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The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation. Transplantation 2021; 106:938-949. [PMID: 34753893 DOI: 10.1097/tp.0000000000003973] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Liver transplantation (LT) survival rates have continued to improve over the last decades, mostly due to the reduction of mortality early after transplantation. The advancement is facilitating a liberalization of access to LT, with more patients with higher risk profiles being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of high-risk donors. This is facilitated by novel technologies such as machine perfusion. Owing to these developments, reconsideration of the current and emerging endpoints for the assessment of the efficacy of existing and new therapies is warranted. While conventional early endpoints in LT have focused on the damage induced to the parenchyma, the fate of the bile duct and the recurrence of the underlying disease have a stronger impact on the long-term outcome. In light of this evolving landscape, we here attempt to reflect on the appropriateness of the currently used endpoints in the field of LT trials.
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Potential Bias and Misconceptions in Liver Transplantation for Alcohol- and Obesity-Related Liver Disease. Am J Gastroenterol 2021; 116:2089-2097. [PMID: 34193797 DOI: 10.14309/ajg.0000000000001349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/28/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Bias and misconceptions surrounding alcohol-related liver disease (ALD) and obesity-related liver disease (OLD) may lead to transplant listing inequities. The aim of this study was to evaluate patients, medical students, residents, fellows, and attending physicians for bias and misconceptions regarding liver transplantation (LT) for patients with ALD and OLD. METHODS Participants took a survey asking them whether patients with ALD who continue/discontinue drinking alcohol or patients with OLD who do/do not commit to a weight loss program deserve equal LT rights. A Likert scale was used for their responses. Participants also estimated 5-year survival and advanced fibrosis recurrence after LT. The primary outcome of the study was bias measured by expected agreement or disagreement to questions using a Likert scale, significant underestimation of a 5-year survival rate after LT, and significant overestimation of 5-year advanced fibrosis recurrence after LT. RESULTS A total of 381 participants were included in the analysis: 153 residents/fellows, 31 attending physicians, 98 medical students, and 99 patients. A higher percentage from all 4 participating groups either were neutral or disagreed with equal LT rights for patients with ALD who discontinue drinking compared with patients with OLD who commit to weight loss program. The attending physician group was the only group with a majority estimating >60% 5-year survival after LT in patients with ALD and OLD (P < 0.05). All 4 groups had a majority estimate >20% 5-year advanced fibrosis recurrence in patients with ALD and OLD (P > 0.05). DISCUSSION There seems to be current bias and misconceptions regarding LT for patients with ALD and OLD.
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Characteristics of Psychosocial Factors in Liver Transplantation Candidates with Alcoholic Liver Disease before Transplantation: A Retrospective Study in a Single Center in Taiwan. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17228696. [PMID: 33238532 PMCID: PMC7700481 DOI: 10.3390/ijerph17228696] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 11/16/2020] [Accepted: 11/19/2020] [Indexed: 12/21/2022]
Abstract
Liver transplantation (LT) is an essential treatment for end-stage alcoholic liver disease (ALD). The patients’ psychosocial condition plays a vital role in post-transplantation prognosis. A survey of the candidates’ psychosocial wellbeing is necessary before LT. This study aims to investigate the psychosocial characteristics, including the depression degree, family function, alcohol use duration, and alcohol abstinence period, of LT candidates with ALD. In addition, 451 candidates for LT due to ALD were enrolled. They received psychosocial evaluations, including depression scale (Hamilton depression rating scale) and family functioning assessment (adaptability, partnership, growth, affection, resolve (APGAR) index). The test scores were analyzed according to age, alcohol use duration, and alcohol abstinence period. The Hamilton depression rating scale (HAM-D) score and the family APGAR index score differentiated significantly according to the age, alcohol use duration, and abstinence period of the LT candidates. The patients with shorter alcohol use duration tended to have more severe depressive symptoms and poorer family support. The younger patients showed a significantly shorter abstinence period, more severe depression, and poorer family functioning than older patients. The younger ALD patients and patients with shorter alcohol use duration showed an increased severity of depression before transplantation. They need more mental health care over time.
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Gitto S, Aspite S, Golfieri L, Caputo F, Vizzutti F, Grandi S, Patussi V, Marra F. Alcohol use disorder and liver transplant: new perspectives and critical issues. Korean J Intern Med 2020; 35:797-810. [PMID: 32241080 PMCID: PMC7373982 DOI: 10.3904/kjim.2019.409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 03/03/2020] [Indexed: 12/13/2022] Open
Abstract
Alcoholic liver disease is a consolidated indication for liver transplantation, but many unsolved issues can be highlighted. Patients with alcohol use disorder develop peculiar comorbidities that can become contraindications for transplantation. Moreover, a number of social and psychological patterns should be evaluated to select candidates with a low risk of alcohol relapse and adequate post-transplant adherence. In this context, the 6-month rule is too rigid to be widely applied. A short period of abstinence (1 to 3 months) is useful to estimate recovery of liver function and, possibly to avoid transplant. Cardiovascular disorders and extra-hepatic malignancies represent the main clinical issues after transplant. Patients transplanted due to alcoholic disease are a major risk for other liver diseases. Severe corticosteroid-resistant alcoholic acute hepatitis is a debated indication for transplant. However, available data indicate that well-selected patients have excellent post-transplant outcomes. Behavioral therapy, continued psychological support and a multidisciplinary team are essential to achieve and maintain complete alcohol abstinence during the transplant process. Alcoholic liver disease is an excellent indication for a liver transplant but patients with alcohol use disorder deserve a personalized approach and dedicated resources.
