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Magyar CTJ, Jones O, Rajendran L, Carrique L, Lynch MJ, Li Z, Claasen MPAW, Ivanics T, Choi WJ, Gaviria F, Ghanekar A, Winter E, Bucur R, Shwaartz C, Reichman T, Sayed BA, Selzner M, Bhat M, Tsien C, Jaeckel E, Lilly LB, McGilvray ID, Cattral MS, Sapisochin G, Selzner N. Living Donor Liver Transplantation for Alcohol-related Liver Disease: An Intention-to-treat Analysis. Transplantation 2025:00007890-990000000-01070. [PMID: 40269339 DOI: 10.1097/tp.0000000000005410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2025]
Abstract
BACKGROUND Alcohol-associated liver disease (ALD) is the leading indication for liver transplantation (LT) in the Western world. Although 6 mo of abstinence is no longer a criterion for patients with ALD, the outcomes of living donor LT (LDLT) versus deceased donor LT (DDLT) are not well established. METHODSS We performed an intention-to-treat analysis to evaluate the impact of listing and pursuing primary LDLT (pLDLT) compared with primary DDLT (pDDLT). The primary endpoint was overall survival from date of listing, evaluated using Cox regression (hazard ratios). RESULTS Two hundred thirty-three patients with ALD were listed for LT, of which 27 (12%) were pLDLT. The overall median model for end-stage liver disease (MELD) score at listing was 20 and Na-MELD 24, a median abstinence of 4.5 mo, and 128 (55%) underwent transplantation. There was no statistically significant adjusted difference at 3-y overall survival between pLDLT versus pDDLT (adjusted hazard ratio [HR] 0.72; P = 0.550) and in the as-treated analysis (HR 1.22; P = 0.741). No patients were delisted in the pLDLT group, whereas 86 (42%) patients were delisted in the pDDLT group; primarily because of death (46 [50%]) and medical improvement (24 [28%]). Alcohol use since the time of listing was documented in 29 (13%) patients; immortal time bias adjusted analysis found no significant difference between pLDLT and pDDLT (adjusted HR 1.07; P = 0.900) and the as-treated analysis (HR 2.95; P = 0.130). CONCLUSIONS Patients with ALD benefit from intention pLDLT with lower rates of waitlist dropout and delisting, attributable to mortality or medical deterioration, and should be encouraged to pursue this option.
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Affiliation(s)
- Christian T J Magyar
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Owen Jones
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Luckshi Rajendran
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Lauren Carrique
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Marie-Josée Lynch
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Centre for Mental Health, University Health Network, Toronto, ON, Canada
| | - Zhihao Li
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Marco P A W Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, Henry Ford Hospital, Detroit, MI
- Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Woo Jin Choi
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Felipe Gaviria
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Anand Ghanekar
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Erin Winter
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Roxana Bucur
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Chaya Shwaartz
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Trevor Reichman
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Blayne A Sayed
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Markus Selzner
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Cynthia Tsien
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Elmar Jaeckel
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Leslie B Lilly
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Ian D McGilvray
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Mark S Cattral
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
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Liukkonen V, Semenova M, Hyvärinen K, Lauronen J, Partanen J, Arola J, Nordin A, Färkkilä M, Åberg F. Genetic Risk Factors for Steatotic Liver Disease After Liver Transplantation. Liver Int 2025; 45:e70067. [PMID: 40087975 DOI: 10.1111/liv.70067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 02/26/2025] [Accepted: 03/05/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND The role of genetic risk factors for steatotic liver disease (SLD) is intriguing in liver transplantation (LT), as both donor and recipient genetic factors may play a role. There are only a few small-scale studies published so far. METHODS We analysed the incidence and risk factors for post-LT SLD and the impact of 56 SLD-associated genetic variants in 595 donor-recipient pairs with liver biopsy available ≥ 6 months after LT. We evaluated whether the polygenic risk score (PRS-5) improves the ability to predict post-LT SLD in addition to non-genetic risk factors. RESULTS SLD after LT was diagnosed in 34.5% of patients during a median 7.6-year follow-up. In multivariate analysis including non-genetic risk factors, donor PNPLA3 rs738409-G (HR for SLD: C/G 1.34, p = 0.051, G/G 2.25, p = 0.004), donor HSD17B13 rs72613567-TA (HR for SLD: TA/T 0.68, p = 0.02 TA/TA HR 0.50, p = 0.10) and recipient UCP2 rs695366-G (HR for SLD: A/G 0.63, p = 0.002, G/G HR 0.50, p = 0.04) appeared as the most important genetic risk factors for post-LT SLD. The addition of PRS-5 to a multivariate regression model (including non-genetic risk factors) improved the predictive ability for SLD only modestly (AUC 0.78 to 0.80). CONCLUSIONS Various genetic variants contribute to post-LT SLD with separate variants among recipients and donors, with donor PNPLA3 rs738409-G as the most significant risk allele. Still, donor and recipient genotyping provide only modest additional value for individual risk stratification over phenotype data, highlighting the role of modifiable risk factors.
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Affiliation(s)
- Ville Liukkonen
- North Karelia Central Hospital, Gastroenterology, University of Helsinki, Faculty of Medicine, Helsinki, Finland
| | - Maria Semenova
- Finnish Red Cross Blood Service, Research & Development, Helsinki, Finland
| | - Kati Hyvärinen
- Finnish Red Cross Blood Service, Research & Development, Helsinki, Finland
| | - Jouni Lauronen
- Finnish Red Cross Blood Service, Research & Development, Helsinki, Finland
| | - Jukka Partanen
- Finnish Red Cross Blood Service, Research & Development, Helsinki, Finland
| | - Johanna Arola
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Pathology, Helsinki University Hospital, Diagnostic Centre, Helsinki, Finland
| | - Arno Nordin
- Transplantation and Liver Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Martti Färkkilä
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Fredrik Åberg
- Transplantation and Liver Surgery, Helsinki University Hospital, University of Helsinki, Faculty of Medicine, Helsinki, Finland
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3
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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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4
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Singal AK, Vatsalya V, Agrawal R. Integrated Multidisciplinary Care Model to Manage the Dual Pathology of Alcohol Use Disorder and of Liver Disease. Clin Liver Dis 2024; 28:793-807. [PMID: 39362722 DOI: 10.1016/j.cld.2024.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
Alcohol-associated liver disease (ALD) is the most common cause of liver disease and an indication for liver transplantation. Identification of ALD at an earlier stage and treatment of concomitant alcohol use disorder (AUD) could potentially prevent or delay the progression to advanced stages of ALD like alcohol-associated cirrhosis and alcohol-associated hepatitis. However, screening for alcohol use is often not performed and treatment of AUD is rarely administered in ALD patients, due to several barriers at the level of patients, clinicians, and administrative levels.
