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1
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Simonetto DA, Winder GS, Connor AA, Terrault NA. Liver transplantation for alcohol-associated liver disease. Hepatology 2024; 80:1441-1461. [PMID: 38889100 DOI: 10.1097/hep.0000000000000978] [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] [Received: 02/20/2024] [Accepted: 05/31/2024] [Indexed: 06/20/2024]
Abstract
Alcohol-associated liver disease (ALD) is a major cause of morbidity and mortality worldwide, and a leading indication for liver transplantation (LT) in many countries, including the United States. However, LT for ALD is a complex and evolving field with ethical, social, and medical challenges. Thus, it requires a multidisciplinary approach and individualized decision-making. Short-term and long-term patient and graft survival of patients undergoing LT for ALD are comparable to other indications, but there is a continued need to develop better tools to identify patients who may benefit from LT, improve the pretransplant and posttransplant management of ALD, and evaluate the impact of LT for ALD on the organ donation and transplantation systems. In this review, we summarize the current evidence on LT for ALD, from alcohol-associated hepatitis to decompensated alcohol-associated cirrhosis. We discuss the indications, criteria, outcomes, and controversies of LT for these conditions and highlight the knowledge gaps and research priorities in this field.
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Affiliation(s)
- Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Ashton A Connor
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, California, USA
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2
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Brown C, Khan S, Parekh TM, Muir AJ, Sudore RL. Barriers and Strategies to Effective Serious Illness Communication for Patients with End-Stage Liver Disease in the Intensive Care Setting. J Intensive Care Med 2024:8850666241280892. [PMID: 39247992 PMCID: PMC11890205 DOI: 10.1177/08850666241280892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2024]
Abstract
Background: Patients with end-stage liver disease (ESLD) often require Intensive Care Unit (ICU) admission during the disease trajectory, but aggressive medical treatment has not resulted in increased quality of life for patients or caregivers. Methods: This narrative review synthesizes relevant data thematically exploring the current state of serious illness communication in the ICU with identification of barriers and potential strategies to improve performance. We provide a conceptual model underscoring the importance of providing comprehensible disease and prognosis knowledge, eliciting patient values and aligning these values with available goals of care options through a series of discussions. Achieving effective serious illness communication supports the delivery of goal concordant care (care aligned with the patient's stated values) and improved quality of life. Results: General barriers to effective serious illness communication include lack of outpatient serious illness communication discussions; formalized provider training, literacy and culturally appropriate patient-directed serious illness communication tools; and unoptimized electronic health records. ESLD-specific barriers to effective serious illness communication include stigma, discussing the uncertainty of prognosis and provider discomfort with serious illness communication. Evidence-based strategies to address general barriers include using the Ask-Tell-Ask communication framework; clinician training to discuss patients' goals and expectations; PREPARE for Your Care literacy and culturally appropriate written and online tools for patients, caregivers, and clinicians; and standardization of documentation in the electronic health record. Evidence-based strategies to address ESLD-specific barriers include practicing with empathy; using the "Best-Case, Worst Case" prognostic framework; and developing interdisciplinary solutions in the ICU. Conclusion: Improving clinician training, providing patients and caregivers easy-to-understand communication tools, standardizing EHR documentation, and improving interdisciplinary communication, including palliative care, may increase goal concordant care and quality of life for critically ill patients with ESLD.
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Affiliation(s)
- Cristal Brown
- Department of Medicine, University of Texas at Austin, Dell Medical School, Austin, TX, USA
- Department of Medicine, Ascension Seton and Seton Family of Doctors, Austin, TX, USA
| | - Saif Khan
- Department of Medicine, University of Texas at Austin, Austin, TX, USA
| | - Trisha M. Parekh
- Department of Medicine, University of Texas at Austin, Dell Medical School, Austin, TX, USA
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Rebecca L. Sudore
- Division of Geriatrics, Department of Medicine, University of California, San Francisco, CA, USA
- Department of Medicine, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA
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3
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Malamon JS, Kaplan B, Jackson WE, Saben JL, Schold JD, Pomfret EA, Pomposelli JJ. Reassessing the survival benefit of deceased donor liver transplantation: retrospective cohort study. Int J Surg 2023; 109:2714-2720. [PMID: 37226874 PMCID: PMC10498891 DOI: 10.1097/js9.0000000000000498] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 05/08/2023] [Indexed: 05/26/2023]
Abstract
INTRODUCTION Currently in the United States, deceased donor liver transplant (DDLT) allocation priority is based on the model for end-stage liver disease including sodium (MELD-Na) score. The United Network for organ sharing's 'Share-15' policy states that candidates with MELD-Na scores of 15 or greater have priority to receive local organ offers compared to candidates with lower MELD-Na scores. Since the inception of this policy, major changes in the primary etiologies of end-stage liver disease have occurred and previous assumptions need to be recalibrated. METHODS The authors retrospectively analyzed the Scientific Registry of Transplant Recipients database between 2012 and 2021 to determine life years saved by DDLT at each interval of MELD-Na score and the time-to-equal risk and time-to-equal survival versus remaining on the waitlist. The authors stratified our analysis by MELD exception points, primary disease etiology, and MELD score. RESULTS On aggregate, compared to remaining on the waitlist, a significant 1-year survival advantage of DDLT at MELD-Na scores as low as 12 was found. The median life years saved at this score after a liver transplant was estimated to be greater than 9 years. While the total life years saved were comparable across all MELD-Na scores, the time-to-equal risk and time-to-equal survival decreased exponentially as MELD-Na scores increased. CONCLUSION Herein, the authors challenge the perception as to the timing of DDLT and when that benefit occurs. The national liver allocation policy is transitioning to a continuous distribution framework and these data will be instrumental to defining the attributes of the continuos allocation score.
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Affiliation(s)
- John S. Malamon
- Department of Surgery
- Department of Medicine, University of Colorado Anschutz Medical Campus
| | - Bruce Kaplan
- Department of Surgery
- Department of Medicine, University of Colorado Anschutz Medical Campus
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado, USA
| | - Whitney E. Jackson
- Department of Medicine, University of Colorado Anschutz Medical Campus
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado, USA
| | - Jessica L. Saben
- Department of Surgery
- Department of Medicine, University of Colorado Anschutz Medical Campus
| | - Jesse D. Schold
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado, USA
| | - Elizabeth A. Pomfret
- Department of Surgery
- Department of Medicine, University of Colorado Anschutz Medical Campus
| | - James J. Pomposelli
- Department of Surgery
- Department of Medicine, University of Colorado Anschutz Medical Campus
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Bergsmark T, Engesæter LK, Rasmussen A, Bennet W, Nordin A, Pall V, Line PD, Ericzon BG, Melum E. Long-term survival after liver transplantation for alcohol-related liver disease in the Nordic countries. Scand J Gastroenterol 2023; 58:923-930. [PMID: 36872559 DOI: 10.1080/00365521.2023.2184193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/17/2023] [Accepted: 02/20/2023] [Indexed: 03/07/2023]
Abstract
OBJECTIVES Alcohol-related liver disease (ALD) is among the most common indications for liver transplantation (LTX) in Europe and North America, with good five-year survival rates post-LTX. Here we evaluated survival up to and beyond 20 years after LTX for patients with ALD compared to a comparison group. METHODS Patients with ALD and a comparison group transplanted in the Nordic countries between 1982 and 2020 were included. Data were analyzed using descriptive statistics, Kaplan-Meier curves and predictors of survival were assessed with Cox-regressions. RESULTS 831 patients with ALD and 2979 patients in the comparison group were included in the study. Patients with ALD were older at the time of LTX (p < .001) and more likely to be male (p < .001). The estimated median follow-up time was 9.1 years for the ALD-group and 11.1 years for the comparison group. 333 (40.1%) patients with ALD and 1010 (33.9%) patients in the comparison group died during follow-up. The overall survival was impaired for patients with ALD compared to the comparison group (p < .001) and was evident for male and female patients, patients transplanted before and after 2005, and observed in all age-groups except patients over 60 years. Age at transplant, waiting time, year of LTX and country of LTX were associated with decreased survival after LTX for patients with ALD. CONCLUSIONS Patients with ALD have a decreased long-term survival following LTX. This difference was evident in most sub-groups of patients and warrants close follow-up of liver transplanted patients with ALD with focus on risk reduction.
