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1
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Karvellas CJ, Bajaj JS, Kamath PS, Napolitano L, O'Leary JG, Solà E, Subramanian R, Wong F, Asrani SK. AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology 2024; 79:1463-1502. [PMID: 37939273 DOI: 10.1097/hep.0000000000000671] [Citation(s) in RCA: 30] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 11/10/2023]
Affiliation(s)
- Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
| | - Jasmohan S Bajaj
- Virginia Commonwealth University, Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Jacqueline G O'Leary
- Department of Medicine, Dallas Veterans Medical Center, University of Texas Southwestern Medical Center Dallas, Texas, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
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2
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Liu H, Sethi V, Li X, Xiao Y, Humar A. Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future. Semin Liver Dis 2024; 44:79-98. [PMID: 38211621 DOI: 10.1055/a-2242-7543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes. Additionally, we examined the transplant-associated survival benefits and the difficulties in accurately calculating these benefits. We also reviewed recent advancements in targeted therapy and checkpoint inhibitors for advanced, inoperable HCC and projected their integration into LT for HCC. We further discussed the growing use of living donor liver transplants in the United States and compared its outcomes with those of deceased donor liver transplants. Furthermore, we examined the progress in machine perfusion techniques, which have shown potential in improving patient outcomes and enlarging the donor pool. These advancements present opportunities to enhance LT patient survivals, refine selection criteria, establish new priority metrics, develop innovative bridging and downstaging strategies, and formulate redesigned LT strategies for HCC treatments.
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Affiliation(s)
- Hao Liu
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Vrishketan Sethi
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Xingjie Li
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona
| | - Yao Xiao
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Abhinav Humar
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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3
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Varghese RK, Handing GE, Montgomery AE, Rana AA, Goss JA. Retrospective Analysis of the Impact of High- and Low-Quality Donor Livers for Patients with High-Acuity Illness. Ann Transplant 2024; 29:e941931. [PMID: 38192097 PMCID: PMC10787593 DOI: 10.12659/aot.941931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2024] Open
Abstract
BACKGROUND Patients with high-acuity liver failure have increased access to marginal and split liver options, owing to historically high waitlist mortality rates. While most research states that donor liver quality has no impact on patients with high-acuity illness, there have been inconsistencies in recent research on how liver quality impacts post-transplant outcomes for these patients. We aimed to quantify donor liver quality with various post-transplantation patient outcomes for patients with high-acuity illness. MATERIAL AND METHODS Using the liver donor risk index (LDRI), model for end stage liver disease (MELD), and clinically relevant recipient factors, we used multivariate logistic regression to analyze how donor liver quality affects varying measures of patient outcomes for 9923 high-acuity patients from June 18, 2013, to June 18, 2022. RESULTS Using LDRI, high-quality livers had a significant protective impact on high-acuity patient mortality, compared with low-quality livers (OR=0.695 [0.549, 0.879], P=0.002). High-quality livers also had significant impact on graft survival (OR=0.706 [0.558, 0.894], P=0.004). Two sensitivity patient mortality analyses, excluding patients with status 1A and hepatocellular carcinoma, showed significant protective findings for high-quality livers. High-quality livers had insignificant outcomes on long-term survivor mortality, length of hospitalization, and primary non-function outcomes, compared with low-quality donor livers. CONCLUSIONS While our findings suggest donor quality has an impact on high-acuity patient outcomes, these findings indicate further research is needed in intent-to-treat analysis on clinical offer data to provide a clearer finding of how donor quality affects patients with high-acuity illness.
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Affiliation(s)
- Ron K Varghese
- Office of Student Affairs, Baylor University, Waco, TX, USA
| | - Greta E Handing
- Office of Student Affairs, Baylor College of Medicine, Houston, TX, USA
| | | | - Abbas A Rana
- Division of Abdominal Transplantation, Michael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - John A Goss
- Division of Abdominal Transplantation, Michael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
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4
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Fink MA, Gow PJ, McCaughan GW, Hodgkinson P, Chen J, McCall J, Jaques B, Crawford M, Strasser SI, Hardikar W, Brooke-Smith M, Starkey G, Jeffrey GP, Gane E, Stormon M, Evans H, Tallis C, Byrne AJ, Jones RM. Impact of Share 35 liver transplantation allocation in Australia and New Zealand. Clin Transplant 2024; 38:e15203. [PMID: 38088459 DOI: 10.1111/ctr.15203] [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: 03/14/2023] [Revised: 10/30/2023] [Accepted: 11/19/2023] [Indexed: 01/31/2024]
Abstract
Patients with high model for end-stage liver disease (MELD) scores waiting for liver transplantation in Australia and New Zealand (ANZ) have had limited access to deceased donor livers and therefore binational sharing of livers, for patients with a MELD score ≥35 was introduced in February 2016. Waiting list mortality, post-transplant outcomes and intention-to-treat survival were compared between patients whose MELD score reached 35 on the waiting list between October 2013 and April 2015 (Pre-Share 35 group, n = 23) and patients who were Share 35 listed between February 2016 and May 2022 (Share 35 group, n = 112). There was significantly reduced waiting list mortality in share 35 listed patients in comparison to the pre-Share 35 group (11.7% vs. 52.2%, OR .120 95% CI .044-.328, P < .001). Post-transplant patient and graft survival were not significantly different between the groups (5-year patient survival 82% vs. 84%, P = .991, 5-year graft survival 82% vs. 76%, P = .543). Intention-to-treat survival was superior in the Share 35 group (HR .302, 95% CI .149-.614, P < .001). Introduction of Share 35 in ANZ resulted in a 78% risk reduction in waiting list mortality, equivalent post-transplant survival and an improvement in intention-to-treat survival.
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Affiliation(s)
- Michael A Fink
- Department of Surgery, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Australia and New Zealand Liver and Intestinal Transplant Registry, Melbourne, Australia
| | - Paul J Gow
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Geoffrey W McCaughan
- University of Sydney, Sydney, New South Wales, Australia
- Liver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia
| | - Peter Hodgkinson
- Queensland Liver Transplant Service, Princess Alexandra Hospital and Queensland Children's Hospital, Brisbane, Australia
| | - John Chen
- Flinders Medical Centre, Adelaide, South Australia, Australia
| | - John McCall
- University of Auckland, Auckland, New Zealand
- New Zealand Liver Transplant Service, Auckland City Hospital, Auckland, New Zealand
| | - Bryon Jaques
- Western Australian Liver Transplant Unit, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Michael Crawford
- University of Sydney, Sydney, New South Wales, Australia
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia
| | - Simone I Strasser
- University of Sydney, Sydney, New South Wales, Australia
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia
| | - Winita Hardikar
- Gastroenterology and Clinical Nutrition Department Royal Children's Hospital, Melbourne, Victoria, Australia
| | | | - Graham Starkey
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Gary P Jeffrey
- Western Australian Liver Transplant Unit, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
- Medical School, The University of Western Australia, Perth, Western Australia, Australia
| | - Ed Gane
- University of Auckland, Auckland, New Zealand
- New Zealand Liver Transplant Service, Auckland City Hospital, Auckland, New Zealand
| | - Michael Stormon
- University of Sydney, Sydney, New South Wales, Australia
- Australian National Liver Transplantation Service, Children's Hospital at Westmead, Sydney, New South Wales, Australia
| | - Helen Evans
- University of Auckland, Auckland, New Zealand
- Department of Paediatric Gastroenterology, Starship Child Health, Auckland, New Zealand
| | - Caroline Tallis
- Queensland Liver Transplant Service, Princess Alexandra Hospital and Queensland Children's Hospital, Brisbane, Australia
| | - Amanda J Byrne
- Australia and New Zealand Liver and Intestinal Transplant Registry, Melbourne, Australia
| | - Robert M Jones
- Department of Surgery, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
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5
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Hirukawa K, Shinoda M, Hasegawa Y, Obara H, Kitago M, Yagi H, Abe Y, Yamada Y, Tanabe M, Kitagawa Y. Long-term outcomes following ABO-incompatible living donor liver transplantation for acute liver failure: a single-center experience of over 20 years. Surg Today 2023; 53:1160-1172. [PMID: 37272972 DOI: 10.1007/s00595-023-02678-w] [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: 12/09/2022] [Accepted: 02/21/2023] [Indexed: 06/06/2023]
Abstract
PURPOSE Acute liver failure is a life-threatening condition for which ABO-incompatible living donor liver transplantation (ABOi-LDLT) is sometimes the only life-saving treatment option. We reviewed a single-center experience of adult ABOi-LDLT treatment for acute liver failure (ALF). METHODS Preoperative treatment, immune indices (B cell marker, anti-donor blood-type antibody), and postoperative outcomes were compared between ALF and non-ALF groups. RESULTS There were 5 and 33 patients in the ALF and non-ALF groups, respectively. The ALF group received higher doses of steroids, underwent more rounds of plasma exchange (PE), and underwent transplantation for ALF with a shorter interval following preoperative rituximab (RTx) administration (median: 2 vs 13 days; P < 0.05) than the non-ALF group. Preoperatively, CD19-positive lymphocytes in the peripheral blood were sufficiently depleted in all of the non-ALF group patients, whereas they were poorly depleted in the ALF group. Postoperatively, neither group suffered anti-donor blood-type antibody titer rebound or antibody-mediated rejection. The ALF group had a comparable 5-year survival rate to the non-ALF group (80.0% vs 77.9%). CONCLUSIONS Despite the delayed preoperative administration of RTx, the ALF group showed an uneventful immunological response and acceptable long-term survival rate. Thus, ABOi-LDLT seems a viable treatment option for ALF.
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Affiliation(s)
- Kazuya Hirukawa
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
- Digestive Diseases Center, Mita Hospital, International University of Health and Welfare, 1-4-3 Mita, Minato-Ku, Tokyo, 108-0073, Japan.
| | - Yasushi Hasegawa
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Hideaki Obara
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Yohei Yamada
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Minoru Tanabe
- Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
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Fatima I, Jahagirdar V, Kulkarni AV, Reddy R, Sharma M, Menon B, Reddy DN, Rao PN. Liver Transplantation: Protocol for Recipient Selection, Evaluation, and Assessment. J Clin Exp Hepatol 2023; 13:841-853. [PMID: 37693258 PMCID: PMC10483012 DOI: 10.1016/j.jceh.2023.04.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 04/13/2023] [Indexed: 09/12/2023] Open
Abstract
Liver transplantation (LT) is the definitive therapy for patients with end-stage liver disease, acute liver failure, acute-on-chronic liver failure, hepatocellular carcinoma, and metabolic liver diseases. The acceptance of LT in Asia has been gradually increasing and so is the expertise to perform LT. Preparing a patient with cirrhosis for LT is the most important aspect of a successful LT. The preparation for LT begins with the first index decompensation for a patient with cirrhosis. Patients planned for LT should undergo a thorough screening for infections, and a complete cardiac, pulmonology, and psychosocial evaluation pre-LT. In this review, we discuss the indications and contraindications of LT and the evaluation and assessment of patients with liver disease planned for LT.