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Affiliation(s)
- Ashwani K Singal
- University of Louisville, 505 South Hancock Street, Louisville, KY 40202, USA.
| | - Vatsalya Vatsalya
- University of Louisville, 505 South Hancock Street, Louisville, KY 40202, USA
| | - Ruchita Agrawal
- Department of Psychiatry and Behavioral Sciences, Seven Counties Services, Inc, 530 South Jackson Street, Louisville, KY 40202, USA
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5
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Al-Salmay Y, Singal AK. Positive phosphatidyl-ethanol test in liver disease patients: You can't handle the truth! Dig Liver Dis 2024; 56:1213-1214. [PMID: 38462431 DOI: 10.1016/j.dld.2024.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 02/15/2024] [Indexed: 03/12/2024]
Affiliation(s)
- Yaser Al-Salmay
- Hiram C. Polk, Jr, MD Department of Surgery, Division of Transplantation, University of Louisville, Louisville, KY, USA
| | - Ashwani K Singal
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY, USA.
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6
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Desalegn H, Diaz LA, Rehm J, Arab JP. Impact of alcohol use on liver disease outcomes. Clin Liver Dis (Hoboken) 2024; 23:e0192. [PMID: 38860129 PMCID: PMC11164003 DOI: 10.1097/cld.0000000000000192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/01/2024] [Indexed: 06/12/2024] Open
Affiliation(s)
- Hailemichael Desalegn
- Division of Gastroenterology, Department of Medicine, Western University, London Health Sciences Center, London, Ontario, Canada
- Alimentiv, London, Ontario, Canada
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jürgen Rehm
- Centre for Addiction and Mental Health, Institute for Mental Health Policy Research, Toronto, Ontario, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Centre for Addiction and Mental Health, World Health Organization/Pan American Health Organization Collaborating Centre, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Centre for Interdisciplinary Addiction Research, University of Hamburg, Hamburg, Germany
- Program on Substance Abuse & WHO Collaborating Center on Substance Use, Noncommunicable Diseases, and Policy Impact Public Health Agency of Catalonia, Barcelona Spain
| | - Juan Pablo Arab
- Division of Gastroenterology, Department of Medicine, Western University, London Health Sciences Center, London, Ontario, Canada
- Alimentiv, London, Ontario, Canada
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada
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7
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Testino G, Pellicano R, Caputo F. Alcohol consumption, alcohol use disorder and organ transplantation. Minerva Gastroenterol (Torino) 2023; 69:553-565. [PMID: 36222679 DOI: 10.23736/s2724-5985.22.03281-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Abstract
In the present experience we have evaluated the link alcohol consumption/alcohol use disorder (AUD) and organ transplantation (OT) in order to provide adequate suggestions. The data used for the preparation of these recommendations are based on a detailed analysis of the scientific literature published before August 31, 2022 (Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted the guidelines/position papers of the scientific societies. With regard to the liver transplantation, there are position papers/guidelines that clearly define indications and contraindications for including the AUD patient in the transplant list. One of the major difficulties in this area is psychosocial assessment which can be influenced by stigma. To solve this problem, it is necessary to use objective tools. However, this assessment should be carried out after providing the patient and family adequate tools to be able to create or recreate reliable socio-family support. This behavior should also be used in the case of other OTs. For the latter, however, adequate guidelines must be created which at the moment do not exist or if there are, as in the case of heart transplantation, they are not sufficient. Even in the absence of obvious alcohol addiction, it is recommended to use alcohol use disorder identification test and to include the addiction specialist in the multidisciplinary transplant team. Besides, providing family members with the tools necessary to better support the patient is essential. They are patients with alcohol use disorder/ possible presence of psychopathological manifestations and alcohol-related pathology (cirrhosis, cardiomyopathy, liver-kidney disfunction, etc.). A cardiovascular and oncologic surveillance post-OT is recommended. For the selection of patients to be included in the list for non-LT (heart, lung, kidney, multivisceral, etc.) it is mandatory to include the diagnosis and treatment of AUDs in the guidelines. What has already been indicated for LT may be useful. Timing of alcoholic abstention in relation to clinical severity, optimal psychosocial activity, anticraving therapy in relation to the type of underlying disease and clinical severity. Close collaboration between scientific societies is required to better manage AUD patients who need OT.
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology, Alcohological Regional Center, ASL3 Liguria, IRCCS San Martino University Hospital, Genoa, Italy -
- Centro Studi Mutual-self-help, Community Programs and Caregiver Training, ASL3 Liguria, Genoa, Italy -
| | | | - Fabio Caputo
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Department of Internal Medicine, Santissima Annunziata Hospital, University of Ferrara, Ferrara, Italy
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8
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Kulkarni AV, Singal AK. Screening for alcohol use disorder and monitoring for alcohol use in the liver clinic. Clin Liver Dis (Hoboken) 2023; 22:219-224. [PMID: 38143805 PMCID: PMC10745230 DOI: 10.1097/cld.0000000000000053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 04/10/2023] [Indexed: 12/26/2023] Open
Affiliation(s)
- Anand V. Kulkarni
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, India
| | - Ashwani K. Singal
- Department of Medicine, University of South Dakota, South Dakota, USA
- Department of Hepatology, Avera Transplant Institute and Division of Hepatology, South Dakota, USA
- Department of Internal Medicine, VA Medical Center, Sioux Falls, South Dakota, USA
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9
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Holbeck M, DeVries HS, Singal AK. Integrated Multidisciplinary Management of Alcohol-associated Liver Disease. J Clin Transl Hepatol 2023; 11:1404-1412. [PMID: 37719958 PMCID: PMC10500286 DOI: 10.14218/jcth.2023.00002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 04/12/2023] [Accepted: 04/25/2023] [Indexed: 07/03/2023] Open
Abstract
Alcohol-associated liver disease (ALD) is one of the most common liver diseases and indications for liver transplantation (LT). Alcohol use disorder (AUD), a frequent accompaniment in ALD patients, may also be associated with psychiatric comorbidities such as depression and anxiety. Identification of ALD at an earlier stage, and treatment of AUD may help prevent progression to advanced stage of ALD such as cirrhosis and alcoholic hepatitis. Screening for alcohol use and AUD treatment in ALD patients is often not performed due to several barriers at the level of patients, clinicians, and administrative levels. This review details the integrated multidisciplinary care model especially on the specific role of the hepatologist, psychiatrist, addiction counselor, and social worker in providing complete management for the dual pathology of liver disease and of AUD. Laboratory assessment, pharmacological and behavioral therapies, and recommended assessments for follow-up care by the respective specialists is outlined. We provide perspective along with the literature support, with the goal of providing team based comprehensive care of patients with ALD.