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Affiliation(s)
- Thomas Bergsmark
- Section of Gastroenterology, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Lise Katrine Engesæter
- Section of Gastroenterology, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Liver Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - William Bennet
- Transplant Institute, Sahlgrenska University Hospital, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Arno Nordin
- Department of Transplantation and Liver Surgery, University Hospital, Helsinki, Finland
| | - Virge Pall
- Transplantation Centre, Tartu University Hospital, Tartu, Estonia
| | - Pål-Dag Line
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Transplantation Surgery, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Bo-Göran Ericzon
- Division of Transplantation Surgery, Karolinska Institutet, CLINTEC, Stockholm, Sweden
| | - Espen Melum
- Section of Gastroenterology, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
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6
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Zeraati H, Madreseh E, Mahmoudi M, Nassiri Toosi M, Abolghasemi J. The effects of prognostic factors on transplant and mortality of patients with end-stage liver disease using Markov multistate model. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2023; 28:28. [DOI: 10.4103/jrms.jrms_1091_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 09/13/2022] [Accepted: 11/14/2022] [Indexed: 04/09/2023]
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7
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Jackson WE, Malamon JS, Kaplan B, Saben JL, Schold JD, Pomposelli JJ, Pomfret EA. Survival Benefit of Living-Donor Liver Transplant. JAMA Surg 2022; 157:926-932. [PMID: 35921119 PMCID: PMC9350845 DOI: 10.1001/jamasurg.2022.3327] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Importance Despite the acceptance of living-donor liver transplant (LDLT) as a lifesaving procedure for end-stage liver disease, it remains underused in the United States. Quantification of lifetime survival benefit and the Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score range at which benefit outweighs risk in LDLT is necessary to demonstrate its safety and effectiveness. Objective To assess the survival benefit, life-years saved, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. Design, Setting, and Participants This case-control study was a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database of 119 275 US liver transplant candidates and recipients from January 1, 2012, to September 2, 2021. Liver transplant candidates aged 18 years or older who were assigned to the wait list (N = 116 455) or received LDLT (N = 2820) were included. Patients listed for retransplant or multiorgan transplant and those with prior kidney or liver transplants were excluded. Exposures Living-donor liver transplant vs remaining on the wait list. Main Outcomes and Measures The primary outcome of this study was life-years saved from receiving an LDLT. Secondary outcomes included 1-year relative mortality and risk, time to equal risk, time to equal survival, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. MELD-Na score ranges from 6 to 40 and is well correlated with short-term survival. Higher MELD-Na scores (>20) are associated with an increased risk of death. Results The mean (SD) age of the 119 275 study participants was 55.1 (11.2) years, 63% were male, 0.9% were American Indian or Alaska Native, 4.3% were Asian, 8.2% were Black or African American, 15.8% were Hispanic or Latino, 0.2% were Native Hawaiian or Other Pacific Islander, and 70.2% were White. Mortality risk and survival models confirmed a significant survival benefit for patients receiving an LDLT who had a MELD-Na score of 11 or higher (adjusted hazard ratio, 0.64 [95% CI, 0.47-0.88]; P = .006). Living-donor liver transplant recipients gained an additional 13 to 17 life-years compared with patients who never received an LDLT. Conclusions and Relevance An LDLT is associated with a substantial survival benefit to patients with end-stage liver disease even at MELD-Na scores as low as 11. The findings of this study suggest that the life-years gained are comparable to or greater than those conferred by any other lifesaving procedure or by a deceased-donor liver transplant. This study's findings challenge current perceptions regarding when LDLT survival benefit occurs.
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Affiliation(s)
- Whitney E Jackson
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora.,Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora
| | - John S Malamon
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora.,Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Bruce Kaplan
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora.,Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora.,Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Jessica L Saben
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora.,Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Jesse D Schold
- Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - James J Pomposelli
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora.,Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Elizabeth A Pomfret
- Colorado Center for Transplantation Care, Research, and Education, University of Colorado Anschutz Medical Campus, Aurora.,Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
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8
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Sedki M, Ahmed A, Goel A. Ethical and allocation issues in liver transplant candidates with alcohol related liver disease. Transl Gastroenterol Hepatol 2022; 7:26. [PMID: 35892052 PMCID: PMC9257533 DOI: 10.21037/tgh-2020-13] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 09/17/2020] [Indexed: 09/01/2024] Open
Abstract
In the past decade, alcohol-related liver disease (ALD) has become the leading indication for liver transplantation (LT) in the United States. Despite this major development, there still remains some controversy in a distinct subset of this patient population, those presenting with alcoholic hepatitis (AH). There is significant debate within the transplant community regarding acceptance criteria for patients with AH requiring LT, especially those with less than 6 months of sobriety. With that being said, LT in the setting of ALD and AH has shown an improvement in survival rates; additionally, many studies have reported that careful selection of patients with ALD has produced excellent post-transplant outcomes even if transplant occurred with less than 6 months of sobriety. In this review, we aim to discuss the ethical and allocation-associated issues that arise when considering ALD and/or AH for LT; furthermore, we delve into the history, controversies, current guidelines, and future directions of LT in this subgroup.
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Affiliation(s)
- Mai Sedki
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Aparna Goel
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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9
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Cohen SM, Alexander RS, Holt SR. The Spectrum of Alcohol Use: Epidemiology, Diagnosis, and Treatment. Med Clin North Am 2022; 106:43-60. [PMID: 34823734 DOI: 10.1016/j.mcna.2021.08.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In the United States, alcohol is the most common substance used and the spectrum of unhealthy alcohol use is highly prevalent. Complications of unhealthy alcohol use affect nearly every organ system. One of the most frequent and potentially life-threatening of these complications is alcohol withdrawal syndrome for which benzodiazepines remain first-line therapy. Pharmacologic treatment of alcohol use disorder, the most severe form of unhealthy alcohol use, is underutilized despite the availability of multiple effective medications. Although behavioral therapies are an important component of treatment, they are overemphasized at the expense of pharmacotherapy.
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Affiliation(s)
- Shawn M Cohen
- Program in Addiction Medicine, Section of General Internal Medicine, Yale School of Medicine, 367 Cedar Street, Harkness Hal A, Suite 417A, New Haven, CT 06510, USA.
| | - Ryan S Alexander
- Program in Addiction Medicine, Section of General Internal Medicine, Yale School of Medicine, 367 Cedar Street, Harkness Hal A, Suite 417A, New Haven, CT 06510, USA; Department of Preventive Medicine, Griffin Hospital, Derby, CT 06418, USA; Department of Internal Medicine, Griffin Hospital, Derby, CT 06418, USA
| | - Stephen R Holt
- Program in Addiction Medicine, Section of General Internal Medicine, Yale School of Medicine, 367 Cedar Street, Harkness Hal A, Suite 417A, New Haven, CT 06510, USA
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10
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Shavelle RM, Saur RC, Kwak JH, Brooks JC, Hameed B. Life Expectancy After Liver Transplantation for Alcoholic Cirrhosis. Prog Transplant 2021; 31:345-356. [PMID: 34779671 DOI: 10.1177/15269248211046004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Alcohol-associated liver disease is the leading cause of liver transplantation in the western world. For these patients we calculated life expectancies both at time of transplant and several years later, stratified by key risk factors, and determined if survival has improved in recent years. METHODS Data on 14 962 patients with alcohol-associated liver disease who underwent liver transplantation in the MELD era (2002-2018) from the United States Organ Procurement and Transplantation Network database were analyzed using the Cox proportional hazards regression model and life table methods. RESULTS Demographic and past medical history factors related to survival were patient age, presence of diabetes or severe hepatic encephalopathy, and length of hospital stay. Survival improved over the study period, at roughly 3% per calendar year during the first 5 years posttransplant and 1% per year thereafter. CONCLUSIONS Life expectancy in transplanted patients with alcohol-associated liver disease was much reduced from normal, and varied according to age, medical risk factors, and functional status. Survival improved modestly over the study period. Information on patient longevity can be helpful in making treatment decisions.
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Affiliation(s)
| | - Rachel C Saur
- Life Expectancy Project, San Francisco, California, USA
| | - Ji Hun Kwak
- Life Expectancy Project, San Francisco, California, USA
| | | | - Bilal Hameed
- Division of Gastroenterology, University of California, San Francisco, USA
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11
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Hammond C, Hussaini T, Yoshida EM. Medical adherence and liver transplantation: a brief review. CANADIAN LIVER JOURNAL 2021; 4:8-15. [PMID: 35991471 PMCID: PMC9203162 DOI: 10.3138/canlivj-2020-0016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 06/16/2020] [Indexed: 11/13/2023]
Abstract
Liver transplantation remains the only feasible long-term treatment option for patients with end-stage liver disease. Despite significant medical and surgical advances over the decades, liver transplantation remains a complex undertaking with the need for indefinite immunosuppression and avoidance of patient behaviours that may jeopardize the allograft. Adherence (formerly called "compliance") to medical recommendations in terms of anti-rejection medications and-in the case of alcoholic liver disease, abstinence-is considered a key cornerstone to long-term allograft and patient survival. Not surprisingly, a history of habitual non-adherence is considered a contraindication to liver transplantation, especially re-transplantation. It is often assumed that non-adherence policies are "self-evidential" based on "common sense" and "expert opinion." In fact, non-adherence and its negative effects have been well studied in medicine, including in solid organ transplantation. In this review, we present the evidence that non-adherence to medical advice is clearly associated with worse medical outcomes, supporting the concept that efforts to support patient adherence post-transplant need to be optimized at all times.
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Affiliation(s)
- Carl Hammond
- Department of Gastroenterology, University Hospital Coventry & Warwickshire, United Kingdom
| | - Trana Hussaini
- Department of Pharmacy, Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, the University of British Columbia, Vancouver, British Columbia, Canada
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12
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Hause J, Rice JP. Transplants for Acute Alcoholic Hepatitis: Controversies and Early Successes. Clin Liver Dis 2021; 25:229-252. [PMID: 33978581 DOI: 10.1016/j.cld.2020.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver transplant for severe alcohol-associated hepatitis remains a controversial practice despite evidence for a substantial survival benefit compared with medical therapy and posttransplant alcohol relapse rates comparable with previously published studies in alcohol-associated cirrhosis. The controversy stems in part from concern regarding patient selection practices, lack of long-term follow-up data, and the potential negative public perception of the practice affecting organ donation. Despite these concerns, it seems that early liver transplant for alcohol-associated hepatitis is increasingly being offered to selected patients across the United States and the world.
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Affiliation(s)
- Jessica Hause
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 4th Floor MFCB, 1685 Highland Avenue, Madison, WI 53705, USA
| | - John P Rice
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 4th Floor MFCB, 1685 Highland Avenue, Madison, WI 53705, USA.
