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Yilma M, Dalal N, Wadhwani SI, Hirose R, Mehta N. Geographic disparities in access to liver transplantation. Liver Transpl 2023; 29:987-997. [PMID: 37232214 PMCID: PMC10914246 DOI: 10.1097/lvt.0000000000000182] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 04/08/2023] [Indexed: 05/27/2023]
Abstract
Since the Final Rule regarding transplantation was published in 1999, organ distribution policies have been implemented to reduce geographic disparity. While a recent change in liver allocation, termed acuity circles, eliminated the donor service area as a unit of distribution to decrease the geographic disparity of waitlisted patients to liver transplantation, recently published results highlight the complexity of addressing geographic disparity. From geographic variation in donor supply, as well as liver disease burden and differing model for end-stage liver disease (MELD) scores of candidates and MELD scores necessary to receive liver transplantation, to the urban-rural disparity in specialty care access, and to neighborhood deprivation (community measure of socioeconomic status) in liver transplant access, addressing disparities of access will require a multipronged approach at the patient, transplant center, and national level. Herein, we review the current knowledge of these disparities-from variation in larger (regional) to smaller (census tract or zip code) levels to the common etiologies of liver disease, which are particularly affected by these geographic boundaries. The geographic disparity in liver transplant access must balance the limited organ supply with the growing demand. We must identify patient-level factors that contribute to their geographic disparity and incorporate these findings at the transplant center level to develop targeted interventions. We must simultaneously work at the national level to standardize and share patient data (including socioeconomic status and geographic social deprivation indices) to better understand the factors that contribute to the geographic disparity. The complex interplay between organ distribution policy, referral patterns, and variable waitlisting practices with the proportion of high MELD patients and differences in potential donor supply must all be considered to create a national policy strategy to address the inequities in the system.
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Affiliation(s)
- Mignote Yilma
- Department of Surgery, University of California San Francisco
- National Clinician Scholars Program, University of California San Francisco
| | - Nicole Dalal
- Department of Medicine, University of California San Francisco
| | | | - Ryutaro Hirose
- Department of Transplant, University of California San Francisco
| | - Neil Mehta
- Department of Medicine, University of California San Francisco
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Kharbanda KK, Farokhnia M, Deschaine SL, Bhargava R, Rodriguez-Flores M, Casey CA, Goldstone AP, Jerlhag E, Leggio L, Rasineni K. Role of the ghrelin system in alcohol use disorder and alcohol-associated liver disease: A narrative review. Alcohol Clin Exp Res 2022; 46:2149-2159. [PMID: 36316764 PMCID: PMC9772086 DOI: 10.1111/acer.14967] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/21/2022] [Accepted: 10/28/2022] [Indexed: 11/07/2022]
Abstract
Unhealthy alcohol consumption is a global health problem. Adverse individual, public health, and socioeconomic consequences are attributable to harmful alcohol use. Epidemiological studies have shown that alcohol use disorder (AUD) and alcohol-associated liver disease (ALD) are the top two pathologies among alcohol-related diseases. Consistent with the major role that the liver plays in alcohol metabolism, uncontrolled drinking may cause significant damage to the liver. This damage is initiated by excessive fat accumulation in the liver, which can further progress to advanced liver disease. The only effective therapeutic strategies currently available for ALD are alcohol abstinence or liver transplantation. Any molecule with dual-pronged effects at the central and peripheral organs controlling addictive behaviors and associated metabolic pathways are a potentially important therapeutic target for treating AUD and ALD. Ghrelin, a hormone primarily derived from the stomach, has such properties, and regulates both behavioral and metabolic functions. In this review, we highlight recent advances in understanding the peripheral and central functions of the ghrelin system and its role in AUD and ALD pathogenesis. We first discuss the correlation between blood ghrelin concentrations and alcohol use or abstinence. Next, we discuss the role of ghrelin in alcohol-seeking behaviors and finally its role in the development of fatty liver by metabolic regulations and organ crosstalk. We propose that a better understanding of the ghrelin system could open an innovative avenue for improved treatments for AUD and associated medical consequences, including ALD.
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Affiliation(s)
- Kusum K. Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Mehdi Farokhnia
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland, USA
- Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Sara L. Deschaine
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland, USA
| | - Raghav Bhargava
- PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK
| | - Marcela Rodriguez-Flores
- PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK
| | - Carol A. Casey
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Anthony P. Goldstone
- PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK
| | - Elisabet Jerlhag
- Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Lorenzo Leggio
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland, USA
- Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA
- Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island, USA
- Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
- Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA
| | - Karuna Rasineni
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
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3
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Winder GS, Fernandez AC, Mellinger JL. Integrated Care of Alcohol-Related Liver Disease. J Clin Exp Hepatol 2022; 12:1069-1082. [PMID: 35814517 PMCID: PMC9257883 DOI: 10.1016/j.jceh.2022.01.010] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 01/22/2022] [Indexed: 12/12/2022] Open
Abstract
Background/Aims Alcohol-related liver disease (ALD) is the medical manifestation of alcohol use disorder, a prevalent psychiatric condition. Acute and chronic manifestations of ALD have risen in recent years especially in young people and ALD is now a leading indication of liver transplantation (LT) worldwide. Such alarming trends raise urgent and unanswered questions about how medical and psychiatric care can be sustainably integrated to better manage ALD patients before and after LT. Methods Critical evaluation of the interprofessional implications of broad and multifaceted ALD pathophysiology, general principles of and barriers to interprofessional teamwork and care integration, and measures that clinicians and institutions can implement for improved and integrated ALD care. Results The breadth of ALD pathophysiology, and its numerous medical and psychiatric comorbidities, ensures that no single medical or psychiatric discipline is adequately trained and equipped to manage the disease alone. Conclusions Early models of feasible ALD care integration have emerged in recent years but much more work is needed to develop and study them. The future of ALD care is an integrated approach led jointly by interprofessional medical and psychiatric clinicians.
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Affiliation(s)
- Gerald S. Winder
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA
| | - Anne C. Fernandez
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
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Gray C, Arney J, Clark JA, Walling AM, Kanwal F, Naik AD. The chosen and the unchosen: How eligibility for liver transplant influences the lived experiences of patients with advanced liver disease. Soc Sci Med 2022; 305:115113. [PMID: 35690034 DOI: 10.1016/j.socscimed.2022.115113] [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: 01/10/2022] [Revised: 05/31/2022] [Accepted: 06/03/2022] [Indexed: 02/07/2023]
Abstract
Advanced liver disease is often uncurable and fatal. Liver transplant is the only curative option for patients with advanced, irreversible liver disease, but the need for new livers far exceeds the supply. Patients with the greatest need as well as the greatest likelihood of benefit, based on a complex array of biomedical and psychosocial considerations, are prioritized for transplant. The opportunity to receive a life-saving surgery no doubt has enormous consequences for patients and their healthcare providers, as does the absence of that opportunity. But these consequences are poorly characterized, especially for patients deemed poor candidates for liver transplant. Through in-depth interviews with patients living with advanced liver disease and the providers who care for them, we explore how eligibility status affects illness experiences, including patients' interactions with clinicians, knowledge about their disease, expectations for the future, and efforts to come to terms with a life-limiting illness. We describe how the clinical and social requirements needed to secure eligibility for liver transplant lend themselves to a clinical and cultural logic that delineates "worthy" and "unworthy" patients. We describe how providers and candidates discuss the possibility of moral redemption for such patients through transplant surgeries, a discourse notably absent among patients not eligible for transplant.