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Affiliation(s)
- Malia Holbeck
- Addiction Medicine, Avera McKennan University Hospital, University of South Dakota, Sioux Falls, SD, USA
| | - Hannah Statz DeVries
- Psychiatry, Avera McKennan University Hospital, University of South Dakota, Sioux Falls, SD, USA
| | - Ashwani K. Singal
- Transplant Hepatology, Avera McKennan University Hospital, University of South Dakota, Sioux Falls, SD, USA
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10
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Chálim Rebelo C, Félix C, Cardoso FS, Bagulho L, Sousa M, Mendes M, Glória H, Mateus É, Mega I, Jara M, Pinto Marques H, Nolasco F, Martins A, Perdigoto R. Alcohol Consumption Post-Liver Transplantation: A Cross-Sectional Study. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2023; 30:343-349. [PMID: 37868639 PMCID: PMC10586211 DOI: 10.1159/000525808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 02/16/2022] [Indexed: 10/24/2023]
Abstract
Background Listing patients with alcohol-associated liver disease (ALD) for liver transplant (LT) remains challenging especially due to the risk of alcohol resumption post-LT. We aimed to evaluate post-LT alcohol consumption at a Portuguese transplant center. Methods We conducted a cross-sectional study including LT recipients from 2019 at Curry Cabral Hospital, Lisbon, Portugal. A pretested survey and a validated Portuguese translation of the Alcohol Use Disorder Identification Test (AUDIT) were applied via a telephone call. Alcohol consumption was defined by patients' self-reports or a positive AUDIT. Results In 2019, 122 patients underwent LT, and 99 patients answered the survey (June 2021). The mean (SD) age was 57 (10) years, 70 patients (70.7%) were males, and 49 (49.5%) underwent ALD-related LT. During a median (IQR) follow-up of 24 (20-26) months post-index LT, 22 (22.2%) recipients consumed any amount of alcohol: 14 had a drink monthly or less and 8 drank 2-4 times/month. On drinking days, 18 patients usually consumed 1-2 drinks and the remainder no more than 3-4 drinks. One patient reported having drunk ≥6 drinks on one occasion. All post-LT drinking recipients were considered low risk (score <8) as per the AUDIT score (median [IQR] of 1 [1-2]). No patient reported alcohol-related problems, whether self-inflicted or toward others. Drinking recipients were younger (53 vs. 59 years, p = 0.020), had more non-ALD-related LT (72.7 vs. 44.2%, p = 0.018) and active smoking (31.8 vs. 10.4%, p = 0.037) than abstinent ones. Conclusion In our cohort, about a quarter of LT recipients consumed alcohol early posttransplant, all with a low-risk pattern according to the AUDIT score.
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Affiliation(s)
| | - Catarina Félix
- Gastroenterology Division, Western Lisbon Hospital Center, Lisbon, Portugal
| | - Filipe S. Cardoso
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Luis Bagulho
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Monica Sousa
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Milena Mendes
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Helena Glória
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Élia Mateus
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Inês Mega
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Miguel Jara
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Hugo Pinto Marques
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Fernando Nolasco
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Américo Martins
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Rui Perdigoto
- Transplant Unit, Curry Cabral Hospital, Central Lisbon University Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
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11
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Umman V, Gumus T, Korucuk E, Temel R, Sertoz OO, Gunsar F, Uguz A, Zeytunlu M, Emre S. A new method for predicting alcohol relapse in patients undergoing liver transplantation for alcohol-related liver failure: Barratt scale. HEPATOLOGY FORUM 2023; 4:118-122. [PMID: 37822308 PMCID: PMC10564253 DOI: 10.14744/hf.2023.2023.0048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/02/2023] [Accepted: 09/04/2023] [Indexed: 10/13/2023]
Abstract
Background and Aim Alcohol-induced liver disease has become one of the major causes of chronic liver disease worldwide with the increasing use of alcohol in society. The most important step in treatment is cessation of alcohol consumption. In patients with advanced liver disease, the most effective treatment is liver transplantation. Careful evaluation of patients with alcoholic liver disease before transplantation can help identify those at high risk of relapsing. Materials and Methods Of a total of 42 patients who underwent liver transplantation for alcohol-related liver failure in our hospital between 2011 and 2022, 26 surviving patients were included in the study. Patient data were analyzed retrospectively. Demographic data, MELD score, history of alcohol consumption, alcohol treatment, post-transplant prognosis and survival were analyzed. The Barratt Impulsivity Scale-11 Short Form (BIS-11 SF) was applied to the surviving patients for impulsivity analysis to predict the possibility of relapse. Results Of the 26 patients who were included in the study, all were male. The mean age at transplantation was 53 (31-71) years. Mean MELD score was 22.31 (9-36). 12 patients (46.2%) received living donor liver transplantation and 14 patients (53.8%) received cadaveric liver transplantation. 25 patients (96.2%) had no post-transplant dependence, while 1 patient (3.8%) had post-transplant dependence. 5 patients (19.2%) continued to consume alcohol after transplantation. Conclusion In our study, we observed that patients with high motor impulsivity tendency according to BSI-11 SF had alcohol relapse. We believe that revising this scale with more detailed questions for alcohol-dependent liver patients and applying it to patients before transplantation will be effective in better selection for transplantation and guiding patients to appropriate therapy and thus preventing relapse after transplantation.
