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Feng S, Roll GR, Rouhani FJ, Sanchez Fueyo A. The future of liver transplantation. Hepatology 2024; 80:674-697. [PMID: 38537154 DOI: 10.1097/hep.0000000000000873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 03/02/2024] [Indexed: 06/15/2024]
Abstract
Over the last 50 years, liver transplantation has evolved into a procedure routinely performed in many countries worldwide. Those able to access this therapy frequently experience a miraculous risk-benefit ratio, particularly if they face the imminently life-threatening disease. Over the decades, the success of liver transplantation, with dramatic improvements in early posttransplant survival, has aggressively driven demand. However, despite the emergence of living donors to augment deceased donors as a source of organs, supply has lagged far behind demand. As a result, rationing has been an unfortunate focus in recent decades. Recent shifts in the epidemiology of liver disease combined with transformative innovations in liver preservation suggest that the underlying premise of organ shortage may erode in the foreseeable future. The focus will sharpen on improving equitable access while mitigating constraints related to workforce training, infrastructure for organ recovery and rehabilitation, and their associated costs. Research efforts in liver preservation will undoubtedly blossom with the aim of optimizing both the timing and conditions of transplantation. Coupled with advances in genetic engineering, regenerative biology, and cellular therapies, the portfolio of innovation, both broad and deep, offers the promise that, in the future, liver transplantation will not only be broadly available to those in need but also represent a highly durable life-saving therapy.
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Affiliation(s)
- Sandy Feng
- Department of Surgery, Division of Transplant Surgery, University of California, San Francisco, California, USA
| | - Garrett R Roll
- Department of Surgery, Division of Transplant Surgery, University of California, San Francisco, California, USA
| | - Foad J Rouhani
- Tissue Regeneration and Clonal Evolution Laboratory, The Francis Crick Institute, London, UK
- Institute of Liver Studies, King's College London, King's College Hospital, NHS Foundation Trust, London, UK
| | - Alberto Sanchez Fueyo
- Institute of Liver Studies, King's College London, King's College Hospital, NHS Foundation Trust, London, UK
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2
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Chaib E, Pessoa JLE, Struchiner CJ, D'Albuquerque LAC, Massad E. THE OPTIMUM LEVEL OF MELD TO MINIMIZE THE MORTALITY ON LIVER TRANSPLANTATION WAITING LIST, AND LIVER TRANSPLANTED PATIENT IN SÃO PAULO STATE, BRAZIL. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1746. [PMID: 37729279 PMCID: PMC10510095 DOI: 10.1590/0102-672020230028e1746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/20/2023] [Indexed: 09/22/2023]
Abstract
BACKGROUND After validation in multiple types of liver disease patients, the MELD score was adopted as a standard by which liver transplant candidates with end-stage liver disease were prioritized for organ allocation in the United States since 2002, and in Brazil, since 2006. AIMS To analyze the mortality profile of patients on the liver transplant waiting list correlated to MELD score at the moment of transplantation. METHODS This study used the data from the Secretary of Health of the São Paulo State, Brazil, which listed 22,522 patients, from 2006 (when MELD score was introduced in Brazil) until June 2009. Patients with acute hepatic failure and tumors were included as well. We also considered the mortality of both non-transplanted and transplanted patients as a function of the MELD score at presentation. RESULTS Our model showed that the best MELD score for patients on the liver transplant waiting list associated to better results after liver transplantation was 26. CONCLUSIONS We found that the best score for applying to liver transplant waiting list in the State of São Paulo was 26. This is the score that minimizes the mortality in both non-transplanted and liver transplanted patients.
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Affiliation(s)
- Eleazar Chaib
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo - São Paulo (SP), Brazil
| | | | - Claudio José Struchiner
- Applied Mathematics, School of Applied Mathematics, Fundação Getulio Vargas - Rio de Janeiro (RJ), Brazil
| | | | - Eduardo Massad
- Applied Mathematics, School of Applied Mathematics, Fundação Getulio Vargas - Rio de Janeiro (RJ), Brazil
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3
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Dirchwolf M, Becchetti C, Gschwend SG, Toso C, Dutkowski P, Immer F, Beyeler F, Rossi S, Schropp J, Dufour JF, Banz V. The MELD upgrade exception: a successful strategy to optimize access to liver transplantation for patients with high waiting list mortality. HPB (Oxford) 2022; 24:1168-1176. [PMID: 35065891 DOI: 10.1016/j.hpb.2021.12.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND MELD exceptions are designed to equipoise liver transplant waiting list survival. We aimed to analyze the impact of the MELD Upgrade rule and all other MELD exceptions on the liver transplant waiting list outcomes during 2012-2017 in Switzerland. METHODS We conducted a nationwide cohort study including all adult patients registered on the Swiss liver transplant waiting list between 2012 and 2017. Waiting list mortality and access to transplantation were analyzed, considering MELD exceptions as time-dependent covariates. RESULTS 730 patients were included. Patients with MELD Upgrade exceptions had a higher risk of dying while on the waiting list (OR 2.13; CI 95% 1.30-3.47) and also an increased likelihood of receiving a liver transplantation, when compared to patients without MELD exceptions. Patients with any type of MELD exceptions were more likely to be transplanted when compared to patients without MELD exceptions. The proportion of patients with MELD exceptions increased from 2012 to 2017 (44% vs 88%). Allocation MELD at the time of transplantation showed an annual increase (23 ± 8 points vs 32 ± 5 points, p < 0.001). CONCLUSION Only patients with MELD Upgrade exceptions had the expected combination of higher waiting list mortality and quicker access to liver transplantation.
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Affiliation(s)
- Melisa Dirchwolf
- Novartis Fellowship in Hepatology, Department of Biomedical Research, University of Bern Murtenstrasse 35, 3008 Bern, Switzerland; Liver Unit, Hospital Privado de Rosario Presidente Roca 2440, 2000 Rosario, Santa Fe, Argentina.
| | - Chiara Becchetti
- Department of Visceral Surgery and Medicine, Berne University Hospital, University of Berne, Berne, Switzerland Freiburgstrasse 18, 3010 Bern, Switzerland
| | - Sarah G Gschwend
- Department of Visceral Surgery and Medicine, Berne University Hospital, University of Berne, Berne, Switzerland Freiburgstrasse 18, 3010 Bern, Switzerland
| | - Christian Toso
- Abdominal Surgery, Geneva University Hospital of Geneva Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland
| | - Philipp Dutkowski
- Abdominal Transplant Surgery, University Hospital of Zürich Rämistrasse 100, 8091 Zürich, Switzerland
| | - Franz Immer
- Swisstransplant, The Swiss National Foundation for Organ Donation and Transplantation Effingerstrasse 1, 3011 Bern, Switzerland
| | - Franziska Beyeler
- Swisstransplant, The Swiss National Foundation for Organ Donation and Transplantation Effingerstrasse 1, 3011 Bern, Switzerland
| | - Simona Rossi
- Swiss Transplant Cohort Study (STCS), Data Center, Spitalstrasse 12, 4031 Basel, Switzerland
| | - Jonas Schropp
- Department of Visceral Surgery and Medicine, Berne University Hospital, University of Berne, Berne, Switzerland Freiburgstrasse 18, 3010 Bern, Switzerland; Department of Computer Science, Open University of Cyprus, Giannou Kranidioti 33, Latsia 2220, Cyprus; Department of Psychology, University of Cyprus, Kallipoleos 75, Nicosia 1678, Cyprus
| | - Jean-François Dufour
- Department of Visceral Surgery and Medicine, Berne University Hospital, University of Berne, Berne, Switzerland Freiburgstrasse 18, 3010 Bern, Switzerland
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Berne University Hospital, University of Berne, Berne, Switzerland Freiburgstrasse 18, 3010 Bern, Switzerland.