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Affiliation(s)
- Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Silvia Aspite
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Lucia Golfieri
- Department of Psychology, University of Bologna, Bologna, Italy
| | - Fabio Caputo
- Department of Internal Medicine, SS Annunziata Hospital, University of Ferrara, Cento, Italy
| | - Francesco Vizzutti
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Silvana Grandi
- Department of Psychology, University of Bologna, Bologna, Italy
| | | | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Research Center Denothe, University of Florence, Italy
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Marroni CA, Fleck Jr ADM, Fernandes SA, Galant LH, Mucenic M, de Mattos Meine MH, Mariante-Neto G, Brandão ABDM. Liver transplantation and alcoholic liver disease: History, controversies, and considerations. World J Gastroenterol 2018; 24:2785-2805. [PMID: 30018475 PMCID: PMC6048431 DOI: 10.3748/wjg.v24.i26.2785] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 05/23/2018] [Accepted: 06/16/2018] [Indexed: 02/06/2023] Open
Abstract
Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease (ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation (LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a “self-inflicted disease”. One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this “6-mo rule” is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy.
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Affiliation(s)
- Claudio Augusto Marroni
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Alfeu de Medeiros Fleck Jr
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Sabrina Alves Fernandes
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
- Nutrition at the Centro Universitário Metodista (IPA), Porto Alegre 90420-060, RS, Brazil
| | - Lucas Homercher Galant
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Marcos Mucenic
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Mario Henrique de Mattos Meine
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Guilherme Mariante-Neto
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
| | - Ajacio Bandeira de Mello Brandão
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90430-080, RS, Brazil
- Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil
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The gastroenterologist's guide to management of the post-liver transplant patient. Am J Gastroenterol 2018; 113:819-828. [PMID: 29748558 DOI: 10.1038/s41395-018-0049-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 02/11/2018] [Indexed: 12/11/2022]
Abstract
The management of the post-liver transplant patient is complex and involves a large interdisciplinary team. After referral to a transplant center, evaluation and listing, and eventual transplantation, the patient is cared for closely by the transplant center. Once deemed ready for discharge, the patient returns to the primary care provider for ongoing management of the various issues that increase in incidence post transplant such as osteoporosis, cardiovascular, and renal diseases, as well as metabolic syndrome. The role of the gastroenterologist is not well defined, but certainly, he or she may be called upon for the initial evaluation and ongoing management of gastrointestinal as well as hepatobiliary issues. This includes but is not limited to the investigation of abnormal liver tests, non-specific gastrointestinal complaints such as nausea, vomiting, or diarrhea, biliary complications, and even recurrent hepatic disease. Having familiarity with post-transplant immunosuppressive agents, drug interactions, and potential infectious and malignancy-related complications of transplant is essential, as the primary gastroenterologist may be expected in some situations to field the initial work-up, if patient access to the transplant center is limited. The aim of this review is to summarize the gastroenterologist's role in the management of the post-liver transplant patient.
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Daswani R, Kumar A, Sharma P, Singla V, Bansal N, Arora A. Role of liver transplantation in severe alcoholic hepatitis. Clin Mol Hepatol 2018; 24:43-50. [PMID: 29316778 PMCID: PMC5875200 DOI: 10.3350/cmh.2017.0027] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 11/20/2017] [Indexed: 12/12/2022] Open
Abstract
Severe alcoholic hepatitis has very high short term mortality and corticosteroids have been the mainstay of treatment for decades. Patients with Lille score >0.45 are considered non-responders to steroids and have poor outcome. Recently Orthotopic Liver Transplantation (OLT) is being increasingly used as rescue treatment for these patients, without waiting for 6 months of abstinence. Liver transplant is the only rescue treatment which can potentially provide long term benefit for patients who are steroid non-responders. However, with scarcity of organs being a concern, all patients of severe alcoholic hepatitis cannot be chosen for transplantation in an arbitrary way. There is a need for development of predictive tools and objective protocols to select patients who can justify the use of precious liver grafts. With a stringent criteria for selection of patients receiving the graft, liver transplantation in severe alcoholic hepatitis can become a viable rescue therapeutic option conferring significant survival advantage of both short- and long-term basis. The optimal criteria for selection will also prevent misuse of the liver donor pool as well as to prevent mortality in salvageable patients. Further research needs to be done to identify subset of patients which are at low risk of recidivism and also cannot be managed with pharmacotherapy alone. We reviewed the current knowledge on role of OLT in patient with acute severe alcoholic hepatitis in the present review.