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Affiliation(s)
- Ifrah Fatima
- University of Missouri-Kansas City School of Medicine, MO, USA
| | | | | | - Raghuram Reddy
- Department of Liver Transplantation Surgery, AIG Hospitals, Hyderabad, India
| | - Mithun Sharma
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Balchandran Menon
- Department of Liver Transplantation Surgery, AIG Hospitals, Hyderabad, India
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Abstract
In recent years there has been a significant increase in the incidence of acute-on-chronic liver failure (ACLF). This syndrome is characterized by infections, organ failures, and high short-term mortality. Although progress in the management of these sick patients has been evident, liver transplantation (LT) remains the best treatment modality to date. Several studies have reported LT as a feasible option, despite organ failures. The outcomes following LT are inversely related to the grade of ACLF. This review discusses the current literature on the feasibility, futility, timing, and outcomes of LT in patients with ACLF.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad-500032, India
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, 2 Dulles, Liver Transplant Office 3400 Spruce Street, Philadelphia, PA 19104, USA.
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8
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Kathawate RG, Ibeabuchi T, Abt PL, Bittermann T. Utilization and outcomes of rescue hepatectomy among U.S. liver retransplant candidates. Clin Transplant 2023; 37:e14890. [PMID: 36544328 PMCID: PMC9911400 DOI: 10.1111/ctr.14890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 10/06/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The frequency and outcomes of anhepatic patients listed for transplantation in the United States have not been studied. The United Network for Organ Sharing (UNOS) records anhepatic status for patients listed as Status 1A for hepatic artery thrombosis (HAT) or primary non-function (PNF). METHODS Using the UNOS database from 2005 to 2020, demographics and waitlist outcomes of anhepatic candidates relisted as Status 1A for HAT or PNF were assessed. RESULTS Among 1364 adult Status 1A patients relisted for PNF or HAT across 120 distinct transplant centres, 75 (5.5%) patients were anhepatic and 1289 (94.5%) were non-anhepatic. A substantial number of centres (n = 51) had experience with ≥1 anhepatic patient relisted for either PNF or HAT, with individual centre rates ranging from 0% to 11.4%. Waitlist mortality was more than twice as high for anhepatic patients: 42.5% versus 17.0% non-anhepatic patients (p < .001). The post-transplant outcomes of anhepatic patients were markedly inferior to non-anhepatic patients. For example, 41.9% of anhepatic patients died during the index admission versus 23.4% of the non-anhepatic group (p = .006). Patient survival for the anhepatic and non-anhepatic groups was 48.3% versus 66.2% at 1-year and 29.3% versus 46.2% at 5-years, respectively (log-rank test for overall survival p = .014). CONCLUSIONS Rescue hepatectomy after initial liver transplantation is not only associated with high waitlist mortality, but also markedly worse post-transplant outcomes. With less than half of anhepatic patients surviving to the first year post-LT, further research is warranted to better delineate which patients should be considered for rescue hepatectomy.
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Affiliation(s)
- Ranganath G. Kathawate
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Tobenna Ibeabuchi
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Peter L. Abt
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Therese Bittermann
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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9
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Hassan A, Sharma P. CAQ Corner: Evolution of liver allocation policy. Liver Transpl 2022; 28:1785-1795. [PMID: 35531883 DOI: 10.1002/lt.26497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 04/18/2022] [Accepted: 04/29/2022] [Indexed: 01/13/2023]
Affiliation(s)
- Ammar Hassan
- Division of Gastroenterology, University of Michigan Health West, Grand Rapids, Michigan, USA.,Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Pratima Sharma
- Division of Gastroenterology, University of Michigan Health West, Grand Rapids, Michigan, USA
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10
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Ionescu VA, Diaconu CC, Bungau S, Jinga V, Gheorghe G. Current Approaches in the Allocation of Liver Transplantation. J Pers Med 2022; 12:jpm12101661. [PMID: 36294801 PMCID: PMC9605642 DOI: 10.3390/jpm12101661] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/26/2022] [Accepted: 10/04/2022] [Indexed: 11/07/2022] Open
Abstract
In recent decades, important advances have been made in the field of liver transplantation. One of the major problems remaining in this area is the small number of donors. Thus, recent data bring multiple updates of the indications and contraindications of this therapeutic method. The main goal is to increase the number of patients who can benefit from liver transplantation, a therapeutic method that can improve life expectancy and the quality of life of patients with end-stage liver disease. Another goal in the management of these patients is represented by the optimal care of those on the waiting list during that period. A multidisciplinary team approach is necessary to obtain the best results for both the donor and the recipient.
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Affiliation(s)
- Vlad Alexandru Ionescu
- “Prof. Dr. Theodor Burghele” Clinical Hospital, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Camelia Cristina Diaconu
- “Prof. Dr. Theodor Burghele” Clinical Hospital, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Medical Sciences Section, Academy of Romanian Scientists, 050085 Bucharest, Romania
- Correspondence: (C.C.D.); (S.B.); Tel.: +40-726-377-300 (C.C.D.)
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
- Correspondence: (C.C.D.); (S.B.); Tel.: +40-726-377-300 (C.C.D.)
| | - Viorel Jinga
- “Prof. Dr. Theodor Burghele” Clinical Hospital, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania
- Medical Sciences Section, Academy of Romanian Scientists, 050085 Bucharest, Romania
- Department of Urology, “Prof. Dr. Theodor Burghele” Hospital, 050653 Bucharest, Romania
| | - Gina Gheorghe
- “Prof. Dr. Theodor Burghele” Clinical Hospital, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
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11
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Wang L, Zhu S, Liu Y, Zheng L, Xu W, Luo Q, Zhang Y, Deng H, Li X, Xie C, Peng L. Prognostic value of decline in model for end-stage liver disease score and hepatic encephalopathy in hepatitis B-related acute-on-chronic liver failure patients treated with plasma exchange. Scand J Gastroenterol 2022; 57:1089-1096. [PMID: 35435091 DOI: 10.1080/00365521.2022.2063032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/25/2022] [Accepted: 04/01/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). METHODS A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. RESULTS Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p < .05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005-0.768; OR = 1.328, 95%CI: 1.153-1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187-43.796, p < 0.001). CONCLUSION We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020.
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Affiliation(s)
- Lu Wang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shu Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ying Liu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
| | - Lihua Zheng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
| | - Qiumin Luo
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yeqiong Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xinhua Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chan Xie
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
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12
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The Role of von Willebrand Factor Antigen in Predicting Survival of Patients with HBV-Related Cirrhosis. Can J Gastroenterol Hepatol 2022; 2022:9035971. [PMID: 35360443 PMCID: PMC8964228 DOI: 10.1155/2022/9035971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 02/20/2022] [Accepted: 03/01/2022] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE The model for end-stage liver disease (MELD) scoring system cannot be used to assess the deterioration of patients with liver cirrhosis caused by infection and portal hypertension. Elevated von Willebrand factor antigen (vWF-Ag) in plasma is associated with portal pressure and complications in patients with liver cirrhosis. We aimed to evaluate whether the addition of vWF-Ag can improve the risk prediction ability of the MELD scoring system. METHODS A total of 228 patients with hepatitis B virus (HBV)-related liver cirrhosis were eligible for inclusion in this retrospective study. The vWF-Ag level was assessed by enzyme-linked immunosorbent assay (ELISA). The endpoint of this study was defined as the time to liver transplantation or death. Univariate and multivariate analyses were performed to assess the risk factors associated with transplant-free mortality. Receiver operating characteristic (ROC) curve analysis was used to assess potential discriminatory variables for transplant-free mortality. RESULTS During a median follow-up interval of 30.23 months, 124 patients (54.4%) reached the endpoint of this study. Patients who died or underwent liver transplantation had elevated levels of MELD and vWF-Ag. Moreover, vWF-Ag and MELD showed comparable predictive potential for transplant-free survival (area under the curve [AUC], vWF-Ag = 0.71; AUC, MELD = 0.73). Ultimately, vWF-Ag can significantly improve the predictive potential of MELD in determining transplant-free mortality (AUC, MELD-vWF-Ag = 0.79, P = 0.006). CONCLUSION An elevated vWF-Ag level was independently associated with transplant-free mortality in patients with liver cirrhosis. The inclusion of vWF-Ag in the MELD scoring system can improve mortality predictions in patients with liver cirrhosis.
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Laique SN, Zhang N, Hewitt WR, Bajaj J, Vargas HE. Increased access to liver transplantation for patients with acute on chronic liver failure after implementation of Share 35 Rule: An analysis from the UNOS database. Ann Hepatol 2022; 23:100288. [PMID: 33217586 DOI: 10.1016/j.aohep.2020.100288] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 11/04/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Acute on chronic liver failure (ACLF), leads to high mortality. These patients are at risk of being delisted for liver transplantation (LT). Emerging data shows 1y post-transplant survival of 80-92%. The Share 35 (S35) policy was implemented to prioritize patients with MELD ≥35 on the LT waitlist. Our aim was to compare the LT outcomes of ACLF patients as a result of S35. MATERIALS AND METHODS Data from the UNOS scientific registry were used to classify ACLF patients using the NACSELD criteria. For the analyses, data were divided into two eras; 2 years before S35 (Era 1) and 2 years after S35 (Era 2). Waitlist status was classified into categories: Transplanted, Death or Too Sick to Transplant and Still Waiting/Other. LT cumulative incidence between the populations in the eras was calculated using Fine and Gray's method. A proportional hazards model was used to investigate the era effect on cumulative incidence of LT. RESULTS 46,861 patients were reviewed, of which 817 had ACLF. 366 patients (mean MELD: 37.1) were identified in Era 1 and 451 patients (mean MELD: 37.3) in Era 2. We found that ACLF patients were more likely to receive a liver transplant in Era 2 (p=0.0074). In both eras, transplanted patients had a significantly higher survival than those who were not transplanted (p<0.0001). CONCLUSIONS Our study shows that S35 improved LT rate for ACLF suggesting that there should be broader recognition of ACLF and early transplantation should be pursued.
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Affiliation(s)
- Sobia N Laique
- Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, United States
| | - Nan Zhang
- Health Sciences Research, Mayo Clinic, Scottsdale, AZ, United States
| | - Winston R Hewitt
- Transplantation Surgery, Mayo Clinic, Scottsdale, AZ, United States
| | - Jasmohan Bajaj
- Gastroenterology and Hepatology, Virginia Commonwealth, University and McGuire VA Medical Center, Richmond, Virginia, United States
| | - Hugo E Vargas
- Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, United States.
