were older. After adjusting for age, MELD, gender and the donor risk index (DRI), survival was lower in the HCC+/HCV+ group (59.5% at 5 yrs) and the hazard ratio (HR) was 1.90 [95% confidence interval (CI),1.24-2.95, P = 0.003] and 1.45 (95% CI, 0.99-2.12, P = 0.054) for HCC-/HCV+. HCC survival was similar to controls (HR 1.18, 95% CI, 0.71-1.93, P = 0.508). HCC+/HCV- patients exceeded the Milan criteria (50% versus 31%, P < 0.04) and had more micro-vascular invasion (37.5% versus 20.6%, P = 0.042). HCC+/HCV+ versus HCC+/HCV- survival remained lower (HR 1.94, 95% CI, 1.06-3.81, P = 0.041) after correcting for tumour characteristics and treatment. CONCLUSION HCV patients had lower survival post-LT. HCC alone had no impact on survival. Patient survival decreased in the HCC+/HCV+ group and this appears to be as a consequence of HCV recurrence.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Jean I Tchervenkov
- Correspondence Jean I. Tchervenkov, Royal Victoria Hospital, 687 Pine Avenue West, Room S10.26, Montreal, Quebec, Canada, H3A 1A1. Tel: +1 514 934 1934 ext. 34042. Fax: +1 514 843 1503. E-mail:
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Gelley F, Gámán G, Gerlei Z, Zádori G, Görög D, Kóbori L, Fehérvári I, Schuller J, Szőnyi L, Nagy P, Doros A, Fazakas J, Lengyel G, Schaff Z, Kiss A, Sárváry E, Nemes B. Hepatitis C virus recurrence after liver transplantation in Hungary. Trends over the past 10 years. Orv Hetil 2013; 154:1058-66. [DOI: 10.1556/oh.2013.29647] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Introduction: Management of hepatitis C virus recurrence is a challenge after liver transplantation. Aim: The aim of the authors was to analyse the outcome of liver transplantation performed in hepatitis C virus positive patients during the past ten years and to compare recent data with a previous report of the authors. Method: The authors retrospectively evaluated the data (donors, recipients, perioperative characteristics, patient and graft survival, serum titer of hepatitis C virus RNA, histology) of 409 patients who underwent liver transplantation between 2003 and 2012. Results: 156 patients were transplanted due to hepatitis C virus associated liver cirrhosis (38%). Worse outcome was observed in these patients in comparison to hepatitis C virus negative recipients. The cumulative patient survival rates at 1, 5, and 10 year were 80%, 61%, 51% in the hepatitis C virus positive group and 92%, 85%, 79% in the hepatitis C virus negative group, respectively (p<0.001). The cumulative graft survival rates at 1, 5 and 10 year were 79%, 59% and 50% in hepatitis C virus positive and 89%, 80% and 70% in hepatitis C virus negative patients (p<0.001). Hepatitis C virus recurrence was observed in the majority of the patients (132 patients, 85%), mainly within the first year (83%). The authors observed recurrence within 6 months in 71 patients (56%), and within 3 months in 26 patients (20%). The mean hepatitis C virus recurrence free survival was 243 days. Higher rate of de novo diabetes was detected in case of early recurrence. The cumulative patient survival rates at 1, 3, 5, 10 years were 98%, 89.5%, 81% and 65% when hepatitis C virus recurrence exceeded 3 months and 64%, 53%, 30.5% and 30.5% in patients with early recurrence (p<0.001). Conclusions: Poor outcome of liver transplantation in hepatitis C virus positive patients is still a challenge. Hepatitis C virus recurrence is observed earlier after liver transplantation in comparison with a previous report of the authors. De novo diabetes occurs more frequently in case of early recurrence. Despite an immediate start of antiviral treatment, early recurrence has a significant negative impact on the outcome of transplantation. Orv. Hetil., 2013, 154, 1058–1066.
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Affiliation(s)
- Fanni Gelley
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - György Gámán
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - Zsuzsanna Gerlei
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - Gergely Zádori
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - Dénes Görög
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - László Kóbori
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - Imre Fehérvári
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - János Schuller
- Egyesített Szent István és Szent László Kórház – Rendelőintézet Hepatológiai Osztály Budapest
| | - László Szőnyi
- Semmelweis Egyetem, Általános Orvostudományi Kar I. Gyermekgyógyászati Klinika, Általános Belgyógyászati és Gasztroenterológiai Osztály Budapest
| | - Péter Nagy
- Semmelweis Egyetem, Általános Orvostudományi Kar I. Patológiai és Kísérleti Rákkutató Intézet Budapest
| | - Attila Doros
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - János Fazakas
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - Gabriella Lengyel
- Semmelweis Egyetem, Általános Orvostudományi Kar II. Belgyógyászati Klinika Budapest
| | - Zsuzsa Schaff
- Semmelweis Egyetem, Általános Orvostudományi Kar II. Patológiai Intézet Budapest
| | - András Kiss
- Semmelweis Egyetem, Általános Orvostudományi Kar II. Patológiai Intézet Budapest
| | - Enikő Sárváry
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
| | - Balázs Nemes
- Semmelweis Egyetem, Általános Orvostudományi Kar Transzplantációs és Sebészeti Klinika Budapest
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