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Affiliation(s)
- Caroline Gray
- Center for Innovation to Implementation, VA Palo Alto Health Care System, 795 Willow Road (152-MPD), Menlo Park, CA, 94025, USA.
| | - Jennifer Arney
- Department of Sociology, University of Houston-Clear Lake, 2700 Bay Area Boulevard, Houston, TX, 77058, USA; VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, 2450 Holcombe Blvd Suite 01Y, Houston, TX, 77021, USA.
| | - Jack A Clark
- Department of Health Law, Policy, and Management, Boston University School of Public Health, 715 Albany Street, Boston, MA, 02118, USA.
| | - Anne M Walling
- VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA, 90073, USA; Department of Medicine, Division of General Internal Medicine and Health Services Research University of California at Los Angeles, 1100 Glendon Ave STE 850, Los Angeles, CA, 90024, USA.
| | - Fasiha Kanwal
- VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, 2450 Holcombe Blvd Suite 01Y, Houston, TX, 77021, USA; Department of Medicine, Health Services Research and Gastroenterology and Hepatology, Baylor College of Medicine, 7200 Cambridge St., Houston, TX, 77030, USA.
| | - Aanand D Naik
- VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, 2450 Holcombe Blvd Suite 01Y, Houston, TX, 77021, USA; Department of Medicine, Department of Health Services Research, Geriatrics and Palliative Medicine, Baylor College of Medicine, Houston, TX 7200 Cambridge St., Houston, TX, 77030, USA.
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Management of alcohol use disorder in patients with cirrhosis in the setting of liver transplantation. Nat Rev Gastroenterol Hepatol 2022; 19:45-59. [PMID: 34725498 PMCID: PMC8559139 DOI: 10.1038/s41575-021-00527-0] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/21/2021] [Indexed: 02/07/2023]
Abstract
The prevalence of alcohol use disorder (AUD) has been steadily increasing over the past decade. In parallel, alcohol-associated liver disease (ALD) has been increasing at an alarming rate, especially among young patients. Data suggest that most patients with ALD do not receive AUD therapy. Although liver transplantation is the only curative therapy for end-stage ALD, transplant candidacy is often a matter of debate given concerns about patients being under-treated for AUD and fears of post-transplantation relapse affecting the allograft. In this Review, we discuss diagnosis, predictors and effects of relapse, behavioural therapies and pharmacotherapies, and we also propose an integrative, multidisciplinary and multimodality approach for treating AUD in patients with cirrhosis, especially in the setting of liver transplantation. Notably, this approach takes into account the utility of AUD pharmacotherapy in patients on immunosuppressive medications and those with renal impairment after liver transplantation. We also propose a comprehensive and objective definition of relapse utilizing contemporary biomarkers to guide future clinical trials. Future research using the proposed approach and definition is warranted with the goal of optimizing AUD treatment in patients with cirrhosis, the transplant selection process and post-transplantation care of patients with AUD.
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Direct Alcohol Biomarkers Prediction Capacity on Relapse and Mortality in Liver Transplantation Candidates: A Follow-Up Study. TRANSPLANTOLOGY 2021. [DOI: 10.3390/transplantology2030023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Liver transplantation is a complex procedure that requires multiple evaluations, including abstinence monitorization. While literature assessing the impact of different variables on relapse, survival, and graft loss exists, little is known about the predictive capacity of direct alcohol biomarkers. The primary aim of this study was to evaluate the prediction capacity of direct alcohol biomarkers regarding patient survival and clinical relapse. We hypothesized that patients screening positive for any of the experimental biomarkers would show an increased risk of clinical alcohol relapse and death. We conducted a retrospective data recollection from medical files of patients awaiting liver transplantation, who were at baseline screened with Peth, EtG in hair and urine, and EtS. We tested the prediction capacity of the biomarkers with two Cox-regression models. A total of 50 patients were included (84% men, mean age 59 years (SD = 6)). Biomarkers at baseline were positive in 18 patients. The mean follow-up time for this study was 26 months (SD = 10.4). Twelve patients died, liver transplantation was carried out in 12 patients, and clinical relapse was observed in eight patients. The only significant covariate in the Cox-regression models was age with clinical relapse, with younger patients being at greater risk of relapse. This study could not find a significant prediction capacity of direct alcohol biomarkers for mortality or clinical relapse during follow-up. Higher sample sizes might be needed to detect statistically significant differences. All in all, we believe that direct alcohol biomarkers should be widely used in liver transplantation settings due to their high sensitivity for the detection of recent drinking.
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Kwon TJ, Kang W, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Sinn DH, Paik SW. Outcome of patients with severe alcoholic hepatitis after Model for End-Stage Liver Disease-based allocation system implementation in Korea. KOREAN JOURNAL OF TRANSPLANTATION 2021; 35:24-32. [PMID: 35769621 PMCID: PMC9235328 DOI: 10.4285/kjt.20.0054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/26/2021] [Accepted: 01/27/2021] [Indexed: 12/13/2022] Open
Abstract
Background The Model for End-Stage Liver Disease (MELD)-based allocation system was implemented in Korea in July 2016 without a mandatory abstinence period for liver transplantation (LT) listing. However, the impact of the allocation policy has not been evaluated in patients with severe alcoholic hepatitis (AH). Methods A total of 81 consecutive patients with severe AH between January 2014 and December 2018 were analyzed. The clinical course of patients before and after the implementation of the MELD-based allocation system was assessed. Results More patients received LT (25%–65%) after the MELD allocation system was implemented. The increase in patients receiving deceased donor LT was dramatic (17%–51%, P=0.001) compared to patients receiving living donor LT (7%–14%, P=0.30). The overall survival was better for those who received LT (88% vs. 44% at 1 year, P<0.001), and after the MELD era (1-year survival rate 80% vs. 50%, P=0.005). Post-LT mortality was observed in six patients, with one case of mortality related to recidivism. Baseline MELD and steroid response were factors associated with transplant-free survival. Conclusions After implementation of the MELD-based allocation system, deceased donor LT dramatically increased in patients with severe AH. This translated into increased overall survival, but at a cost of mortality due to recidivism. Urgent evaluation is warranted to identify criteria to justify the use of precious liver grafts from deceased donors for severe AH patients in Korea.