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13
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Gitto S, Aspite S, Golfieri L, Caputo F, Vizzutti F, Grandi S, Patussi V, Marra F. Alcohol use disorder and liver transplant: new perspectives and critical issues. Korean J Intern Med 2020; 35:797-810. [PMID: 32241080 PMCID: PMC7373982 DOI: 10.3904/kjim.2019.409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 03/03/2020] [Indexed: 12/13/2022] Open
Abstract
Alcoholic liver disease is a consolidated indication for liver transplantation, but many unsolved issues can be highlighted. Patients with alcohol use disorder develop peculiar comorbidities that can become contraindications for transplantation. Moreover, a number of social and psychological patterns should be evaluated to select candidates with a low risk of alcohol relapse and adequate post-transplant adherence. In this context, the 6-month rule is too rigid to be widely applied. A short period of abstinence (1 to 3 months) is useful to estimate recovery of liver function and, possibly to avoid transplant. Cardiovascular disorders and extra-hepatic malignancies represent the main clinical issues after transplant. Patients transplanted due to alcoholic disease are a major risk for other liver diseases. Severe corticosteroid-resistant alcoholic acute hepatitis is a debated indication for transplant. However, available data indicate that well-selected patients have excellent post-transplant outcomes. Behavioral therapy, continued psychological support and a multidisciplinary team are essential to achieve and maintain complete alcohol abstinence during the transplant process. Alcoholic liver disease is an excellent indication for a liver transplant but patients with alcohol use disorder deserve a personalized approach and dedicated resources.
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Affiliation(s)
- Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Silvia Aspite
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Lucia Golfieri
- Department of Psychology, University of Bologna, Bologna, Italy
| | - Fabio Caputo
- Department of Internal Medicine, SS Annunziata Hospital, University of Ferrara, Cento, Italy
| | - Francesco Vizzutti
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Silvana Grandi
- Department of Psychology, University of Bologna, Bologna, Italy
| | | | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Research Center Denothe, University of Florence, Italy
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14
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Artru F, Bou Saleh M, Maggiotto F, Lassailly G, Ningarhari M, Demaret J, Ntandja-Wandji LC, Pais de Barros JP, Labreuche J, Drumez E, Helou DG, Dharancy S, Gantier E, Périanin A, Chollet-Martin S, Bataller R, Mathurin P, Dubuquoy L, Louvet A. IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis. J Hepatol 2020; 72:1052-1061. [PMID: 31953139 DOI: 10.1016/j.jhep.2019.12.017] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 11/30/2019] [Accepted: 12/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Severe alcoholic hepatitis (SAH) is associated with a high risk of infection. The IL-33/ST2 pathway is involved in sepsis control but data regarding its role in alcohol-related liver disease (ALD) are lacking. We aimed to characterize the role of IL-33/ST2 in the polymorphonuclear neutrophils (PMNs) of patients with ALD and SAH. METHODS Serum and circulating neutrophils were collected from patients with SAH, alcoholic cirrhosis and healthy controls. We quantified IL-33/ST2 pathway activity and CXCR2 at baseline and after exposure to IL-33. We also determined the migration capacity of PMNs. RESULTS The decoy receptor of IL-33 (soluble ST2 [sST2]) was increased in SAH vs. cirrhosis and controls, demonstrating the defect in this pathway during ALD. The sST2 level was associated with response to treatment, 2-month survival, infection-free survival and probability of infection in SAH. Endotoxemia was weakly correlated with sST2. GRK2, a negative regulator of CXCR2, was overexpressed in PMNs of patients with SAH and cirrhosis and was decreased by IL-33. CXCR2 levels on PMNs were lower in SAH vs. cirrhosis and controls. Treatment with IL-33 partially restored CXCR2 expression in SAH and cirrhosis. PMN migration upon IL-8 was lower in patients with SAH and cirrhosis vs. controls. Treatment with IL-33 partially restored migration in those with SAH and cirrhosis. Interestingly, the migration capacity of PMNs and the response to IL-33 were enhanced in responders to corticosteroids (Lille <0.45) compared to non-responders. CONCLUSION The IL33/ST2 pathway is defective in SAH and predicts outcome. This defect is associated with decreased CXCR2 expression on the surface of PMNs and lower migration capacity, which can be corrected by IL-33, especially in patients responding to steroids. These results suggest that IL-33 has therapeutic potential for SAH and its infectious complications. LAY SUMMARY The neutrophils of patients with severe alcoholic hepatitis are associated with a defect in the IL-33/ST2 pathway. This defect is associated with lower migration capacities in neutrophils and a higher probability of getting infected. Administration of IL-33 to the neutrophils at least partly restores this defect and may be effective at reducing the risk of infection in patients with severe alcoholic hepatitis.
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Affiliation(s)
- Florent Artru
- Hôpital Claude-Huriez, Service Maladies de l'Appareil Digestif, CHU Lille, Lille, France; Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | - Mohamed Bou Saleh
- Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | - François Maggiotto
- Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | - Guillaume Lassailly
- Hôpital Claude-Huriez, Service Maladies de l'Appareil Digestif, CHU Lille, Lille, France; Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | - Massih Ningarhari
- Hôpital Claude-Huriez, Service Maladies de l'Appareil Digestif, CHU Lille, Lille, France; Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | - Julie Demaret
- Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France; Centre de Biologie-Pathologie, CHU de Lille, Lille, France
| | - Line-Carolle Ntandja-Wandji
- Hôpital Claude-Huriez, Service Maladies de l'Appareil Digestif, CHU Lille, Lille, France; Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | | | | | - Elodie Drumez
- Département de biostatistiques, CHU de Lille, Lille, France
| | - Doumet Georges Helou
- Inserm/Université Paris-Sud/Université Paris-Saclay, UMR996, Chatenay-Malabry, France; Assistance publique-Hôpitaux de Paris, Hôpital Bichat, Laboratoire d'immunologie « Autoimmunité et Hypersensibilités », Paris, France
| | - Sébastien Dharancy
- Hôpital Claude-Huriez, Service Maladies de l'Appareil Digestif, CHU Lille, Lille, France; Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | - Emilie Gantier
- Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | - Axel Périanin
- Inserm/Faculté de Médecine Xavier Bichat, UMRS-1149, Paris, France; CNRS, ERL-8252 Centre de Recherche sur l'Inflammation, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence INFLAMEX, Paris, France
| | - Sylvie Chollet-Martin
- Inserm/Université Paris-Sud/Université Paris-Saclay, UMR996, Chatenay-Malabry, France; Assistance publique-Hôpitaux de Paris, Hôpital Bichat, Laboratoire d'immunologie « Autoimmunité et Hypersensibilités », Paris, France
| | - Ramon Bataller
- Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Philippe Mathurin
- Hôpital Claude-Huriez, Service Maladies de l'Appareil Digestif, CHU Lille, Lille, France; Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France
| | - Laurent Dubuquoy
- Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France.
| | - Alexandre Louvet
- Hôpital Claude-Huriez, Service Maladies de l'Appareil Digestif, CHU Lille, Lille, France; Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France.
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15
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Hepatoprotective Effects of Steamed and Freeze-Dried Mature Silkworm Larval Powder against Ethanol-Induced Fatty Liver Disease in Rats. Foods 2020; 9:foods9030285. [PMID: 32143357 PMCID: PMC7142575 DOI: 10.3390/foods9030285] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 02/27/2020] [Accepted: 02/29/2020] [Indexed: 12/16/2022] Open
Abstract
Silkworm, Bombyx mori, contains high amounts of beneficial nutrients, including amino acids, proteins, essential minerals, and omega-3 fatty acids. We have previously reported a technique for producing steamed and freeze-dried mature silkworm larval powder (SMSP), which makes it easier to digest mature silkworm. In this study, we investigated the preventive effects of SMSP on alcoholic fatty liver disease and elucidated its mechanism of action. Male Sprague-Dawley rats treated with SMSP (50 mg/kg) or normal diet (AIN-76A) were administered 25% ethanol (3 g/kg body weight) by oral gavage for 4 weeks. SMSP administration for 4 weeks significantly decreased hepatic fat accumulation in ethanol-treated rats by modulating lipogenesis and fatty acid oxidation-related molecules such as sirtuin 1, AMP-activated protein kinase, and acetyl-CoA carboxylase 1. Moreover, SMSP administration significantly diminished the levels of triglyceride in liver tissues by as much as 35%, as well as lowering the serum levels of triglyceride, gamma glutamyl transpeptidase, alanine transaminase, and aspartate aminotransferase in ethanol-treated rats. SMSP supplementation also decreased the pro-inflammatory tumor necrosis factor-alpha and interleukin 1 beta levels and cytochrome P450 2E1 generating oxidative stress. These results suggest that SMSP administration may be possible for the prevention of alcoholic liver disease.
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16
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Crabb DW, Im GY, Szabo G, Mellinger JL, Lucey MR. Diagnosis and Treatment of Alcohol-Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology 2020; 71:306-333. [PMID: 31314133 DOI: 10.1002/hep.30866] [Citation(s) in RCA: 549] [Impact Index Per Article: 109.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Affiliation(s)
- David W Crabb
- Indiana University School of Medicine, Indianapolis, IN
| | - Gene Y Im
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Gyongyi Szabo
- University of Massachusetts Medical School, Worcester, MA
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Giard JM, Dodge JL, Terrault N. Superior Wait-List Outcomes in Patients with Alcohol-Associated Liver Disease Compared With Other Indications for Liver Transplantation. Liver Transpl 2019; 25:1310-1320. [PMID: 31063642 PMCID: PMC8544021 DOI: 10.1002/lt.25485] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 04/17/2019] [Indexed: 01/18/2023]
Abstract
Alcohol-associated liver disease (ALD) is the most common indication for liver transplantation (LT) in the United States and Europe. A 6-month alcohol abstinence period has been required by many transplant programs prior to listing, which may influence wait-list (WL) outcomes. Therefore, we examined WL events in patients with ALD versus non-ALD with a special interest in whether these outcomes differed by sex. All US adults listed for LT from January 2002 to December 2016 were eligible except status 1 patients, Model for End-Stage Liver Disease exceptions, retransplants and those with acute alcoholic hepatitis. The outcomes of interest were cumulative WL death or being too sick and WL removal for improvement within 2 years of listing. Competing risk regression models were used to evaluate recipient factors associated with the outcomes. Among the 83,348 eligible WL patients, 23% had ALD. Unadjusted cumulative WL removal within 2 years was 19.0% for ALD versus 21.1% for non-ALD (P < 0.001). In fully adjusted models, ALD was associated with a significantly lower risk of WL removal for death or being too sick (subhazard ratio [SHR], 0.84; 95% confidence interval [CI], 0.81-0.87; P < 0.001) and a higher risk of removal for improvement (SHR, 2.91; 95% CI, 2.35-3.61; P < 0.001) versus non-ALD patients. After adjusting for potential confounders, women with ALD had a higher risk of removal for death or being too sick (SHR, 1.09; 95% CI, 1.00-1.08; P < 0.001) and a higher chance for improvement (SHR, 2.91; 95% CI, 2.35-3.61; P < 0.001) than men with ALD. In conclusion, WL candidates with ALD have more favorable WL outcomes than non-ALD patients with a 16% lower risk of removal for deterioration and 191% higher risk of removal for improvement. This result likely reflects the benefits of alcohol abstinence, but it suggests that listing criteria for ALD may be too restrictive, with patients who might derive benefit from LT not being listed.