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14
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Wood NL, VanDerwerken DN, King EA, Segev DL, Gentry SE. Life expectancy without a transplant for status 1A liver transplant candidates. Am J Transplant 2022; 22:274-278. [PMID: 34487636 PMCID: PMC8720063 DOI: 10.1111/ajt.16830] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 08/10/2021] [Accepted: 09/01/2021] [Indexed: 01/25/2023]
Abstract
Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. Organ Procurement and Transplantation Network (OPTN) policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than 7 days for that candidate to be given status 1A. Additionally, candidates receiving status 1A must have one of six medical conditions listed in policy. Using Scientific Registry of Transplant Recipients data from all prevalent liver transplant candidates from 2010 to 2020, we used a bias-corrected Kaplan-Meier model to calculate the survival of status 1A candidates and to determine their life expectancy without a transplant. We found that status 1A candidates have a life expectancy without a transplant of 24 (95% CI 20-46) days-over three times longer than what policy requires for status 1A designation. We repeated the analysis for subgroups of status 1A candidates based on the medical conditions that grant status 1A. We found that none of these subgroups met the life expectancy requirement. Harmonizing OPTN policy with observed data would sustain the integrity of the allocation process.
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Affiliation(s)
- Nicholas L. Wood
- Department of Mathematics, United States Naval Academy, Annapolis, MD
| | | | | | - Dorry L. Segev
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD
- Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD
| | - Sommer E. Gentry
- Department of Mathematics, United States Naval Academy, Annapolis, MD
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15
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Lee WC, Cheng CH, Lee CF, Hung HC, Lee JC, Wu TH, Wang YC, Wu TJ, Chou HS, Chan KM. Quick preparation of ABO-incompatible living donor liver transplantation for acute liver failure. Clin Transplant 2021; 36:e14555. [PMID: 34874071 DOI: 10.1111/ctr.14555] [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: 06/11/2021] [Revised: 11/09/2021] [Accepted: 11/25/2021] [Indexed: 11/29/2022]
Abstract
Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375mg/m2 ) on post-operative day one to deplete B-cells. Eight patients received this quick preparation regimen to undergo ABO-I LDLT for acute liver failure from 2012 to 2019. They aged between 50 and 60 years. The median MELD score was 39 with a range from 35 to 48. It took 4.75 ± 1.58 days to prepare such an urgent ABO-I LDLT. All the patients had successful liver transplantations, but one patient died of antibody-mediated rejection at post-operative month 6. The 3-month, 6-month, and 1-year graft/patient survival were 100%, 87.5%, and 75%, respectively. In conclusion, this quick preparation regimen can reduce isoagglutinin titers quickly and make timely ABO-I LDLT feasible for acute liver failure. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hao-Chien Hung
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Jin-Chiao Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu-Chao Wang
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taiwan.,Chang-Gung University College of Medicine, Taoyuan, Taiwan
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16
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Goudsmit BFJ, Braat AE, Tushuizen ME, Vogelaar S, Pirenne J, Alwayn IPJ, van Hoek B, Putter H. Joint modeling of liver transplant candidates outperforms the model for end-stage liver disease: The effect of disease development over time on patient outcome. Am J Transplant 2021; 21:3583-3592. [PMID: 34174149 PMCID: PMC8597089 DOI: 10.1111/ajt.16730] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 06/03/2021] [Accepted: 06/21/2021] [Indexed: 01/25/2023]
Abstract
Liver function is measured regularly in liver transplantation (LT) candidates. Currently, these previous disease development data are not used for survival prediction. By constructing and validating joint models (JMs), we aimed to predict the outcome based on all available data, using both disease severity and its rate of change over time. Adult LT candidates listed in Eurotransplant between 2007 and 2018 (n = 16 283) and UNOS between 2016 and 2019 (n = 30 533) were included. Patients with acute liver failure, exception points, or priority status were excluded. Longitudinal MELD(-Na) data were modeled using spline-based mixed effects. Waiting list survival was modeled with Cox proportional hazards models. The JMs combined the longitudinal and survival analysis. JM 90-day mortality prediction performance was compared to MELD(-Na) in the validation cohorts. MELD(-Na) score and its rate of change over time significantly influenced patient survival. The JMs significantly outperformed the MELD(-Na) score at baseline and during follow-up. At baseline, MELD-JM AUC and MELD AUC were 0.94 (0.92-0.95) and 0.87 (0.85-0.89), respectively. MELDNa-JM AUC was 0.91 (0.89-0.93) and MELD-Na AUC was 0.84 (0.81-0.87). The JMs were significantly (p < .001) more accurate than MELD(-Na). After 90 days, we ranked patients for LT based on their MELD-Na and MELDNa-JM survival rates, showing that MELDNa-JM-prioritized patients had three times higher waiting list mortality.
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Affiliation(s)
- Ben F. J. Goudsmit
- Division of TransplantationDepartment of SurgeryLeiden University Medical CentreThe Netherlands,Eurotransplant International FoundationLeidenThe Netherlands,Department of Gastroenterology and HepatologyLeiden University Medical CentreThe Netherlands
| | - Andries E. Braat
- Division of TransplantationDepartment of SurgeryLeiden University Medical CentreThe Netherlands
| | - Maarten E. Tushuizen
- Department of Gastroenterology and HepatologyLeiden University Medical CentreThe Netherlands,Transplant CenterLeiden University Medical CentreThe Netherlands
| | - Serge Vogelaar
- Eurotransplant International FoundationLeidenThe Netherlands
| | - Jacques Pirenne
- Department of Abdominal Transplant SurgeryUniversity Hospitals LeuvenLeuvenBelgium,Eurotransplant Liver Intestine Advisory CommitteeLeuvenBelgium
| | - Ian P. J. Alwayn
- Division of TransplantationDepartment of SurgeryLeiden University Medical CentreThe Netherlands,Transplant CenterLeiden University Medical CentreThe Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and HepatologyLeiden University Medical CentreThe Netherlands,Transplant CenterLeiden University Medical CentreThe Netherlands
| | - Hein Putter
- Department of Biomedical Data SciencesLeiden University Medical CentreThe Netherlands
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17
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Polyak A, Kuo A, Sundaram V. Evolution of liver transplant organ allocation policy: Current limitations and future directions. World J Hepatol 2021; 13:830-839. [PMID: 34552690 PMCID: PMC8422916 DOI: 10.4254/wjh.v13.i8.830] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 06/22/2021] [Accepted: 07/22/2021] [Indexed: 02/06/2023] Open
Abstract
Since the adoption of the model for end-stage liver disease (MELD) score for organ allocation in 2002, numerous changes to the system of liver allocation and distribution have been made with the goal of decreasing waitlist mortality and minimizing geographic variability in median MELD score at time of transplant without worsening post-transplant outcomes. These changes include the creation and adoption of the MELD-Na score for allocation, Regional Share 15, Regional Share for Status 1, Regional Share 35/National Share 15, and, most recently, the Acuity Circles Distribution Model. However, geographic differences in median MELD at time of transplant remain as well as limits to the MELD score for allocation, as etiology of liver disease and need for transplant changes. Acute-on-chronic liver failure (ACLF) is a subset of liver failure where prevalence is rising and has been shown to have an increased mortality rate and need for transplantation that is under-demonstrated by the MELD score. This underscores the limitations of the MELD score and raises the question of whether MELD is the most accurate, objective allocation system. Alternatives to the MELD score have been proposed and studied, however MELD score remains as the current system used for allocation. This review highlights policy changes since the adoption of the MELD score, addresses limitations of the MELD score, reviews proposed alternatives to MELD, and examines the specific implications of these changes and alternatives for ACLF.
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Affiliation(s)
- Alexander Polyak
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Alexander Kuo
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Vinay Sundaram
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
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18
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VanDerwerken DN, Wood NL, Segev DL, Gentry SE. The Precise Relationship Between Model for End-Stage Liver Disease and Survival Without a Liver Transplant. Hepatology 2021; 74:950-960. [PMID: 33655565 DOI: 10.1002/hep.31781] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 10/21/2020] [Accepted: 02/01/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Scores from the Model for End-Stage Liver Disease (MELD), which are used to prioritize candidates for deceased donor livers, are widely acknowledged to be negatively correlated with the 90-day survival rate without a liver transplant. However, inconsistent and outdated estimates of survival probabilities by MELD preclude useful applications of the MELD score. APPROACH AND RESULTS Using data from all prevalent liver waitlist candidates from 2016 to 2019, we estimated 3-day, 7-day, 14-day, 30-day, and 90-day without-transplant survival probabilities (with confidence intervals) for each MELD score and status 1A. We used an adjusted Kaplan-Meier model to avoid unrealistic assumptions and multiple observations per person instead of just the observation at listing. We found that 90-day without-transplant survival has improved over the last decade, with survival rates increasing >10% (in absolute terms) for some MELD scores. We demonstrated that MELD correctly prioritizes candidates in terms of without-transplant survival probability but that status 1A candidates' short-term without-transplant survival is higher than that of MELD 40 candidates and lower than that of MELD 39 candidates. Our primary result is the updated survival functions themselves. CONCLUSIONS We calculated without-transplant survival probabilities for each MELD score (and status 1A). The survival function is an invaluable tool for many applications in liver transplantation: awarding of exception points, calculating the relative demand for deceased donor livers in different geographic areas, calibrating the pediatric end-stage liver disease score, and deciding whether to accept an offered liver.
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Affiliation(s)
| | | | - Dorry L Segev
- Department of EpidemiologySchool of Public HealthJohns Hopkins UniversityBaltimoreMD.,Scientific Registry of Transplant RecipientsMinneapolisMN.,Johns Hopkins University School of MedicineBaltimoreMD
| | - Sommer E Gentry
- Department of MathematicsUS Naval AcademyAnnapolisMD.,Scientific Registry of Transplant RecipientsMinneapolisMN.,Johns Hopkins University School of MedicineBaltimoreMD
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19
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Sharma P, Sui Z, Zhang M, Magee JC, Barman P, Patel Y, Schluger A, Walter K, Biggins SW, Cullaro G, Wong R, Lai JC, Jo J, Sinha J, VanWagner L, Verna EC. Renal Outcomes After Simultaneous Liver-Kidney Transplantation: Results from the US Multicenter Simultaneous Liver-Kidney Transplantation Consortium. Liver Transpl 2021; 27:1144-1153. [PMID: 33641218 PMCID: PMC8823286 DOI: 10.1002/lt.26032] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 12/29/2020] [Accepted: 01/26/2021] [Indexed: 12/19/2022]
Abstract
Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m2 or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51-64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol-related liver disease; 68% developed ≥ stage 3 CKD at the end of follow-up. The 1-year, 3-year, and 5-year incidence rates of post-SLKT stage 4-5 CKD were 10%, 12%, and 16%, respectively. Pre-SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00-2.15), NASH (HR, 1.58; 95% CI, 1.01-2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10-2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22-0.89) reduced the risk. Women (β = -6.22 ± 2.16 mL/minute/1.73 m2 ; P = 0.004), NASH (β = -7.27 ± 3.27 mL/minute/1.73 m2 ; P = 0.027), and delayed kidney graft function (β = -7.25 ± 2.26 mL/minute/1.73 m2 ; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow-up. Stage 4-5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients.