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Affiliation(s)
- Veysel Umman
- Department of General Surgery, Ege University Hospital, Izmir, Turkiye
| | - Tufan Gumus
- Department of General Surgery, Ege University Hospital, Izmir, Turkiye
| | - Ebubekir Korucuk
- Department of General Surgery, Ege University Hospital, Izmir, Turkiye
| | - Recep Temel
- Department of General Surgery, Ege University Hospital, Izmir, Turkiye
| | - Ozen Onen Sertoz
- Department of Psychiatry, Ege University Hospital, Izmir, Turkiye
| | - Fulya Gunsar
- Department of Gastroenterology, Ege University Hospital, Izmir, Turkiye
| | - Alper Uguz
- Department of General Surgery, Ege University Hospital, Izmir, Turkiye
| | - Murat Zeytunlu
- Department of General Surgery, Ege University Hospital, Izmir, Turkiye
| | - Sukru Emre
- Department of General Surgery, Ege University Hospital, Izmir, Turkiye
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12
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Harding-Theobald E, Kriss M. Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now? Clin Liver Dis (Hoboken) 2023; 21:178-186. [PMID: 37361257 PMCID: PMC10287122 DOI: 10.1097/cld.0000000000000057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 03/25/2023] [Indexed: 06/28/2023] Open
Affiliation(s)
- Emily Harding-Theobald
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Michael Kriss
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education (CCTCARE), University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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13
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Simultaneous Management of Alcohol Use Disorder and Liver Disease: A Systematic Review and Meta-analysis. J Addict Med 2023; 17:e119-e128. [PMID: 36259647 DOI: 10.1097/adm.0000000000001084] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES Management of alcohol use disorder (AUD) is rarely used in patients with liver disease. We performed a systematic review to examine the impact of AUD management among patients with liver disease. METHODS Twenty studies fulfilling the inclusion and exclusion criteria on 38,329 patients (7072 receiving AUD intervention) with liver disease (15 with liver disease and 6 liver transplant [LT] recipients) were analyzed. One study was common to both groups. Variable follow-up period across studies was weighted for sample size and converting to person-years. Primary outcome was alcohol use, and secondary outcomes were liver decompensation and patient mortality. RESULTS Abstinence and alcohol relapse rates/person-year with AUD intervention among liver disease patients were 0.41 (0.27-0.55) and 0.42 (0.30-0.755), similar for integrated (colocated liver and addiction clinics) versus concomitant (separate hepatology and addiction clinics) intervention. Compared with standard of care, odds for decompensation with AUD intervention (n = 1), 30-day readmission (n = 1), and patient mortality (n = 2) were lower by 44%, 59%, and 58% respectively. Similar figures were 1.24 (0.86-1.80) for abstinence and 0.52 (0.24-0.14) for relapse. Among LT recipients, odds for alcohol relapse and mortality with follow-up integrated with addiction team versus hepatology alone were 0.48 (0.25-0.72) and 0.29 (0.08-0.99), respectively. CONCLUSIONS Follow-up of LT recipients in an integrated clinic with addiction team is associated with improved outcomes. Simultaneous management of AUD in patients with liver disease improves liver-related outcomes. Large prospective studies are needed to examine benefits of AUD intervention in patients with liver disease.
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14
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Castedal M, Schult A, Kotopouli MI, Bottai M, Franck J, Ericzon BG, Stål P, Stokkeland K. Alcohol as a risk factor for mortality in liver transplant patients in Sweden. Scand J Gastroenterol 2023; 58:269-275. [PMID: 36093679 DOI: 10.1080/00365521.2022.2121938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Liver transplantation (LT) is the only available cure for end-stage liver disease and one of the best treatment options for hepatocellular carcinomas (HCC). Patients with known alcohol-associated cirrhosis (AC) are routinely assessed for alcohol dependence or abuse before LT. Patients with other liver diseases than AC may consume alcohol both before and after LT. The aim of this study was to assess the effects of alcohol drinking before and after LT on patient and graft survival regardless of the etiology of liver disease. MATERIALS AND METHODS Between April 2012 and December 2015, 200 LT-recipients were interviewed using the Lifetime Drinking History and the Addiction Severity Index questionnaire. Patients were categorized as having AC, n = 24, HCC and/or hepatitis C cirrhosis (HCV), n = 69 or other liver diseases, n = 107. Patients were monitored and interviewed by transplantation-independent staff for two years after LT with questions regarding their alcohol consumption. Patient and graft survival data were retrieved in October 2019. RESULTS Patients with AC had an increased hazard ratio (HR) for death after LT (crude HR: 4.05, 95% CI: 1.07-15.33, p = 0.04) and for graft loss adjusted for age and gender (adjusted HR: 3.24, 95% CI 1.08-9.77, p = 0.04) compared to the other patients in the cohort. There was no significant effect of the volume of alcohol consumed before or after LT on graft loss or overall survival. CONCLUSION Patients transplanted for AC have a worse prognosis, but we found no correlation between alcohol consumed before or after LT and graft or patient survival.
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Affiliation(s)
- Maria Castedal
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.,Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Andreas Schult
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.,Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Maria Ioanna Kotopouli
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden
| | - Matteo Bottai
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden
| | - Johan Franck
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Bo-Göran Ericzon
- Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden.,Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Per Stål
- Unit of Liver Diseases, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Knut Stokkeland
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Stockholm Centre for Dependency Disorders, Stockholm, Sweden
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15
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DiMartini AF, Leggio L, Singal AK. Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models. Lancet Gastroenterol Hepatol 2022; 7:186-195. [DOI: 10.1016/s2468-1253(21)00191-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 02/07/2023]
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16
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Jophlin L, Singal AK. Liver Biopsy in Patients With Alcohol-Associated Liver Disease With Acute-on-Chronic Liver Failure. J Clin Exp Hepatol 2022; 12:544-550. [PMID: 35535109 PMCID: PMC9077173 DOI: 10.1016/j.jceh.2021.08.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 08/09/2021] [Indexed: 01/11/2023] Open
Abstract
Patients with alcohol-associated liver disease may develop severe forms of presentation of acute-on-chronic liver failure, with a high risk for short-term mortality. Alcoholic hepatitis should be suspected among patients with alcohol-associated liver disease who present with acute-on-chronic liver failure. In this review, we discuss the need and feasibility of liver biopsy in the diagnosis of alcoholic hepatitis and predicting its prognosis among decompensated patients with alcohol-associated liver disease and acute-on-chronic liver failure.