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Affiliation(s)
- Tae Jin Kwon
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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8
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Chung HG, Sinn DH, Kang W, Choi GS, Kim JM, Joh JW. Incidence of and Risk Factors for Alcohol Relapse After Liver Transplantation for Alcoholic Liver Disease: Comparison Between Deceased Donor and Living Donor Liver Transplantation. J Gastrointest Surg 2021; 25:672-680. [PMID: 32095927 DOI: 10.1007/s11605-020-04540-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 02/02/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND There are controversies over whether patients with alcohol-related liver disease (ALD) should follow the "6-month abstinence rule" before undergoing liver transplantation (LT), especially in case of living donor LT (LDLT). We analyzed the risk of alcohol relapse among ALD patients who received LT according to donor types and abstinence period before LT. METHODS A total of 129 patients (mean 50.7 ± 9.2 years, male 78.3%) who underwent LT between January 2000 and July 2017 for ALD at Samsung Medical Center, Seoul, Korea, were analyzed. Alcohol relapse was defined as any use of alcohol after LT. RESULTS The alcohol relapse rate was lower in LDLT recipients compared with that in DDLT recipients (13.9% vs. 31.7% at 3 years, P = 0.013). DDLT recipient, short abstinence period (< 6 months), and current smoking status were factors associated with alcohol relapse. The alcohol relapse rate was highest (54.5% at 3 years) for current smokers without 6-month sobriety who received DDLT, and it was lowest for never/ex-smoker with 6-month sobriety who received LDLT (4.3% at 3 years). For LDLT recipients, the alcohol relapse rate was not different according to abstinence period (17.7% vs. 11.6% at 3 years for short abstinent period < 3 months vs. ≥ 3 months, P = 0.92), but it was higher for current smokers compared with that for non/ex-smokers (22.4% vs. 5.8% at 3 years, P = 0.05). CONCLUSION When considering LDLT for ALD, sobriety period may not be an absolute contraindication as abstinence period showed a weak association with alcohol relapse. Smokers need careful attention for alcohol relapse.
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Affiliation(s)
- Hye Gyo Chung
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
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Guorgui J, Ito T, Markovic D, Aziz A, Younan S, Severance A, Lu M, Lee J, DiNorcia J, Agopian VG, Farmer DG, Busuttil RW, Kaldas FM. The impact of marijuana use on liver transplant recipients: A 900 patient single center experience. Clin Transplant 2021; 35:e14215. [PMID: 33406299 DOI: 10.1111/ctr.14215] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 09/16/2020] [Accepted: 12/21/2020] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Increased societal prevalence of marijuana continues to challenge liver transplant (LT) programs. This study aimed to examine the potential effects of marijuana use on outcomes. METHODS This retrospective study included recipients who underwent LT between 1/2012 and 6/2018. According to pre-LT marijuana use, patients were classified into recent (≤6 months of LT), former (chronic use but not ≤6 months), or non-users. Additionally, the impact of post-LT marijuana use on survival was assessed. RESULTS Of 926 eligible patients, 184 were pre-LT marijuana users (42 recent; 142 former) (median follow-up: 30.3 months). Pre-users were more likely to be male, White, and have histories of tobacco, alcohol, and illicit drug use. Additionally, recent users were of higher acuity, with higher MELD and requiring ICU admission. Patient survival at 1-year was 89% in non-users, 94% (HR: 0.494, 95% CI: 0.239-1.022 vs. non-users) in former users, and 83% (HR: 1.516, 95% CI: 0.701-3.282) in recent users. Post-operative complications in pre-LT users and the survival analysis for post-LT marijuana users vs. non-users did not show significance. CONCLUSIONS Our results demonstrated that marijuana use did not have an adverse impact on post-LT outcomes; however, further studies utilizing larger cohorts are warranted.
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Affiliation(s)
- Jacob Guorgui
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Takahiro Ito
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Daniela Markovic
- Department of Medicine Statics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Antony Aziz
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Stephanie Younan
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Alyscia Severance
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Michelle Lu
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Jane Lee
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Joseph DiNorcia
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Vatche G Agopian
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Douglas G Farmer
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Ronald W Busuttil
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Fady M Kaldas
- Department of Surgery, The Dumont-UCLA Transplant and Liver Cancer, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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10
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Affiliation(s)
- Gerald Scott Winder
- Departments of Psychiatry and Surgery, University of Michigan, Ann Arbor, MI
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11
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Liver transplantation in patients with alcohol-related liver disease: current status and future directions. Lancet Gastroenterol Hepatol 2020; 5:507-514. [DOI: 10.1016/s2468-1253(19)30451-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 12/15/2019] [Accepted: 12/19/2019] [Indexed: 12/19/2022]
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Kitajima T, Nagai S, Segal A, Magee M, Blackburn S, Ellithorpe D, Yeddula S, Qadeer Y, Yoshida A, Moonka D, Brown K, Abouljoud MS. Posttransplant Complications Predict Alcohol Relapse in Liver Transplant Recipients. Liver Transpl 2020; 26:379-389. [PMID: 31872969 DOI: 10.1002/lt.25712] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 12/05/2019] [Indexed: 02/07/2023]
Abstract
Alcohol relapse after liver transplantation (LT) in patients with alcohol-related liver disease (ALD) is a major challenge. Although its association with pretransplant psychosocial factors was extensively studied, the impacts of posttransplant courses on alcohol relapse have not been well investigated. The aim of this study is to analyze peritransplant factors associated with posttransplant alcohol relapse in patients with ALD. This study evaluated 190 adult LT patients with ALD from 2013 to 2019. Risk factors for alcohol relapse were analyzed, focusing on posttransplant chronic complications, which were classified as Clavien-Dindo classification 3a or higher that lasted over 30 days. The posttransplant alcohol relapse rate was 13.7% (26/190) with a median onset time of 18.6 months after transplant. Multivariate Cox regression analysis revealed that posttransplant chronic complications were an independent risk factor for posttransplant alcohol relapse (hazard ratio [HR], 5.40; P = 0.001), along with psychiatric comorbidity (HR, 3.93; P = 0.001), history of alcohol relapse before LT (HR, 3.00; P = 0.008), and an abstinence period <1.5 years (HR, 12.05; P = 0.001). A risk prediction model was created using 3 pretransplant risk factors (psychiatric comorbidity, alcohol relapse before LT, and abstinence period <1.5 years). This model clearly stratified the risk of alcohol relapse into high-, moderate-, and low-risk groups (P < 0.001). Of the 26 patients who relapsed, 11 (42.3%) continued drinking, of whom 3 died of severe alcoholic hepatitis, and 13 (50.0%) achieved sobriety (outcomes for 2 patients were unknown). In conclusion, posttransplant chronic complications increased the risk of alcohol relapse. Recognition of posttransplant chronic complications in conjunction with the risk stratification model by pretransplant psychosocial factors would help with the prediction of posttransplant alcohol relapse.