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Affiliation(s)
- Ravi Daswani
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Vikas Singla
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Naresh Bansal
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
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8
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Albertsen A. Drinking in the last chance saloon: luck egalitarianism, alcohol consumption, and the organ transplant waiting list. MEDICINE, HEALTH CARE, AND PHILOSOPHY 2016; 19:325-338. [PMID: 26838765 DOI: 10.1007/s11019-016-9684-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
The scarcity of livers available for transplants forces tough choices upon us. Lives for those not receiving a transplant are likely to be short. One large group of potential recipients needs a new liver because of alcohol consumption, while others suffer for reasons unrelated to their own behaviour. Should the former group receive lower priority when scarce livers are allocated? This discussion connects with one of the most pertinent issues in contemporary political philosophy; the role of personal responsibility in distributive justice. One prominent theory of distributive justice, luck egalitarianism, assesses distributions as just if, and only if, people's relative positions reflect their exercises of responsibility. There is a principled luck egalitarian case for giving lower priority to those who are responsible for their need. Compared to the existing literature favouring such differentiation, luck egalitarianism provides a clearer rationale of fairness, acknowledges the need for individual assessments of responsibility, and requires initiatives both inside and outside of the allocation systems aimed at mitigating the influence from social circumstances. Furthermore, the concrete policies that luck egalitarians can recommend are neither too harsh on those who make imprudent choices nor excessively intrusive towards those whose exercises of responsibility are assessed.
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Affiliation(s)
- Andreas Albertsen
- Department of Political Science and Government, School of Business and Social Sciences, Aarhus University, Bartholins Alle 7, 8000, Aarhus C, Denmark.
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9
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Rosato V, Abenavoli L, Federico A, Masarone M, Persico M. Pharmacotherapy of alcoholic liver disease in clinical practice. Int J Clin Pract 2016; 70:119-31. [PMID: 26709723 DOI: 10.1111/ijcp.12764] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
AIMS Alcohol is the most commonly used addictive substance and alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide, responsible for 47.9% of all liver chronic deaths. Despite ALD has a significant burden on the health, few therapeutic advances have been made in the last 40 years, particularly in the long-term management of these patients. METHODS we searched in PubMed, Scopus, Google Scholar, and MEDLINE databases to identify relevant English language publications focused on long-term therapy of ALD. RESULTS From the huge literature on this topic, including about 755 studies, 75 were selected as eligible including clinical trials and meta-analysis. CONCLUSIONS Abstinence remains the cornerstone of ALD therapy but it is also the most difficult therapeutic target to achieve and the risk of recidivism is very high at any time. Several drugs (disulfiram, naltrexone, acamprosate, sodium oxybate) have proven to be effective to prevent alcohol relapse and increase the abstinence, although the psychotherapeutic support remains crucial. Baclofen seems to be effective to improve abstinence, showing an excellent safety and tolerability. ALD is often complicated by a state of malnutrition, which is related to a worst mortality. A nutritional therapy may improve survival in cirrhotic patients, reversing muscle wasting, weight loss and specific nutritional deficiencies. While in aggressive forms of alcoholic hepatitis are recommended specific drug treatments, including glucocorticoids or pentoxifylline, for the long-term treatment of ALD, specific treatments aimed at stopping the progression of fibrosis are not yet approved, but there are some future perspective in this field, including probiotics and antibiotics, caspase inhibitors, osteopontin and endocannabinoids.
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Affiliation(s)
- V Rosato
- Internal Medicine and Hepatology Department, Second University of Naples, Naples, Italy
| | - L Abenavoli
- Department of Health Science, University Magna Graecia, Catanzaro, Italy
| | - A Federico
- Gastroenterology and Endoscopy Unit, Second University of Naples, Naples, Italy
| | - M Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Baronissi, Italy
| | - M Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Baronissi, Italy
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10
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Mathurin P, Bataller R. Trends in the management and burden of alcoholic liver disease. J Hepatol 2015; 62:S38-46. [PMID: 25920088 PMCID: PMC5013530 DOI: 10.1016/j.jhep.2015.03.006] [Citation(s) in RCA: 213] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 03/05/2015] [Accepted: 03/05/2015] [Indexed: 12/16/2022]
Abstract
Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe and is the leading cause of death among adults with excessive alcohol consumption. There is a dose-response relationship between the amount of alcohol consumed and the risk of ALD. The relative risk of cirrhosis increases in subjects who consume more than 25 g/day. The burden of alcohol-attributable liver cirrhosis and liver cancer is high and is entirely preventable. Health agencies should develop population-based policies to reduce the prevalence of harmful and/or hazardous alcohol consumption and foster research in this field to provide new diagnostic and therapeutic tools. Disease progression of patients with ALD is heavily influenced by both genetic and environmental factors. Non-invasive methods for the diagnosis of fibrosis have opened new perspectives in the early detection of advanced ALD in asymptomatic patients. Alcoholic hepatitis, the most severe form of ALD, carries a high short-term mortality (around 30-50% at 3 months). Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis but duration of therapy should be adapted to early response. Liver transplantation is the best option for patients with severe liver dysfunction. However, alcohol relapse after transplantation remains a critical issue and drinking habits of transplanted patients need to be routinely screened.
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Affiliation(s)
- Philippe Mathurin
- Service Maladie de l'Appareil Digestif and INSERM U995, Univ Lille 2, CHRU Lille, France.
| | - Ramon Bataller
- Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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11
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Berlakovich GA. Challenges in transplantation for alcoholic liver disease. World J Gastroenterol 2014; 20:8033-8039. [PMID: 25009374 PMCID: PMC4081673 DOI: 10.3748/wjg.v20.i25.8033] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 01/28/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist’s assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient’s pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key factor determining the outcome of transplantation for alcoholic cirrhosis is intensive lifelong medical and psychological care. Post-transplant surveillance might be much more important than pre-transplant selection.