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Reszegi A, Tátrai P, Regős E, Kovalszky I, Baghy K. Syndecan-1 in liver pathophysiology. Am J Physiol Cell Physiol 2022; 323:C289-C294. [PMID: 35704700 DOI: 10.1152/ajpcell.00039.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Syndecan-1 is a heparan sulfate/chondroitin sulfate proteoglycan (PG) of the cell surface and the extracellular matrix, which regulates a broad spectrum of physiological and pathological processes such as cell proliferation, migration, inflammation, matrix remodeling, wound healing, or tumorigenesis. Syndecan-1 represents the major PG of the liver, expressed by hepatocytes and cholangiocytes, and its elevated expression is a characteristic feature of liver diseases. The highest syndecan-1 expression is found in liver cirrhosis and in hepatocellular carcinoma (HCC) developed in cirrhotic livers. In addition, as being a hepatitis C receptor, hepatitis C virus (HCV) infected livers produce extremely large amounts of syndecan-1. The serum levels of the cleaved (shedded) extracellular domain has clinical significance, as its increased concentration reflects on poor prognosis in cirrhosis as well as in cancer. In vivo experiments confirmed that syndecan-1 protects against early stages of fibrogenesis mainly by enhanced clearance of transforming growth factor beta (TGFβ1) and thrombospondin-1 via circulation, and against hepatocarcinogenesis by interfering with several signaling pathways and enhancing cell cycle blockade. In addition, syndecan-1 is capable to hinder lipid metabolism and ribosomal biogenesis in induced cancer models.. These observations together with its participation in the uptake of viruses (e.g. HCV, SARS-CoV-2) indicate that syndecan-1 is a central player in liver pathologies.
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Affiliation(s)
- Andrea Reszegi
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | | | - Eszter Regős
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Ilona Kovalszky
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Kornelia Baghy
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
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5
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Yi SG, Mobley C, Ghobrial RM. Graft and Patient Survival after Liver Transplantation. TEXTBOOK OF LIVER TRANSPLANTATION 2022:433-448. [DOI: 10.1007/978-3-030-82930-8_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Moeckli B, Majno P, Orci LA, Peloso A, Toso C. Liver Transplantation Selection and Allocation Criteria for Hepatocellular Carcinoma: A European Perspective. Semin Liver Dis 2021; 41:172-181. [PMID: 33957694 DOI: 10.1055/s-0041-1723032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
For patients with early-stage hepatocellular carcinoma (HCC), liver transplantation offers the best chance of cure. Over the past two decades, selection criteria to determine eligibility for liver transplantation have been constantly refined but a fair allocation strategy of liver grafts to HCC patients remains challenging. In Europe, over a dozen transplantation networks apply different liver transplantation criteria for HCC patients. In this review, we explore and compare candidate selection and liver graft allocation strategies for patients with HCC with a European perspective and discuss the ethical and technical challenges involved. In addition, we suggest possible paths for future improvement such as transitioning from fixed selection and allocation criteria to a more flexible model of benefit, which includes criteria concerning the graft, response to treatment, the biology of the tumor, and other relevant recipient factors.
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Affiliation(s)
- Beat Moeckli
- Department of Visceral and Transplantation Surgery, University of Geneva Hospitals, Geneva, Switzerland
| | - Pietro Majno
- Epatocentro, Ospedale Regionale di Lugano, Lugano, Switzerland
| | - Lorenzo A Orci
- Department of Visceral and Transplantation Surgery, University of Geneva Hospitals, Geneva, Switzerland
| | - Andrea Peloso
- Department of Visceral and Transplantation Surgery, University of Geneva Hospitals, Geneva, Switzerland
| | - Christian Toso
- Department of Visceral and Transplantation Surgery, University of Geneva Hospitals, Geneva, Switzerland
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Goosmann L, Buchholz A, Bangert K, Fuhrmann V, Kluge S, Lohse AW, Huber S, Fischer L, Sterneck M, Huebener P. Liver transplantation for acute-on-chronic liver failure predicts post-transplant mortality and impaired long-term quality of life. Liver Int 2021; 41:574-584. [PMID: 34542228 DOI: 10.1111/liv.14756] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 11/05/2020] [Accepted: 12/01/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Among patients with cirrhosis, candidate selection and timing of liver transplantation (LT) remain problematic. Acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis with excessive short-term mortality rates under conservative therapeutic measures. The role of LT in the management of ACLF is uncertain. OBJECTIVE To assess the impact of ACLF on post-LT survival and long-term graft function, morbidity and quality of life (QoL). METHODS We retrospectively analysed all cirrhosis patients undergoing LT at our institution between 01/2009 and 12/2014. Median follow-up was 8.7 years. Long-term LT survivors were interviewed with established QoL questionnaires. RESULTS Of 250 LT recipients, 98 fulfilled the EASL diagnostic ACLF criteria before LT ('ACLF-LT'). ACLF associated with reduced post-LT survival (HR for 6-month survival compared to non-ACLF-LT: 0.18; HR for 10-year-survival: 0.47; both P < .001) depending on ACLF severity before LT, and mainly inferred by infections both in the early and late phases after LT. In ACLF patients, CLIFc-OFs was superior to MELD score in predicting post-LT mortality. Long-term follow-up revealed comparable graft functions and comorbidity burden in ACLF-LT and non-ACLF-LT survivors. ACLF-LT patients reported significantly impaired health and QoL, particularly with regards to anxiety/depression and physical and psychological health (all P < .05). LabMELD score, presence of ACLF at LT and duration of post-LT intensive care associated with poor long-term QoL. CONCLUSION ACLF predicts impaired post-LT survival. While long-term graft function and extrahepatic comorbidities are comparable in ACLF and non-ACLF LT survivors, the strikingly low QoL in many ACLF-LT recipients warrants consideration during follow-up patient care.
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Affiliation(s)
- Lukas Goosmann
- Department of Internal Medicine, I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Angela Buchholz
- Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katrin Bangert
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Valentin Fuhrmann
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Stefan Kluge
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W Lohse
- Department of Internal Medicine, I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Samuel Huber
- Department of Internal Medicine, I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lutz Fischer
- Department of Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Sterneck
- Department of Internal Medicine, I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Peter Huebener
- Department of Internal Medicine, I. Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Regős E, Karászi K, Reszegi A, Kiss A, Schaff Z, Baghy K, Kovalszky I. Syndecan-1 in Liver Diseases. Pathol Oncol Res 2019; 26:813-819. [PMID: 30826971 PMCID: PMC7242248 DOI: 10.1007/s12253-019-00617-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 02/15/2019] [Indexed: 12/14/2022]
Abstract
Liver diseases such as liver cirrhosis, primary and metastatic liver cancers are still a major medical challenge. Syndecan-1 is one of the most important proteoglycans in the liver. Syndecan-1 is normally expressed on the surfaces of hepatocytes and cholangiocytes. Due to liver diseases the amount of syndecan-1 increases in the liver. Despite the emerging data of the biological function of syndecan-1, the clinical usefulness of this proteoglycan is still unknown. In our study we correlated syndecan-1 expression to clinico-pathological data. We found that syndecan-1 proved to be a good marker for hepatitis C virus based hepatocellular carcinoma and increased with liver dysfunction.
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Affiliation(s)
- Eszter Regős
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői Street 26, Budapest, 1085, Hungary
| | - Katalin Karászi
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői Street 26, Budapest, 1085, Hungary
| | - Andrea Reszegi
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői Street 26, Budapest, 1085, Hungary
| | - András Kiss
- 2nd Department of Pathology, Semmelweis University, Üllői street 93, Budapest, 1091, Hungary
| | - Zsuzsa Schaff
- 2nd Department of Pathology, Semmelweis University, Üllői street 93, Budapest, 1091, Hungary
| | - Kornélia Baghy
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői Street 26, Budapest, 1085, Hungary
| | - Ilona Kovalszky
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői Street 26, Budapest, 1085, Hungary.