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Affiliation(s)
- Toshihiro Kitajima
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Shunji Nagai
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Antu Segal
- Department of Transplant Psychology, Henry Ford Hospital, Detroit, MI
| | - Michelle Magee
- Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
| | | | - Donna Ellithorpe
- Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
| | - Siri Yeddula
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Yusuf Qadeer
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Atsushi Yoshida
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Dilip Moonka
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI
| | - Kimberly Brown
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI
| | - Marwan S Abouljoud
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
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13
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Chuncharunee L, Yamashiki N, Thakkinstian A, Sobhonslidsuk A. Alcohol relapse and its predictors after liver transplantation for alcoholic liver disease: a systematic review and meta-analysis. BMC Gastroenterol 2019; 19:150. [PMID: 31438857 PMCID: PMC6704694 DOI: 10.1186/s12876-019-1050-9] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 07/17/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Alcoholic liver disease (ALD) is the leading cause of liver transplantation (LT). The magnitude and risk factors of post-LT alcohol relapse are not well described. We conducted a meta-analysis to evaluate alcohol relapse rate and its predictors after LT. METHODS Searches of MEDLINE and SCOPUS identified eligible published studies of alcohol relapse after LT published up to 31 March 2018. Alcohol relapse was defined as any alcohol consumption post-LT, and heavy alcohol relapse was defined as a relapse of alcohol consumption that was associated with a significant harm. Data for the proportion of alcohol relapse was pooled using a meta-analysis for pooling proportion. An odds ratio (OR) of the predictor of alcohol relapse was extracted and pooled using meta-analysis for the pooling risk factor. Data were analyzed using a random effect model if heterogeneity was presented; otherwise, a fixed effect model was applied. The study was registered at PROSPERO (CRD42017052659). RESULTS Ninety-two studies with over 8000 cases were recruited for pooling proportion of alcohol relapse. The alcohol relapse rate and heavy alcohol relapse rate after LT during the mean follow-up time of 48.4 ± 24.7 months were 22% (95% confidence interval (CI): 19-25%) and 14% (95%CI: 12-16%). Psychiatric comorbidities (odds ratio (OR) 3.46, 95%CI: 1.87-6.39), pre-transplant abstinence of less than 6 months (OR 2.76, 95%CI: 2.10-3.61), unmarried status (OR 1.84, 95%CI: 1.39-2.43), and smoking (OR 1.72, 95%CI: 1.21-2.46) were associated with alcohol relapse after LT. However, we noticed publication bias of unpublished negative studies and high heterogeneity of results. CONCLUSIONS Post-transplant alcohol relapse occurred in about one-fifth of patients who underwent alcohol-related LT. Psychiatric comorbidities represented the strongest predictor of alcohol relapse. Psychiatric comorbidities monitoring and pre-LT alcohol abstinence for at least 6 months may decrease alcohol relapse after LT.
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Affiliation(s)
- Lancharat Chuncharunee
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Bangkok, 10400, Thailand
| | | | - Ammarin Thakkinstian
- Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Abhasnee Sobhonslidsuk
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Bangkok, 10400, Thailand.
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14
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Neuberger J. Liver Transplantation and Marijuana Use: Needing a Joint Approach. Liver Transpl 2019; 25:688-689. [PMID: 30913351 DOI: 10.1002/lt.25456] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 03/22/2019] [Indexed: 02/07/2023]
Affiliation(s)
- James Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom
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15
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Contemporary Policies Regarding Alcohol and Marijuana Use Among Liver Transplant Programs in the United States. Transplantation 2018; 102:433-439. [PMID: 29019813 DOI: 10.1097/tp.0000000000001969] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Alcoholic liver disease is a common indication for orthotopic liver transplantation (OLT). Although OLT has been shown to confer survival benefit to patients with acute alcoholic hepatitis (AAH), historically most programs require a 6-month abstinence period before OLT which excludes patients with AAH. Marijuana has become legal in more than half the states in the United States. This survey of liver transplant programs was conducted to evaluate current policies regarding alcohol, marijuana and methadone use. METHODS A questionnaire was distributed to 100 United Network for Organ Sharing-approved liver transplant programs in North America that have performed at least 30 liver transplants/year in the last 5 years. RESULTS Forty-nine programs responded. Only 43% of the programs required a specific period of abstinence before transplant for alcoholic liver disease and only 26% enforced 6-month abstinence policy. For patients with AAH, 71% programs waived the 6-month abstinence requirement and considered psychosocial factors, such as family support, patient's motivation, or commitment to rehabilitate. Few programs used validated instruments to assess risk of relapse in AAH patients. Fourteen percent of programs transplant patients actively using marijuana and an additional 28% of programs listed patients using marijuana provided they discontinue by the time of OLT. Active methadone users were accepted in 45% of the programs. CONCLUSIONS Policies regarding alcohol use have become more flexible particularly toward patients with AAH. Marijuana use is also more accepted. Although policies regarding alcohol and marijuana have changed significantly in the last decade, they remain highly variable among programs.
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16
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Abstract
Alcoholic liver disease (ALD) is an escalating global problem accounting for more than 3 million deaths annually. Bacterial infections are diagnosed in 25-47% of hospitalized patients with cirrhosis and represent the most important trigger for acute decompensation, multi-organ failure, septic shock and death. Current guidelines recommend intensive antibiotic therapy, but this has led to the emergence of multi-drug resistant bacteria, which are associated with increased morbidity and mortality rates. As such, there is a pressing need to explore new paradigms for anti-infective therapy and host-directed immunomodulatory therapies are a promising approach. Paradoxically, cirrhotic patients are characterised by heightened immune activity and exacerbated inflammatory processes but are unable to contend with bacterial infection, demonstrating that whilst immune effector cells are primed, their antibacterial effector functions are switched-off, reflecting a skewed homeostatic balance between anti-pathogen immunity and host-induced immunopathology. Preservation of this equilibrium physiologically is maintained by multiple immune-regulatory checkpoints and these feedback receptors serve as pivotal regulators of the host immunity. Checkpoint receptor blockade is proving to be effective at rescuing deranged/exhausted immunity in pre-clinical studies for chronic viral infection and sepsis. This approach has also obtained FDA approval for restoring anti-tumor immunity, with improved response rates and good safety profiles. To date, no clinical studies have investigated checkpoint blockade in ALD, highlighting an area for development of host-targeted immunotherapeutic strategies in ALD, for which there are no current specific treatment options. This review aims at framing current knowledge on immune checkpoints and the possibility of their therapeutic utility in ALD-associated immune dysfunctions.
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Affiliation(s)
- Antonio Riva
- Institute of Hepatology London, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT UK
- Faculty of Life Sciences and Medicine, King’s College London, London, UK
| | - Shilpa Chokshi
- Institute of Hepatology London, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT UK
- Faculty of Life Sciences and Medicine, King’s College London, London, UK
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17
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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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18
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Abstract
Because of the high prevalence of alcohol relapse after liver transplantation, transplant programs are challenged to evaluate alcoholism among liver transplant patients. Relapse after liver transplantation can have detrimental outcomes such as organ rejection, medical and social resource exhaustion, financial burden to the family and society, and negative public perception of organ transplantation. The purpose of this project was to improve post-liver transplant assessment for the risk of relapse to heavy alcohol use by implementing a protocol using the High-Risk Alcoholism Relapse (HRAR) scale (DiMartini et al., 2000; Yates et al., 1993). The project was conducted in an urban organ transplant center's outpatient post liver transplant clinic. Chart reviews assessed the process of patients identified as being at high risk and the transplant providers' completion of the HRAR scale. Eleven percent of patients assessed were identified as being at high risk for relapse of heavy alcohol use and 85% of providers used the HRAR scale in their clinic interviews. This project demonstrates that further refinements in techniques of predicting the risks of relapse are necessary, and nurses are in ideal positions to screen patients for alcohol use.
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19
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Leon M, Varon J, Surani S. When a liver transplant recipient goes back to alcohol abuse: Should we be more selective? World J Gastroenterol 2016; 22:4789-4793. [PMID: 27239105 PMCID: PMC4873871 DOI: 10.3748/wjg.v22.i20.4789] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Revised: 04/02/2016] [Accepted: 05/04/2016] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is one of the most common indications for liver transplantation (LT). However, it has always remained as a complicated topic from both medical and ethical grounds, as it is seen for many a "self-inflicted disease". Over the years, the survival rate of transplanted patients has significantly improved. The allocation system and the inclusion criteria for LT has also undergone some modifications. Early LT for acute alcoholic hepatitis has been subject to recent clinical studies with encouraging results in highly selected patients. We have learned from studies the importance of a multidisciplinary evaluation of candidates for LT. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Risk factors for relapse include the presence of anxiety or depressive disorder, short duration of sobriety pre-LT and lack of social support. The identification of risk factors and the strengthen of social support system may decrease relapse among these patients. Family counseling of candidates is highly encouraged to prevent relapse to alcohol. Relapse has been associated with different histopathological changes, graft damage, graft loss and even decrease in survival among some studies. Therefore, each patient should be carefully selected and priority is to continue to lean on patients with high probability of success. The ethical issue remains as to the patient returning to drinking after the LT, hindering the way for other patients who could have received the same organ.