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12
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Friedrich K, Wannhoff A, Kattner S, Brune M, Hov JR, Weiss KH, Antoni C, Dollinger M, Neumann-Haefelin C, Seufferlein T, Schemmer P, Schirmacher P, Stremmel W, Gotthardt DN. PNPLA3 in end-stage liver disease: alcohol consumption, hepatocellular carcinoma development, and transplantation-free survival. J Gastroenterol Hepatol 2014; 29:1477-84. [PMID: 25273282 DOI: 10.1111/jgh.12540] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/26/2014] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS The rs738409 variant (I148M) of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene is associated with several liver malfunctions. Its impact on end-stage liver disease has not been addressed yet. METHODS The I148M polymorphism was genotyped in a well-characterized cohort of 421 Caucasian patients and retrospectively analyzed from the time of enrollment at Eurotransplant. RESULTS The G allele of the I148M variant was significantly overrepresented in patients with alcoholic liver disease (ALD, P < 0.001) and associated with hepatocellular carcinoma (HCC) development (odds ratio [OR] = 2.399; 95% confidence interval [CI]: 1.292-4.455; P = 0.008) while not affecting the other liver disease entities. Time until hydropic decompensation (P = 0.04) and hepatic encephalopathy (P = 0.043) was significantly impaired for ALD patients carrying either one or two mutated G alleles. Actuarial survival free of liver transplantation was further reduced for ALD carriers of the I148M variant (CC = 30.7 months ± 7.9, 95% CI: 15.1-46.2 vs CG/GG: 17.1 months ± 3.3, 95% CI: 3.3-10.6; P = 0.012) compared with wild-type patients. Cox multivariate analysis identified the PNPLA3 I148M genotype as an independent predictor actuarial survival free of liver transplantation (OR = 1.77; 95% CI: 1.27-2.47; P = 0.001). CONCLUSIONS In end-stage liver disease patients, we identified ALD to be predominantly affected by the PNPLA3 I148M variant resulting in an increased risk of HCC and reduced transplantation free survival. Genetic testing of the I148M genotype in ALD patients awaiting liver transplantation might be beneficial for these patients.
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Affiliation(s)
- Kilian Friedrich
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany; Joint Division Molecular Metabolic Control, German Cancer Research Center (DKFZ), Heidelberg, Germany
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13
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Ahn CS, Hwang S, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Park GC, Kang SH, Jung BH, Kim N, Lee SG. Long-Term Outcome of Living Donor Liver Transplantation for Patients With Alcoholic Liver Disease. Transplant Proc 2014; 46:761-6. [DOI: 10.1016/j.transproceed.2013.12.032] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 11/30/2013] [Accepted: 12/11/2013] [Indexed: 12/14/2022]
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14
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Pateria P, de Boer B, MacQuillan G. Liver abnormalities in drug and substance abusers. Best Pract Res Clin Gastroenterol 2013; 27:577-96. [PMID: 24090944 DOI: 10.1016/j.bpg.2013.08.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 08/11/2013] [Indexed: 01/31/2023]
Abstract
Drug and substance abuse remains a major medical problem. Alcohol use, abuse and dependence are highly prevalent conditions. Alcohol related liver disease can present as simple steatosis, steatohepatitis, alcoholic hepatitis or liver cirrhosis. Paracetamol hepatotoxicity secondary to accidental or deliberate overdose is another common problem. While the adverse cardiovascular, neurological, renal and psychiatric consequences of various illicit substance abuses are widely studied and publicized, less attention has been directed towards possible hepatotoxic effects. Illicit drug abuse can cause a range of liver abnormalities ranging from asymptomatic derangement of liver function tests to fulminant hepatic failure. This article reviews the epidemiology, risk factors, clinical manifestations, pathogenesis, investigations, management and prognostic factors of alcohol related liver disease and paracetamol hepatotoxicity as well as the current knowledge pertaining to hepatotoxicity of the more commonly used illicit substances including cannabis, amphetamine type stimulants, cocaine, khat chewing and complementary and alternate medicine.
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Affiliation(s)
- Puraskar Pateria
- Western Australian Liver Transplant Service, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009, Australia.
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Park YH, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Park GC, Namgoong JM, Park HW, Park CS, Kang SH, Jung BH, Lee SG. Living donor liver transplantation for patients with alcoholic liver disease. KOREAN JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 2013; 17:14-20. [PMID: 26155208 PMCID: PMC4304503 DOI: 10.14701/kjhbps.2013.17.1.14] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 02/05/2013] [Accepted: 02/18/2013] [Indexed: 12/20/2022]
Abstract
Backgrounds/Aims Since most transplantation studies for alcoholic liver disease (ALD) were performed on deceased donor liver transplantation, little was known following living donor liver transplantation (LDLT). Methods The clinical outcome of 18 ALD patients who underwent LDLT from Febraury 1997 to December 2004 in a large-volume liver transplantation center was assessed retrospectively. Results The model for end-stage liver disease score was 23±11, and mean pretransplant abstinence period was 16±13 months, with 14 (77.8%) patients being abstinent for at least 6 months. Graft types were right lobe grafts in 11, left lobe grafts in 2 and dual grafts in 5. Graft to recipient body weight ratio was 0.94±0.16. The relapse rates in patients who did and did not maintain 6 months of abstinence were 7.1% and 50%, respectively (p=0.097). Younger recipient age was a significant risk factor for alcohol relapse (p=0.027). Five recipients with antibody to hepatitis B surface antigen (HBsAg) received core antibody-positive liver graft, but two of them showed positive HBsAg seroconversion. Overall 5-year patient survival rate following LDLT was 87.8%, with a 5-year relapse rate of 16.7%. Conclusions Pretransplant abstinence for 6 months appears to be benefical for preventing posttransplant relapse. Life-long prophylactic measure should be followed after use of anti-HBc-positive liver grafts regardless of hepatitis B viral marker status of the recipient.