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Key Words
- AARC, Asia-Pacific ACLF Research Consortium
- ACLF
- ACLF, acute-on-chronic liver failure
- AH
- AH, alcoholic hepatitis
- AHHS, alcoholic hepatitis histologic score
- ALD
- ALD, alcohol-associated liver disease
- AUD, alcohol use disorder
- DF, discriminant function
- EUS, endoscopic ultrasound
- EtG, ethyl glucuronide
- NIAAA, National Institute on Alcoholism and Alcohol Abuse
- PEth, phosphatidylethanol
- SALVE, Study of Alcohol-related LiVer disease in Europe
- histology
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Affiliation(s)
- Loretta Jophlin
- Department of Gastroenterology and Hepatology, University of Louisville, Louisville, KY, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, Department of Medicine, University of South Dakota Sanford School of Medicine, South Dakota, USA,Address for correspondence:. Ashwani K. Singal, Professor of Medicine, University of South Dakota Sanford School of Medicine, Transplant Hepatologist and Chief Clinical Research Affairs, Avera McKennan University Hospital Transplant Institute, Sioux Falls, SD, 57105, USA. Tel.: +605 322-8545; fax: +605 322 8536.
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17
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Liver transplantation for alcohol-related liver disease in the UK: revised UK Liver Advisory Group recommendations for referral. Lancet Gastroenterol Hepatol 2021; 6:947-955. [PMID: 34626562 DOI: 10.1016/s2468-1253(21)00195-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 05/17/2021] [Accepted: 05/24/2021] [Indexed: 12/11/2022]
Abstract
Liver disease, of which liver cirrhosis is the most advanced stage, constitutes the fourth most common cause of life-years lost in men and women younger than 75 years in England, where mortality rates from liver disease have increased by 25% in the past decade. Alcohol consumption is the most common modifiable risk factor for disease progression in these individuals, but within the UK, there is substantial variation in the distribution, prevalence, and outcome of alcohol-related liver disease, and no equity of access to tertiary transplantation services. These revised recommendations were agreed by an expert panel convened by the UK Liver Advisory Group, with the purpose of providing consensus on referral for transplant assessment in patients with alcohol-related disease, and clarifying the terminology and definitions of alcohol use in liver injury. By standardising clinical management in these patients, it is hoped that there will be an improvement in the quality of care and better access to liver transplant assessment for patients with alcohol-related liver disease in the UK.
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18
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Grottenthaler JM, Konzelmann A, Stiegler A, Hinterleitner C, Bott SM, Klag T, Werner CR, Hinterleitner M, Königsrainer A, Batra A, Malek NP, Nadalin S, Berg CP. Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation - development of a risk score. Transpl Int 2021; 34:2257-2265. [PMID: 34358363 DOI: 10.1111/tri.14007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND & AIMS Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) - a metabolite of ethanol - in patients after liver transplantation. METHODS Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. RESULTS 48 patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pre transplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pre transplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). CONCLUSIONS Routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.
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Affiliation(s)
- Julia M Grottenthaler
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany
| | - Annette Konzelmann
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany
| | - Anette Stiegler
- Department of Psychiatry and Psychotherapy, Section Addiction Medicine and Addiction Research, University Hospital Tuebingen, Tuebingen, Germany
| | - Clemens Hinterleitner
- Department of Medical Oncology and Pneumology, University Hospital Tuebingen, Tuebingen, Germany
| | - Sarah M Bott
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany
| | - Thomas Klag
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany
| | - Christoph R Werner
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany
| | - Martina Hinterleitner
- Department of Medical Oncology and Pneumology, University Hospital Tuebingen, Tuebingen, Germany
| | - Alfred Königsrainer
- Department of General-, Visceral- and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany
| | - Anil Batra
- Department of Psychiatry and Psychotherapy, Section Addiction Medicine and Addiction Research, University Hospital Tuebingen, Tuebingen, Germany
| | - Nisar P Malek
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany
| | - Silvio Nadalin
- Department of General-, Visceral- and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany
| | - Christoph P Berg
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University Hospital Tuebingen, Tuebingen, Germany
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19
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Neuberger J. Liver Transplantation for Alcoholic Liver Disease: What Is the Risk and Consequence of Relapse? Dig Dis Sci 2020; 65:1600-1607. [PMID: 32060813 DOI: 10.1007/s10620-020-06127-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Although short- and medium-term outcomes after liver transplantation for alcohol-related liver disease (ARLD) are generally excellent and similar to outcomes for transplantation for other indications, a return to alcohol consumption commonly occurs even though rates of alcohol consumption after transplantation for ARLD are comparable to those seen in other indications. Transplant recipients should be questioned about alcohol use post-transplantation and, where appropriate, monitored; those drinking significant amounts should be offered treatment with the help of a multi-disciplinary team. Although short-term significant alcohol use is associated with an increased risk of non-compliance and rejection, medium-term outcomes are similar to other groups. Patients transplanted for ARLD have a greater risk of some de novo malignancies, especially of the lung and the upper GI tract. More work is required both to identify those at risk of a return to destructive patterns of alcohol use at an early stage and to develop effective treatments aimed at reaching and maintaining abstinence.