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20
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Im GY, Kim-Schluger L, Shenoy A, Schubert E, Goel A, Friedman SL, Florman S, Schiano TD. Early Liver Transplantation for Severe Alcoholic Hepatitis in the United States--A Single-Center Experience. Am J Transplant 2016; 16:841-9. [PMID: 26710309 DOI: 10.1111/ajt.13586] [Citation(s) in RCA: 189] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 08/16/2015] [Accepted: 08/31/2015] [Indexed: 01/25/2023]
Abstract
Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6-month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p<0.001). Eight recipients are alive at a median of 735 days with 1 alcohol relapse. Early LT for severe AH can achieve excellent clinical outcomes with low impact on the donor pool and low rates of alcohol relapse in highly selected patients in the United States.
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Affiliation(s)
- G Y Im
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - L Kim-Schluger
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - A Shenoy
- Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - E Schubert
- Social Work Services, The Mount Sinai Medical Center, New York, NY
| | - A Goel
- Division of Liver Diseases, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - S L Friedman
- Division of Liver Diseases, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - S Florman
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY
| | - T D Schiano
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY
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21
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Neuberger J. An update on liver transplantation: A critical review. J Autoimmun 2016; 66:51-59. [PMID: 26350881 DOI: 10.1016/j.jaut.2015.08.021] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 08/26/2015] [Indexed: 02/08/2023]
Abstract
Liver transplantation, although now a routine procedure, with defined indications and usually excellent outcomes, still has challenges. Donor shortage remains a key issue. Transplanted organs are not free of risk and may transmit cancer, infection, metabolic or autoimmune disease. Approaches to the donor shortage include use of organs from donors after circulatory death, from living donors and from those previously infected with Hepatitis B and C and even HIV for selected recipients. Normothermic regional and/or machine perfusion, whether static or pulsatile, normo- or hypothermic, are being explored and will be likely to have a major place in improving donation rates and outcomes. The main indications for liver replacement are alcoholic liver disease, HCV, non-alcoholic liver disease and liver cancer. Recent studies have shown that selected patients with severe alcoholic hepatitis may also benefit from liver transplant. The advent of new and highly effective treatments for HCV, whether given before or after transplant will have a major impact on outcomes. The role of transplantation for those with liver cell cancer continues to evolve as other interventions become more effective. Immunosuppression is usually required life-long and adherence remains a challenge, especially in adolescents. Immunosuppression with calcineurin inhibitors (primarily tacrolimus), antimetabolites (azathioprine or mycophenolate) and corticosteroids remains standard. Outcomes after transplantation are good but not normal in quality or quantity. Premature death may be due to increased risk of cardiovascular disease, de novo cancer, recurrent disease or late technical problems.
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Affiliation(s)
- James Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK; Organ Donation and Transplantation, NHS Blood and Transplant, Fox Den Road, Bristol, BS34 8RR, UK.
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22
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Dom G, Peuskens H. Addiction specialist's role in liver transplantation procedures for alcoholic liver disease. World J Hepatol 2015; 7:2091-2099. [PMID: 26301051 PMCID: PMC4539402 DOI: 10.4254/wjh.v7.i17.2091] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 07/09/2015] [Accepted: 08/11/2015] [Indexed: 02/06/2023] Open
Abstract
Although liver transplantation (LT) is performed increasingly for patients with end-stage alcoholic liver disease (ALD), the topic remains controversial. Traditionally, the role of an addiction specialist focused on the screening and identification of patients with a high risk on relapse in heavy alcohol use. These patients were in many cases subsequently excluded from a further LT procedure. Recently, awareness is growing that not only screening of patients but also offering treatment, helping patients regain and maintain abstinence is essential, opening up a broader role for the addiction specialist (team) within the whole of the transplant procedure. Within this context, high-risk assessment is proposed to be an indication of increasing addiction treatment intensity, instead of being an exclusion criterion. In this review we present an overview regarding the state of the art on alcohol relapse assessment and treatment in patients with alcohol use disorders, both with and without ALD. Screening, treatment and monitoring is suggested as central roles for the addiction specialist (team) integrated within transplant centers.
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23
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Kawaguchi Y, Sugawara Y, Akamatsu N, Kaneko J, Tanaka T, Tamura S, Aoki T, Sakamoto Y, Hasegawa K, Kokudo N. Perceptions of post-transplant recidivism in liver transplantation for alcoholic liver disease. World J Hepatol 2014; 6:812-817. [PMID: 25429319 PMCID: PMC4243155 DOI: 10.4254/wjh.v6.i11.812] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Revised: 08/27/2014] [Accepted: 09/16/2014] [Indexed: 02/06/2023] Open
Abstract
Although alcoholic liver disease (ALD) is regarded as a common indication for liver transplantation (LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD.
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Affiliation(s)
- Yoshikuni Kawaguchi
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Yasuhiko Sugawara
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Nobuhisa Akamatsu
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Junichi Kaneko
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Tomohiro Tanaka
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Sumihito Tamura
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Taku Aoki
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Yoshihiro Sakamoto
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Kiyoshi Hasegawa
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
| | - Norihiro Kokudo
- Yoshikuni Kawaguchi, Yasuhiko Sugawara, Nobuhisa Akamatsu, Junichi Kaneko, Sumihito Tamura, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
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24
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Grąt M, Lewandowski Z, Grąt K, Wronka KM, Krasnodębski M, Barski K, Zborowska H, Patkowski W, Zieniewicz K, Krawczyk M. Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post-transplant year. Clin Transplant 2014; 28:1112-1120. [PMID: 25059535 DOI: 10.1111/ctr.12427] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/20/2014] [Indexed: 12/15/2022]
Abstract
Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long-term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post-transplant year (p = 0.655) but worse during the five subsequent years among the five-yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post-transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post-transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non-ALD recipients up to the fifth post-transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre-transplant diagnosis of ALD yields negative effects on post-transplant outcomes beyond the fifth post-transplant year, not attributable to recidivism.