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Affiliation(s)
- Yo-Han Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung-Man Namgoong
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyung-Woo Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chun-Soo Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Hwa Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Bo-Hyeon Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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16
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Grover S, Sarkar S. Liver transplant-psychiatric and psychosocial aspects. J Clin Exp Hepatol 2012; 2:382-92. [PMID: 25755459 PMCID: PMC3940381 DOI: 10.1016/j.jceh.2012.08.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 08/17/2012] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation is a life saving surgical procedure that is associated with improved longevity and enhanced quality of life. The number of successful liver transplants is growing worldwide. The procedure requires a dedicated and trained team of experts. A psychiatrist plays an important role in such a team. Psychiatric and psychosocial assessment is considered imperative to evaluate the candidate's suitability as a transplant recipient. Many psychiatric disorders may lead to the need for liver transplant, and if kept unchecked can adversely affect outcomes. Psychiatric problems arising in the post-transplant period may also require intervention of the psychiatrist. The donor too needs to be evaluated adequately to assess for psychological fitness for the procedure. This article provides broad overview of the various psychiatric and psychosocial issues pertaining to liver transplantation.
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Affiliation(s)
- Sandeep Grover
- Address for correspondence: Dr. Sandeep Grover, Assistant Professor, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India. Tel.: +91 172 2756807 (O); fax: +91 172 2744401, +91 172 2745078.
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17
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Faure S, Herrero A, Jung B, Duny Y, Daures JP, Mura T, Assenat E, Bismuth M, Bouyabrine H, Donnadieu-Rigole H, Navarro F, Jaber S, Larrey D, Pageaux GP. Excessive alcohol consumption after liver transplantation impacts on long-term survival, whatever the primary indication. J Hepatol 2012; 57:306-12. [PMID: 22521352 DOI: 10.1016/j.jhep.2012.03.014] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2011] [Revised: 02/24/2012] [Accepted: 03/02/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Beyond 5 years, poorer survival, related to alcohol relapse, is observed in patients with liver transplant for alcohol-related liver disease (ALD). However, alcohol consumption has been significantly understudied in non-ALD transplant recipients. We aimed at analyzing the impact of alcohol consumption on long-term survival irrespective of the indication for transplantation. METHODS This observational study included consecutive adult recipients of a primary liver graft between 1991 and 2007 in our hospital, who survived >6 months. Patients without ALD as primary indication, but with a history of excessive alcohol consumption before transplantation, were classified as secondary indication ALD. We studied the impact on survival of excessive consumption of alcohol after transplantation and several other variables. RESULTS The 441 patients had mean follow-up of 81.7 months. Among the 281 patients with excessive alcohol consumption before transplantation, 206 had ALD as primary indication. After transplantation, alcohol consumption was reported by 32.3% of the study population, 43.7% in primary indication ALD, and 24.3% in non-ALD patients. Survival was 82% at 5 years and 49% at 10 years for patients with excessive alcohol relapse, compared with 86% and 75%, respectively, for patients without persistent excessive alcohol relapse. By multivariable analysis, the independent risk factors of death were: excessive alcohol relapse, age >51 years, post-transplantation diabetes mellitus, cyclosporine-based immunosuppression, and non-hepatic cancer. CONCLUSIONS Excessive alcohol consumption has a negative impact on long-term survival after liver transplant, irrespective of the primary indication. Death is mainly due to recurrence of liver disease and non-hepatic cancer.
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Affiliation(s)
- Stéphanie Faure
- Liver Transplantation Unit, CHU Saint Eloi, Montpellier, France
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18
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Leggio L, Ferrulli A, Zambon A, Caputo F, Kenna G, Swift R, Addolorato G. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection. Addict Behav 2012; 37:561-4. [PMID: 22244707 DOI: 10.1016/j.addbeh.2011.12.010] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2011] [Accepted: 12/19/2011] [Indexed: 12/20/2022]
Abstract
Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABA(B) receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some Liver Function Tests (LFTs) (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients.
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Basra S, Anand BS. Definition, epidemiology and magnitude of alcoholic hepatitis. World J Hepatol 2011; 3:108-13. [PMID: 21731902 PMCID: PMC3124876 DOI: 10.4254/wjh.v3.i5.108] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Revised: 03/06/2011] [Accepted: 03/13/2011] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is a major cause of alcohol-related morbidity and mortality. Its presentation ranges from fatty liver to alcoholic hepatitis (AH), cirrhosis, and hepatocellular carcinoma. Although the amount and pattern of alcohol consumption is a well recognized predisposing factor for the development of serious liver pathology, environmental factors and the host's genetic make-up may also play significant roles that have not yet been entirely explored. Continuing alcohol consumption is a major factor that influences the survival of patients with AH. The presence of cirrhosis at presentation or its development on follow up is a major factor determining the outcome in the long run. This chapter deals with the epidemiology and magnitude of ALD in general and AH in particular.