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Affiliation(s)
- Jeanne-Marie Giard
- University of California San Francisco, San Francisco, CA, United States.,Université de Montréal, Montréal, Québec, Canada
| | - Jennifer L. Dodge
- University of California San Francisco, San Francisco, CA, United States
| | - Norah Terrault
- University of California San Francisco, San Francisco, CA, United States
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18
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Skladany L, Selcanova SA, Koller T. Alcohol Use Relapse Following Liver Transplantation for Alcoholic Liver Disease. Ann Transplant 2019; 24:359-366. [PMID: 31209197 PMCID: PMC6597142 DOI: 10.12659/aot.914690] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 04/04/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Alcohol use disorders affect 10% of the European population. Alcohol-related liver disease (ALD) is the most common indication for liver transplantation in Slovakia. The aim of this study was to determine the proportion of patients with ALD who received a liver transplant who had alcohol relapsed, and the risk factors for alcohol relapse, as well as to compare clinical outcomes according to relapse. MATERIAL AND METHODS A retrospective study of consecutive patients with ALD, who underwent liver transplantation in a single transplant center between May 2008 and December 2017. We included adult patients who received a liver transplant due to ALD and excluded those who died <1 month after liver transplantation. We recorded demographic and clinical characteristics, graft injury, and overall mortality and compared them between relapsers and abstainers. RESULTS During the study period, we reviewed 196 cases of liver transplantation in 191 patients. We excluded 87 patients for non-ALD etiology and 15 patients by predefined criteria. The final analysis was carried out in 89 patients, mean aged 55 years; 24.7% were female. We diagnosed relapse in 23 patients (26%) with harmful drinking in 52% and occasional drinking in 48% of relapsers. The independent risk factors associated with relapse were: smoking (OR=5.92, P=0.006), loss of social status (OR=7.61, P=0.002), and time after liver transplantation (OR=1.0008, P=0.015). Graft injury was more frequent in relapsers with 2 independent risk factors: occasional drinking (OR=12.7, P=0.0005), and harmful drinking (OR=36.6, P<0.0001); overall survival was unaffected. CONCLUSIONS We found relapse to alcohol drinking in 26% of patients who received a liver transplant for ALD. Risk factors associated with alcohol drinking relapse were time, cigarette smoking, and loss of social status. Graft injury was more frequent in relapsers, but mortality was similar between relapsers and non-relapsers.
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Affiliation(s)
- Lubomir Skladany
- HEGITO (Division Hepatology, Gastroenterology and Liver Transplantation) of Department of Internal Medicine II, Faculty of Medicine, Slovak Medical University, FD Roosevelt Hospital, Banska Bystrica, Slovakia
| | - Svetlana Adamcova Selcanova
- HEGITO (Division Hepatology, Gastroenterology and Liver Transplantation) of Department of Internal Medicine II, Faculty of Medicine, Slovak Medical University, FD Roosevelt Hospital, Banska Bystrica, Slovakia
| | - Tomas Koller
- 5 Department of Internal Medicine, Comenius University Faculty of Medicine, University Hospital Bratislava Ruzinov, Bratislava, Slovakia
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19
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Jena AB, Snider JT, Diaz Espinosa O, Ingram A, Sanchez Gonzalez Y, Lakdawalla D. How Does Treating Chronic Hepatitis C Affect Individuals in Need of Organ Transplants in the United Kingdom? VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2019; 22:669-676. [PMID: 31198184 DOI: 10.1016/j.jval.2018.09.2923] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 07/31/2018] [Accepted: 09/10/2018] [Indexed: 06/09/2023]
Abstract
OBJECTIVES To estimate the impact of cures for chronic hepatitis C (CHC) infection on organ donation in the United Kingdom. Curing CHC infection reduces the need for liver transplants and enables cured individuals to donate organs of all types. METHODS We adapted a double-queuing model of organ allocation to estimate the effects of CHC infection cures on liver, lung, heart, and kidney transplants in the United Kingdom. We assumed that cured individuals would donate organs at similar rates as the general population and no longer require liver transplants because of CHC infection. We estimated how curing CHC infection influences waitlist lengths for each organ and the annual net present value to society on the basis of quality-adjusted life-years gained through additional transplants under opt-in and opt-out organ donation policies. RESULTS Curing CHC generates the most value for patients on the liver waitlist, because it increases the number of transplantable livers and reduces the need for transplants. Under the current opt-in policy, liver waitlist length falls by 24%, generating £34.3 million of annual net present value. Growth in the number of uninfected lungs, hearts, and kidneys generates an additional £19.2 million annually, with £18.7 million from kidneys. Implementing the opt-out policy, liver waitlist length would decrease by 75%, implying that treating CHC eliminates one-third of the excess liver waitlist due to an opt-in policy. CONCLUSIONS Treating CHC has large positive spillovers to uninfected individuals by reducing the need for liver transplants and allowing cured individuals to donate organs. These spillovers have not been included in traditional value assessments of CHC treatment.
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20
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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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21
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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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22
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Davis JP, Reutemann BA, Argo CK. Pro: The Abstinence Period Should Be the Same for All Patients Undergoing Evaluation for Transplant. Clin Liver Dis (Hoboken) 2019; 13:82-86. [PMID: 30988943 PMCID: PMC6446445 DOI: 10.1002/cld.747] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Accepted: 07/20/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
- Jessica P. Davis
- Division of Gastroenterology and HepatologyUniversity of Virginia Health SystemCharlottesvilleVA
| | - Bethany A. Reutemann
- Division of Gastroenterology and HepatologyUniversity of Virginia Health SystemCharlottesvilleVA
| | - Curtis K. Argo
- Division of Gastroenterology and HepatologyUniversity of Virginia Health SystemCharlottesvilleVA
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23
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Lee BP, Vittinghoff E, Dodge JL, Cullaro G, Terrault NA. National Trends and Long-term Outcomes of Liver Transplant for Alcohol-Associated Liver Disease in the United States. JAMA Intern Med 2019; 179:340-348. [PMID: 30667468 PMCID: PMC6439700 DOI: 10.1001/jamainternmed.2018.6536] [Citation(s) in RCA: 142] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
IMPORTANCE Alcohol-associated liver disease (ALD) has emerged as the most common indication for liver transplant in the United States, but data on the reasons for this increase and long-term post-liver transplant outcomes among liver transplant recipients are sparse. OBJECTIVE To characterize trends and long-term outcomes of liver transplant for ALD in the United States between 2002 and 2016. DESIGN, SETTING, AND PARTICIPANTS This multicenter, prospective, national cohort study used data from the United Network for Organ Sharing database to evaluate all liver transplants performed in the United States between January 1, 2002, and December 31, 2016. MAIN OUTCOMES AND MEASURES National and regional trends in liver transplant for ALD, with a sensitivity analysis with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) included, and early (≤90 days after liver transplant) and late (>90 days after liver transplant) patient and graft survival. RESULTS The cohort consisted of 32 913 patients, including 9438 with ALD and 23 475 without ALD (patients who had HCV infection and HCC indications were excluded). Median age of patients with ALD was 54 years (interquartile range, 47-60 years) and of patients without ALD was 54 years (interquartile range, 44-61 years). Patients with ALD (vs non-ALD) were more frequently male (7197 of 9438 [76.2%] vs 11 767 of 23 475 [50.1%]; P < .001) and white (7544 [80.0%] vs 17 251 [73.5%]; P < .001). The proportion of liver transplants for ALD increased from 24.2% (433 of 1791) in 2002 to 27.2% (556 of 2044) in 2010 and 36.7% (1253 of 3419) in 2016. With HCV infection included, the proportions of liver transplant for ALD were 15.3% in 2002, 18.6% in 2010, and 30.6% in 2016, representing a 100% increase in liver transplant for ALD, of which 48% was associated with a decrease in HCV infection as an indication for liver transplant. The magnitude of increase in ALD was regionally heterogeneous and associated with changes in patient characteristics suggestive of alcoholic hepatitis: decreasing age (χ2 = 36.5; P = .005) and increasing model for end-stage liver disease score (χ2 = 69.1; P < .001). Cumulative unadjusted 5-year posttransplant survival was 79% (95% CI, 78%-80%) for ALD vs 80% (95% CI, 79%-80%) for non-ALD; cumulative unadjusted 10-year posttransplant survival was 63% (95% CI, 61%-64%) for ALD vs 68% (95% CI, 67%-69%) for non-ALD (P = .006). In multivariable analysis, ALD was associated with increased risk of late death after liver transplant (adjusted hazard ratio, 1.11; 95% CI, 1.03-1.20; P = .006). CONCLUSIONS AND RELEVANCE The findings suggest that early liver transplant for alcoholic hepatitis may be leading to broader acceptance of ALD for liver transplant. Late survival among liver transplant recipients with ALD was inferior to that among recipients with non-ALD indications, suggesting a need for future studies to identify patient profiles associated with best outcomes. Regional differences suggest heterogeneity in policies toward liver transplant for ALD.