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Affiliation(s)
- Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
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Rustad JK, Stern TA, Prabhakar M, Musselman D. Risk factors for alcohol relapse following orthotopic liver transplantation: a systematic review. PSYCHOSOMATICS 2014; 56:21-35. [PMID: 25619671 DOI: 10.1016/j.psym.2014.09.006] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 09/03/2014] [Accepted: 09/04/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Each year, 5000-6000 individuals undergo orthotopic liver transplantation (OLT) in the United States, and of these, nearly 18% have alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients with OLT for alcoholic liver disease. OBJECTIVES We sought to identify factors that predict relapse to alcohol or medication nonadherence following OLT in patients with alcoholic liver disease and to review what randomized clinical interventions have addressed these factors following OLT. Our hypothesis was that there would be factors before and after OLT that predict relapse to alcohol following OLT, and that these, if targeted, might improve sobriety and associated outcomes of adherence with medications and appointments. METHODS We performed a review (focusing on articles published since 2004) with PubMed and MEDLINE searches using the following search terms: liver transplantation, recidivism, alcohol relapse, and predictors of alcohol relapse. We supplemented the online searches with manual reviews of article reference lists and selected relevant articles for further review by author consensus. RESULTS In largely white populations, prospective studies document that shorter length of pretransplantation sobriety is a significant predictor of time to first drink and time to binge use. Presence of psychiatric comorbidity, high score on standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are predictive of posttransplantation alcohol relapse. Pretransplantation alcohol use history variables (e.g., family history of alcoholism) reliably discriminate between complete abstainers and those who drink, while medical and psychosocial characteristics at early post-liver transplantation period (e.g., more bodily pain) maximally discriminate patterns of alcohol use. Alcoholic individuals with early-onset, rapidly accelerating moderate use and early-onset, continuously increasing heavy use have more than double the prevalence of steatohepatitis or rejection on biopsy and graft failure and more frequent mortality resulting from recurrent alcoholic liver disease than late-onset (i.e., peak of heaviest drinking at 6y posttransplantation) alcohol users do. Fortunately, pretransplantation screening combined with a structured pretransplantation management program and a 12-step program attendance reduced recidivism. No randomized clinical trials have been performed that target pretransplantation risk factors in individuals with alcoholic liver disease before or after OLT to improve post-OLT outcomes. CONCLUSIONS Recent research findings suggest that screening can reveal individuals who are vulnerable to alcohol relapse and targeted intervention can prevent their relapse to alcohol. Based on existing addiction treatments (e.g., relapse prevention plan construction), randomized clinical trials tailored to post-OLT patients should be conducted to improve their survival and quality of life.
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Affiliation(s)
- James K Rustad
- Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL (JKR).
| | - Theodore A Stern
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA (TAS)
| | - Maithri Prabhakar
- Department of Epidemiology, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL (MP)
| | - Dominique Musselman
- Department of Psychiatry and Behavioral Sciences, University of Miami Leonard H. Miller School of Medicine, Miami, FL (DM)
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26
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Papastergiou V, Burroughs AK, Tsochatzis EA. Prognosis and treatment of patients with acute alcoholic hepatitis. Expert Rev Gastroenterol Hepatol 2014; 8:471-86. [PMID: 24716632 DOI: 10.1586/17474124.2014.903800] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Despite alcoholic hepatitis (AH) is the most acute manifestation of alcohol-related liver disease, its treatment remains controversial. Corticosteroids, given either as monotherapy or together with N-acetylecysteine, have been associated with a moderate short-term survival benefit in patients with severe disease. The Maddrey's discriminant function; Glasgow alcoholic hepatitis score; age, bilirubin, INR and creatinine score; and the Model for end-stage liver disease have been proposed for stratifying prognosis in AH enabling selection of the patients to treat. Definition of treatment non-responders using the Lille model after 7 days of therapy may prevent a detrimental impact of prolonged corticosteroids. Pentoxifylline is an effective alternative reducing the occurrence of hepatorenal syndrome. Emerging evidence supports use of liver transplantation in a strictly selected subset of corticosteroid non-responders.
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Affiliation(s)
- Vassilios Papastergiou
- The Royal Free Sheila Sherlock Liver Centre and UCL Institute of Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
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Rodrigue JR, Hanto DW, Curry MP. The Alcohol Relapse Risk Assessment: a scoring system to predict the risk of relapse to any alcohol use after liver transplant. Prog Transplant 2014; 23:310-8. [PMID: 24311394 DOI: 10.7182/pit2013604] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
CONTEXT Alcohol relapse after liver transplant heightens concern about recurrent disease, nonadherence to the immunosuppression regimen, and death. OBJECTIVES To develop a scoring system to stratify risk of alcohol relapse after liver transplant. DESIGN Retrospective medical record review. SETTING AND PARTICIPANTS All adult liver transplants performed from May 2002 to February 2011 at a single center in the United States. MAIN OUTCOME MEASURE The incidence of return to any alcohol consumption after liver transplant. RESULTS Thirty-four percent (40/118) of patients with a history of alcohol abuse/dependency relapsed to use of any alcohol after liver transplant. Nine of 25 hypothesized risk factors were predictive of alcohol relapse after liver transplant: absence of hepatocellular carcinoma, tobacco dependence, continued alcohol use after liver disease diagnosis, low motivation for alcohol treatment, poor stress management skills, no rehabilitation relationship, limited social support, lack of nonmedical behavioral consequences, and continued engagement in social activities with alcohol present. Each independent predictor was assigned an Alcohol Relapse Risk Assessment (ARRA) risk value of 1 point, and patients were classified into 1 of 4 groups by ARRA score: ARRA I = 0, ARRA II = 1 to 3, ARRA III = 4 to 6, and ARRA IV = 7 to 9. Patients in the 2 higher ARRA classifications had significantly higher rates of alcohol relapse and were more likely to return to pretransplant levels of drinking. CONCLUSION Alcohol relapse rates are moderately high after liver transplant. The ARRA is a valid and practical tool for identifying pretransplant patients with alcohol abuse or dependency at elevated risk of any alcohol use after liver transplant.
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Affiliation(s)
- James R Rodrigue
- Beth Israel Deaconess Medical Center and the Harvard Medical School, Boston, Massachusetts
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28
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Egawa H, Nishimura K, Teramukai S, Yamamoto M, Umeshita K, Furukawa H, Uemoto S. Risk factors for alcohol relapse after liver transplantation for alcoholic cirrhosis in Japan. Liver Transpl 2014; 20:298-310. [PMID: 24470014 DOI: 10.1002/lt.23797] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Accepted: 11/17/2013] [Indexed: 12/20/2022]
Abstract
Alcoholic liver cirrhosis (ALC) is an established indication for liver transplantation (LT). Most LT procedures in Japan are living donor liver transplantation (LDLT) because of an extreme shortage of deceased donors. Social circumstances enabling LDLT could be favorable for preventing relapse. The aims of this retrospective study were to analyze the outcomes of LDLT for ALC and to evaluate risk factors for relapse in this cohort. One hundred ninety-five subjects underwent LT [LDLT (n = 187), deceased donor LT (n = 5), or domino LT (n = 3)] for ALC in Japan from November 1997 to December 2011. Risk factors for alcohol relapse and the impact of relapse on outcomes were analyzed for 140 patients after the exclusion of 26 patients who died in the hospital and 29 patients without information about alcohol relapse. The incidence of alcohol consumption after LT was 22.9%. The risk factors for patient survival were a donor age ≥ 50 years (P < 0.01) and a Model for End-Stage Liver Disease score ≥ 19 (P = 0.03). The 10-year patient survival rates were 21.9% and 73.8% for patients who had relapsed and patients who had not relapsed 18 months after LT, respectively (P = 0.01). The relapse rates were 50.0%, 34.5%, 13.3%, 19.7%, and 14.3% for patients who had received livers from parents, siblings, spouses, sons/daughters, and deceased or domino donors, respectively. A history of treatment for psychological diseases other than alcoholism before LT was a significant indicator for the risk of recidivism (P = 0.02), and noncompliance with clinic visits after LT and smoking after transplantation were promising indicators for the risk of recidivism (P = 0.06, and P = 0.05, respectively). Preoperative alcohol consumption was not a risk factor. In conclusion, rather than selecting patients on the basis of preoperative alcohol use, we should provide sociomedical support to improve adherence after LT for ALC in Japan.