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Affiliation(s)
- Pratima Sharma
- Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, MI
| | - Zhiyu Sui
- Department of Biostatistics, School of Public Health, Michigan Medicine, Ann Arbor, MI
| | - Min Zhang
- Department of Biostatistics, School of Public Health, Michigan Medicine, Ann Arbor, MI
| | - John C. Magee
- Department of Surgery, Michigan Medicine, Ann Arbor, MI
| | - Pranab Barman
- Division of Gastroenterology and Hepatology, University of California, San Diego, CA
| | - Yuval Patel
- Division of Gastroenterology, Duke University, Durham, NC
| | - Aaron Schluger
- Section of Internal Medicine, Westchester Medical Center, Westchester, NY
| | - Kara Walter
- Division of Digestive Diseases, University of California, Los Angeles, CA
| | - Scott W. Biggins
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA
| | - Giuseppe Cullaro
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY
| | - Randi Wong
- Division of Gastroenterology and Hepatology, University of California, San Francisco, CA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, University of California, San Francisco, CA
| | - Jennifer Jo
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL
| | - Jasmine Sinha
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL
| | - Lisa VanWagner
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL
| | - Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY
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20
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Györi GP, Pereyra D, Rumpf B, Hackl H, Köditz C, Ortmayr G, Reiberger T, Trauner M, Berlakovich GA, Starlinger P. The von Willebrand Factor Facilitates Model for End-Stage Liver Disease-Independent Risk Stratification on the Waiting List for Liver Transplantation. Hepatology 2020; 72:584-594. [PMID: 31773739 PMCID: PMC7497135 DOI: 10.1002/hep.31047] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 11/07/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS The Model for End-Stage Liver Disease (MELD) is used for clinical decision-making and organ allocation for orthotopic liver transplantation (OLT) and was previously upgraded through inclusion of serum sodium (Na) concentrations (MELD-Na). However, MELD-Na may underestimate complications arising from portal hypertension or infection. The von Willebrand factor (vWF) antigen (vWF-Ag) correlates with portal pressure and seems capable of predicting complications in patients with cirrhosis. Accordingly, this study aimed to evaluate vWF-Ag as an adjunct surrogate marker for risk stratification on the waiting list for OLT. APPROACH AND RESULTS Hence, WF-Ag at time of listing was assessed in patients listed for OLT. Clinical characteristics, MELD-Na, and mortality on the waiting list were recorded. Prediction of 3-month waiting-list survival was assessed by receiver operating characteristics and net reclassification improvement. Interestingly, patients dying within 3 months on the waiting list displayed elevated levels of vWF-Ag (P < 0.001). MELD-Na and vWF-Ag were comparable and independent in their predictive potential for 3-month mortality on the waiting list (area under the curve [AUC], vWF-Ag = 0.739; MELD-Na = 0.764). Importantly, a vWF-Ag cutoff at 413% identified patients at risk for death within 3 months of listing with a higher odds ratio (OR) than the previously published cutoff at a MELD-Na of 20 points (vWF-Ag, OR = 10.873, 95% confidence interval [CI], 3.160, 36.084; MELD-Na, OR = 7.594, 95% CI, 2.578, 22.372; P < 0.001, respectively). Ultimately, inclusion of vWF-Ag into the MELD-Na equation significantly improved prediction of 3-month waiting-list mortality (AUC, MELD-Na-vWF = 0.804). CONCLUSIONS A single measurement of vWF-Ag at listing for OLT predicts early mortality. Combining vWF-Ag levels with MELD-Na improves risk stratification and may help to prioritize organ allocation to decrease waiting-list mortality.
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Affiliation(s)
- Georg P. Györi
- Division of TransplantationDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - David Pereyra
- Division of General SurgeryDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Benedikt Rumpf
- Division of General SurgeryDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Hubert Hackl
- Division of Bioinformatics, BiocenterMedical University of InnsbruckInnsbruckAustria
| | - Christoph Köditz
- Division of General SurgeryDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Gregor Ortmayr
- Division of General SurgeryDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Gabriela A. Berlakovich
- Division of TransplantationDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
| | - Patrick Starlinger
- Division of General SurgeryDepartment of SurgeryMedical University of ViennaGeneral Hospital ViennaViennaAustria
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21
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22
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Spaggiari M, Okoye O, Tulla K, Di Cocco P, Almario J, Benedetti E, Tzvetanov I. Geographic Disparities in Liver Allocation and Distribution in the United States: Where Are We Now? Transplant Proc 2019; 51:3205-3212. [PMID: 31732201 DOI: 10.1016/j.transproceed.2019.07.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 05/24/2019] [Accepted: 07/09/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Equitable deceased donor liver allocation and distribution has remained a heated topic in transplant medicine. Despite the establishment of numerous policies, mixed reports regarding organ allocation persist. METHODS Patient data was obtained from the United Network for Organ Sharing liver transplant database between January 2016 and September 2017. A total of 20,190 patients were included in the analysis. Of this number, 8790 transplanted patients had a median Model for End-Stage Liver Disease (MELD) score of 25 (17-33), after a wait time of 129 (32-273) days. Patients were grouped into low MELD and high MELD regions using a score 25 as the cutoff. RESULTS Significant differences were noted between low and high MELD regions in ethnicity (white 77.4% vs 60.4%, Hispanic 8.1% vs 24.5%; P < .001) and highest level of education (grade school 4.8% vs 8.5%, Associate/Bachelor's degree 19% vs 15.7%, P < .001), respectively. Patients in high MELD regions were more likely to be multiply listed if they had a diagnosis of hepatocellular carcinoma (12.1% vs 15%, P = .046). Wait-list mortality (4.8% vs 6%, P < .001) and wait-list time (110 [27-238] vs 156 [42-309] days, P < .001) were greater in the high MELD regions. CONCLUSIONS These results highlight some of the existing disparities in the recently updated allocation and distribution policy of deceased donor livers. Our findings are consistent with previous work and support the liver distribution policy revision.
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Affiliation(s)
- Mario Spaggiari
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois.
| | - Obi Okoye
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Kiara Tulla
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Pierpaolo Di Cocco
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Jorge Almario
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - E Benedetti
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Ivo Tzvetanov
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
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Alshamsi F, Alshammari K, Belley-Cote E, Dionne J, Albrahim T, Albudoor B, Ismail M, Al-Judaibi B, Baw B, Subramanian RM, Steadman R, Galusca D, Huang DT, Nanchal R, Al Quraini M, Yuan Y, Alhazzani W. Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials. Intensive Care Med 2019; 46:1-16. [PMID: 31588983 DOI: 10.1007/s00134-019-05783-y] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure. METHODS We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. RESULTS We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain. CONCLUSIONS ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.
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Affiliation(s)
- Fayez Alshamsi
- Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates
| | - Khalil Alshammari
- Department of Internal Medicine, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Emilie Belley-Cote
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Joanna Dionne
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Talal Albrahim
- Department of Anesthesiology and Critical Care Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Budoor Albudoor
- Department of Critical Care Medicine, Shaikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Mona Ismail
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Al-Khobar, Saudi Arabia
| | - Bandar Al-Judaibi
- Transplant Hepatology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, USA, 14642
| | - Bandar Baw
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Ram M Subramanian
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Randolph Steadman
- Department of Anesthesiology and Perioperative Medicine, Ronald Reagan Medical Center, University of California Los Angeles, Los Angeles, USA
| | - Dragos Galusca
- Department of Anesthesiology, Henry Ford Hospital, Detroit, MI, USA
| | - David T Huang
- Department of Critical Care Medicine, Director Multidisciplinary Acute Care Research Organization (MACRO), University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Rahul Nanchal
- Department of Pulmonary, Critical Care and Sleep Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mustafa Al Quraini
- Department of Pulmonary and Critical Care Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Yuhong Yuan
- Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Waleed Alhazzani
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada.
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada.
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24
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Is living donor liver transplantation justified in high model for end-stage liver disease candidates (35+)? Curr Opin Organ Transplant 2019; 24:637-643. [DOI: 10.1097/mot.0000000000000689] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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25
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Should All Status 1A Patients Be Prioritized Over High MELD Patients? Concept of Risk Stratification in Extremely Ill Liver Transplant Recipients. Transplantation 2019; 103:2121-2129. [DOI: 10.1097/tp.0000000000002651] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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26
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Niewinski G, Raszeja-Wyszomirska J, Hrenczuk M, Rozga A, Malkowski P, Rozga J. Intermittent high-flux albumin dialysis with continuous venovenous hemodialysis for acute-on-chronic liver failure and acute kidney injury. Artif Organs 2019; 44:91-99. [PMID: 31267563 DOI: 10.1111/aor.13532] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 06/13/2019] [Accepted: 06/25/2019] [Indexed: 12/14/2022]
Abstract
Acute-on-chronic liver failure (ACLF) requiring intensive medical care and associated with acute kidney injury (AKI) has a mortality rate as high as 90% due to the lack of effective therapies. In this study, we assessed the effects of intermittent high-flux single-pass albumin dialysis (SPAD) coupled with continuous venovenous hemodialysis (CVVHD) on 28-day and 90-day survival and an array of clinical and laboratory parameters in patients with severe ACLF and renal insufficiency. Sixteen patients were studied. The diagnosis of ACLF and AKI was made in accordance with current EASL Clinical Practice Guidelines, including the recommendations of the International Club of Ascites. All patients received SPAD/CVVHD treatments as the blood purification therapy to support liver, kidneys, and other organs. Five patients were transplanted and 11 were not listed for transplantation because of active alcoholism. Data at the initiation of SPAD/CVVHD were compared with early morning data after the termination of the extracorporeal treatment phase. All patients had ACLF and renal insufficiency with 13/16 additionally fulfilling the AKI criteria. A total of 37 SPAD/CVVHD treatments were performed [2.3 ± 1.4]. The baseline MELD-Na score was 37.6 ± 6.6 and decreased to 33.4 ± 8.7 after SPAD/CVVHD (P < 0.001). In parallel, the CLIF-C ACLF grade and OF score, estimated at 28- and 90-day mortality, AKI stage, hepatic encephalopathy grade, and liver function tests were lowered (P = 0.001-0.032). The 28- and 90-day survivals were 56.2% overall and 53.8% in AKI. Survival in patients not transplanted (n = 11) was 45.4%. In patients with severe ACLF and AKI, the renal replacement therapy coupled with high-performance albumin dialysis improved estimated 28- and 90-day survival and several key clinical and laboratory parameters. It is postulated that these results may be further improved with earlier intervention and more SPAD treatments per patient. High-performance albumin dialysis improves survival and key clinical and laboratory parameters in severe ACLF and AKI.