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Arisar FAQ, Abid S, Shaikh PA, Awan S. Impact of sepsis and non-communicable diseases on prognostic models to predict the outcome of hospitalized chronic liver disease patients. World J Hepatol 2018; 10:944-955. [DOI: doi.org/10.4254/wjh.v10.i12.944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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Qazi Arisar FA, Abid S, Shaikh PA, Awan S. Impact of sepsis and non-communicable diseases on prognostic models to predict the outcome of hospitalized chronic liver disease patients. World J Hepatol 2018; 10:944-955. [PMID: 30631399 PMCID: PMC6323522 DOI: 10.4254/wjh.v10.i12.944] [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: 08/04/2018] [Revised: 09/07/2018] [Accepted: 10/17/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the impact of sepsis and non-communicable diseases (NCDs) on the outcome of decompensated chronic liver disease (CLD) patients. METHODS In this cross-sectional study, medical records of patients with CLD admitted to the Gastroenterology unit at the Aga Khan University Hospital were reviewed. Patients older than 18 years with decompensation of CLD (i.e., jaundice, ascites, encephalopathy, and/or upper gastrointestinal bleed) as the primary reason for admission were included, while those who were admitted for reasons other than decompensation of CLD were excluded. Each patient was followed for 6 wk after index admission to assess mortality, prolonged hospital stay (> 5 d), and early readmission (within 7 d). RESULTS A total of 399 patients were enrolled. The mean age was 54.3 ± 11.7 years and 64.6% (n = 258) were male. Six-week mortality was 13% (n = 52). Prolonged hospital stay and readmission were present in 18% (n = 72) and 7% (n = 28) of patients, respectively. NCDs were found in 47.4% (n = 189) of patients. Acute kidney injury, sepsis, and non-ST elevation myocardial infarction were found in 41% (n = 165), 17.5% (n = 70), and 1.75% (n = 7) of patients, respectively. Upon multivariate analysis, acute kidney injury, non-ST elevation myocardial infarction, sepsis, and coagulopathy were found to be statistically significant predictors of mortality. While chronic kidney disease (CKD), low albumin, and high Model for End-Stage Liver Disease (MELD)-Na score were found to be statistically significant predictors of morbidity. Addition of sepsis in conventional MELD score predicted mortality even better than MELD-Na (area under receiver operating characteristic: 0.735 vs 0.686; P < 0.001). Among NCDs, CKD was found to increase morbidity independently. CONCLUSION Addition of sepsis improved the predictability of MELD score as a prognostic marker for mortality in patients with CLD. Presence of CKD increases the morbidity of patients with CLD.
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Affiliation(s)
- Fakhar Ali Qazi Arisar
- Section of Gastroenterology, Department of Medicine, Faculty Offices Building, the Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Shahab Abid
- Section of Gastroenterology, Department of Medicine, Faculty Offices Building, the Aga Khan University Hospital, Karachi 74800, Pakistan.
| | - Preet Ayoub Shaikh
- Section of Gastroenterology, Department of Medicine, Faculty Offices Building, the Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Safia Awan
- Section of Gastroenterology, Department of Medicine, Faculty Offices Building, the Aga Khan University Hospital, Karachi 74800, Pakistan
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12
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Umgelter A, Hapfelmeier A, Kopp W, van Rosmalen M, Rogiers X, Guba M. Disparities in Eurotransplant liver transplantation wait-list outcome between patients with and without model for end-stage liver disease exceptions. Liver Transpl 2017. [PMID: 28650098 DOI: 10.1002/lt.24805] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The sickest-first principle in donor-liver allocation can be implemented by allocating organs to patients with cirrhosis with the highest Model for End-Stage Liver Disease (MELD) scores. For patients with other risk factors, standard exceptions (SEs) and nonstandard exceptions (NSEs) have been developed. We investigated whether this system of matched MELD scores achieves similar outcomes on the liver transplant waiting list for various diagnostic groups in Eurotransplant (ET) countries with MELD-based individual allocation (Belgium, the Netherlands, and Germany). A retrospective analysis of the ET wait-list outflow from December 2006 until December 2015 was conducted to investigate the relation of the unified MELD-based allocation to the risk of a negative wait-list outcome (death on the waiting list or delisting as too sick) as opposed to a positive wait-list outcome (transplantation or delisting as recovered). A total of 16,926 patients left the waiting list with a positive (11,580) or negative (5346) outcome; 3548 patients had a SE, and 330 had a NSE. A negative outcome was more common among patients without a SE or NSE (34.3%) than among patients with a SE (22.6%) or NSE (18.6%; P < 0.001). Analysis by model-based recursive partitioning detected 5 risk groups with different relations of matched MELD to a negative outcome. In Germany, we found the following: (1) no SE or NSE, SE for biliary sepsis (BS); (2) SE for hepatocellular carcinoma (HCC), hepatopulmonary syndrome (HPS), or portopulmonary hypertension (PPH); and (3) SE for primary sclerosing cholangitis (PSC) or polycystic liver disease (PcLD). In Belgium and the Netherlands, we found the following: (4) SE or NSE, or SE for HPS or PPH; and (5) SE for BS, HCC, PcLD, or PSC. In conclusion, SEs and NSEs do not even out risks across different diagnostic groups. Patients with SEs or NSEs appear advantaged toward patients with cirrhosis without SEs or NSEs. Liver Transplantation 23 1256-1265 2017 AASLD.
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Affiliation(s)
- Andreas Umgelter
- 2nd Medical Department, Technische Universität München, Munich, Germany
| | - Alexander Hapfelmeier
- Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany
| | - Wouter Kopp
- Eurotransplant International Foundation, Leiden, the Netherlands
| | | | - Xavier Rogiers
- Department of Surgery, Gent University Hospital Medical School, Gent, Belgium
| | - Markus Guba
- Department of General, Visceral and Transplant Surgery, Großhadern Clinic, University of Munich, Munich, Germany
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A Concentric Neighborhood Solution to Disparity in Liver Access That Contains Current UNOS Districts. Transplantation 2017; 102:255-278. [PMID: 28885499 DOI: 10.1097/tp.0000000000001934] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Policymakers are deliberating reforms to reduce geographic disparity in liver allocation. Public comments and the United Network for Organ Sharing Liver and Intestinal Committee have expressed interest in refining the neighborhoods approach. Share 35 and Share 15 policies affect geographic disparity. METHODS We construct concentric neighborhoods superimposing the current 11 regions. Using concepts from concentric circles, we construct neighborhoods for each donor service area (DSA) that consider all DSAs within 400, 500, or 600 miles as neighbors. We consider limiting each neighborhood to 10 DSAs and use no metrics for liver supplies and demands. We change Model for End-Stage Liver Disease (MELD) thresholds for the Share 15 policy to 18 or 20 and apply 3- and 5-point MELD proximity boosts to enhance local priority, control travel distances, and reduce disparity. We conduct simulations comparing current allocation with the neighborhoods and sharing policies. RESULTS Concentric neighborhoods structures provide an array of solutions where simulation results indicate that they reduce geographic disparity, annual mortalities, and the airplane travel distances by varying degrees. Tuning of the parameters and policy combinations can lead to beneficial improvements with acceptable transplant volume loss and reductions in geographic disparity and travel distance. Particularly, the 10-DSA, 500-mile neighborhood solution with Share 35, Share 15, and 0-point MELD boost achieves such while limiting transplant volume losses to below 10%. CONCLUSIONS The current 11 districts can be adapted systematically by adding neighboring DSAs to improve geographic disparity, mortality, and airplane travel distance. Modifications to Share 35 and Share 15 policies result in further improvements. The solutions may be refined further for implementation.