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Affiliation(s)
- Hiroto Egawa
- Departments of Surgery and Tokyo Women's Medical University, Tokyo, Japan
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29
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Abstract
Liver transplantation represents an established component of the therapeutic repertoire for irreversible chronic liver diseases. Liver transplantation is confronted by a shortage of donor allografts as well as by an increasing overall number of potentially useful indications, which leads to a rationing of this therapeutic option. Since December 2006 the priority for liver transplantation is determined by the model for end-stage liver disease (MELD) and not by the length of waiting time. The evaluation of indications which are prioritized according to laboratory values (serum creatine, serum bilirubin and coagulation) and the so-called standard exception categories which have to fulfil specific criteria place increased demands on the interdisciplinary transplantation team, on the evaluation for liver transplantation and the prediction of the success of transplantation required by the Transplantation Act. The establishment and implementation of robust, objective and transparent systems to assess not only preoperative priorities but also postoperative benefits represents a major challenge for transplantation medicine.
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Affiliation(s)
- C P Strassburg
- Medizinischen Klinik und Poliklinik I, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland.
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Iruzubieta P, Crespo J, Fábrega E. Long-term survival after liver transplantation for alcoholic liver disease. World J Gastroenterol 2013; 19:9198-9208. [PMID: 24409048 PMCID: PMC3882394 DOI: 10.3748/wjg.v19.i48.9198] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 10/26/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
Currently, alcoholic cirrhosis is the second leading indication for liver transplantation in the United States and Europe. The quality of life and survival after a liver transplantation (LT) in patients with alcoholic liver disease (ALD) are similar to those in patients with other cirrhosis etiologies. The alcoholic relapse rate after a LT varies from 10%-50%, and these relapse patients are the ones who present a reduced long-term survival, mainly due to cardiovascular diseases and the onset of de novo neoplasms, including lung and upper aerodigestive tract. Nearly 40% of ALD recipients resume smoking and resume it early post-LT. Therefore, our pre-and post-LT follow-up efforts regarding ALD should be focused not only on alcoholic relapse but also on treating and avoiding other modifiable risk factors such as tobacco. The psychiatric and psychosocial pre-LT evaluation and the post-LT follow-up with physicians, psychiatrists and addiction specialists are important for reversing these problems because these professionals help to identify patients at risk for relapse as well as those patients who have relapsed, thus enabling responsive actions.
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31
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Parker R, Armstrong MJ, Corbett C, Day EJ, Neuberger JM. Alcohol and substance abuse in solid-organ transplant recipients. Transplantation 2013; 96:1015-1024. [PMID: 24025323 DOI: 10.1097/tp.0b013e31829f7579] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This review focuses on alcohol and substance abuse in the context of solid-organ transplantation. Alcohol and substance abuse are common and may lead to a need for solid-organ transplantation and may also contribute to significant physical and psychologic problems that impact upon the recipient. Damaging levels of alcohol intake can occur in the absence of dependence. Alcohol or substance abuse after transplantation is associated with poor medication compliance and this may increase risk of graft loss. Intravenous drug use is associated with increased risk of infections (especially secondary to opportunistic organisms-bacterial, viral, protozoal, and others-and such infections may be more severe in the immunosuppressed), but there is only anecdotal evidence that such behavior has a worse outcome in transplant recipients. Whereas previous alcohol excess and drug use in kidney recipients are both associated with a small but statistically significantly increased risk of adverse outcomes (hazard ratio, 1.16-1.56), alcohol use within recommended guidelines after transplantation appears safe and possibly beneficial. Robust data are lacking for other organs, but those available suggest that heart transplantation is safe in individuals with a history of alcohol or substance abuse. Health specialists in drug or alcohol addiction should carefully screen all potential transplant candidates for these conditions, and where there is evidence of dependency or abuse, effective psychologic and physical treatment should be offered. Studies have shown that interventions such as psychologic intervention have improved alcohol behavior in the context of liver transplantation. Although there are no comparable studies with other solid-organ recipients, it is reasonable to expect transferable outcomes.
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Affiliation(s)
- Richard Parker
- 1 National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. 2 Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 3 Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK. 4 NHS Blood and Transplant, Bristol, UK. 5 Address correspondence to: Richard Parker, M.B.Ch.B., M.R.C.P., National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, 5th Floor IBR, Birmingham, UK B15 2TT
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32
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Rodrigue JR, Hanto DW, Curry MP. Substance abuse treatment and its association with relapse to alcohol use after liver transplantation. Liver Transpl 2013; 19:1387-95. [PMID: 24123780 DOI: 10.1002/lt.23747] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Accepted: 08/31/2013] [Indexed: 12/20/2022]
Abstract
Many liver transplantation (LT) programs require substance abuse (SA) treatment for candidates with a history of alcohol abuse. However, there are no data indicating that SA treatment prevents post-LT alcohol relapse. We examined 118 adults who underwent LT from May 2002 to February 2011 to explore the relationship between SA treatment and post-LT relapse to any alcohol use. Sixty-one patients (52%) with a history of alcohol abuse or dependence received SA treatment before LT. Relapse to any alcohol use was identified in 40 LT recipients (34%). Patients who received SA treatment before LT did not differ significantly in the rate of post-LT alcohol relapse from patients who did not receive treatment before transplantation(30% versus 39%, P = 0.20). However, patients who received SA treatment both before and after transplantation had significantly lower rates of alcohol relapse (16%) than patients who received no SA treatment (41%) or SA treatment only before LT (45%, P = 0.03). Our findings suggest that LT programs should consider placing more emphasis on the continuation of some type of SA treatment after transplantation. Future research should prospectively examine the optimal timing for SA treatment that will attenuate the risk of alcohol relapse after transplantation.