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Affiliation(s)
- Brian P Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco
| | - Eric Vittinghoff
- Department of Epidemiology and Biostatistics, University of California, San Francisco
| | | | - Giuseppe Cullaro
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco
| | - Norah A Terrault
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco
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Thursz M, Gual A, Lackner C, Mathurin P, Moreno C, Spahr L, Sterneck M, Cortez-Pinto H. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol 2018; 69:154-181. [PMID: 29628280 DOI: 10.1016/j.jhep.2018.03.018] [Citation(s) in RCA: 573] [Impact Index Per Article: 81.9] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 12/12/2022]
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25
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Attilia ML, Lattanzi B, Ledda R, Galli AM, Farcomeni A, Rotondo C, Di Gregorio V, Mennini G, Poli E, Attilia F, Ginanni Corradini S, Rossi M, Merli M. The multidisciplinary support in preventing alcohol relapse after liver transplantation: A single-center experience. Clin Transplant 2018; 32:e13243. [PMID: 29573476 DOI: 10.1111/ctr.13243] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Alcoholic liver disease (ALD) represents a frequent indication for liver transplantation (LT). Since 2004, we have adopted a program of multidisciplinary support(MS) to assist patients undergoing LT for ALD. We aimed at analyzing the relapse rate and the risk factors for relapse. The relapse rate was also compared with that of a historical group of patients who underwent transplantation. Their survival rate was also analyzed. PATIENTS AND METHODS Consecutive patients with ALD transplanted from 2004 were included. The most important demographic, psychosocial, and clinical characteristics known to be associated with alcohol relapse were recorded. RESULTS Sixty-nine patients underwent MS: 8.7% presented alcohol relapse. At multivariate analysis female gender (sHR 9.02, 95% CI 1.71-47.56, P = .009), alcohol withdrawal syndrome (sHR 5.89, 95% CI 1.42-24.46, P = .015) and a shorter time of MS program before LT (sHR 0.928 per month, 95% CI 0.870-0.988, P = .021) were identified as independent risk factors for relapse. The rate of alcohol relapse was significantly lower than that of the historical group who did not undergo MS (sHR 0.21, 95% CI: 0.06-0.68; P = .009). CONCLUSION This study shows that a MS program may contribute to alcohol relapse prevention after LT in ALD patients. However, the relevance of this support needs to be confirmed by clinical trials.
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Affiliation(s)
- Maria Luisa Attilia
- Department of Clinical Medicine, Alcohol Dependence Unit, Sapienza University of Rome, Rome, Italy
| | - Barbara Lattanzi
- Department of Clinical Medicine, Gastroenterology Unit, Sapienza University of Rome, Rome, Italy
| | - Roberta Ledda
- Department of Clinical Medicine, Alcohol Dependence Unit, Sapienza University of Rome, Rome, Italy
| | - Anna Maria Galli
- Department of Clinical Medicine, Alcohol Dependence Unit, Sapienza University of Rome, Rome, Italy
| | - Alessio Farcomeni
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Claudia Rotondo
- Department of Clinical Medicine, Alcohol Dependence Unit, Sapienza University of Rome, Rome, Italy
| | - Vincenza Di Gregorio
- Department of Clinical Medicine, Gastroenterology Unit, Sapienza University of Rome, Rome, Italy
| | - Gianluca Mennini
- Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | - Edoardo Poli
- Department of Clinical Medicine, Gastroenterology Unit, Sapienza University of Rome, Rome, Italy
| | - Fabio Attilia
- Department of Clinical Medicine, Alcohol Dependence Unit, Sapienza University of Rome, Rome, Italy
| | | | - Massimo Rossi
- Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | - Manuela Merli
- Department of Clinical Medicine, Gastroenterology Unit, Sapienza University of Rome, Rome, Italy
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Abstract
Anesthesiologists have clearly established their place in the history of medical ethics. Our involvement goes back to 1966 when Henri Beecher published his landmark paper on research and informed consent. Participation in the ethics of transplantation is no less important than our previous work. Organ transplant has been life saving for many but also has given rise to many misunderstandings not just from the public but also among our own colleagues. These include methods of allocation and donation, the role that affluence may play in receiving an organ, the definition of death and donation after circulatory death. As perioperative physicians and important members of the transplant team, anesthesiologists are expected to participate in all aspects of care including ethical judgments. This article discusses some of the issues that seem to cause the most confusion and angst for those of us involved in both liver transplantation and in the procurement of organs. It will discuss the definition of death, donation after circulatory death, the anesthesiologists' role on the selection committee, living donor liver transplantation, and transplantation of patients with alcohol-related liver disease.
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Affiliation(s)
- James M West
- 1 Methodist-LeBonheur Healthcare, Memphis, TN, USA
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27
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Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol 2018; 113:175-194. [PMID: 29336434 PMCID: PMC6524956 DOI: 10.1038/ajg.2017.469] [Citation(s) in RCA: 549] [Impact Index Per Article: 78.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 11/08/2017] [Indexed: 02/07/2023]
Abstract
Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most patients are diagnosed at advanced stages and data on the prevalence and profile of patients with early disease are limited. Diagnosis of ALD requires documentation of chronic heavy alcohol use and exclusion of other causes of liver disease. Prolonged abstinence is the most effective strategy to prevent disease progression. AH presents with rapid onset or worsening of jaundice, and in severe cases may transition to acute on chronic liver failure when the risk for mortality, depending on the number of extra-hepatic organ failures, may be as high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in about half of treated patients with severe AH and long-term mortality is related to severity of underlying liver disease and is dependent on abstinence from alcohol. General measures in patients hospitalized with ALD include inpatient management of liver disease complications, management of alcohol withdrawal syndrome, surveillance for infections and early effective antibiotic therapy, nutritional supplementation, and treatment of the underlying alcohol-use disorder. Liver transplantation, a definitive treatment option in patients with advanced alcoholic cirrhosis, may also be considered in selected patients with AH cases, who do not respond to medical therapy. There is a clinical unmet need to develop more effective and safer therapies for patients with ALD.
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Affiliation(s)
- Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham School of Medicine , Birmingham , Alabama , USA
| | - Ramon Bataller
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Liver Research Center , Pittsburgh , Pennsylvania , USA
| | - Joseph Ahn
- Division of Gastroenterology and Hepatology, Oregon Health and Science University , Portland , Oregon , USA
| | - Patrick S. Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic , Rochester , Minnesota ,USA
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic , Rochester , Minnesota ,USA
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28
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Rogal S, Shenai N, Kruckenberg K, Rosenberger E, Dew MA, DiMartini A. Post-transplant Outcomes of Persons Receiving a Liver Graft for Alcoholic Liver Disease. Alcohol Alcohol 2017; 53:157-165. [DOI: 10.1093/alcalc/agx100] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Accepted: 11/13/2017] [Indexed: 12/20/2022] Open
Affiliation(s)
- Shari Rogal
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University Drive, Pittsburgh, PA 15240, USA
- Department of Surgery, University of Pittsburgh School of Medicine, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA
| | - Neeta Shenai
- Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213, USA
| | - Katherine Kruckenberg
- University Pittsburgh School of Medicine, 3550 Terrace St, Pittsburgh, PA 15213, USA
| | - Emily Rosenberger
- Department of Clinical and Translational Science, University of Pittsburgh School of Medicine, Clinical and Translational Science Institute, 401 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261
| | - Mary Amanda Dew
- Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213, USA
- Department of Clinical and Translational Science, University of Pittsburgh School of Medicine, Clinical and Translational Science Institute, 401 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261
- Departments of Psychology, Epidemiology, and Biostatistics, University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, PA 15260, USA
| | - Andrea DiMartini
- Department of Surgery, University of Pittsburgh School of Medicine, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA
- Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213, USA
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30
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Ursic-Bedoya J, Donnadieu-Rigole H, Faure S, Pageaux GP. The Influence of Alcohol Use on Outcomes in Patients Transplanted for Non-alcoholic Liver Disease. Alcohol Alcohol 2017; 53:184-186. [DOI: 10.1093/alcalc/agx096] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Accepted: 11/13/2017] [Indexed: 12/14/2022] Open
Affiliation(s)
- José Ursic-Bedoya
- Liver Transplantation Unit, Digestive Department, Saint Eloi University Hospital, University of Montpellier, 34295 Montpellier Cedex 5, France
| | - Hélène Donnadieu-Rigole
- Addictology Department, Saint Eloi University Hospital, University of Montpellier, 34295 Montpellier Cedex 5, France
| | - Stéphanie Faure
- Liver Transplantation Unit, Digestive Department, Saint Eloi University Hospital, University of Montpellier, 34295 Montpellier Cedex 5, France
| | - Georges-Philippe Pageaux
- Liver Transplantation Unit, Digestive Department, Saint Eloi University Hospital, University of Montpellier, 34295 Montpellier Cedex 5, France
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31
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Kodali S, Kaif M, Tariq R, Singal AK. Alcohol Relapse After Liver Transplantation for Alcoholic Cirrhosis—Impact on Liver Graft and Patient Survival: A Meta-analysis. Alcohol Alcohol 2017; 53:166-172. [DOI: 10.1093/alcalc/agx098] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 11/13/2017] [Indexed: 12/15/2022] Open
Affiliation(s)
- Sudha Kodali
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294-0012, USA
| | - Mohamed Kaif
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294-0012, USA
| | - Raseen Tariq
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294-0012, USA
| | - Ashwani K Singal
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294-0012, USA
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32
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Lim J, Curry MP, Sundaram V. Risk factors and outcomes associated with alcohol relapse after liver transplantation. World J Hepatol 2017; 9:771-780. [PMID: 28660011 PMCID: PMC5474723 DOI: 10.4254/wjh.v9.i17.771] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 03/07/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT) in the United States and Europe. Unlike other indications for LT, transplantation for ALD may be controversial due to the concern for alcohol relapse and non-compliance after LT. However, the overall survival in patients transplanted for ALD is comparable or higher than in patients transplanted for other etiologies of liver disease. While the rate of alcohol use after liver transplantation does not differ among various etiologies of liver disease, alcohol relapse after transplantation for ALD has been associated with complications such as graft rejection, graft loss, recurrent alcoholic cirrhosis and reduced long-term patient survival. Given these potential complications, our review aimed to discuss risk factors associated with alcohol relapse and the efficacy of various interventions attempted to reduce the risk of alcohol relapse. We also describe the impact of alcohol relapse on post-transplant outcomes including graft and patient survival. Overall, alcohol liver disease remains an appropriate indication for liver transplantation, and long-term mortality in this group of patients is primarily attributed to cardiovascular disease or de novo malignancies rather than alcohol related hepatic complications, among those who relapse.