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14
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Nadim MK, DiNorcia J, Ji L, Groshen S, Levitsky J, Sung RS, Kim WR, Andreoni K, Mulligan D, Genyk YS. Inequity in organ allocation for patients awaiting liver transplantation: Rationale for uncapping the model for end-stage liver disease. J Hepatol 2017; 67:517-525. [PMID: 28483678 PMCID: PMC7735955 DOI: 10.1016/j.jhep.2017.04.022] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Revised: 03/23/2017] [Accepted: 04/17/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIM The goal of organ allocation is to distribute a scarce resource equitably to the sickest patients. In the United States, the Model for End-stage Liver Disease (MELD) is used to allocate livers for transplantation. Patients with greater MELD scores are at greater risk of death on the waitlist and are prioritized for liver transplant (LT). The MELD is capped at 40 however, and patients with calculated MELD scores >40 are not prioritized despite increased mortality. We aimed to evaluate waitlist and post-transplant survival stratified by MELD to determine outcomes in patients with MELD >40. METHODS Using United Network for Organ Sharing data, we identified patients listed for LT from February 2002 through to December 2012. Waitlist candidates with MELD ⩾40 were followed for 30days or until the earliest occurrence of death or transplant. RESULTS Of 65,776 waitlisted patients, 3.3% had MELD ⩾40 at registration, and an additional 7.3% had MELD scores increase to ⩾40 after waitlist registration. A total of 30,369 (46.2%) underwent LT, of which 2,615 (8.6%) had MELD ⩾40 at transplant. Compared to MELD 40, the hazard ratio of death within 30days of registration was 1.4 (95% CI 1.2-1.6) for patients with MELD 41-44, 2.6 (95% CI 2.1-3.1) for MELD 45-49, and 5.0 (95% CI 4.1-6.1) for MELD ⩾50. There was no difference in 1- and 3-year survival for patients transplanted with MELD >40 compared to MELD=40. A survival benefit associated with LT was seen as MELD increased above 40. CONCLUSIONS Patients with MELD >40 have significantly greater waitlist mortality but comparable post-transplant outcomes to patients with MELD=40 and, therefore, should be given priority for LT. Uncapping the MELD will allow more equitable organ distribution aligned with the principle of prioritizing patients most in need. Lay summary: In the United States (US), organs for liver transplantation are allocated by an objective scoring system called the Model for End-stage Liver Disease (MELD), which aims to prioritize the sickest patients for transplant. The greater the MELD score, the greater the mortality without liver transplant. The MELD score, however, is artificially capped at 40 and thus actually disadvantages the sickest patients with end-stage liver disease. Analysis of the data advocates uncapping the MELD score to appropriately prioritize the patients most in need of a liver transplant.
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Affiliation(s)
- Mitra K Nadim
- Division of Nephrology and Hypertension, University of Southern California, Los Angeles, CA, United States.
| | - Joseph DiNorcia
- Division of Hepatobiliary, Pancreas, and Abdominal Organ Transplant Surgery, University of Southern California, Los Angeles, CA, United States
| | - Lingyun Ji
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States
| | - Susan Groshen
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Randall S Sung
- Section of Transplant Surgery, University of Michigan, Ann Arbor, MI, United States
| | - W Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, United States
| | - Kenneth Andreoni
- Division of Abdominal Transplantation Surgery, University of Florida, Gainesville, FL, United States
| | - David Mulligan
- Section of Transplantation and Immunology, Yale University School of Medicine, New Haven, CT, United States
| | - Yuri S Genyk
- Division of Hepatobiliary, Pancreas, and Abdominal Organ Transplant Surgery, University of Southern California, Los Angeles, CA, United States
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15
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Machicao VI. Model for End-Stage Liver Disease-Sodium Score: The Evolution in the Prioritization of Liver Transplantation. Clin Liver Dis 2017; 21:275-287. [PMID: 28364813 DOI: 10.1016/j.cld.2016.12.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The adoption of the model of end-stage liver disease (MELD) score as surrogate marker of liver disease severity has been the greatest change in liver allocation. Since its implementation, waiting time has lost significance. The MELD score calculation was later modified to reflect the contribution of hyponatremia in the estimation of mortality risk. However, the MELD score does not capture accurately the risk of mortality of patients with hepatocellular carcinoma (HCC). Therefore the arbitrary assignment of MELD points has been used for HCC patients. The current allocation system still prioritizes transplantation in HCC patients.
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Affiliation(s)
- Victor Ilich Machicao
- Division of Gastroenterology, Hepatology and Nutrition, McGovern Medical School, University of Texas Health Science Center at Houston, 6400 Fannin Street, MSB 4.234, Houston, TX 77030, USA.
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16
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Salvalaggio PR, Felga GE, Guardia BD, Almeida MD, Pandullo FL, Matielo CE, Evangelista A, Curvelo L, Rocco RA, Alves JA, Meirelles RF, Filho SPM, de Rezende MB, Pedroso PT, Diaz LG, Rusi MB, Viveiros MM, Neves DB. Time of Dropout From the Liver Transplant List in Patients With Hepatocellular Carcinoma: Clinical Behavior According to Tumor Characteristics and Severity of Liver Disease. Transplant Proc 2017; 48:2319-2322. [PMID: 27742288 DOI: 10.1016/j.transproceed.2016.06.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Prolonged time on the waiting list affects post-transplant survival of patients with hepatocellular carcinoma (HCC). However, it is not yet known which patients will be at higher risk for early dropout from the list. We investigate specific risk factors for early waiting list dropout in patients with HCC. METHODS This was a single-center, intention-to-treat analysis of adults with HCC, within the Milan criteria, from July 2006 through September 2013. Patients were divided into groups according to waiting list time. The main end point was dropout from the list. RESULTS The dropout rates of the study cohort at 3, 6, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Patients who dropped out from the list tended to be older, with blood types A and O, and with higher Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. They also had larger nodules, responded poorly to trans-arterial chemo-embolization (TACE), and had a higher alpha-fetoprotein. Those with blood types B and AB appeared to be protected for dropout (odds ratio [OR] = 0.21, P = .02). Patients who responded to TACE were also protected (OR = 0.22, P < .001). When we looked into time to dropout, the only baseline characteristic that stood out was a higher MELD score (13 for those dropping out up to 90 days vs 10 for those dropping out after 180 days, P = .0025). CONCLUSIONS We conclude that patients who drop out early from the list are primarily driven by the severity of liver disease. Patients who had progressive HCC had a high tumor load and poor response to loco-regional therapies, dropping out from the list after 180 days of inclusion.
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Affiliation(s)
- P R Salvalaggio
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil.
| | - G E Felga
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - B D Guardia
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - M D Almeida
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - F L Pandullo
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - C E Matielo
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - A Evangelista
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - L Curvelo
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - R A Rocco
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - J A Alves
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - R F Meirelles
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - S P M Filho
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - M B de Rezende
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - P T Pedroso
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - L G Diaz
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - M B Rusi
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - M M Viveiros
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - D B Neves
- Liver Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
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17
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18
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Reddy SS, Civan JM. From Child-Pugh to Model for End-Stage Liver Disease: Deciding Who Needs a Liver Transplant. Med Clin North Am 2016; 100:449-64. [PMID: 27095638 DOI: 10.1016/j.mcna.2015.12.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
This article reviews the historical evolution of the liver transplant organ allocation policy and the indications/contraindications for liver transplant, and provides an overview of the liver transplant evaluation process. The article is intended to help internists determine whether and when referral to a liver transplant center is indicated, and to help internists to counsel patients whose initial evaluation at a transplant center is pending.
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Affiliation(s)
- Sheela S Reddy
- Division of Gastroenterology & Hepatology, Department of Medicine, Thomas Jefferson University, Suite 480 Main Building, 132 South 10th Street, Philadelphia, PA 19107, USA
| | - Jesse M Civan
- Division of Gastroenterology & Hepatology, Department of Medicine, Thomas Jefferson University, Suite 480 Main Building, 132 South 10th Street, Philadelphia, PA 19107, USA.
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19
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Fernandez H, Weber J, Barnes K, Wright L, Levy M. Financial Impact of Liver Sharing and Organ Procurement Organizations' Experience With Share 35: Implications for National Broader Sharing. Am J Transplant 2016; 16:287-91. [PMID: 26372681 DOI: 10.1111/ajt.13436] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Revised: 06/11/2015] [Accepted: 06/24/2015] [Indexed: 01/25/2023]
Abstract
The Share 35 policy for organ allocation, which was adopted in June 2013, allocates livers regionally for candidates with Model for End-Stage Liver Disease scores of 35 or greater. The authors analyzed the costs resulting from the increased movement of allografts related to this new policy. Using a sample of nine organ procurement organizations, representing 17% of the US population and 19% of the deceased donors in 2013, data were obtained on import and export costs before Share 35 implementation (June 15, 2012, to June 14, 2013) and after Share 35 implementation (June 15, 2013, to June 14, 2014). Results showed that liver import rates increased 42%, with an increased cost of 51%, while export rates increased 112%, with an increased cost of 127%. When the costs of importing and exporting allografts were combined, the total change in costs for all nine organ procurement organizations was $11 011 321 after Share 35 implementation. Extrapolating these costs nationally resulted in an increased yearly cost of $68 820 756 by population or $55 056 605 by number of organ donors. Any alternative allocation proposal needs to account for the financial implications to the transplant infrastructure.