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Affiliation(s)
- James Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
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20
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Asrani SK, Trotter J, Lake J, Ahmad A, Bonagura A, Cameron A, DiMartini A, Gonzalez S, Im G, Martin P, Mathurin P, Mellinger J, Rice JP, Shah V, Terrault N, Wall A, Winder S, Klintmalm G. Meeting Report: The Dallas Consensus Conference on Liver Transplantation for Alcohol Associated Hepatitis. Liver Transpl 2020; 26:127-140. [PMID: 31743578 PMCID: PMC8151800 DOI: 10.1002/lt.25681] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 10/29/2019] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT) for alcohol associated hepatitis (AH) remains controversial. We convened a consensus conference to examine various aspects of LT for AH. The goal was not to unequivocally endorse LT for AH; instead, it was to propose recommendations for programs that perform or plan to perform LT for AH. Criteria were established to determine candidacy for LT in the setting of AH and included the following: (1) AH patients presenting for the first time with decompensated liver disease that are nonresponders to medical therapy without severe medical or psychiatric comorbidities; (2) a fixed period of abstinence prior to transplantation is not required; and (3) assessment with a multidisciplinary psychosocial team, including a social worker and an addiction specialist/mental health professional with addiction and transplantation expertise. Supporting factors included lack of repeated unsuccessful attempts at addiction rehabilitation, lack of other substance use/dependency, acceptance of diagnosis/insight with a commitment of the patient/family to sobriety, and formalized agreement to adhere to total alcohol abstinence and counseling. LT should be avoided in AH patients who are likely to spontaneously recover. Short-term and longterm survival comparable to other indications for LT must be achieved. There should not be further disparity in LT either by indication, geography, or other sociodemographic factors. Treatment of alcohol-use disorders should be incorporated into pre- and post-LT care. The restrictive and focused evaluation process described in the initial LT experience for AH worldwide may not endure as this indication gains wider acceptance at more LT programs. Transparency in the selection process is crucial and requires the collection of objective data to assess outcomes and minimize center variation in listing. Oversight of program adherence is important to harmonize listing practices and outcomes.
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Affiliation(s)
- Sumeet K Asrani
- Baylor University Medical Center, Dallas, Texas,Corresponding author: Sumeet K Asrani MD MSc, Associate Professor of Medicine, Baylor University Medical Center, Dallas Texas, , Tele: 214 820 8500, Fax: 214 820 0993
| | | | - Jack Lake
- University of Minnesota, Minneapolis, Minnesota
| | | | | | | | | | | | | | - Paul Martin
- University of Miami health system, Miami, Florida
| | - Philippe Mathurin
- Service d’Hépato-gastroentérologie, Hôpital Claude Huriez, Lille, France
| | | | | | | | - Norah Terrault
- University of Southern California, Los Angeles, California
| | - Anji Wall
- Baylor University Medical Center, Dallas, Texas
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21
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Bataller R, Cabezas J, Aller R, Ventura-Cots M, Abad J, Albillos A, Altamirano J, Arias-Loste MT, Bañares R, Caballería J, Caballería L, Carrión JA, Diago M, Fernández Rodríguez C, Gallego R, García-Cortes M, García-Monzón C, Genescà J, Ginés P, Hernandez-Guerra M, Jorquera F, Lligoña A, Molina E, Pareja MJ, Planas R, Tomé S, Salmerón J, Romero-Gómez M. Alcohol-related liver disease. Clinical practice guidelines. Consensus document sponsored by AEEH. GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 42:657-676. [PMID: 31771785 DOI: 10.1016/j.gastrohep.2019.09.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 09/02/2019] [Indexed: 02/07/2023]
Abstract
Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.
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Affiliation(s)
- Ramón Bataller
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, Estados Unidos.
| | - Joaquín Cabezas
- Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Instituto de investigación Sanitaria Valdecilla (IDIVAL), Santander, Cantabria, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España
| | - Rocío Aller
- Servicio de Gastroenterología, Hospital Clínico Universitario de Valladolid, Valladolid, España; Facultad de Medicina, Universidad de Valladolid, Valladolid, España; Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina de Valladolid, Valladolid, España
| | - Meritxell Ventura-Cots
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, Estados Unidos; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España
| | - Javier Abad
- Servicio de Gastroenterología y Hepatología, Hospital Puerta de Hierro, Madrid, España
| | - Agustín Albillos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, España
| | - José Altamirano
- Deparmento de Medicina Interna, Hospital Quironsalud, Barcelona, España
| | - María Teresa Arias-Loste
- Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Instituto de investigación Sanitaria Valdecilla (IDIVAL), Santander, Cantabria, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España
| | - Rafael Bañares
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Servicio de Gastroenterología y Hepatología, Hospital Gregorio Marañón, Madrid, España
| | - Juan Caballería
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Unidad de Hepatología, Hospital Clínic, IDIBAPS, Barcelona, España
| | - Llorenç Caballería
- Unidad de Apoyo a la Investigación de la Atención Primaria en la Metropolitana Norte, Barcelona, España
| | | | - Moisés Diago
- Servicio de Aparato Digestivo, Hospital General de Valencia, Valencia, España
| | - Conrado Fernández Rodríguez
- Servicio de Gastroenterología, Hospital Universitario Fundación Alcorcón. Facultad de Medicina, Universidad Rey Juan Carlos, Alcorcón, Madrid, España
| | - Rocío Gallego
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; UGC Aparato Digestivo, Instituto de Biomedicina de Sevilla. Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, España
| | | | | | - Joan Genescà
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Servicio de Medicina Interna-Hepatología, Hospital Universitario Vall d'Hebron, Institut de Recerca Vall d'Hebron (VHIR), Universitat Autònoma de Barcelona, Barcelona, España
| | - Pere Ginés
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Unidad de Apoyo a la Investigación de la Atención Primaria en la Metropolitana Norte, Barcelona, España
| | | | - Francisco Jorquera
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, IBIOMED, León, España
| | - Anna Lligoña
- Unidad de Alcohologia, Departamento de Psiquiatría, Hospital Clínic. Barcelona, España
| | - Esther Molina
- Unidad de Hepatología, Servicio de Aparato Digestivo, Hospital Clínico-Xerencia de Xestión Integrada de Santiago de Compostela, Santiago de Compostela, La Coruña, España
| | | | - Ramón Planas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Departamento de Hepatología, Hospital Germans Trias i Pujol, Badalona, Barcelona, España
| | - Santiago Tomé
- Unidad de Trasplante Hepático, Hospital Clínico Universitario, Santiago de Compostela, La Coruña, España
| | - Javier Salmerón
- UGC de Aparato Digestivo, Hospital San Cecilio, Granada, España
| | - Manuel Romero-Gómez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; UGC Aparato Digestivo, Instituto de Biomedicina de Sevilla. Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, España
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22
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Schult A, Stokkeland K, Ericzon BG, Hultcrantz R, Franck J, Stål P, Castedal M. Alcohol and drug use prior to liver transplantation: more common than expected in patients with non-alcoholic liver disease. Scand J Gastroenterol 2019; 54:1146-1154. [PMID: 31453745 DOI: 10.1080/00365521.2019.1656772] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease, acute liver failure or hepatocellular carcinoma (HCC). Patients with known alcoholic liver cirrhosis (ALC) are usually assessed by an addiction specialist, but patients with other liver diseases may also exhibit harmful drinking. This study aims to assess the drinking habits in LT-recipients with or without a diagnosis of ALC. Patients and methods: Between April 2012 and December 2015, 190 LT-recipients were interviewed using the Lifetime Drinking History (LDH) and the Addiction Severity Index (ASI). Patients were categorized according to their diagnoses: ALC (group A, n = 39), HCC or hepatitis C (group B, n = 56) or other liver diseases (group C, n = 95). Data were analysed using descriptive statistic methods. Results: Fifteen of 95 patients (15.8%) in group C - a cohort without suspected addiction problems - had either alcohol consumption or binge drinking within the upper quartile of the overall cohort. The aetiology of liver disease in this subgroup included mainly cholestatic and cryptogenic liver disease. Illicit drugs had been used by 35% of all patients. Cannabis and amphetamine were the most common drugs and had the longest duration of regular use. Conclusions: LT candidates without known alcohol or drug use may have a clinically significant consumption of alcohol and previous illicit drug use. Efforts should be put on identification of these patients during LT evaluation. The use of structured questionnaires such as the ASI and the LDH could facilitate detection of alcohol and drug problems.