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33
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Abstract
Alcohol-related liver disease is the second most frequent indication for liver transplantation (LT), yet as many as 90% to 95% of patients with alcohol-related end-stage liver disease are never formally evaluated for LT. Furthermore, despite its significance as a cause of chronic liver disease and indication for LT, it has received little attention in recent years for several reasons, including the good posttransplant short-term results, and the lack of specific "drugs" used for this disease. A writing group, endorsed by the International Liver Transplant Society, was convened to write guidelines on Liver Transplantation for Alcoholic Liver Disease to summarize current knowledge and provide answers to controversial and delicate ethical as well as clinical problems. We report here a short version of the guidelines (long version available at www.ilts.org) with the final recommendations graded for level of evidence. The writing group membership is expected to remain active for 5 years, reviewing the guideline annually, and updating the online version when appropriate.
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34
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Cheong J, Galanko JA, Arora S, Cabezas J, Ndugga NJ, Lucey MR, Hayashi PH, Barritt AS, Bataller R. Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation. Liver Int 2017; 37:290-298. [PMID: 27258535 PMCID: PMC5136341 DOI: 10.1111/liv.13182] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Accepted: 06/02/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. METHODS We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. RESULTS The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P < 0.001). In multivariate analysis, renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P < 0.0001). Importantly, the impact of renal failure was less marked in patients with ALD (HR = 1.31, P < 0.0001) than in patients with NASH (HR = 1.73, P < 0.0001) or HCV (HR = 1.52, P < 0.0001). Despite a higher model for end-stage liver disease (MELD) score at the time of LT, ALD patients with renal failure had better long-term prognosis than non-ALD patients. CONCLUSIONS Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT.
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Affiliation(s)
- Jaeyoun Cheong
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC,Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Joseph A. Galanko
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Sumant Arora
- Department of Medicine, University of Alabama at Birmingham, Montgomery, AL
| | - Joaquin Cabezas
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC,Department of Gastroenterology and Hepatology, University Hospital Marques de Valdecilla, Santander, Spain
| | - Nambi J. Ndugga
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Michael R. Lucey
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin, Madison, WI
| | - Paul H. Hayashi
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Ramon Bataller
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC
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35
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Siddiqui MS, Charlton M. Liver Transplantation for Alcoholic and Nonalcoholic Fatty Liver Disease: Pretransplant Selection and Posttransplant Management. Gastroenterology 2016; 150:1849-62. [PMID: 26971826 DOI: 10.1053/j.gastro.2016.02.077] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 02/12/2016] [Accepted: 02/16/2016] [Indexed: 02/07/2023]
Abstract
Alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease throughout the world. Although they have similar histologic features, a diagnosis of NAFLD requires the absence of significant alcohol use. ALD is seen commonly in patients with a long-standing history of excessive alcohol use, whereas NAFLD is encountered commonly in patients who have developed complications of obesity, such as insulin resistance, hypertension, and dyslipidemia. Lifestyle contributes to the development and progression of both diseases. Although alcohol abstinence can cause regression of ALD, and weight loss can cause regression of NAFLD, many patients with these diseases develop cirrhosis. ALD and NAFLD account for nearly 30% of liver transplants performed in the United States. Patients receiving liver transplants for ALD or NAFLD have similar survival times as patients receiving transplants for other liver disorders. Although ALD and NAFLD recur frequently after liver transplantation, graft loss from disease recurrence after transplantation is uncommon. Cardiovascular disease and de novo malignancy are leading causes of long-term mortality in liver transplant recipients with ALD or NAFLD.
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Affiliation(s)
- M Shadab Siddiqui
- Division of Gastroenterology & Hepatology, Virginia Commonwealth University, Richmond, Virginia
| | - Michael Charlton
- Division of Transplant Hepatology, Intermountain Medical Center, Murry, Utah
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36
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Staufer K, Yegles M. Biomarkers for detection of alcohol consumption in liver transplantation. World J Gastroenterol 2016; 22:3725-3734. [PMID: 27076757 PMCID: PMC4814735 DOI: 10.3748/wjg.v22.i14.3725] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 01/26/2016] [Accepted: 02/22/2016] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease is an established, yet controversial, indication for liver transplantation. Although an abstinence period of up to 6 mo prior to transplantation is mandatory, alcohol relapse after transplantation is a common event. In case of recurrence of heavy drinking, graft survival is significantly impaired. Guidelines on detection and surveillance of alcohol consumption in this patient cohort are lacking. This review summarizes the challenge of patient selection as well as the current knowledge on established and novel alcohol biomarkers with special focus on liver transplant candidates and recipients.
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37
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Legaz I, Navarro-Noguera E, Bolarín JM, García-Alonso AM, Luna Maldonado A, Mrowiec A, Campillo JA, Gimeno L, Moya-Quiles R, Álvarez-López MDR, Minguela Puras A, Miras M, Sánchez-Bueno F, Muro M. Epidemiology, Evolution, and Long-Term Survival of Alcoholic Cirrhosis Patients Submitted to Liver Transplantation in Southeastern Spain. Alcohol Clin Exp Res 2016; 40:794-805. [PMID: 27012317 DOI: 10.1111/acer.13013] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 01/14/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Alcoholic cirrhosis (AC) is a common cause of death among individuals abusing alcohol. In the last resort, liver transplantation (LT) is considered the only solution to save the patient's life, generating socioeconomic and public health problems. Clinical and sociodemographic characteristics, rejection frequency, and short- and long-term graft survival are not well known in end-term AC patients undergoing LT. The aim was to determine the sociodemographic and clinical characteristics, their incidence in LT, main pre- and posttransplant complications, and short- and long-term post-transplant graft survival in AC patients in southeastern Spain. METHODS The medical records of 1,026 patients who underwent LT over the last 23 years were retrospectively reviewed, and demographic data and posttransplant survivals were analyzed and compared. Biochemical characteristics, major pre- and posttransplant complications and short- and long-term survivals were analyzed in a total of 398 male patients with AC undergoing LT. RESULTS AC and viral cirrhosis are the main indications for LT in our study. Mostly represented in our study are AC men without associated viral infections with a mean age of 53.06 years. Main pretransplant complications in AC patients are ascites (78.3%) and encephalopathy (43.5%), while acute graft rejection is the most common liver posttransplant complication (26.6%), nevertheless with low graft loss frequency (1.1%). AC and autoimmune cirrhosis show the best posttransplant survival in both the short and long term. Patients with AC included on the waiting list for LT were Child-Pugh class B (52.1%) and Model for End-Stage Liver Disease score of 10 to 19 (71.2%). The highest percentage of AC patient survival was observed at 1 year posttransplant (81.2%) and progressively decreased over time up to 10 years posttransplant (69.6%). Pretransplant complications such as ascites and encephalopathy did not have an influence on the percentage of posttransplant survivals, although better survival rates were observed in nonviral AC patients. CONCLUSIONS AC without viral infections is the main indication for LT in southeastern Spain although its frequency has decreased in last decade. AC is a good indication for LT for its high survival rate and few posttransplant complications. Despite having a high percentage of pretransplant complications (ascites and encephalopathy) but does not appear to influence survivals being observed posttransplant survival rates above those expected. Conversely, viral infections in the patient with AC decrease patient survivals. The main future goals are design new strategies to detect, treat, and reduce AC frequency in our population and know alcoholic recidivism rate posttransplant in our population.