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Affiliation(s)
- Sarpreet Basra
- Sarpreet Basra, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, United States
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20
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El-Masry M, Puig CA, Saab S, Saab S. Recurrence of non-viral liver disease after orthotopic liver transplantation. Liver Int 2011; 31:291-302. [PMID: 21281429 DOI: 10.1111/j.1478-3231.2010.02434.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplant remains the ultimate treatment for decompensated liver disease. However, many diseases do recur after orthotopic liver transplant, which may affect recipients' quality of life and survival rate. We performed a systematic review of relevant epidemiological studies available on Medline that provided information on the recurrence of non-viral hepatitis after orthotopic liver transplantation in adult patients published until August 2010. All data were compiled from either review articles or retrospective studies. Primary sclerosing cholangitis, primary biliary cirrhosis, autoimmune hepatitis, non-alcoholic steatohepatitis, alcoholic steatohepatitis and haemochromatosis can recur after liver transplantation. The rates for disease recurrence varied according to the indication for transplantation, and ranged from 7 to 50%. Although the survival rate of patients with liver disease has increased with the advent of liver transplantation and novel immunosuppressive protocols, recurrence of the primary liver disease remains a concern. The recurrence rates differ not only according to the cause of underlying liver disease but also vary within the indication for transplant. Further studies are needed to elucidate the risk factors for varied disease recurrence.
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Affiliation(s)
- Monica El-Masry
- Department of Medicine, Olive View - UCLA Medical Center, Sylmar, CA, USA
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21
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Abstract
Alcoholic liver disease (ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe. Controversies surround the indications and allocation of scarce and expensive resource for this so called self inflicted disease. Controversies stem from the apprehension that alcoholic recipients are likely to relapse and cause damage to the graft. There is a need to select those candidates with lower risk for relapse with the available predictive factors and scores. Substance abuse specialist and psychiatrists are mandatory in the pre-transplant evaluation and in the post-transplant follow-up. There is conflicting evidence to support a fixed period of pretransplant abstinence, although most units do follow this. Alcoholic hepatitis (AH) continues to be a contraindication for transplantation, however there is a need for further research in this field as a subset of patients with AH who do not respond to medical treatment, have high early mortality and could benefit from transplantation. One year, 3-year, and 5-year survival post-transplant is similar for both ALD and non-ALD recipients. The incidence of post-transplant rejection and retransplantation is also similar to other recipients. ALD with viral hepatitis especially hepatitis C virus leads to a more aggressive liver disease with early presentation for transplantation. ALD patients are more prone to develop de-novo malignancy; this is attributed to the long term effect of alcohol, tobacco combined with immunosuppression. Post-transplant surveillance is important to detect early relapse to alcoholism, presence of de-novo malignancy and treat the same adequately.
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Abstract
These recommendations provide a data-supported approach. They are based on the following: (i) a formal review and analysis of the recently published world literature on the topic (Medline search); (ii) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines (1); (iii) guideline policies, including the American Association for the Study of Liver Diseases (AASLD) Policy on the development and use of practice guidelines and the AGA Policy Statement on Guidelines (2); and (iv) the experience of the authors in the specified topic. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. They are intended to be flexible, in contrast to the standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the quality of evidence supporting the recommendations, the Practice Guideline Committee of the AASLD requires a Class (reflecting the benefit vs. risk) and Level (assessing the strength or certainty) of Evidence to be assigned and reported with each recommendation (Table 1, adapted from the American College of Cardiology and the American Heart Association Practice Guidelines) (3,4).
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Affiliation(s)
- Robert S O'Shea
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Ohio 44195, USA
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23
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Burra P, Senzolo M, Adam R, Delvart V, Karam V, Germani G, Neuberger J. Liver transplantation for alcoholic liver disease in Europe: a study from the ELTR (European Liver Transplant Registry). Am J Transplant 2010; 10:138-48. [PMID: 19951276 DOI: 10.1111/j.1600-6143.2009.02869.x] [Citation(s) in RCA: 244] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation (LT). Long-term outcome after LT for ALD versus other etiologies is still under debate. The aim of this study was to compare outcome after LT of patients with ALD, viral (VIR), and cryptogenic cirrhosis. Donor, graft and recipient ELTR variables were analysed in transplants for alcoholic and nonalcoholic cirrhosis (1988-2005) and were correlated with patient survival. Causes of death and/or graft failure were compared between groups. Nine thousand eight hundred eighty ALD, 10,943 VIR, 1478 ALD+VIR and 2410 cryptogenic (CRYP) liver transplants were evaluated. One, 3, 5 and 10 years graft survival rates after LT in ALD patients were 84%, 78%, 73%, 58%, significantly higher than in VIR and CRYP (p=0.04, p=0.05). By multivariate analysis, ALD+VIR (RR 1.14) and viral alone (RR 1.06) were significant risk factors for mortality. De novo tumors, cardiovascular and social causes were causes of death/graft failure in higher percentage in ALD groups versus other etiologies. LT for ALD cirrhosis has a favorable outcome, however, hepatitis C virus co-infection seems to eliminate this advantage. Screening for de novo tumors and prevention of cardiovascular complications are essential to provide better long-term results.