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Affiliation(s)
- Andreas Schult
- The Transplant Institute, Sahlgrenska University Hospital , Gothenburg , Sweden.,Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Knut Stokkeland
- Department of Medicine, Visby Hospital , Visby , Sweden.,Department of Clinical Neuroscience, Karolinska Institutet , Stockholm , Sweden
| | - Bo-Göran Ericzon
- Division of Transplantation Surgery, CLINTEC, Karolinska Institutet , Stockholm , Sweden.,Department of Transplantation Surgery, Karolinska University Hospital , Stockholm , Sweden
| | - Rolf Hultcrantz
- Department of Medicine, Solna, Karolinska Institutet , Stockholm , Sweden
| | - Johan Franck
- Department of Clinical Neuroscience, Karolinska Institutet , Stockholm , Sweden
| | - Per Stål
- Department of Upper GI Diseases, Unit of Liver Diseases, Karolinska University Hospital , Stockholm , Sweden.,Department of Medicine, Huddinge, Karolinska Institutet , Stockholm , Sweden
| | - Maria Castedal
- The Transplant Institute, Sahlgrenska University Hospital , Gothenburg , Sweden.,Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
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23
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Godfrey EL, Stribling R, Rana A. Liver Transplantation for Alcoholic Liver Disease: An Update. Clin Liver Dis 2019; 23:127-139. [PMID: 30454827 DOI: 10.1016/j.cld.2018.09.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Alcoholic liver disease is a serious and increasing contributor to the global liver disease burden. Extensive selection criteria, including a minimum abstinence period, has previously been used to secure good outcomes but new research questions the effectiveness of abstinence periods and has recommended changes in integrated alcohol use treatment to effectively prevent relapse. Patients have unique health concerns, including posttransplantation risks of malignancy and metabolic complications, but overall very good long-term outcomes. Severe alcoholic hepatitis has been increasingly treated with early transplantation without a set sobriety period, with overall favorable outcomes, even with respect to recidivism.
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Affiliation(s)
- Elizabeth L Godfrey
- Department of Student Affairs, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
| | | | - Abbas Rana
- 6620 Main Street, Suite 1425, Houston, TX 77030, USA
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24
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Abstract
Age-standardised mortality from liver disease in the United Kingdom has risen by 400% since 1970, with three-quarters of deaths from alcohol-related liver disease (ARLD). The 2013 National Confidential Enquiry into Patient Outcome and Death report found that only 47% of the patients dying in hospital from liver disease experienced 'good' care. We discuss common complications in the care of patients with ARLD and the evidence-based best practice that can improve patient outcomes, with a focus on the initial management of patients presenting acutely to the medical take.
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Affiliation(s)
- Luke D Tyson
- Imperial College Healthcare NHS Trust, London, UK
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25
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Beresford TP, Lucey MR. Towards Standardizing the Alcoholism Evaluation Of Potential Liver Transplant Recipients. Alcohol Alcohol 2018; 53:135-144. [PMID: 29211831 DOI: 10.1093/alcalc/agx104] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Accepted: 11/28/2017] [Indexed: 12/12/2022] Open
Abstract
Aims For teams around the world, alcoholic liver disease patients comprise the largest, and clinically most controversial, group applying for liver transplant. And yet evaluation decisions for them remain highly variable by locale. Methods Targeting standardized assessment, we provide guidelines on what information the transplant team should seek, from what sources, and how best to make use of it. This report focuses on 'what to do and how to do it' in providing appropriate assessments for this complex patient group. Results Proper evaluation includes (a) taking the clinical history from the patient and a required, corroborating third person, (b) assessing patient cognition, (c) establishing alcohol/substance use diagnosis to differentiate alcohol dependence, abuse and polysubstance dependence, (d) assessing ambivalence in primary alcohol addiction, (e) measuring social stability and (f) using Vaillant's factors for abstinence prognosis. Conclusions Properly applied, these six factors will allow standardized selection in most cases taken across programs despite differences in resources, available expertise and decision practices. Short Summary This report focuses on the essentials of the psychiatric/behavioral evaluation for 'alcoholic' persons referred for liver transplant. Attention to those essentials offers clinical standardization across transplant programs in different locales.