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Affiliation(s)
- Grzegorz Niewinski
- 2nd Department of Anesthesiology and Intensive Medical Care, Central Independent Public Clinical Hospital, Medical University of Warsaw, Warsaw, Poland
| | - Joanna Raszeja-Wyszomirska
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Marta Hrenczuk
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
| | - Agata Rozga
- School of Interactive Computing, Georgia Institute of Technology, Atlanta, Georgia
| | - Piotr Malkowski
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
| | - Jacek Rozga
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
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27
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Sundaram V, Shah P, Wong RJ, Karvellas CJ, Fortune BE, Mahmud N, Kuo A, Jalan R. Patients With Acute on Chronic Liver Failure Grade 3 Have Greater 14-Day Waitlist Mortality Than Status-1a Patients. Hepatology 2019; 70:334-345. [PMID: 30908660 PMCID: PMC6597310 DOI: 10.1002/hep.30624] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 03/11/2019] [Indexed: 12/15/2022]
Abstract
Patients listed for liver transplantation (LT) as status 1a currently receive the highest priority on the waiting list. The presence of acute on chronic liver failure (ACLF) with three or more organs failing (ACLF-3) portends low survival without transplantation, which may not be reflected by the Model for End-Stage Liver Disease-Sodium (MELD-Na) score. We compared short-term waitlist mortality for patients listed status 1a and those with ACLF-3 at listing. Data were analyzed from the United Network for Organ Sharing database, years 2002-2014, for 3,377 patients listed status 1a and 5,099 patients with ACLF-3. Candidates with ACLF were identified based on the European Association for the Study of the Liver Chronic Liver Failure Consortium criteria. MELD-Na score was treated as a categorical variable of scores <36, 36-40, and >40. We used competing risks regression to assess waitlist mortality risk. Evaluation of outcomes through 21 days after listing demonstrated a rising trend in mortality among ACLF-3 patients at 7 days (18.0%), 14 days (27.7%), and 21 days (32.7%) (P < 0.001) compared to a stable trend in mortality among individuals listed as status 1a at 7 days (17.9%), 14 days (19.3%), and 21 days (19.8%) (P = 0.709). Multivariable modeling with adjustment for MELD-Na category revealed that patients with ACLF-3 had significantly greater mortality (subhazard ratio, 1.45; 95% confidence interval, 1.31-1.61) within 14 days of listing compared to status-1a candidates. Analysis of the interaction between MELD-Na category and ACLF-3 showed that patients with ACLF-3 had greater risk of 14-day mortality than status-1a-listed patients, across all three MELD-Na categories. Conclusion: Patients with ACLF-3 at the time of listing have greater 14-day mortality than those listed as status 1a, independent of MELD-Na score; these findings illustrate the importance of early transplant evaluation and consideration of transplant priority for patients with ACLF-3.
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Affiliation(s)
- Vinay Sundaram
- Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Parth Shah
- Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Robert J. Wong
- Division of Gastroenterology and Hepatology, Alameda Health System, Highland Hospital, Oakland, CA
| | - Constantine J. Karvellas
- Department of Critical Care and Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Brett E. Fortune
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | - Nadim Mahmud
- Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Alexander Kuo
- Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London Medical School, London, UK
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28
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de Boer JD, Braat AE, Putter H, de Vries E, Strassburg CH, Máthé Z, van Hoek B, Braun F, van den Berg AP, Mikulic D, Michielsen P, Trotovsek B, Zoller H, de Boer J, van Rosmalen MD, Samuel U, Berlakovich G, Guba M. Outcome of Liver Transplant Patients With High Urgent Priority: Are We Doing the Right Thing? Transplantation 2019; 103:1181-1190. [PMID: 30489481 DOI: 10.1097/tp.0000000000002526] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND About 15% of liver transplantations (LTs) in Eurotransplant are currently performed in patients with a high-urgency (HU) status. Patients who have acute liver failure (ALF) or require an acute retransplantation can apply for this status. This study aims to evaluate the efficacy of this prioritization. METHODS Patients who were listed for LT with HU status from January 1, 2007, up to December 31, 2015, were included. Waiting list and posttransplantation outcomes were evaluated and compared with a reference group of patients with laboratory Model for End-Stage Liver Disease (MELD) score (labMELD) scores ≥40 (MELD 40+). RESULTS In the study period, 2299 HU patients were listed for LT. Ten days after listing, 72% of all HU patients were transplanted and 14% of patients deceased. Patients with HU status for primary ALF showed better patient survival at 3 years (69%) when compared with patients in the MELD 40+ group (57%). HU patients with labMELD ≥45 and patients with HU status for acute retransplantation and labMELD ≥35 have significantly inferior survival at 3-year follow-up of 46% and 42%, respectively. CONCLUSIONS Current prioritization for patients with ALF is highly effective in preventing mortality on the waiting list. Although patients with HU status for ALF have good outcomes, survival is significantly inferior for patients with a high MELD score or for retransplantations. With the current scarcity of livers in mind, we should discuss whether potential recipients for a second or even third retransplantation should still receive absolute priority, with HU status, over other recipients with an expected, substantially better prognosis after transplantation.
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Affiliation(s)
- Jacob D de Boer
- Eurotransplant International Foundation, Leiden, The Netherlands
- Division of Transplantation, Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Andries E Braat
- Division of Transplantation, Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Hein Putter
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Erwin de Vries
- Eurotransplant International Foundation, Leiden, The Netherlands
| | | | - Zoltán Máthé
- Department of Transplantation and Surgery, Semmelweis Medical University, Budapest, Hungary
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Felix Braun
- Klinik fur Allgemeine, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schleswig-Holstein Campus Kiel, Kiel, Germany
| | - Aad P van den Berg
- Department of Gastroenterology, University Medical Center Groningen, Groningen, The Netherlands
| | - Danko Mikulic
- Department of Surgery, Clinical Hospital Merkur, Zagreb, Croatia
| | - Peter Michielsen
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerpen, Belgium
| | - Blaz Trotovsek
- Department of Abdominal Surgery, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Heinz Zoller
- Klinik für Innere Medizin II-Hepatologie, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Jan de Boer
- Eurotransplant International Foundation, Leiden, The Netherlands
| | | | - Undine Samuel
- Eurotransplant International Foundation, Leiden, The Netherlands
| | - Gabriela Berlakovich
- Division of Transplantation, Department of Surgery, Medical University of Vienna, Austria
| | - Markus Guba
- Department of General-, Visceral-, and Transplant Surgery, University of Munich, Munich, Germany
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29
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Waiting List Mortality and Transplant Rates for NASH Cirrhosis When Compared With Cryptogenic, Alcoholic, or AIH Cirrhosis. Transplantation 2019; 103:113-121. [PMID: 29985186 DOI: 10.1097/tp.0000000000002355] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Patients with nonalcoholic steatohepatitis (NASH) cirrhosis have excellent postliver transplant survival despite having many comorbidities. We hypothesized that this could be due to a selection bias. METHODS We analyzed the United Network for Organ Sharing data from 2002 to 2016 and compared postliver transplant survival of NASH (n = 7935) patients with cryptogenic cirrhosis (CC) (n = 6087), alcoholic cirrhosis (AC) (n = 16 810), and autoimmune hepatitis cirrhosis (AIH) (n = 2734). RESULTS By 3 years of listing, the cumulative incidence (CI) of death or deterioration was 29% for NASH, 28% for CC and AC, and 24% for AIH, but when adjusted for risk factors, the CI was similar for NASH and AIH. The factors that increased the risk of waiting list removal due to death/deterioration were poor performance status, encephalopathy, diabetes, high Model for End-stage Liver Disease, Hispanic race, older age and a low serum albumin. Most patients were transplanted within the first year (median, 2 months; interquartile range, 1-7 months) of listing and by 5 years, the unadjusted CI of transplantation was 54% for NASH, 52% for CC, 51% for AIH, and 48% for AC. The adjusted CI of transplantation within 2 months of listing was higher for AC (subhazard ratio [SHR], 1.17), AIH (SHR, 1.17), and CC (SHR, 1.13) when compared with NASH, but after 2 months, adjusted transplantation rates decreased in AC (SHR, 0.6), AIH (SHR, 0.78), and CC (SHR, 0.95). The negative predictors of receiving a transplant were dialysis, female sex, nonwhite race, high albumin, and creatinine. CONCLUSIONS Patients with NASH cirrhosis are not disadvantaged by higher waitlist removal or lower transplantation rates.
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Lee J, Lee JG, Jung I, Joo DJ, Kim SI, Kim MS. Development of a Korean Liver Allocation System using Model for End Stage Liver Disease Scores: A Nationwide, Multicenter study. Sci Rep 2019; 9:7495. [PMID: 31097768 PMCID: PMC6522508 DOI: 10.1038/s41598-019-43965-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 05/01/2019] [Indexed: 02/08/2023] Open
Abstract
The previous Korean liver allocation system was based on Child-Turcotte-Pugh scores, but increasing numbers of deceased donors created a pressing need to develop an equitable, objective allocation system based on model for end-stage liver disease scores (MELD scores). A nationwide, multicenter, retrospective cohort study of candidates registered for liver transplantation from January 2009 to December 2011 was conducted at 11 transplant centers. Classification and regression tree (CART) analysis was used to stratify MELD score ranges according to waitlist survival. Of the 2702 patients that registered for liver transplantation, 2248 chronic liver disease patients were eligible. CART analysis indicated several MELD scores significantly predicted waitlist survival. The 90-day waitlist survival rates of patients with MELD scores of 31-40, 21-30, and ≤20 were 16.2%, 64.1%, and 95.9%, respectively (P < 0.001). Furthermore, the 14-day waitlist survival rates of severely ill patients (MELD 31-40, n = 240) with MELD scores of 31-37 (n = 140) and 38-40 (n = 100) were 64% and 43.4%, respectively (P = 0.001). Among patients with MELD > 20, presence of HCC did not affect waitlist survival (P = 0.405). Considering the lack of donor organs and geographic disparities in Korea, we proposed the use of a national broader sharing of liver for the sickest patients (MELD ≥ 38) to reduce waitlist mortality. HCC patients with MELD ≤ 20 need additional MELD points to allow them equitable access to transplantation. Based on these results, the Korean Network for Organ Sharing implemented the MELD allocation system in 2016.
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Affiliation(s)
- Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Advisory Committee on Improving Liver Allocation, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Inkyung Jung
- Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Soon Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Advisory Committee on Improving Liver Allocation, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
- The Advisory Committee on Improving Liver Allocation, Seoul, Republic of Korea.