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Affiliation(s)
- H Fernandez
- Baylor All Saints Medical Center, Fort Worth, TX
| | - J Weber
- Center of Organ Recovery and Education, Pittsburgh, PA
| | - K Barnes
- Southwest Transplant Alliance, Dallas, TX
| | - L Wright
- Southwest Transplant Alliance, Dallas, TX
| | - M Levy
- Baylor All Saints Medical Center, Fort Worth, TX
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20
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Waller LP, Deshpande V, Pyrsopoulos N. Hepatocellular carcinoma: A comprehensive review. World J Hepatol 2015; 7:2648-2663. [PMID: 26609342 PMCID: PMC4651909 DOI: 10.4254/wjh.v7.i26.2648] [Citation(s) in RCA: 137] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 05/19/2015] [Accepted: 10/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals with chronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival.
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Affiliation(s)
- Lisa P Waller
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Vrushak Deshpande
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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21
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Asrani SK, Kamath PS. Model for end-stage liver disease score and MELD exceptions: 15 years later. Hepatol Int 2015; 9:346-54. [PMID: 26016462 DOI: 10.1007/s12072-015-9631-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 04/06/2015] [Indexed: 02/06/2023]
Abstract
The model for end-stage liver disease (MELD) score has been used as an objective scale of disease severity for management of patients with end-stage liver disease; it currently serves as the basis of an urgency-based organ-allocation policy in several countries. Implementation of the MELD score led to a reduction in waiting-list registration and waiting-list mortality and an increase in the number of deceased-donor transplants without adversely affecting long-term outcomes after liver transplantation (LT). The MELD score has been used for management of non-transplant patients with chronic liver disease. MELD exceptions serve as a mechanism to advance the needs of subsets of patients with liver disease not adequately addressed by MELD-based organ allocation. Several models have been proposed to refine and improve the MELD score as the environment within which it operates continues to evolve toward transplantation for sicker patients. The MELD score continues to serve and be used as a template to improve upon as an objective gauge of disease severity and as a metric enabling optimization of allocation of scarce donor organs for LT.
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Affiliation(s)
- Sumeet K Asrani
- Baylor University Medical Center, 3410 Worth Street Suite 860, Dallas, TX, 75246, USA,
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22
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Salvalaggio PR, Felga G, Axelrod DA, Della Guardia B, Almeida MD, Rezende MB. List and liver transplant survival according to waiting time in patients with hepatocellular carcinoma. Am J Transplant 2015; 15:668-77. [PMID: 25650130 DOI: 10.1111/ajt.13011] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 09/10/2014] [Accepted: 09/11/2014] [Indexed: 01/25/2023]
Abstract
The time that patients with hepatocellular carcinoma (HCC) can safely remain on the waiting list for liver transplantation (LT) is unknown. We investigated whether waiting time on the list impacts transplant survival of HCC candidates and transplant recipients. This is a single-center retrospective study of 283 adults with HCC. Patients were divided in groups according to waiting-list time. The main endpoint was survival. The median waiting time for LT was 4.9 months. The dropout rates at 3-, 6-, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Mortality on the list was 4.8%, but varied depending of the time on the list. Patients who waited less than 3-months had an inferior overall survival when compared to the other groups (p = 0.027). Prolonged time on the list significantly reduced mortality in this analysis (p = 0.02, HR = 0.28). Model for End Stage Liver Disease (MELD) score at transplantation did also independently impact overall survival (p = 0.03, HR = 1.06). MELD was the only factor that independently impacted posttransplant survival (p = 0.048, HR = 1.05). We conclude that waiting time had no relation with posttransplant survival. It is beneficial to prolong the waiting list time for HCC candidates without having a negative impact in posttransplant survival.
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23
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The Impact of the Introduction of MELD on the Dynamics of the Liver Transplantation Waiting List in São Paulo, Brazil. J Transplant 2014; 2014:219789. [PMID: 25525508 PMCID: PMC4265688 DOI: 10.1155/2014/219789] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Revised: 09/15/2014] [Accepted: 11/05/2014] [Indexed: 12/28/2022] Open
Abstract
Until July 15, 2006, the time on the waiting list was the main criterion for allocating deceased donor livers in the state of São Paulo, Brazil. After this date, MELD has been the basis for the allocation of deceased donor livers for adult transplantation. Our aim was to compare the waitlist dynamics before MELD (1997–2005) and after MELD (2006–2012) in our state. A retrospective study was conducted including the data from all the liver transplant candidate waiting lists from July 1997 to December 2012. The data were related to the actual number of liver transplantations (Tr), the incidence of new patients on the list (I), and the number of patients who died while being on the waitlist (D) from 1997 to 2005 (the pre-MELD era) and from 2006 to 2012 (the post-MELD era). The number of transplantations from 1997 to 2005 and from 2006 to 2012 increased nonlinearly, with a clear trend to levelling to equilibrium at approximately 350 and 500 cases per year, respectively. The implementation of the MELD score resulted in a shorter waiting time until liver transplantation. Additionally, there was a significant effect on the waitlist dynamics in the first 4 years; however, the curves diverge from there, implying a null long-range effect on the waitlist by the MELD scores.
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24
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Wedd J, Bambha KM, Stotts M, Laskey H, Colmenero J, Gralla J, Biggins SW. Stage of cirrhosis predicts the risk of liver-related death in patients with low Model for End-Stage Liver Disease scores and cirrhosis awaiting liver transplantation. Liver Transpl 2014; 20:1193-201. [PMID: 24916539 PMCID: PMC4177271 DOI: 10.1002/lt.23929] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Accepted: 06/06/2014] [Indexed: 01/12/2023]
Abstract
The Model for End-Stage Liver Disease (MELD) score has reduced predictive ability in patients with cirrhosis and MELD scores ≤ 20. We aimed to assess whether a 5-stage clinical model could identify liver transplantation (LT) candidates with low MELD scores who are at increased risk for death. We conducted a case-control study of subjects with cirrhosis and MELD scores ≤ 20 who were awaiting LT at a single academic medical center between February 2002 and May 2011. Conditional logistic regression was used to evaluate the risk of liver-related death according to the cirrhosis stage. We identified 41 case subjects who died from liver-related causes with MELD scores ≤ 20 within 90 days of death while they were waiting for LT. The cases were matched with up to 3 controls (66 controls in all) on the basis of the listing year, age, sex, liver disease etiology, presence of hepatocellular carcinoma, and MELD score. The cirrhosis stage was assessed for all subjects: (1) no varices or ascites, (2) varices, (3) variceal bleeding, (4) ascites, and (5) ascites and variceal bleeding. The MELD scores were similar for cases and controls. Clinical states contributing to death in cases were: sepsis 49%, spontaneous bacterial peritonitis 15%, variceal bleeding 24%, and hepatorenal syndrome 22%. In a univariate analysis, variceal bleeding [odds ratio (OR) = 5.6, P = 0.003], albumin (OR = 0.5, P = 0.041), an increasing cirrhosis stage (P = 0.003), reaching cirrhosis stage 2, 3, or 4 versus lower stages (OR = 3.6, P = 0.048; OR = 7.4, P < 0.001; and OR = 4.1, P = 0.008), a sodium level < 135 mmol/L (OR = 3.4, P = 0.006), and hepatic encephalopathy (OR = 2.3, P = 0.082) were associated with liver-related death. In a multivariate model including the cirrhosis stage, albumin, sodium, and hepatic encephalopathy, an increasing cirrhosis stage (P = 0.010) was independently associated with liver-related death. In conclusion, assessing the cirrhosis stage in patients with low MELD scores awaiting LT may help to select candidates for more aggressive monitoring or for living or extended criteria donation.