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Affiliation(s)
- Isabel Legaz
- Immunology Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain.,Department of Legal and Forensic Medicine , University of Murcia, Murcia, Spain
| | - Elena Navarro-Noguera
- Digestive Medicine Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | - Jose M Bolarín
- Immunology Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | - Ana M García-Alonso
- Immunology Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | | | - Anna Mrowiec
- Immunology Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | - Jose A Campillo
- Immunology Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | - Lourdes Gimeno
- Immunology Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | - Rosa Moya-Quiles
- Immunology Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | | | | | - Manuel Miras
- Digestive Medicine Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | - Francisco Sánchez-Bueno
- Digestive Medicine Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
| | - Manuel Muro
- Immunology Service , Clinic University Hospital Virgen de la Arrixaca, Murcia, Spain
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Saigal S, Choudhary NS, Yadav SK, Saraf N, Kumar N, Rai R, Mehrotra S, Rastogi V, Rastogi A, Goja S, Bhangui P, Ramachandra SK, Raut V, Gautam D, Soin AS. Lower relapse rates with good post-transplant outcome in alcoholic liver disease: Experience from a living donor liver transplant center. Indian J Gastroenterol 2016; 35:123-8. [PMID: 27130453 DOI: 10.1007/s12664-016-0646-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 03/15/2016] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Post-transplant relapse is a major factor influencing the long-term outcome in alcoholic liver disease (ALD) patients. AIMS The aim of this study was to evaluate the relapse rates following living donor liver transplantation (LDLT) in patients with ALD in the Indian context with strong family support. METHODS Of 458 patients who underwent LDLT for ALD, 408 were included in the study. Post-transplant relapse was determined by information provided by the patient and/or family by means of outpatient and e-mail questionnaire, supported by clinical/biochemical parameters/liver histopathology. RESULTS All except one were males, with a mean age of 46.9 ± 8.5 years. The overall rate of relapse was 9.5 % at 34.7 months (interquartile range (IQR) 15-57.6), lower than that reported in the literature from the West. The relapse rate was higher in patients with a shorter duration of pre-transplant abstinence (17.4 % and 15.4 % for recipients with pre-transplant abstinence of <3 and <6 months, respectively, p < 0.05). The overall survival was 88.5 % at 3 years. Of 39 patients with relapse, 16 (41 %) were occasional drinkers, 14 (35.8 %) were moderate drinkers, and 9 (23 %) were heavy drinkers. All the heavy drinkers presented with features of graft dysfunction. CONCLUSIONS Good results can be obtained following LDLT for ALD, with significantly lower relapse rates in our setup as compared to the West.
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Affiliation(s)
- Sanjiv Saigal
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India.
| | - Narendra Singh Choudhary
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Sanjay Kumar Yadav
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Neeraj Saraf
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Naveen Kumar
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Rahul Rai
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Saurabh Mehrotra
- Department of Mental Health and Quality of Life, Medanta - The Medicity, Gurgaon, Delhi (NCR), 122 002, India
| | - Vipul Rastogi
- Department of Mental Health and Quality of Life, Medanta - The Medicity, Gurgaon, Delhi (NCR), 122 002, India
| | - Amit Rastogi
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Sanjay Goja
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Sumana K Ramachandra
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Vikram Raut
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
| | - Dheeraj Gautam
- Department of Histopathology, Medanta - The Medicity, Gurgaon, Delhi (NCR), 122 002, India
| | - Arvinder Singh Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, Delhi (NCR), 122 002, India
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Gitto S, Golfieri L, Caputo F, Grandi S, Andreone P. Multidisciplinary View of Alcohol Use Disorder: From a Psychiatric Illness to a Major Liver Disease. Biomolecules 2016; 6:11. [PMID: 26784248 PMCID: PMC4808805 DOI: 10.3390/biom6010011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 12/16/2015] [Accepted: 12/27/2015] [Indexed: 12/20/2022] Open
Abstract
Alcohol use disorder is a significant health problem being a cause of increased morbidity and mortality worldwide. Alcohol-related illness has a relevant economic impact on the society and a negative influence on the life of patients and their family members. Psychosocial support might be useful in the management of people affected by alcohol use disorder since psychiatric and pharmaceutical approaches show some limits. In fact, many drugs are accessible for the treatment of alcohol disorder, but only Baclofen is functional as an anti-craving drug in patients with advanced liver disease. The alcohol-related liver damage represents the most frequent cause of advanced liver disease in Europe, and it is the main cause of death among adults with high alcohol consumption. The multidisciplinary action of clinical-psychologists, psychiatrics and hepatologists, is essential in the management of patients with alcohol liver disease especially in the case of liver transplantation. In general, the multidisciplinary approach is necessary in prevention, in framing patients and in the treatment. More resources should be used in prevention and research with the main aim of decreasing the harmful alcohol consumption.
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Affiliation(s)
- Stefano Gitto
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena 41124, Italy.
| | - Lucia Golfieri
- Department of Psychology, University of Bologna, Bologna 40138, Italy.
| | - Fabio Caputo
- Department of Internal Medicine, SS Annunziata Hospital, Cento, Ferrara 44011, Italy.
- "G. Fontana" Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Clinical Medicine, University of Bologna, Bologna 40138, Italy.
| | - Silvana Grandi
- Department of Psychology, University of Bologna, Bologna 40138, Italy.
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, University of Bologna and Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, Via Massarenti 9, Bologna 40138, Italy.
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Ursic-Bedoya J, Faure S, Donnadieu-Rigole H, Pageaux GP. Liver transplantation for alcoholic liver disease: Lessons learned and unresolved issues. World J Gastroenterol 2015; 21:10994-11002. [PMID: 26494956 PMCID: PMC4607899 DOI: 10.3748/wjg.v21.i39.10994] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/10/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
The use of liver transplantation (LT) as a treatment for alcoholic liver disease (ALD) has been highly controversial since the beginning. The ever increasing shortage of organs has accentuated the low priority given to patients suffering from ALD, which is considered a “self-inflicted” condition. However, by improving the long-term survival rates, making them similar to those from other indications, and recognizing that alcoholism is a primary disease, ALD has become one of the most common indications for LT in Europe and North America, a situation thought unfathomable thirty years ago. Unfortunately, there are still many issues with the use of this procedure for ALD. There are significant relapse rates, and the consequences of excessive drinking after LT range from asymptomatic biochemical and histological abnormalities to graft failure and death. A minimum three-month period of sobriety is required for an improvement in liver function, thus making LT unnecessary, and to demonstrate the patient’s commitment to the project, even though a longer abstinence period does not guarantee lower relapse rates after LT. Recent data have shown that LT is also effective for severe alcoholic hepatitis when the patient is unresponsive to corticosteroids therapy, with low relapse rates in highly selected patients, although these results must be confirmed before LT becomes a standard procedure in this setting. Finally, LT for ALD is accompanied by an increased risk of de novo solid organ cancer, skin cancer, and lymphoproliferative disorders, which has a large impact on the survival rates.
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Sharma P, Schaubel DE, Goodrich NP, Merion RM. Serum sodium and survival benefit of liver transplantation. Liver Transpl 2015; 21:308-13. [PMID: 25504743 PMCID: PMC4354811 DOI: 10.1002/lt.24063] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Accepted: 11/30/2014] [Indexed: 12/13/2022]
Abstract
Hyponatremia is associated with elevated wait-list mortality among end-stage liver disease candidates for liver transplantation (LT). However, the effect of low serum sodium on the survival benefit of LT has not been examined. We sought to determine whether pretransplant hyponatremia is associated with an altered LT survival benefit. Data were obtained from the Scientific Registry of Transplant Recipients. The study population consisted of adults (age ≥ 18 years) placed on the waiting list for LT between January 1, 2005 and December 31, 2012 (n = 69,213). The effect of hyponatremia on the survival benefit was assessed via sequential stratification, an extension of Cox regression. Each transplant recipient was matched to appropriate candidates then active on the waiting list with the same Model for End-Stage Liver Disease (MELD) score and in the same donation service area. The focus of the analysis was the interaction between the serum sodium and the MELD score with respect to the survival benefit of LT; this was defined as the covariate-adjusted hazard ratio contrasting post-LT mortality and pre-LT mortality. The LT survival benefit increased significantly with decreasing serum sodium values when the MELD scores were >11. The survival benefit of LT was not affected by serum sodium for patients with MELD scores ≤ 11. In conclusion, the LT survival benefit (or lack thereof) is independent of serum sodium for patients with MELD scores ≤ 11. The increase in the survival benefit with decreasing serum sodium among patients with MELD scores > 11 is consistent with recently approved changes to the allocation system incorporating serum sodium.
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Affiliation(s)
- Pratima Sharma
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI
| | | | | | - Robert M. Merion
- Department of Surgery, University of Michigan, Ann Arbor, MI,Arbor Research Collaborative for Health, Ann Arbor, MI
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Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, Ahmed A. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology 2015; 148:547-55. [PMID: 25461851 DOI: 10.1053/j.gastro.2014.11.039] [Citation(s) in RCA: 1360] [Impact Index Per Article: 136.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Revised: 11/20/2014] [Accepted: 11/21/2014] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Nonalcoholic steatohepatitis (NASH) has been predicted to become the leading indication for liver transplantation (LT) in the United States. However, few studies have evaluated changes in the etiology of liver diseases among patients awaiting LT, and none have focused on the effects of NASH on liver transplant waitlists in the United States. METHODS We collected data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry from 2004 through 2013, on liver transplant waitlist registrants with hepatitis C virus (HCV) infection, NASH, alcoholic liver disease (ALD), or a combination of HCV infection and ALD. We compared differences in survival within 90 days of registration (90-day survival) and probability of LT among patients with different diseases using Kaplan-Meier and multivariate logistic regression models. RESULTS Between 2004 and 2013, new waitlist registrants with NASH increased by 170% (from 804 to 2174), with ALD increased by 45% (from 1400 to 2024), and with HCV increased by 14% (from 2887 to 3291); registrants with HCV and ALD decreased by 9% (from 880 to 803). In 2013, NASH became the second-leading disease among liver transplant waitlist registrants, after HCV. Patients with ALD had a significantly higher mean Model for End-Stage Liver Disease score at time of waitlist registration than other registrants. However, after multivariate adjustment, patients with ALD were less likely to die within 90 days when compared with patients with NASH (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.67-0.89; P < .001); patients with HCV infection or HCV and ALD had similar odds for 90-day survival compared with NASH patients. Compared with patients with NASH, patients with HCV (OR = 1.45; 95% CI: 1.35-1.55; P < .001), ALD (OR = 1.15; 95% CI: 1.06-1.24; P < .001), or HCV and ALD (OR = 1.29; 95% CI: 1.18-1.42; P < .001) had higher odds for 90-day survival. CONCLUSIONS Based on data from US adult LT databases, since 2004 the number of adults with NASH awaiting LTs has almost tripled. However, patients with NASH are less likely to undergo LT and less likely to survive for 90 days on the waitlist than patients with HCV, ALD, or HCV and ALD.