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31
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Jasseron C, Francoz C, Antoine C, Legeai C, Durand F, Dharancy S. Impact of the new MELD-based allocation system on waiting list and post-transplant survival - a cohort analysis using the French national CRISTAL database. Transpl Int 2019; 32:1061-1073. [PMID: 31074921 DOI: 10.1111/tri.13448] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
Concerns related to equity and efficacy of our previous center-based allocation system have led us to introduce a patient-based allocation system called the "Liver Score" that incorporates the MELD score. The main objective of this study was to compare waitlist and post-transplant survivals before and after implementation of the "Liver Score" using the French transplant registry (period before: 2004-2006 and period after: 2007-2012). Patients transplanted during the second period were sicker and had a higher MELD. One-year waitlist survival (74% versus 76%; p=0.8) and one-year post-transplant survival (86.3% vs 85.7%; p=0.5) were similar between the 2 periods. Cirrhotic recipients with MELD>35 had lower one-year post-transplant survival compared to those with MELD<35 (74.8% vs 86.3%; p<0.01), mainly explained by their higher intubation and renal failure rates. The MELD showed a poor discriminative capacity. In cirrhotic recipients with MELD>35, patients presenting 2 or 3 risk factors (dialysis, intubation or infection) had a lower 1-year survival compared to those with none of these risk factors (61.2% vs 92%; p<0.01). The implementation of the MELD-based allocation system has led to transplant sicker patients with no impact on waitlist and post-transplant survivals. Nevertheless, selection of patients with MELD>35 should be completed to allow safe transplantation. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Carine Jasseron
- Agence de la biomédecine, direction prélèvement greffe organes-tissus, pôle évaluation, 93212, Saint-Denis La Plaine, cedex, France
| | - Claire Francoz
- Hepatology and Liver Intensive Care Unit, Hospital Beaujon, Clichy, France; INSERM U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3France
| | - Corinne Antoine
- Agence de la biomédecine, direction générale médicale et scientifique, direction prélèvement greffe organes-tissus, pôle stratégie prélèvement greffe, 93212, Saint-Denis-la-Plaine cedex, France
| | - Camille Legeai
- Agence de la biomédecine, direction prélèvement greffe organes-tissus, pôle évaluation, 93212, Saint-Denis La Plaine, cedex, France
| | - François Durand
- Hepatology and Liver Intensive Care Unit, Hospital Beaujon, Clichy, France; INSERM U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3France
| | - Sébastien Dharancy
- Inserm, UMR995 - LIRIC, Lille, France Univ Lille, UMR995 - LIRIC, Lille, France CHRU Lille, Service des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital HuriezLille, France
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32
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Artru F, Samuel D. Approaches for patients with very high MELD scores. JHEP Rep 2019; 1:53-65. [PMID: 32039352 PMCID: PMC7001538 DOI: 10.1016/j.jhepr.2019.02.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 01/31/2019] [Accepted: 02/04/2019] [Indexed: 02/08/2023] Open
Abstract
In the era of the "sickest first" policy, patients with very high model for end-stage liver disease (MELD) scores have been increasingly admitted to the intensive care unit with the expectation that they will receive a liver transplant (LT) in the absence of improvement on supportive therapies. Such patients are often admitted in a context of acute-on-chronic liver failure with extrahepatic failures. Sequential assessment of scores or classification based on organ failures within the first days after admission help to stratify the risk of mortality in this population. Although the prognosis of severely ill cirrhotic patients has recently improved, transplant-free mortality remains high. LT is still the only curative treatment in this population. Yet, the increased relative scarcity of graft resource must be considered alongside the increased risk of losing a graft in the initial postoperative period when performing LT in "too sick to transplant" patients. Variables associated with poor immediate post-LT outcomes have been identified in large studies. Despite this, the performance of scores based on these variables is still insufficient. Consideration of a patient's comorbidities and frailty is an appealing predictive approach in this population that has proven of great value in many other diseases. So far, local expertise remains the last safeguard to LT. Using this expertise, data are accumulating on favourable post-LT outcomes in very high MELD populations, particularly when LT is performed in a situation of stabilization/improvement of organ failures in selected candidates. The absence of "definitive" contraindications and the control of "dynamic" contraindications allow a "transplantation window" to be defined. This window must be identified swiftly after admission given the poor short-term survival of patients with very high MELD scores. In the absence of any prospect of LT, withdrawal of care could be discussed to ensure respect of patient life, dignity and wishes.
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Affiliation(s)
- Florent Artru
- Liver Unit, CHRU Lille, France, University of Lille, LIRIC team, Inserm unit 995
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, F-94800, France; Inserm, Unité 1193, Université Paris-Saclay, Villejuif, F-94800, France; Hepatinov, Villejuif, F-94800, France
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33
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Liver Transplant Survival Index for Patients with Model for End-Stage Liver Disease Score ≥ 35: Modeling Risk and Adjusting Expectations in the Share 35 Era. J Am Coll Surg 2018; 228:437-450.e8. [PMID: 30594593 DOI: 10.1016/j.jamcollsurg.2018.12.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 12/10/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND The Share 35 policy for liver allocation prioritizes patients with Model for End-Stage Liver Disease (MELD) scores ≥ 35 for regional sharing of liver allografts. To better assess donor-recipient interactions and inform expectations, this study identified factors affecting graft survival independent of MELD score and derived a risk index for transplantation in the MELD ≥ 35 population. STUDY DESIGN The United Network for Organ Sharing (UNOS) STAR database was evaluated for deceased donor liver transplants with recipients' MELD ≥ 35, between January 2006 and June 2016. Data were randomly split into test and validate cohorts. Four individual models of graft survival spanning 90 days to 5 years were evaluated with univariate and multivariate Cox proportional hazards analyses against donor- and recipient-specific characteristics. Significant factors were compiled to generate the Liver Transplant Survival Index (LTSI-35), and survival analyses were performed. RESULTS Five risk groups (very low, low, moderate, high, and severe) were identified, with 1-year graft survival rates of 90.8% ± 0.2%, 89.3% ± 0.3%, 85.0% ± 0.3%, 79.8% ± 0.3%, and 70.3% ± 0.4% (p < 0.001 across groups), respectively. The greatest risk of graft loss was associated with donation after circulatory death (DCD) donors (1-year hazard ratio [HR] = 1.61 [95% CI 1.26 to 2.05], p = 0.001), recipients' requiring ventilator support (HR 1.32 [95% CI 1.17 to 1.51], p < 0.001), and recipient portal vein thrombosis (HR 1.21 [95% CI 1.03 to 1.42], p = 0.003). Subgroup analysis revealed increased risk of graft loss with graft macrosteatosis ≥ 30% on pre-donation biopsy at 90 days (HR 1.64 [1.33 to 1.99], p < 0.001). CONCLUSIONS The LTSI-35 identifies risk factors for graft loss in a high-MELD population which, when combined, may portend worse outcomes. The LTSI-35 may be used to influence donor selection, organ allocation, and to inform expectations for allograft survival.
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Prevalence of Steatosis Hepatis in the Eurotransplant Region: Impact on Graft Acceptance Rates. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2018; 2018:6094936. [PMID: 30515073 PMCID: PMC6236971 DOI: 10.1155/2018/6094936] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 10/17/2018] [Indexed: 12/11/2022]
Abstract
Due to the shortage of liver allografts and the rising prevalence of fatty liver disease in the general population, steatotic liver grafts are considered for transplantation. This condition is an important risk factor for the outcome after transplantation. We here analyze the characteristics of the donor pool offered to the Charité – Universitätsmedizin Berlin from 2010 to 2016 with respect to liver allograft nonacceptance and steatosis hepatis. Of the 2653 organs offered to our center, 19.9% (n=527) were accepted for transplantation, 58.8% (n=1561) were allocated to other centers, and 21.3% (n = 565) were eventually discarded from transplantation. In parallel to an increase of the incidence of steatosis hepatis in the donor pool from 20% in 2010 to 30% in 2016, the acceptance rates for steatotic organs increased in our center from 22.3% to 51.5% in 2016 (p < 0.001), with the majority (86.9%; p > 0.001) having less than 30% macrovesicular steatosis hepatis. However, by 2016, the number of canceled transplantations due to higher grades of steatosis hepatis had significantly increased from 14.7% (n = 15) to 63.6% (42; p < 0.001). The rising prevalence of steatosis hepatis in the donor pool has led to higher acceptance rates of steatotic allografts. Nonetheless, steatosis hepatis remains a predominant phenomenon in discarded organs necessitating future concepts such as organ reconditioning to increase graft utilization.
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Marked Decrease in Urgent Listing for Liver Transplantation Over Time: Evolution of Characteristics and Outcomes of Status-1 Liver Transplantation. Transplantation 2018; 102:e18-e25. [PMID: 28968354 DOI: 10.1097/tp.0000000000001967] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Approximately 5% of liver transplants annually are performed urgently with "status-1" designation. This study aims to determine if the demand, characteristics, and outcome for status-1 liver transplantation has changed over time. METHODS We used the Scientific Registry of Transplant Patients (2003-2015) to characterize 2352 adult patients who underwent 2408 status-1 liver transplants and compared them between Era1 (2003-6/2009) and Era2 (7/2009-2015). RESULTS Overall, there were fewer liver transplants performed with the status-1 designation in Era2 than Era1 (1099 vs 1309). Although the number of urgent liver transplants was relatively constant with successive years, the proportion transplanted with status-1 designation decreased markedly over time. Era2 patients were older (43.2 years vs 41.7 years, P = 0.01) and less likely be ABO-incompatible (1.1% vs 2.4%, P = 0.01) or retransplant (77 vs 124, P = 0.03). In terms of disease etiology, the largest group was "acute liver failure (ALF), nonspecified" (43.4%). There was no difference in proportion with drug-induced liver injury (DILI), but the subset of herbal/dietary supplements increased in Era2 (1.3% vs 0.46%, P = 0.04). Survival was increased in Era2 in the overall cohort and for patients with autoimmune disease (P < 0.05), despite longer waiting times for this etiology (186 days vs 149 days). DILI or nonspecified ALF had shorter waiting times, and 90% were transplanted within 7 days. CONCLUSIONS Liver transplantation for the most urgent indications (status-1) is decreasing while survival remains excellent. Fewer incidences of ALF are classified as indeterminate, mostly as a result of increasing awareness of autoimmune hepatitis and DILI as causes of the syndrome.