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Affiliation(s)
- Joel Wedd
- University of Colorado Denver Division of Gastroenterology and Hepatology
| | - Kiran M. Bambha
- University of Colorado Denver Division of Gastroenterology and Hepatology
| | - Matt Stotts
- Saint Louis University Division of Gastroenterology and Hepatology
| | - Heather Laskey
- University of Colorado Denver Division of Gastroenterology and Hepatology
| | - Jordi Colmenero
- University of Colorado Denver Division of Gastroenterology and Hepatology
,Liver Transplant Unit, Hospital Clinic, Institut D’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona
| | - Jane Gralla
- University of Colorado Denver Departments of Pediatrics and Biostatistics and Informatics
| | - Scott W. Biggins
- University of Colorado Denver Division of Gastroenterology and Hepatology
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25
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MRI-based estimation of liver function: Gd-EOB-DTPA-enhanced T1 relaxometry of 3T vs. the MELD score. Sci Rep 2014; 4:5621. [PMID: 25001391 PMCID: PMC4085628 DOI: 10.1038/srep05621] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 06/20/2014] [Indexed: 12/15/2022] Open
Abstract
Gd-EOB-DTPA is a hepatocyte-specific MRI contrast agent. Due to its hepatocyte-specific uptake and paramagnetic properties, functioning areas of the liver exhibit shortening of the T1 relaxation time. We report the potential use of T1 relaxometry of the liver with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for estimating the liver function as expressed by the MELD score. 3 T MRI relaxometry was performed before and 20 min after Gd-EOB-DTPA administration. A strong correlation between changes in the T1 relaxometry and the extent of liver disease, expressed by the MELD score, was documented. Reduced liver function correlates with decreased Gd-EOB-DTPA accumulation in the hepatocytes during the hepatobiliary phase. MRI-based T1 relaxometry with Gd-EOB-DTPA may be a useful method for assessing overall and segmental liver function.
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Abstract
Critical care of the general surgical patient requires synthesis of the patient's physiology, intraoperative events, and preexisting comorbidities. Evaluating an abdominal solid-organ transplant recipient after surgery adds a new dimension to clinical decisions because the transplanted allograft has undergone its own physiologic challenges and now must adapt to a new environment. This donor-recipient interaction forms the foundation for assessment of early allograft function (EAF). The intensivist must accurately assess and support EAF within the context of the recipient's current physiology and preexisting comorbidities. Optimizing EAF is essential because allograft failure is a significant predictor of recipient morbidity and mortality.
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Affiliation(s)
- Geraldine C Diaz
- Department of Anesthesia and Critical Care, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
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27
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Wedd JP, Harper AM, Biggins SW. MELD score, allocation, and distribution in the United States. Clin Liver Dis (Hoboken) 2013; 2:148-151. [PMID: 30992850 PMCID: PMC6448651 DOI: 10.1002/cld.233] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Joel P. Wedd
- Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO
| | | | - Scott W. Biggins
- Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO
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28
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Abstract
Model for end-stage liver disease (MELD) score, initially developed to predict survival following transjugular intrahepatic portosystemic shunt was subsequently found to be accurate predictor of mortality amongst patents with end-stage liver disease. Since 2002, MELD score using 3 objective variables (serum bilirubin, serum creatinine, and institutional normalized ratio) has been used worldwide for listing and transplanting patients with end-stage liver disease allowing transplanting sicker patients first irrespective of the wait time on the list. MELD score has also been shown to be accurate predictor of survival amongst patients with alcoholic hepatitis, following variceal hemorrhage, infections in cirrhosis, after surgery in patients with cirrhosis including liver resection, trauma, and hepatorenal syndrome (HRS). Although, MELD score is closest to the ideal score, there are some limitations including its inaccuracy in predicting survival in 15-20% cases. Over the last decade, many efforts have been made to further improve and refine MELD score. Until, a better score is developed, liver allocation would continue based on the currently used MELD score.
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Key Words
- AH, alcoholic hepatitis
- BAR, balance risk
- CTP, Child–Pugh–Turcotte
- Cirrhosis
- DFI, discriminate function index
- EDC, extended donor criteria
- ESLD, end-stage liver disease
- FHF, fulminant hepatic failure
- GFR, glomerular filtration rate
- HVPG, hepatic venous pressure gradient
- LT, liver transplantation
- Liver transplantation
- MDRD, modification of diet in renal disease
- MELD
- MELD, model for end-stage liver disease
- MLP, multi-layer perceptron
- QALY, quality adjusted life years
- SLK, simultaneous liver kidney transplantation
- SOFA, sequential organ failure assessment
- SOFT, survival outcomes following transplantation
- TIPS, transjugular intrahepatic portosystemic
- UKELD, UK end stage liver disease score
- UNOS, United Network for Organ Sharing
- VH, variceal hemorrhage
- deMELD, drop-out equivalent MELD
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Affiliation(s)
| | - Patrick S. Kamath
- Address for correspondence: Patrick S. Kamath, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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29
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Abstract
The Model for End-Stage Liver Disease (MELD) score incorporates serum bilirubin, creatinine, and the international normalized ratio (INR) into a formula that provides a continuous variable that is a very accurate predictor of 90-day mortality in patients with cirrhosis. It is currently utilized in the United States to prioritize deceased donor organ allocation for patients listed for liver transplantation. The MELD score is superior to other prognostic models in patients with end-stage liver disease, such as the Child-Turcotte-Pugh score, since it uses only objective criteria, and its implementation in 2002 led to a sharp reduction in the number of people waiting for liver transplant and reduced mortality on the waiting list without affecting posttransplant survival. Although mainly adopted for use in patients waiting for liver transplant, the MELD score has also proved to be an effective predictor of outcome in other situations, such as patients with cirrhosis going for surgery and patients with fulminant hepatic failure or alcoholic hepatitis. Several variations of the original MELD score, involving the addition of serum sodium or looking at the change in MELD over time, have been examined, and these may slightly improve its accuracy. The MELD score does have limitations in situations where the INR or creatinine may be elevated due to reasons other than liver disease, and its implementation for organ allocation purposes does not take into consideration several conditions that benefit from liver transplantation. The application of the MELD score in prioritizing patients for liver transplantation has been successful, but further studies and legislation are required to ensure a fair and equitable system.
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Affiliation(s)
- Tsang Lau
- Division of Liver Diseases, Mount Sinai School of Medicine, New York, USA
| | - Jawad Ahmad
- Division of Liver Diseases, Mount Sinai School of Medicine, New York, USA
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Smith JM, Biggins SW, Haselby DG, Kim WR, Wedd J, Lamb K, Thompson B, Segev DL, Gustafson S, Kandaswamy R, Stock PG, Matas AJ, Samana CJ, Sleeman EF, Stewart D, Harper A, Edwards E, Snyder JJ, Kasiske BL, Israni AK. Kidney, pancreas and liver allocation and distribution in the United States. Am J Transplant 2012; 12:3191-212. [PMID: 23157207 PMCID: PMC3565841 DOI: 10.1111/j.1600-6143.2012.04259.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Kidney transplant and liver transplant are the treatments of choice for patients with end-stage renal disease and end-stage liver disease, respectively. Pancreas transplant is most commonly performed along with kidney transplant in diabetic end-stage renal disease patients. Despite a steady increase in the numbers of kidney and liver transplants performed each year in the United States, a significant shortage of kidneys and livers available for transplant remains. Organ allocation is the process the Organ Procurement and Transplantation Network (OPTN) uses to determine which candidates are offered which deceased donor organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation. The policy has changed incrementally over time in efforts to optimize allocation to meet these often competing goals. This review describes the history, current status and future direction of policies regarding the allocation of abdominal organs for transplant, namely the kidney, liver and pancreas, in the United States.