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Affiliation(s)
- James R. Rodrigue
- Center for Transplant Outcomes and Quality Improvement, Transplant Institute; Beth Israel Deaconess Medical Center; Boston MA
- Harvard Medical School; Boston MA
| | - Douglas W. Hanto
- Continuing Medical Education Office; Washington University School of Medicine; St. Louis MO
| | - Michael P. Curry
- Center for Transplant Outcomes and Quality Improvement, Transplant Institute; Beth Israel Deaconess Medical Center; Boston MA
- Harvard Medical School; Boston MA
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Potts JR, Goubet S, Heneghan MA, Verma S. Determinants of long-term outcome in severe alcoholic hepatitis. Aliment Pharmacol Ther 2013; 38:584-95. [PMID: 23879720 DOI: 10.1111/apt.12427] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2013] [Revised: 05/02/2013] [Accepted: 07/04/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Although short-term outcome in severe alcoholic hepatitis (SAH) is well described, its long-term course remains uncharacterised. AIM To assess determinants of long-term outcome in SAH. METHODS Data were recorded from a cohort with SAH (admission Discriminant Function (DF) ≥32). Kaplan-Meier (KM) and Cox proportional hazards survival analyses were performed to determine predictors of outcome. RESULTS One hundred and nine patients were included; 63.3% male, aged 49.6 ± 9.4 years with median follow-up of 40.7 months (95% CI 37.2-44.3). Median DF was 58, 86.2% had cirrhosis and 65.1% received corticosteroids and/or pentoxifylline. Overall mortality was 57.8%, 96.8% of deaths being liver-related and 65.1% occurring after the index hospitalisation. Estimated 5-year survival was 31.8%. Hepatorenal syndrome was the only baseline factor independently associated with mortality (HR 3.78, 95% CI 1.98-7.19, P < 0.0001), although it predicted short-term, rather than long-term outcome (median survival 0.52 months, 95% CI 0.43-0.61). Of the 87 patients (79.8%) who survived index hospitalisation, 65.1% experienced recidivism. Abstinence at last follow-up remained the only independent predictor of survival in multivariate analysis (HR 0.370, 95% CI 0.168-0.818, P = 0.014). Five-year survival was higher in abstainers (75.3%) compared with relapsed and continued drinkers (26.8% and 21.0%, respectively, P = 0.005). However, the survival benefit from abstinence only became statistically significant at 18 months postdischarge (HR 2.714, 95% CI 0.995-7.404, P = 0.051). CONCLUSIONS Estimated 5-year survival after index hospitalisation with SAH is 31.8% with alcohol relapse occurring in two-thirds of patients. Abstinence remains the only independent predictor of long-term survival. Novel strategies to improve abstinence after admission with SAH are urgently needed.
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Affiliation(s)
- J R Potts
- Department of Medicine, Brighton and Sussex Medical School, Brighton, UK
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34
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Testino G, Sumberaz A, Borro P. Comment to "liver transplantation for patients with alcoholic liver disease: an open question". Dig Liver Dis 2013; 45:80-1. [PMID: 22770950 DOI: 10.1016/j.dld.2012.06.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2011] [Revised: 05/30/2012] [Accepted: 06/04/2012] [Indexed: 12/11/2022]
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Abstract
Alcoholic hepatitis is a severe form of alcohol-related liver injury and one of the most frequent liver presentations seen by acute medical services. The condition typically affects young and middle-aged adults who present with jaundice and coagulopathy. Many patients fulfil the criteria for acute-on-chronic liver failure, though often the diagnosis of cirrhosis is only made after hospitalization. Despite over four decades of study, controversy surrounds many aspects of diagnosis and management, and short-term mortality in severe disease remains high. This review summarizes recent and important literature of relevance to clinicians, including aids to diagnosis, clinical prognostic scores and evidence for current medical therapies. Contentious issues such as the need for liver biopsy in diagnosis and the role for liver transplantation in those who fail to respond to medical treatment are also discussed.
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Affiliation(s)
- Jonathan R Potts
- Department of Medicine, Brighton and Sussex Medical School, Brighton, UK.
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36
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Burroughs AK. Liver transplantation for severe alcoholic hepatitis saves lives. J Hepatol 2012; 57:451-2. [PMID: 22285999 DOI: 10.1016/j.jhep.2012.01.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Revised: 01/04/2012] [Accepted: 01/04/2012] [Indexed: 12/13/2022]
Affiliation(s)
- Andrew K Burroughs
- The Royal Free Sheila Sherlock Liver Centre and University Department of Surgery - University College London and Royal Free Hospital, London, UK.
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37
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Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallée JC. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med 2011; 365:1790-800. [PMID: 22070476 DOI: 10.1056/nejmoa1105703] [Citation(s) in RCA: 652] [Impact Index Per Article: 46.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND A 6-month abstinence from alcohol is usually required before patients with severe alcoholic hepatitis are considered for liver transplantation. Patients whose hepatitis is not responding to medical therapy have a 6-month survival rate of approximately 30%. Since most alcoholic hepatitis deaths occur within 2 months, early liver transplantation is attractive but controversial. METHODS We selected patients from seven centers for early liver transplantation. The patients had no prior episodes of alcoholic hepatitis and had scores of 0.45 or higher according to the Lille model (which calculates scores ranging from 0 to 1, with a score ≥ 0.45 indicating nonresponse to medical therapy and an increased risk of death in the absence of transplantation) or rapid worsening of liver function despite medical therapy. Selected patients also had supportive family members, no severe coexisting conditions, and a commitment to alcohol abstinence. Survival was compared between patients who underwent early liver transplantation and matched patients who did not. RESULTS In all, 26 patients with severe alcoholic hepatitis at high risk of death (median Lille score, 0.88) were selected and placed on the list for a liver transplant within a median of 13 days after nonresponse to medical therapy. Fewer than 2% of patients admitted for an episode of severe alcoholic hepatitis were selected. The centers used 2.9% of available grafts for this indication. The cumulative 6-month survival rate (±SE) was higher among patients who received early transplantation than among those who did not (77 ± 8% vs. 23 ± 8%, P<0.001). This benefit of early transplantation was maintained through 2 years of follow-up (hazard ratio, 6.08; P = 0.004). Three patients resumed drinking alcohol: one at 720 days, one at 740 days, and one at 1140 days after transplantation. CONCLUSIONS Early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy. (Funded by Société Nationale Française de Gastroentérologie.).
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Affiliation(s)
- Philippe Mathurin
- Hôpital Claude Huriez, Services Maladies de l'Appareil Digestif and INSERM Unité 995, Centre Hospitalier Universitaire, de Lille and Université Nord de France, Lille
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Abstract
Although alcoholic liver disease (ALD) is one of the most common indications for liver transplantation (LT), there are still unresolved controversies about the goals of treatment, the referral, evaluation, and selection of patients with ALD for LT, and their care after LT. It is uncertain whether there is a large unmet need for LT among patients with ALD because of the unmeasured effects of recent drinking, relapse, and recovery with abstinence in this population. A careful assessment of the extrahepatic effects of alcohol-related end-organ damage is needed for ALD patients who are referred for an LT evaluation. Although there clearly is a relationship between the length of sobriety and future abstinence, the present methods for predicting future drinking are inexact. The survival of ALD patients after LT is as good as the survival of non-ALD patients, although patients with coincident ALD and hepatitis C virus have higher mortality and morbidity rates. After LT, ALD patients have an increased risk of developing malignancies and cardiovascular disease. These risks appear to be linked to cigarette smoking. Covert drinking occurs both before and after transplantation, and approximately 20% of patients return to harmful drinking after LT. Harmful drinking after LT (instead of slips) causes liver damage and reduces survival. Better therapies for controlling addictions to alcohol and nicotine are needed for ALD patients both before and after LT.
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Affiliation(s)
- Michael R Lucey
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin, Madison, WI 53792, USA.
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Braillon A. Severe alcoholic hepatitis: Glucocorticoid saves lives and transplantation is promising. World J Gastroenterol 2011; 17:2454. [PMID: 21633648 PMCID: PMC3103801 DOI: 10.3748/wjg.v17.i19.2454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2010] [Revised: 02/15/2011] [Accepted: 02/22/2011] [Indexed: 02/06/2023] Open
Abstract
Glucocorticosteroids have been used as the only treatment for a long time which significantly reduced the mortality of the patients with severe alcoholic hepatitis. The efficacy of transplantation has been recently addressed in a pilot study. The result seems promising but needs larger multicenter trials.
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