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Affiliation(s)
- Thomas P Beresford
- Department of Veterans Affairs Medical Center and School of Medicine, University of Colorado Denver, (116), 1055 Clermont Street, Denver, CO 80220-0116, USA
| | - Michael R Lucey
- Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA
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26
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Singal AK, Louvet A, Shah VH, Kamath PS. Grand Rounds: Alcoholic Hepatitis. J Hepatol 2018; 69:534-543. [PMID: 29753761 PMCID: PMC6258018 DOI: 10.1016/j.jhep.2018.05.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 04/20/2018] [Accepted: 05/01/2018] [Indexed: 12/17/2022]
Abstract
A 33-year-old Caucasian male was admitted to hospital with recent onset of jaundice of 2-3 weeks duration. He reported heavy use of alcohol for the last 10 years with the last drink a day prior to the onset of symptoms. At admission, he was alert and oriented to time, place, and person, and was deeply jaundiced. His laboratory profile can be summarised as follows: haemoglobin 12.1 g/dl, white blood cell count 18,700 with 81% neutrophils, serum bilirubin 33 (direct 22) mg/dl, aspartate aminotransferase 147 IU/L, alanine aminotransferase 62 IU/L, alkaline phosphatase 117 IU/L, serum albumin 2.8 gm/dl, serum creatinine 0.6 mg/dl, prothrombin time 18.3 (control 14.5) seconds, and international normalized ratio 1.48. He was diagnosed with severe alcoholic hepatitis (Maddrey discriminant function score of 50) and treated with prednisolone for 28 days with symptomatic and biochemical improvement. His Lille score at seven days was 0.4, and his serum bilirubin had decreased to 3.5 mg/dl at the end of treatment. He was also seen by the addiction team during hospitalisation; he agreed to follow through on recommendations. He was dismissed after completing a three-week inpatient rehabilitation programme but relapsed to alcohol use three months later, and was readmitted with alcohol withdrawal. He was readmitted two months later (about six months from the first episode) for a second episode of severe alcoholic hepatitis. At admission, his model for end-stage liver disease score was 32 and he was treated again with corticosteroids. His Lille score at seven days was 0.6 and steroids were discontinued. The hospital course was complicated by spontaneous bacterial peritonitis and pneumonia with development of acute kidney injury. He continued to worsen, developing multiorgan failure. After a course of one month, the family's preference was for him to receive comfort measures. This scenario raises several questions.
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Affiliation(s)
- Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL. USA,Corresponding author. Address 1808 7th Ave S, BDB 351, University of Alabama at Birmingham, Birmingham, AL, USA. Tel.: +1 205 934 5623; fax: +1 205 975 0961. (A.K. Singal)
| | - Alexandre Louvet
- Service des maladies de l’appareil digestif, Hôpital Huriez, Rue Polonowski, 59037 Lille cedex, France,Université Lille Nord de France, Lille, France
| | - Vijay H. Shah
- Division of gastroenterology and hepatology, Mayo Clinic, Rochester, MN, USA
| | - Patrick S. Kamath
- Division of gastroenterology and hepatology, Mayo Clinic, Rochester, MN, USA
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27
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Marroni CA, Fleck Jr ADM, Fernandes SA, Galant LH, Mucenic M, de Mattos Meine MH, Mariante-Neto G, Brandão ABDM. Liver transplantation and alcoholic liver disease: History, controversies, and considerations. World J Gastroenterol 2018; 24:2785-2805. [PMID: 30018475 PMCID: PMC6048431 DOI: 10.3748/wjg.v24.i26.2785] [Citation(s) in RCA: 97] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 05/23/2018] [Accepted: 06/16/2018] [Indexed: 02/06/2023] Open
Abstract
Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease (ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation (LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a "self-inflicted disease". One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this "6-mo rule" is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy.
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Affiliation(s)
- Claudio Augusto Marroni
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Alfeu de Medeiros Fleck Jr
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Sabrina Alves Fernandes
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
- Nutrition at the Centro Universitário Metodista (IPA), Porto Alegre 90420-060, RS, Brazil
| | - Lucas Homercher Galant
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Marcos Mucenic
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Mario Henrique de Mattos Meine
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Guilherme Mariante-Neto
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Ajacio Bandeira de Mello Brandão
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
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28
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Abstract
Alcoholic hepatitis is the most severe and acute form of alcoholic liver disease. The mortality rate associated with alcoholic hepatitis is high, largely due to the lack of suitable pharmacological interventions. While there has been substantial research in the area, generating pharmacological interventions has been plagued by the lack of a robust mouse model both for testing and for understanding the underlying pathology. A number of major notable advances have been made in this area recently, with the goal of generating a mouse model of alcoholic hepatitis. The purpose of this article is to review recent advances in modeling alcoholic liver disease both in vitro and in vivo in the mouse, and place them in the context of the greater spectrum of alcoholic liver disease, with a focus on how we can translate current advances into a high-fidelity model of alcoholic hepatitis. In addition, we will review the basic mechanisms of alcoholic hepatitis as it is currently understood, focusing on recent advancements in diagnosis, prognosis and current pathophysiology, especially as it relates to the profound immune dysfunction present during alcoholic hepatitis.
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Affiliation(s)
- Benjamin L. Woolbright
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Hartmut Jaeschke
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA
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29
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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: 545] [Impact Index Per Article: 77.9] [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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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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Russ KB, Chen NW, Kamath PS, Shah VH, Kuo YF, Singal AK. Reply to ''Alcohol and Liver Transplantation''. Alcohol Alcohol 2016; 52:127. [PMID: 27998924 DOI: 10.1093/alcalc/agw057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 07/04/2016] [Accepted: 07/26/2016] [Indexed: 11/14/2022] Open
Affiliation(s)
- Kirk B Russ
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 1720 2nd Ave S Birmingham, AL 35233, USA
| | - Nai-Wei Chen
- Department of Biostatistics, University of Texas Medical Branch, 300 University Blvd, Galveston, TX 77555, USA
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st St SW, Rochestor, MN 55905, USA
| | - Vijay H Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st St SW, Rochestor, MN 55905, USA
| | - Yong-Fang Kuo
- Department of Biostatistics, University of Texas Medical Branch, 300 University Blvd, Galveston, TX 77555, USA
| | - Ashwani K Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 1720 2nd Ave S Birmingham, AL 35233, USA
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32
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Testino G, Leone S. Alcohol and Liver Transplantation. Alcohol Alcohol 2016; 52:126. [PMID: 27600939 DOI: 10.1093/alcalc/agw056] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 07/25/2016] [Accepted: 07/26/2016] [Indexed: 12/21/2022] Open
Affiliation(s)
- Gianni Testino
- Centro Alcologico Regionale - Regione Liguria, IRCCS AOU San Martino-IST, Genova, Italy
| | - Silvia Leone
- Department of Internal Medicine, University of Genova, Piazzale R. Benzi 10, 16132 Genova, Italy
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