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Affiliation(s)
- P Burra
- Gastroenterology, Department of Surgical and Gastroenterological Sciences, University Hospital of Padova, Padova, Italy.
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24
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Affiliation(s)
- Robert S O'Shea
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
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25
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26
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Webb K, Shepherd L, Neuberger J. Illicit drug use and liver transplantation: is there a problem and what is the solution? Transpl Int 2008; 21:923-9. [PMID: 18657088 DOI: 10.1111/j.1432-2277.2008.00724.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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Kalaitzakis E, Wallskog J, Björnsson E. Abstinence in patients with alcoholic liver cirrhosis: A follow-up study. Hepatol Res 2008; 38:869-76. [PMID: 18507691 DOI: 10.1111/j.1872-034x.2008.00353.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM To investigate the proportion of patients with alcoholic cirrhosis who abstained from alcohol after contact with a hepatology unit, the predictors for abstinence, and the role of clinical and psychosocial factors in short-term mortality in these patients. METHODS Eighty-seven consecutive patients with alcoholic cirrhosis from a transplant center were included. Data on cirrhosis severity and complications, as well as on abstinence and psychosocial factors were collected. Patients were followed up for 19 (12-25) months. Data on abstinence during follow up, alcohol abuse treatment, psychiatric contact, severity of cirrhosis, mortality, and liver transplantation were analyzed. RESULTS Prior to inclusion, 53/87 (61%) patients had abstained from alcohol for 24 months (interquartile range: 18-33). Twenty percent had a history of other substance abuse, 47% had undergone alcohol abuse treatment, and 21% had a previous psychiatric diagnosis. Forty-eight percent lived with a partner, 23% worked/studied, and 53% were pensioners. During follow up, 26% died, 20% received a liver transplant, 55% abstained from alcohol, 47% received alcohol abuse treatment, and 33% had psychiatric contact. In a multivariate analysis, abstinence during follow up was found to be related to abstinence upon inclusion in the study, to the model for end-stage liver disease (MELD) score at follow up, and to no abuse treatment in a detoxification unit, whereas mortality was related to index MELD and alcohol abuse treatment during follow up. Neither abstinence nor mortality was related to psychosocial factors. CONCLUSION More than half of patients with alcoholic cirrhosis were found to abstain from alcohol during follow up, which was related to prior documentation of abstinence and cirrhosis severity. Cirrhosis severity (expressed as the MELD) and alcohol abuse treatment during follow up were related to short-term mortality.
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Affiliation(s)
- Evangelos Kalaitzakis
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
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Abstract
A number of philosophers have argued that alcoholics should receive lower priority for liver transplantations because they are morally responsible for their medical conditions. In this paper, I argue that this conclusion is false. Moral responsibility should not be used as a criterion for the allocation of medical resources. The reason I advance goes further than the technical problem of assessing moral responsibility. The deeper problem is that using moral responsibility as an allocation criterion undermines the functioning of medicine.
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Affiliation(s)
- Dien Ho
- School of Arts and Sciences, Massachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USA.
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Dew MA, DiMartini AF, Steel J, De Vito Dabbs A, Myaskovsky L, Unruh M, Greenhouse J. Meta-analysis of risk for relapse to substance use after transplantation of the liver or other solid organs. Liver Transpl 2008; 14:159-72. [PMID: 18236389 PMCID: PMC2883859 DOI: 10.1002/lt.21278] [Citation(s) in RCA: 195] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
For patients receiving liver or other organ transplants for diseases associated with substance use, risk for relapse posttransplantation is a prominent clinical concern. However, there is little consensus regarding either the prevalence or risk factors for relapse to alcohol or illicit drug use in these patients. Moreover, the evidence is inconsistent as to whether patients with pretransplantation substance use histories show poorer posttransplantation medical adherence. We conducted a meta-analysis of studies published between 1983 and 2005 to estimate relapse rates, rates of nonadherence to the medical regimen, and the association of potential risk factors with these rates. The analysis included 54 studies (50 liver, 3 kidney, and 1 heart). Average alcohol relapse rates (examined only in liver studies) were 5.6 cases per 100 patients per year (PPY) for relapse to any alcohol use and 2.5 cases per 100 PPY for relapse with heavy alcohol use. Illicit drug relapse averaged 3.7 cases per 100 PPY, with a significantly lower rate in liver vs. other recipients (1.9 vs. 6.1 cases). Average rates in other areas (tobacco use, immunosuppressant and clinic appointment nonadherence) were 2 to 10 cases per 100 PPY. Risk factors could be examined only for relapse to any alcohol use. Demographics and most pretransplantation characteristics showed little correlation with relapse. Poorer social support, family alcohol history, and pretransplantation abstinence of < or =6 months showed small but significant associations with relapse (r = 0.17-0.21). Future research should focus on improving the prediction of risk for substance use relapse, and on testing interventions to promote continued abstinence posttransplantation.