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Affiliation(s)
- Robert J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System, Highland Hospital Campus, Oakland, California.
| | - Maria Aguilar
- Division of Gastroenterology and Hepatology, Alameda Health System, Highland Hospital Campus, Oakland, California
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Ryan B Perumpail
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Stephen A Harrison
- Division of Gastroenterology, Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, Texas
| | - Zobair M Younossi
- Center of Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
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Flemming JA, Vagefi PA, Freise CE, Yao FY, Terrault NA. Restricting liver transplant recipients to younger donors does not increase the wait-list time or the dropout rate: the hepatitis C experience. Liver Transpl 2014; 20:1202-10. [PMID: 24961679 PMCID: PMC4803440 DOI: 10.1002/lt.23937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Accepted: 06/06/2014] [Indexed: 01/12/2023]
Abstract
Older donor age is associated with lower graft and patient survival among all recipients of liver transplantation (LT). Among patients with hepatitis C virus (HCV), donor age is one of the strongest predictors of fibrosis severity and graft loss. We evaluated the implementation of a donor age restriction policy for LT patients with HCV at a single center and the effects that this policy had on wait-list (WL) and post-LT outcomes for HCV and non-HCV patients. This was a cohort study of 2388 WL patients and 1015 LT recipients between March 2002 and January 2013 and reflected 3 different eras of donor age policies. With the donor age restriction, the median donor age was reduced in LT recipients with HCV versus LT recipients without HCV (30 versus 48 years, P < 0.001) without differences in the WL time (10.6 versus 8.0 months, P = 0.23). According to a competing risks regression, those with HCV and those without HCV had lower subhazard ratios (SHRs) of dropout or death on the WL during the donor age restriction era versus the era without donor age restriction [SHR = 0.68 (P < 0.01) and SHR = 0.64 (P = 0.01), respectively]. No differences were seen in early post-LT survival for patients with or without HCV between eras (P = 0.7 and P = 0.88, respectively). In conclusion, we show that donor age restriction for HCV results in a lower donor age for HCV recipients without obvious adverse WL consequences. Although additional studies are needed, our results demonstrate the feasibility of donor age restriction for LT recipients with HCV, and such information may be relevant to programs with limited access to new antiviral therapies for which modifying the risk of severe disease remains of paramount importance.
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Affiliation(s)
- Jennifer A. Flemming
- Department of Medicine, Queen’s University, Kingston, Canada,Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Canada
| | - Parsia A. Vagefi
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Chris E. Freise
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Francis Y. Yao
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Norah A. Terrault
- Department of Medicine, University of California San Francisco, San Francisco, CA
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Khan R, Singal AK, Anand BS. Outcomes after liver transplantation for combined alcohol and hepatitis C virus infection. World J Gastroenterol 2014; 20:11935-11938. [PMID: 25232228 PMCID: PMC4161779 DOI: 10.3748/wjg.v20.i34.11935] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 03/28/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Alcohol abuse and chronic hepatitis C virus (HCV) infection are two major causes of chronic liver disease in the United States. About 10%-15% of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection. Data on outcomes on graft and patient survival, HCV recurrence, and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature. Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis. However, some other studies do not support these observations. However, most studies are limited to a retrospective design or small sample size. Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers.
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Berlakovich GA. Challenges in transplantation for alcoholic liver disease. World J Gastroenterol 2014; 20:8033-8039. [PMID: 25009374 PMCID: PMC4081673 DOI: 10.3748/wjg.v20.i25.8033] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 01/28/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist’s assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient’s pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key factor determining the outcome of transplantation for alcoholic cirrhosis is intensive lifelong medical and psychological care. Post-transplant surveillance might be much more important than pre-transplant selection.
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Abstract
Alcoholic liver disease (ALD) is the major cause of life-threatening liver disease in Western countries. Abstinence from alcohol is the foundation of all treatment programmes for patients with ALD. Liver transplantation is a valuable option for patients with life-threatening ALD. Although the role of liver transplantation in the treatment of alcoholic hepatitis that is unresponsive to medical therapy is controversial, the latest prospective studies support this approach. No single measure gives a reliable estimate of the risk of drinking relapses before or after liver transplantation, but careful evaluation by an addiction specialist with a particular interest in transplant medicine is the best available approach. Survival, both on the waiting list and after the operation, is better in patients with ALD than in patients with HCV infection. Alcohol relapse may lead to liver damage and increased mortality, albeit usually after many years of renewed drinking. After liver transplantation, patients with ALD have increased rates of mortality and morbidity that are attributable to cardiovascular disease and new-onset cancers of the aerodigestive tract. The latter are probably linked to the high prevalence of smoking in this population. Cessation of smoking is thus an important goal in the care of patients with ALD after they have undergone liver transplantation.
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48
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Affiliation(s)
- Patrizia Burra
- De: Unidad de Gastroenterología y Trasplantes Multiviscerales, Servicio de Cirugía, Oncología y GastroenterologíaHospital Universitario de PaduaPaduaItalia, y
| | - Michael R. Lucey
- Servicio de Gastroenterología y Hepatología, Departamento de MedicinaUniversity of Wisconsin School of Medicine and Public HealthMadisonWI, EE. UU.
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Rice JP, Eickhoff J, Agni R, Ghufran A, Brahmbhatt R, Lucey MR. Abusive drinking after liver transplantation is associated with allograft loss and advanced allograft fibrosis. Liver Transpl 2013; 19:1377-86. [PMID: 24115392 DOI: 10.1002/lt.23762] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 08/31/2013] [Indexed: 12/14/2022]
Abstract
In patients who undergo liver transplantation for alcoholic liver disease (ALD), alcohol relapse is common. A return to abusive or excessive drinking likely decreases overall survival; however, the effects of alcohol use on allograft outcomes and histopathology are less well defined. We reviewed all cases of liver transplantation with ALD as an indication between January 1, 1995 and December 31, 2007. Allograft outcomes and histopathological results were compared for patients who relapsed into alcohol use and patients who maintained abstinence. Three hundred patients who underwent transplantation for ALD during this period survived at least 1 year, and 48 (16.0%) relapsed into alcohol use that came to clinical attention. The pattern of relapse was a single event for 10 patients (20.8%), intermittent relapses for 22 patients (45.8%), and continuous heavy drinking for 16 patients (33.3%). Continuous heavy drinking was associated with allograft loss in a univariate Cox proportional hazards analysis [hazard ratio (HR) = 2.43, 95% confidence interval (CI) = 1.26-4.68, P = 0.008] and in a multivariate Cox proportional hazards regression (HR = 2.57, 95% CI = 1.32-5.00, P = 0.006). A matched-pair analysis that controlled for the hepatitis C virus status and the time to biopsy compared the results of allograft histopathology for patients who relapsed into alcohol use and patients who maintained abstinence. Significant steatosis [odds ratio (OR) = 3.46, 95% CI = 1.29-9.31, P = 0.01], steatohepatitis (OR = 6.2, 95% CI = 1.70-22.71, P = 0.006), and advanced (stage 3 or higher) fibrosis (OR = 23.18, 95% CI = 3.01-177.30, P = 0.003) were associated with alcohol relapse. In conclusion, alcohol relapse after liver transplantation (particularly heavy drinking) is associated with decreased graft survival and advanced allograft fibrosis.
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Affiliation(s)
- John P Rice
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
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50
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Goldberg D, French B, Trotter J, Shetty K, Schiano T, Reddy KR, Halpern SD. Underreporting of liver transplant waitlist removals due to death or clinical deterioration: results at four major centers. Transplantation 2013; 96:211-6. [PMID: 23765112 DOI: 10.1097/tp.0b013e3182970619] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Few studies have evaluated the accuracy of United Network for Organ Sharing (UNOS) or Scientific Registry of Transplant Recipients data among patients listed for liver transplantation. Of particular importance for transplant policy and practice is whether patients' outcomes are coded properly. METHODS Using data from four transplant centers, we identified all liver transplant candidates removed from the waitlist from February 27, 2002 to July 24, 2010, with a specific focus the removal code of "other." RESULTS Among nontransplanted patients at these centers, 2206 patients were removed for death or clinical deterioration. Of these, 8.6% (189 of 2206) were misclassified; they were assigned the UNOS removal code of "other." Among these 189 misclassified patients, 128 became medically unsuitable, 35 died, and 26 became too sick to transplant. Nearly one-half (46.8%) of misclassified patients were removed due to advanced hepatocellular carcinoma. Among true waitlist removals for death, only 35 of 1593 (2.2%) were misclassified. Conversely, of true removals for clinical deterioration, 154 of 612 (25.2%) were misclassified, with significant (P < 0.001) center variation: 4.4% (Baylor), 8.0% (Georgetown), 32.6% (University of Pennsylvania), and 45.0% (Mount Sinai). Extrapolating these data to the entire United States, if "other" patients who truly died or clinically deteriorated were recoded appropriately, there would be an additional 2525 (95% confidence interval, 2046-3102) patients removed from the waitlist due to death (331) or clinical deterioration (2194) since 2002. DISCUSSION A substantial proportion of patients truly removed from the waitlist for death or clinical deterioration were misclassified as "other." Thus, analyses using the UNOS or the Scientific Registry of Transplant Recipients database may underestimate the true proportion of patients removed from the waitlist for clinical deterioration.
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Affiliation(s)
- David Goldberg
- Department of Medicine, Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, USA.
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