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Heise M, Weiler N, Iken S, Welker MW, Zeuzem S, Bechstein WO, Schnitzbauer AA. Liver Transplantation in Acute-on-Chronic Liver Failure: Considerations for a Systematic Approach to Decision Making. Visc Med 2018; 34:291-294. [PMID: 30345287 DOI: 10.1159/000492137] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background Acute-on-chronic liver failure (ACLF) is a complex disease with deteriorating liver and kidney function and associated organ failure in patients with chronic liver disease. Methods This is a concise overview for bedside and algorithmic decision making in patients with ACLF based on the most recent literature. Results Diagnosis and dynamics of ACLF can be easily monitored with the CLIF-C-ACLF calculator, which delivers grading for ACLF and estimates the risk of mortality, as the natural transplant-free course of ACLF is often fatal. Transplantation offers the best results in patients with ACLF that do not recover spontaneously. However, marginal donor organs should be avoided. Conclusion ACLF is an increasingly relevant indication with good outcome after liver transplantation. Adequate donor rates may reduce the incidence by means of timely transplantation of acute decompensated patients in lower stages of urgency. Future challenges comprise specific allocation of donor organs to this group of patients that are at a similar risk of mortality when compared to acute liver failure.
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Affiliation(s)
- Michael Heise
- Clinic for General and Visceral Surgery, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/M., Germany
| | - Nina Weiler
- Clinic for Medicine I, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/M., Germany
| | - Sonja Iken
- Clinic for Anesthesiology, Intensive Care and Pain Care, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/M., Germany
| | - Martin-Walter Welker
- Clinic for Medicine I, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/M., Germany
| | - Stefan Zeuzem
- Clinic for Medicine I, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/M., Germany
| | - Wolf O Bechstein
- Clinic for General and Visceral Surgery, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/M., Germany
| | - Andreas A Schnitzbauer
- Clinic for General and Visceral Surgery, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/M., Germany
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Samuel D, Coilly A. Management of patients with liver diseases on the waiting list for transplantation: a major impact to the success of liver transplantation. BMC Med 2018; 16:113. [PMID: 30064414 PMCID: PMC6069832 DOI: 10.1186/s12916-018-1110-y] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 06/25/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The results of liver transplantation are excellent, with survival rates of over 90 and 80% at 1 and 5 years, respectively. The success of liver transplantation has led to an increase in the indications for liver transplantation. Generally, priorities are given to cirrhotic patients with a high Model for End-Stage Liver Disease (MELD) score on the principle of the sickest first and to patients with hepatocellular carcinoma (HCC) on the principle of priority points according to the size and number of nodules of HCC. These criteria can lead to a 'competition' on the waiting list between the above patients and those who are cirrhotic and have an intermediate MELD score or with life-threatening liver diseases not well described by the MELD score. For this latter group of patients, 'MELD exception' points can be arbitrarily given. DISCUSSION The management of patients on the waiting list is of prime importance to avoid death and drop out from the waiting list as well as to improve post-transplant survival rates. For the more severe cases who may swiftly access liver transplantation, it is essential to rapidly determine whether liver transplantation is indeed indicated, and to organise a fast workup ahead of this. It is also essential to identify the ideal timing for liver transplantation in order to minimise mortality rates. For patients with HCC, a bridge therapy is frequently required to avoid progression of HCC and to maintain patients within the criteria of liver transplantation as well as to reduce the risk of post-transplant recurrence of HCC. For patients with cirrhosis and intermediate MELD score, waiting time can exceed 1 year; therefore, regular follow-up and management are essential to maintain the patient alive on the waiting list and to achieve a good survival after liver transplantation. CONCLUSION There is a diversity of patients on the waiting list for transplantation and equity should be preserved between those with cirrhosis of high and intermediate severity and those with HCC. The management of patients on the waiting list is an essential component of the success of liver transplantation.
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Affiliation(s)
- Didier Samuel
- Centre Hépatobiliaire, Paul Brousse Hospital, University Paris South, Inserm-Paris South Research Unit 1193, 12 Avenue Paul-Vaillant Couturier, Villejuif, 94800, Paris, France.
| | - Audrey Coilly
- Centre Hépatobiliaire, Paul Brousse Hospital, University Paris South, Inserm-Paris South Research Unit 1193, 12 Avenue Paul-Vaillant Couturier, Villejuif, 94800, Paris, France
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Asrani SK, Saracino G, O'Leary JG, Gonzalez S, Kim PT, McKenna GJ, Klintmalm G, Trotter J. Recipient characteristics and morbidity and mortality after liver transplantation. J Hepatol 2018; 69:43-50. [PMID: 29454069 DOI: 10.1016/j.jhep.2018.02.004] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 02/01/2018] [Accepted: 02/08/2018] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIMS Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States. We sought to identify an easily applicable set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within five years after liver transplantation. METHODS We collected national (n = 31,829, 2002-2015) and center-specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (five patients; hazard ratio [HR] 1.59; 95% CI 1.48-1.72); recipient age >60 years (three patients; HR 1.29; 95% CI 1.23-1.36); hemodialysis (three patients; HR 1.26; 95% CI 1.16-1.37); diabetes (two patients; HR 1.20; 95% CI 1.14-1.27); or serum creatinine ≥1.5 mg/dl without hemodialysis (two patients; HR 1.15; 95% CI 1.09-1.22). RESULTS Graft survival within five years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with >8 points, graft survival was 42% (model for end-stage liver disease [MELD] score <25) and 50% (MELD score 25-35) in recipients receiving grafts from donors with a donor risk index >1.7. In center-specific data within the first year, subjects with ≥5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p <0.01), higher admissions for rehabilitation (12.3% vs. 2.7%, p <0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p <0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p = 0.03) within five years. CONCLUSION The impact of co-morbidities in an MELD-based organ allocation system need to be reassessed. The proposed clinical tool may be helpful for center-specific assessment of risk of graft failure in non-HCV patients and for discussion regarding relevant morbidity in selected subsets. LAY SUMMARY Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age >60 years, ventilator status, diabetes, hemodialysis and creatinine >1.5 mg/dl) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics leads to lower survival.
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Affiliation(s)
- Sumeet K Asrani
- Baylor University Medical Center, Dallas, TX, United States.
| | | | | | | | - Peter T Kim
- Baylor University Medical Center, Dallas, TX, United States
| | - Greg J McKenna
- Baylor University Medical Center, Dallas, TX, United States
| | | | - James Trotter
- Baylor University Medical Center, Dallas, TX, United States
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Li L, Liu H, Hu X, Huang Y, Wang Y, He Y, Lei Q. Identification of key genes in non‑alcoholic fatty liver disease progression based on bioinformatics analysis. Mol Med Rep 2018; 17:7708-7720. [PMID: 29620197 PMCID: PMC5983972 DOI: 10.3892/mmr.2018.8852] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 02/22/2018] [Indexed: 12/18/2022] Open
Abstract
Due to economic development and lifestyle changes, the incidence of non-alcoholic fatty liver disease (NAFLD) has gradually increased in recent years. However, the pathogenesis of NAFLD is not yet fully understood. To identify candidate genes that contribute to the development and progression of NAFLD, two microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified and functional enrichment analyses were performed. A protein-protein interaction network was constructed and modules were extracted using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. The enriched functions and pathways of the DEGs included ‘cellular macromolecule biosynthetic process’, ‘cellular response to chemical stimulus’, ‘extracellular matrix organization’, ‘metabolic pathways’, ‘insulin resistance’ and ‘forkhead box protein O1 signaling pathway’. The DEGs, including type-1 angiotensin II receptor, formin-binding protein 1-like, RNA-binding protein with serine-rich domain 1, Ras-related C3 botulinum toxin substrate 1 and polyubiquitin-C, were identified using multiple bioinformatics methods and validated in vitro with reverse transcription-quantitative polymerase chain reaction analysis. In conclusion, five hub genes were identified in the present study, and they may aid in understanding of the molecular mechanisms underlying the development and progression of NAFLD.
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Affiliation(s)
- Lin Li
- Department of Liver Disease, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, P.R. China
| | - Huabao Liu
- Department of Liver Disease, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, P.R. China
| | - Xiaoyu Hu
- Department of Infectious Disease, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China
| | - Yi Huang
- Department of Liver Disease, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, P.R. China
| | - Yanan Wang
- Department of Liver Disease, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, P.R. China
| | - Yansha He
- Department of Liver Disease, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, P.R. China
| | - Qingsong Lei
- Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
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Simultaneous Liver-Kidney Transplantation: Impact on Liver Transplant Patients and the Kidney Transplant Waiting List. CURRENT TRANSPLANTATION REPORTS 2018; 5:1-6. [PMID: 29564203 PMCID: PMC5843696 DOI: 10.1007/s40472-018-0175-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Purpose The number of simultaneous liver-kidney transplants (SLKT) performed in the USA has been rising. The Organ Procurement and Transplantation Network implemented a new policy governing SLKT that specifies eligibility criteria for candidates to receive a kidney with a liver, and creates a kidney waitlist “safety net” for liver recipients with persistent renal failure after transplant. This review explores potential impacts for liver patients and the kidney waitlist. Recent Findings Factors that have contributed to the rise in SLKT including Model for End-stage Liver Disease (MELD)-based allocation, regional sharing for high MELD candidates, and the rising incidence of non-alcoholic steatohepatitis will continue to increase the number of liver transplant candidates with concurrent renal insufficiency. The effect of center behavior based on the new policy is harder to predict, given wide historic variability in SLKT practice. Summary Continued increase in combined liver/kidney failure is likely, and SLKT and kidney after liver transplant may both increase. Impact of the new policy should be carefully monitored, but influences beyond the policy need to be accounted for.
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MELD Stratified Outcomes Among Recipients With Diabetes or Hypertension: Simultaneous Liver Kidney Versus Liver Alone. J Clin Gastroenterol 2018; 52:67-72. [PMID: 28906426 DOI: 10.1097/mcg.0000000000000818] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIM Data are scanty on allocating simultaneous liver kidney (SLK) based on model for end-stage disease (MELD) score. Diabetes mellitus (DM) and hypertension (HTN) are frequent in cirrhosis patients. We analyzed transplant recipients with DM and/or HTN to compare MELD-based outcomes of SLK to liver transplantation alone (LTA). MATERIALS AND METHODS Of 13,584 first deceased donor liver transplantation among patients with DM and/or HTN (1530 or 11.2% SLK), MELD score predicted SLK [1.02 (1.01-1.03)]. SLK was beneficial for 5-year patient survival at MELD score ≥43 (78.6% vs. 62.6%, P=0.017), but not at MELD score <29 (74.8% vs. 76.2%, P=0.63). Among 11,405 recipients (976 SLK) at MELD score <29, SLK (n=816) was beneficial compared with 706 LTA [75% vs. 64%, P<0.001; 0.71 (0.55-0.91)] at serum creatinine (SC) ≥2 but not at SC<2 [73% vs. 76%, P=0.32; 0.85 (0.60-1.2)]. Among patients with MELD score 29 to 42, SLK (n=484) and LTA (n=1403) had similar survival [69% vs. 69%, P=0.58; 0.9 (0.7-1.5)]. Among patients with MELD score ≥43, SLK (n=70) was associated with 35% improved patient survival at 5 years compared with 222 LTA [0.65 (0.46-0.93)]. CONCLUSIONS Among patients with DM and/or HTN, SLK is useful at: (a) MELD score <29 and SC≥2 and (b) MELD score ≥43. Prospective studies are needed to confirm these findings as basis to optimize use of SLK.