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Affiliation(s)
- J. M. Smith
- Department of Pediatrics, University of Washington, Seattle, Washington, DC,Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN
| | - S. W. Biggins
- Division of Gastroenterology and Hepatology, University of Colorado, Denver, CO
| | - D. G. Haselby
- Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN
| | - W. R. Kim
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN,Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - J. Wedd
- Division of Gastroenterology and Hepatology, University of Colorado, Denver, CO
| | - K. Lamb
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN
| | - B. Thompson
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN
| | - D. L. Segev
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN,Department of Transplant Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - S. Gustafson
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN
| | - R. Kandaswamy
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN,Department of Surgery, University of Minnesota, Minneapolis, MN
| | - P. G. Stock
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN,Department of Surgery, University of California, San Francisco, CA
| | - A. J. Matas
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN,Department of Surgery, University of Minnesota, Minneapolis, MN
| | | | | | - D. Stewart
- United Network for Organ Sharing, Richmond, VA
| | - A. Harper
- United Network for Organ Sharing, Richmond, VA
| | - E. Edwards
- United Network for Organ Sharing, Richmond, VA
| | - J. J. Snyder
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN,Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN
| | - B. L. Kasiske
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN,Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN
| | - A. K. Israni
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN,Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN,Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN,Corresponding author: Ajay K. Israni,
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31
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Validation of the Brazilian version of Chronic Liver Disease Questionnaire. Qual Life Res 2012; 22:167-72. [PMID: 22388695 DOI: 10.1007/s11136-012-0138-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/11/2012] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of this study was to validate the Chronic Liver Disease Questionnaire (CLDQ) for use in Brazilian population. METHOD A total of 200 patients with chronic liver disease and varying disease severity answered a socio-demographic questionnaire, t CLDQ, and the Medical Outcome Study Short Form 36 (SF-36). Patients returned in 1-15 days to answer CLDQ again. The Cronbach's alpha of the total CLDQ score was 0.95 and fluctuated between 0.69 and 0.83 in its six domains. RESULTS The intra-class correlation between total CLDQ scores in two evaluations was 0.97 and in all domains was >0.93. CLDQ was moderately correlated with the SF-36, 0.63 (total CLDQ vs. vitality, SF-36), 0.62 (CLDQ and mental health, SF-36), 0.62 (preoccupation, CLDQ, vs. General Health, SF-36), 0.59 (fatigue, CLDQ, vs. vitality, SF-36), 0.59 (activity, CLDQ, vs. vitality, SF-36), and 0.59 (fatigue, CLDQ, vs. mental health, SF-36). The highest scores were found in non-cirrhotic group. Child A patients had higher average scores than Child B and C groups in all domains, while patients with MELD <15 scored higher than patients with MELD ≥15. CONCLUSION CLDQ-BR was validated in Brazilian population and was appropriate for use in patients with liver disease of different etiologies and degrees of severity.
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Abstract
The Model for End-stage Liver Disease (MELD) score is the basis for allocation of liver allografts for transplantation in the United States. The MELD score, as an objective scale of disease severity, is also used in the management of patients with chronic liver disease in the nontransplant setting. Several models have been proposed to improve the MELD score. The authors believe that the MELD score is, by design, continually evolving and lends itself to continued refinement and improvement to serve as a metric to optimize organ allocation in the future.
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Affiliation(s)
- Sumeet K Asrani
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - W. Ray Kim
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
- Corresponding Author, W Ray Kim, 200 First Street SW, Rochester, Minnesota 55905, fax: 507-538-3974, telephone: 507-538-0254,
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Massie AB, Caffo B, Gentry S, Hall EC, Axelrod D, Lentine KL, Schnitzler MA, Gheorghian A, Salvalaggio PR, Segev DL. MELD Exceptions and Rates of Waiting List Outcomes. Am J Transplant 2011; 11:2362-71. [PMID: 21920019 PMCID: PMC3229963 DOI: 10.1111/j.1600-6143.2011.03735.x] [Citation(s) in RCA: 152] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Model for End-stage Liver Disease (MELD)-based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0-21.4% at the OPO-level and 11.9-18.8% at the region level; proportion receiving an exception for other conditions was 0.0%-13.1% (OPO-level) and 3.7-9.5 (region-level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio [OR] = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.
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Affiliation(s)
- Allan B. Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Brian Caffo
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | | | - Erin Carlyle Hall
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - David Axelrod
- Department of Surgery, Dartmouth-Hitchcock Medical Center, Hanover, NH
| | - Krista L. Lentine
- Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO
| | - Mark A. Schnitzler
- Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO
| | - Adrian Gheorghian
- Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO
| | | | - Dorry L. Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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Patkowski W, Zieniewicz K, Skalski M, Krawczyk M. Correlation between selected prognostic factors and postoperative course in liver transplant recipients. Transplant Proc 2010; 41:3091-102. [PMID: 19857685 DOI: 10.1016/j.transproceed.2009.09.038] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM The objective was to identify the major prognostic factors influencing liver function after transplantation that predict the postoperative course and long-term survival among liver transplant recipients. We analyzed the results of biochemical, microbiological, serologic, and pathologic studies of the donor and recipient, as well as intraoperative data. MATERIALS AND METHODS Of 542 liver transplant recipients, 215 (39.7%) were analyzed in the period from 1989 to 2006. Patients were divided according to the mechanism leading to the liver disease: group I, hepatitis C virus (HCV) infection (n = 80, 37.0%); group II, hepatitis B virus (HBV) infection (n = 33, 15.0%); group III, HBV and HCV infection (n = 13, 6.0%); group IV, alcoholic liver disease (ALD) (n = 66, 31.0%); and group V, autoimmune hepatitis (AIH) (n = 23, 11.0%). RESULTS Prediction of patient survival based on clinical parameters showed a better prognostic value than that based only on liver function tests. Transplant urgency scores-Model for End-Stage Liver Disease (MELD), delta MELD and United Network for Organ Sharing (UNOS)-enabled us to predict early and long-term patient survival after liver transplantation. Update of these scores, reflecting the patient's condition, enabled us to evaluate pretransplant life-threatening factors and urgency level. Organ donation predictive factors were age, viral status, and degree of liver steatosis. Cold and warm ischemia times still were major prognostic factor. Routine biliary drainage resulted in worse long-term survival than non-drained patients. Liver transplantation for ALD showed the highest complication rate. Chronic liver rejection occurred more frequently in the AIH transplanted group. The most useful predictive factors for 1-year survival were urea/creatinine and liver function tests: aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase the International normalized ratio, and Quick. CONCLUSION The prognosis of patient outcomes after liver transplantation based on clinical parameters showed greater value than evaluation of the laboratory data.
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Affiliation(s)
- W Patkowski
- Department of General, Transplant & Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
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35
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Alam A, Perrone RD. Management of ESRD in patients with autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 2010; 17:164-72. [PMID: 20219619 DOI: 10.1053/j.ackd.2009.12.006] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2009] [Revised: 12/24/2009] [Accepted: 12/26/2009] [Indexed: 01/13/2023]
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the leading hereditary cause of ESRD in the United States. Because of the renal and extrarenal manifestations of ADPKD, specific challenges exist caring for these patients once they reach ESRD. In this article, we report the overall outcomes of individuals with ADPKD after ESRD as compared with non-ADPKD patients. We also review the available literature concerning issues specific to dialysis or kidney transplantation. For the ADPKD patient on dialysis, we address the use of peritoneal dialysis, the management of renal cystic, and extrarenal complications, and we discuss the significance of the relative polycythemia often observed in this population. For the ADPKD patient undergoing kidney transplantation, we highlight issues of anemia management and aneurysm screening pretransplant, the indications for nephrectomy of the native ADPKD kidneys, the potential benefits of select immunosuppressive agents, the role for combined kidney-liver transplantation, and renal and extrarenal complications of ADPKD postkidney transplantation. In general, patients with ADPKD have more favorable outcomes after ESRD as compared with those with other causes of kidney failure. Most of our knowledge, however, is based on case series and observational studies. Although these reports have certainly been valuable to our understanding, there still remains considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to ESRD. Particular focus needs to be placed on performing clinical trials with the goal of enhancing outcomes and quality of life of patients with ADPKD.
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36
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Ross LF. An ethical and policy analysis of elective transplantation for metabolic conditions diagnosed by newborn screening. J Pediatr 2010; 156:139-44. [PMID: 20006764 DOI: 10.1016/j.jpeds.2009.06.067] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2009] [Revised: 05/26/2009] [Accepted: 06/30/2009] [Indexed: 12/31/2022]
Affiliation(s)
- Lainie Friedman Ross
- Departments of Medicine, Pediatrics, Surgery and the College, MacLean Center for Clinical Medical Ethics, University of Chicago, Chicago, IL 60637, USA.
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37
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Abstract
Model for End-Stage Liver Disease (MELD) allocation has improved the process for ranking patients on the liver transplant list. One unintended consequence has been an increase in the number of simultaneous liver-kidney (SLK) transplants. Some have argued that the system unfairly advantages patients with kidney disease and that some kidneys are being prematurely placed in SLK transplantation. This review summarizes the MELD score, assessment of kidney function in cirrhosis, the impact of kidney function in liver disease, and changes in kidney function status in liver transplant recipients in the MELD era. Finally, recommendations regarding who should receive SLK transplants are reviewed.