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Affiliation(s)
- Mary Amanda Dew
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
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30
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Dumortier J, Guillaud O, Adham M, Boucaud C, Delafosse B, Bouffard Y, Paliard P, Scoazec JY, Boillot O. Negative impact of de novo malignancies rather than alcohol relapse on survival after liver transplantation for alcoholic cirrhosis: a retrospective analysis of 305 patients in a single center. Am J Gastroenterol 2007; 102:1032-41. [PMID: 17313502 DOI: 10.1111/j.1572-0241.2007.01079.x] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Alcoholic liver disease is a leading indication for liver transplantation (LT). The aim of this study was to evaluate long-term results and survival prognostic factors of LT in this indication from a large cohort of patients. METHODS From October 1990 to October 2005, 305 consecutive patients with alcoholic cirrhosis (from 594 patients presenting with cirrhosis, i.e., 51.3%) underwent LT in our center. There were 229 men and 76 women, with a median age of 50 yr (range 30-68). Clinical and biological variables with possible prognostic value were analyzed. RESULTS Global survival rate was 92.6% at 1 yr, 88.5% at 3 yr, 84.3% at 5 yr, and 73.4% at 10 yr, and was similar (P=0.78, log-rank test) to that of patients transplanted for other cirrhosis (88.8% at 1 yr, 84.1% at 3 yr, 80.6% at 5 yr, and 74.7% at 10 yr). Recurrence of alcohol consumption was observed in 37 patients (12.1%). De novo cancer occurred in 35 patients after LT (11.5%). Univariate analysis disclosed that male gender, history of smoking, and de novo carcinoma were significant survival prognostic factors (P<0.05, log-rank test). CONCLUSIONS Our results strongly confirm that alcoholic liver disease is an excellent indication for LT, but long-term survival is reduced because of other target-organ damage of both alcohol and tobacco, especially aero-digestive malignancies, which are greater causes of morbidity and mortality than is recurrent alcohol liver disease.
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Affiliation(s)
- Jérôme Dumortier
- Fédération des Spécialités Digestives, and Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Lyon, France
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31
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The evidence for drug treatment of alcohol dependence in liver transplant patients. Curr Opin Organ Transplant 2007. [DOI: 10.1097/mot.0b013e32803fb77d] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Abstract
PURPOSE OF REVIEW To apprise the reader of advances in 2005 in the epidemiology, pathogenesis, prognosis and treatment of alcoholic liver disease. Alcohol use has declined in developed countries, but the opposite is true elsewhere; alcoholic liver disease is a considerable burden worldwide. RECENT FINDINGS Genetic mechanisms for alcoholic liver disease are being discovered in addition to aggravating cofactors, such as hepatitis C, obesity and iron overload, and ameliorating ones, like coffee and tea drinking. The involvement of the innate immune system and the mechanisms of apoptosis in alcoholic liver disease are better appreciated, especially the emerging role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Steroid use and nutrition for alcoholic hepatitis are being refined, and the validity of the model for end-stage liver disease (MELD) score in predicting the outcome of alcoholic liver disease is upheld. Recidivism after liver transplantation for alcoholic liver disease adversely impacts long-term survival. SUMMARY Inroads are being made into the genetics of alcoholic liver disease and new phenomena are being uncovered in its pathogenesis, but safe and effective therapies for both alcoholic hepatitis and alcoholic cirrhosis are still wanting.
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Affiliation(s)
- Adrian Reuben
- Liver Service, Division of Gastroenterology/Hepatology and Liver Transplant Program, Medical University of South Carolina, Charleston, 29425, USA.
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33
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Perney P, Bismuth M, Sigaud H, Picot MC, Jacquet E, Puche P, Jaber S, Rigole H, Navarro F, Eledjam JJ, Blanc F, Larrey D, Pageaux GP. Are preoperative patterns of alcohol consumption predictive of relapse after liver transplantation for alcoholic liver disease? Transpl Int 2005; 18:1292-7. [PMID: 16221161 DOI: 10.1111/j.1432-2277.2005.00208.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Predictive factors for alcoholic relapse after liver transplantation (LT) performed for alcoholic liver disease (ALD) have been assessed in numerous studies, often with contradictory results. The aim of the study was to assess pretransplantation alcohol consumption characteristics on alcoholic relapse after LT. Patients transplanted for ALD for at least 6 months were included. An anonymous questionnaire assessed socio-demographic characteristics, medical history, and alcohol consumption before and after LT. Relapse was defined as any alcohol use after LT. Severe relapse was defined by heavy drinking: more than 21 units/week for males and 14 units/week for females. A total of 61 patients were studied. The mean follow up after LT was 49 +/- 34 months. Alcoholic relapse occurred in 32 of 61 patients (52%) and severe relapse in eight of 61 patients (13%). Risk factors for severe relapse were: length of abstinence before LT (P = 0.0001), more than one alcohol withdrawal before LT (P = 0.001), alcohol dependence (P = 0.05), alcohol abuse in first relatives (P = 0.05), and younger age (P = 0.05). Information on previous alcohol consumption (dependence, number of withdrawals, family history) helps to predict severe relapse after LT in patients with ALD, allowing early awareness and specific postoperative care.
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Affiliation(s)
- Pascal Perney
- Service de Médecine Interne E, Hôpital Saint Eloi, Montpellier cedex, France
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