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Kwong AJ, Goel A, Mannalithara A, Kim WR. Improved posttransplant mortality after share 35 for liver transplantation. Hepatology 2018; 67:273-281. [PMID: 28586179 PMCID: PMC5756050 DOI: 10.1002/hep.29301] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 05/23/2017] [Accepted: 05/30/2017] [Indexed: 12/12/2022]
Abstract
UNLABELLED The Share 35 policy was implemented in June 2013 to improve equity in access to liver transplantation (LT) between patients with fulminant liver failure and those with cirrhosis and severe hepatic decompensation. The aim of this study was to assess post-LT outcomes after Share 35. Relevant donor, procurement, and recipient data were extracted from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. All adult deceased donor LTs from January 1, 2010, to March 31, 2016, were included in the analysis. One-year patient survival before and after Share 35 was assessed by multivariable Cox proportional hazards analysis, with adjustment for variables known to affect graft survival. Of 34,975 adult LT recipients, 16,472 (47.1%) were transplanted after the implementation of Share 35, of whom 4,599 (27.9%) had a Model for End-Stage Liver Disease (MELD) score ≥35. One-year patient survival improved from 83.9% to 88.4% after Share 35 (P < 0.01) for patients with MELD ≥35. There was no significant impact on survival of patients with MELD <35 (P = 0.69). Quality of donor organs, as measured by a donor risk index without the regional share component, improved for patients with MELD ≥35 (P < 0.01) and worsened for patients with lower MELD (P < 0.01). In multivariable Cox regression analysis, Share 35 was associated with improved 1-year patient survival (hazard ratio, 0.69; 95% confidence interval, 0.60-0.80) in recipients with MELD ≥35. CONCLUSION Share 35 has had a positive impact on survival after transplantation in patients with MELD ≥35, without a reciprocal detriment in patients with lower acuity; this was in part a result of more favorable donor-recipient matching. (Hepatology 2018;67:273-281).
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Affiliation(s)
- Allison J. Kwong
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA, United States
| | - Aparna Goel
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA, United States
| | - Ajitha Mannalithara
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA, United States
| | - W. Ray Kim
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA, United States
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Trieu JA, Bilal M, Hmoud B. Factors associated with waiting time on the liver transplant list: an analysis of the United Network for Organ Sharing (UNOS) database. Ann Gastroenterol 2017; 31:84-89. [PMID: 29333071 PMCID: PMC5759617 DOI: 10.20524/aog.2017.0217] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 10/22/2017] [Indexed: 12/24/2022] Open
Abstract
Background Liver transplantation (LT) is an important treatment for acute liver failure and end-stage liver disease. In 2002, the model for end-stage liver disease (MELD) score was incorporated to prioritize patients awaiting LT. Although there is data on how the MELD score affects waiting times, there is a paucity of literature regarding other components. We aimed to evaluate the factors affecting LT waiting times in the United States. Methods Using the United Network for Organ Sharing (UNOS) database, patients aged 12-75 years listed for LT over the years 2002-2015 were included. Variables tested in the model included patient characteristics, pertinent laboratory values, ABO blood type, region of listing, primary payer, ethnicity, and listing for simultaneous transplantation. Results A total of 75,771 patients were included in the final analysis. The components of the MELD score were associated with shorter waiting times. Other factors associated with shorter waiting times were the need of mechanical ventilation and region 3 of transplantation. ABO blood type, primary payer, and placement of a transjugular intrahepatic porto-systemic shunt also influenced time on the LT waiting list. Conclusions MELD score is utilized in the prioritization of liver allocation, and was expected to predict waiting-list time. Mechanical ventilation and other markers of disease severity are associated with higher MELD scores and thus shorter waiting times. Further research is needed to address reasons for the variation in waiting times between regions and payment systems in an attempt to decrease time to LT, standardize the listing process, and improve patient outcomes.
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Affiliation(s)
- Judy A Trieu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Mohammad Bilal
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Bashar Hmoud
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
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Life Experiences of Hepatitis Patients Waiting for Liver Transplantation. HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.57775] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Goldberg DS, Levine M, Karp S, Gilroy R, Peter L. Share 35 changes in center-level liver acceptance practices. Liver Transpl 2017; 23:604-613. [PMID: 28240804 PMCID: PMC5462450 DOI: 10.1002/lt.24749] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 02/14/2017] [Indexed: 12/31/2022]
Abstract
Share 35 was implemented to provide improved access to organs for patients with Model for End-Stage Liver Disease (MELD) scores ≥ 35. However, little is known about the impact of Share 35 on organ offer acceptance rates. We evaluated all liver offers to adult patients who were ultimately transplanted between January 1, 2011 and December 31, 2015. The analyses focused on patients ranked in the top 5 positions of a given match run and used multilevel mixed-effects models, clustering on individual wait-list candidate and transplant center. There was a significant interaction between Share 35 era and MELD category (P < 0.001). Comparing offers to MELD score ≥ 35 patients, offers after Share 35 were 36% less likely to be accepted compared with offers to MELD score ≥ 35 patients before Share 35 (adjusted odds ratio, 0.64). There was no clinically meaningful difference in the donor risk index of livers that were declined for patients with an allocation MELD score ≥35 in the pre- versus post-Share 35 era. Organ offer acceptance rates for patients with an allocation MELD ≥ 35 decreased in every region after Share 35; the magnitude of these changes was bigger in regions 2, 3, 4, 5, 6, 7, and 11, compared with regions 8 and 9 that had regional sharing in place before Share 35. There were significant changes in organ offer acceptance rates at the center level before versus after Share 35, and these changes varied across centers (P < 0.001). In conclusion, in liver transplantation candidates achieving a MELD score ≥ 35, liver acceptance of offers declined significantly after implementation of Share 35. The alterations in behavior at the center level suggest that practice patterns changed as a direct result of Share 35. Changes in organ acceptance under even broader organ sharing (redistricting) would likely be even greater, posing major logistical and operational challenges, while potentially increasing discard rates, thus decreasing the total number of transplants nationally. Liver Transplantation 23 604-613 2017 AASLD.
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Affiliation(s)
- David S. Goldberg
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania,Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania,Leonard Davis Institute of Health Economics, University of Pennsylvania
| | - Matthew Levine
- Division of Transplantation, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Seth Karp
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Richard Gilroy
- Division of Gastroenterology, Department of Medicine, Intermountain Medical Center, Murray, UT
| | - L Peter
- Division of Transplantation, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
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Croome KP, Lee DD, Harnois D, Taner CB. Effects of the Share 35 Rule on Waitlist and Liver Transplantation Outcomes for Patients with Hepatocellular Carcinoma. PLoS One 2017; 12:e0170673. [PMID: 28122003 PMCID: PMC5266291 DOI: 10.1371/journal.pone.0170673] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 01/09/2017] [Indexed: 12/16/2022] Open
Abstract
Introduction Several studies have investigated the effects following the implementation of the “Share 35” policy; however none have investigated what effect this policy change has had on waitlist and liver transplantation (LT) outcomes for hepatocellular carcinoma(HCC). Methods Data were obtained from the UNOS database and a comparison of the 2 years post-Share 35 with data from the 2 years pre-Share 35 was performed. Results In the pre-Share35 era, 23% of LT were performed for HCC exceptions compared to 22% of LT in the post-Share35 era (p = 0.21). No difference in wait-time for HCC patients was seen in any of the UNOS regions between the 2 eras. Competing risk analysis demonstrated that HCC candidates in post-Share 35 era were more likely to die or be delisted for “too sick” while waiting (7.2% vs. 5.3%; p = 0.005) within 15 months. A higher proportion of ECD (p<0.001) and DCD (p<0.001) livers were used for patients transplanted for HCC, while lower DRI organs were used for those patients transplanted with a MELD≥35 between the 2 eras (p = 0.007). Conclusion No significant change to wait-time for patients listed for HCC was seen following implementation of “Share 35”. Transplant program behavior has changed resulting use of higher proportion of ECD and DCD liver grafts for patients with HCC. A higher rate of wait list mortality was observed in patients with HCC in the post-Share 35 era.
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Affiliation(s)
| | - David D. Lee
- Department of Transplant, Mayo Clinic Florida, Jacksonville, Florida
| | - Denise Harnois
- Department of Transplant, Mayo Clinic Florida, Jacksonville, Florida
| | - C. Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, Florida
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Abstract
BACKGROUND The high demand for livers for transplantation has led to organs of limited quality being accepted to expand the donor pool. This is associated with inferior outcomes due to more pronounced preservation injury. Accordingly, recent research has aimed to develop preservation modalities for improved preservation as well as strategies for liver viability assessment and liver reconditioning. METHODS The PubMed database was searched using the terms 'perfusion', 'liver', 'preservation', and 'reconditioning' in various combinations, and the according literature was reviewed. RESULTS Several perfusion techniques have been developed in recent years with the potential for liver reconditioning. Preclinical and first emerging clinical data suggest feasibility, safety, and superiority over the current gold standard of cold storage. CONCLUSION This review outlines current advances in the field of liver preservation with an emphasis on liver reconditioning methods.
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Affiliation(s)
- Dieter P Hoyer
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Thomas Minor
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
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Abstract
The definition of acute-on-chronic liver failure (ACLF) remains contested. In Europe and North America, the term is generally applied according to the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium guidelines, which defines this condition as a syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure and high short-term mortality. One-third of patients who are hospitalized for acute decompensation present with ACLF at admission or develop the syndrome during hospitalization. ACLF frequently occurs in a closed temporal relationship to a precipitating event, such as bacterial infection or acute alcoholic, drug-induced or viral hepatitis. However, no precipitating event can be identified in approximately 40% of patients. The mechanisms of ACLF involve systemic inflammation due to infections, acute liver damage and, in cases without precipitating events, probably intestinal translocation of bacteria or bacterial products. ACLF is graded into three stages (ACLF grades 1-3) on the basis of the number of organ failures, with higher grades associated with increased mortality. Liver and renal failures are the most common organ failures, followed by coagulation, brain, circulatory and respiratory failure. The 28-day mortality rate associated with ACLF is 30%. Depending on the grade, ACLF can be reversed using standard therapy in only 16-51% of patients, leaving a considerable proportion of patients with ACLF that remains steady or progresses. Liver transplantation in selected patients with ACLF grade 2 and ACLF grade 3 increases the 6-month survival from 10% to 80%.
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End-stage liver disease patients with MELD >40 have higher waitlist mortality compared to Status 1A patients. Hepatol Int 2016; 10:838-46. [DOI: 10.1007/s12072-016-9735-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 04/20/2016] [Indexed: 12/14/2022]
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