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38
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Affiliation(s)
- Richard B Freeman
- Division of Transplantation, Box 40, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
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39
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Berg CL, Steffick DE, Edwards EB, Heimbach JK, Magee JC, Washburn WK, Mazariegos GV. Liver and intestine transplantation in the United States 1998-2007. Am J Transplant 2009; 9:907-31. [PMID: 19341415 DOI: 10.1111/j.1600-6143.2009.02567.x] [Citation(s) in RCA: 142] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Liver transplantation numbers in the United States remained constant from 2004 to 2007, while the number of waiting list candidates has trended down. In 2007, the waiting list was at its smallest since 1999, with adults > or =50 years representing the majority of candidates. Noncholestatic cirrhosis was most commonly diagnosed. Most age groups had decreased waiting list death rates; however, children <1 year had the highest death rate. Use of liver allografts from donation after cardiac death (DCD) donors increased in 2007. Model for end-stage liver disease (MELD)/pediatric model for end-stage liver disease (PELD) scores have changed very little since 2002, with MELD/PELD <15 accounting for 75% of the waiting list. Over the same period, the number of transplants for MELD/PELD <15 decreased from 16.4% to 9.8%. Hepatocellular carcinoma exceptions increased slightly. The intestine transplantation waiting list decreased from 2006, with the majority of candidates being children <5 years old. Death rates improved, but remain unacceptably high. Policy changes have been implemented to improve allocation and recovery of intestine grafts to positively impact mortality. In addition to evaluating trends in liver and intestine transplantation, we review in depth, issues related to organ acceptance rates, DCD, living donor transplantation and MELD/PELD exceptions.
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Affiliation(s)
- C L Berg
- University of Virginia, Charlottesville, VA, USA.
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40
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Perkins JD, Halldorson JB, Bakthavatsalam R, Fix OK, Carithers RL, Reyes JD. Should liver transplantation in patients with model for end-stage liver disease scores <or= 14 be avoided? A decision analysis approach. Liver Transpl 2009; 15:242-54. [PMID: 19177441 DOI: 10.1002/lt.21703] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Studies have shown that liver transplantation offers no survival benefits to patients with Model for End-Stage Liver Disease (MELD) scores <or= 14 in comparison with remaining on the waitlist. The consensus of a 2003 transplant community national conference was that a minimum MELD score should be required for placement on the liver waitlist, but no minimum listing national policy was enacted at that time. We developed a Markov microsimulation model to compare results under the present US liver allocation policy with outcomes under a "Rule 14" policy of barring patients with a MELD score of <or=14 from the waitlist or transplantation. For probabilities in the microsimulation model, we used data on all adult patients (>or=18 years) listed for or undergoing primary liver transplantation in the United States for chronic liver disease from 1/1/2003 through 12/31/2007 with follow-up until 2/1/2008. The "Rule 14" policy gave a 3% improvement in overall patient survival over the present system at 1, 2, 3, and 4 years and predicted a 13% decrease in overall waitlist time for patients with MELD scores of 15 to 40. Patients with the greatest benefit from a "Rule 14" policy were those with MELD scores of 6 to 10, for whom a 17% survival advantage was predicted from waiting on the list versus undergoing transplantation. Our analysis supports changing the national liver allocation policy to not allow liver transplantation for patients with MELD <or= 14.
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Affiliation(s)
- James D Perkins
- Division of Transplantation, Department of Surgery, University of Washington, Seattle, WA 98195, USA.
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41
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Krowka MJ, Fallon MB. Liver transplantation for hepatopulmonary syndrome (HPS): what is the MESSAGE? Am J Transplant 2008; 8:911-2. [PMID: 18325079 DOI: 10.1111/j.1600-6143.2008.02190.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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O'Leary JG, Lepe R, Davis GL. Indications for liver transplantation. Gastroenterology 2008; 134:1764-76. [PMID: 18471553 DOI: 10.1053/j.gastro.2008.02.028] [Citation(s) in RCA: 129] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2007] [Revised: 01/22/2008] [Accepted: 02/12/2008] [Indexed: 12/11/2022]
Abstract
Patients should be considered for liver transplantation if they have evidence of fulminant hepatic failure, a life-threatening systemic complication of liver disease, or a liver-based metabolic defect or, more commonly, cirrhosis with complications such as hepatic encephalopathy, ascites, hepatocellular carcinoma, hepatorenal syndrome, or bleeding caused by portal hypertension. While the complications of cirrhosis can often be managed relatively effectively, they indicate a change in the natural history of the disease that should lead to consideration of liver transplantation. Referral to a liver transplant center is followed by a detailed medical evaluation to ensure that transplantation is technically feasible, medically appropriate, and in the best interest of both the patient and society. Patients approved for transplantation are placed on a national transplant list, although donor organs are allocated locally and regionally. Since 2002, priority for transplantation has been determined by the Model of End-Stage Liver Disease (MELD) score, which provides donor organs to listed patients with the highest estimated short-term mortality.
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Affiliation(s)
- Jacqueline G O'Leary
- Hepatology, Department of Medicine, Baylor University Medical Center, Dallas, Texas 75246, USA
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43
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Freeman RB. Is waiting time a measure of access to liver transplantation? Is shorter necessarily better? Hepatology 2007; 46:602-3. [PMID: 17661416 DOI: 10.1002/hep.21865] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The Model for End-Stage Liver Disease (MELD) score has been used since February 2002 to allocate livers for transplantation from deceased donors according to medical need. Allocation based on MELD scores should ensure that sicker patients receive transplants first regardless of transplantation center volume. OBJECTIVE To determine whether the MELD score at transplantation and waiting time of liver transplant recipients differs by transplantation center volume. DESIGN Analysis of the Organ Procurement and Transplantation Network database. Centers were classified according to the volume of transplantations performed in 2005: high (> or =100 transplantations), medium (50 to 99 transplantations), and low (<50 transplantations). SETTING Transplantation centers in the United States. PATIENTS 20,075 transplant recipients between 27 February 2002 and 30 April 2006. MEASUREMENTS MELD scores and waiting times of liver transplant recipients. RESULTS Transplant recipients at high-volume centers had lower MELD scores (35.1% with MELD scores < or =18 vs. 22.7% and 27.0% at medium- and low-volume centers, respectively; P < 0.001), and the median MELD score was 22 compared with 24 at both medium- and low-volume centers. Despite having lower MELD scores, recipients at high-volume centers also experienced shorter waiting times (median waiting time, 69 days vs. 98 days and 94 days at medium-and low-volume centers, respectively; P < 0.001). LIMITATIONS The definition of transplantation center volume was subjective. The recent implementation of MELD precluded analysis of differences in long-term outcomes related to waiting time or center volume. CONCLUSIONS The MELD scores and waiting time of liver transplant recipients differed by transplantation center volume. High-volume centers have shorter waiting times and perform more transplantations for less sick patients. The reasons for these differences are unclear but warrant further investigation.
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45
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Abstract
The Model for End-stage Liver Disease (MELD) was initially created to predict survival in patients with complications of portal hypertension undergoing elective placement of transjugular intrahepatic portosystemic shunts. The MELD which uses only objective variables was validated subsequently as an accurate predictor of survival among different populations of patients with advanced liver disease. The major use of the MELD score has been in allocation of organs for liver transplantation. However, the MELD score has also been shown to predict survival in patients with cirrhosis who have infections, variceal bleeding, as well as in patients with fulminant hepatic failure and alcoholic hepatitis. MELD may be used in selection of patients for surgery other than liver transplantation and in determining optimal treatment for patients with hepatocellular carcinoma who are not candidates for liver transplantation. Despite the many advantages of the MELD score, there are approximately 15%-20% of patients whose survival cannot be accurately predicted by the MELD score. It is possible that the addition of variables that are better determinants of liver and renal function may improve the predictive accuracy of the model. Efforts at further refinement and validation of the MELD score will continue.
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Affiliation(s)
- Patrick S Kamath
- Advanced Liver Disease Study Group, Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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