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      Liver transplantation and alcoholic liver disease: History, controversies, and considerations

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          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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          Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer.

          To evaluate the use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. An observational study assessing the nutritional status of patients with cancer. Oncology ward of a private tertiary Australian hospital. Seventy-one cancer patients aged 18-92 y. Scored PG-SGA questionnaire, comparison of scored PG-SGA with subjective global assessment (SGA), sensitivity, specificity. Some 24% (17) of 71 patients were well nourished, 59% (42) of patients were moderately or suspected of being malnourished and 17% (12) of patients were severely malnourished according to subjective global assessment (SGA). The PG-SGA score had a sensitivity of 98% and a specificity of 82% at predicting SGA classification. There was a significant difference in the median PG-SGA scores for each of the SGA classifications (P<0.001), with the severely malnourished patients having the highest scores. Re-admission within 30 days of discharge was significantly different between SGA groups (P=0.037). The mortality rate within 30 days of discharge was not significantly different between SGA groups (P=0.305). The median length of stay of well nourished patients (SGA A) was significantly lower than that of the malnourished (SGA B+C) patients (P=0.024). The scored PG-SGA is an easy to use nutrition assessment tool that allows quick identification and prioritisation of malnutrition in hospitalised patients with cancer.
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            ACG Clinical Guideline: Alcoholic Liver Disease.

            Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most patients are diagnosed at advanced stages and data on the prevalence and profile of patients with early disease are limited. Diagnosis of ALD requires documentation of chronic heavy alcohol use and exclusion of other causes of liver disease. Prolonged abstinence is the most effective strategy to prevent disease progression. AH presents with rapid onset or worsening of jaundice, and in severe cases may transition to acute on chronic liver failure when the risk for mortality, depending on the number of extra-hepatic organ failures, may be as high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in about half of treated patients with severe AH and long-term mortality is related to severity of underlying liver disease and is dependent on abstinence from alcohol. General measures in patients hospitalized with ALD include inpatient management of liver disease complications, management of alcohol withdrawal syndrome, surveillance for infections and early effective antibiotic therapy, nutritional supplementation, and treatment of the underlying alcohol-use disorder. Liver transplantation, a definitive treatment option in patients with advanced alcoholic cirrhosis, may also be considered in selected patients with AH cases, who do not respond to medical therapy. There is a clinical unmet need to develop more effective and safer therapies for patients with ALD.
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              Early liver transplantation for severe alcoholic hepatitis.

              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. 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. 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. 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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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                14 July 2018
                14 July 2018
                : 24
                : 26
                : 2785-2805
                Affiliations
                Guilherme Mariante Neto, 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
                Alfeu de Medeiros Fleck Junior, Sabrina Alves Fernandes, Lucas Homercher Galant, Marcos Mucenic, Mario Henrique de Mattos Meine, Guilherme Mariante Neto, Ajacio Bandeira de Mello Brandão, Liver Transplant Adult Group, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90035-072, RS, Brazil. nmarroni@ 123456terra.com.br
                Guilherme Mariante Neto, 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
                Nutrition at the Centro Universitário Metodista (IPA), Porto Alegre 90420-060, RS, Brazil
                Guilherme Mariante Neto, 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
                Author notes

                Author contributions: All authors reviewed and analyzed the literature and contributed to the writing of the manuscript; Marroni CA also provided the overarching intellectual input into the study design and edited the final version of the manuscript.

                Correspondence to: Claudio Augusto Marroni, MD, PhD, Professor, Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua José Kanan Aranha, 102, Jardim Isabel, Porto Alegre 91760-470, RS, Brazil. nmarroni@ 123456terra.com.br

                Telephone: +55-51-999638306 Fax: +55-51-32483202

                Article
                jWJG.v24.i26.pg2785
                10.3748/wjg.v24.i26.2785
                6048431
                30018475
                1f8d8bda-bbfe-41ce-a5c8-5c877c8cc7f6
                ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 3 April 2018
                : 23 May 2018
                : 16 June 2018
                Categories
                Review

                alcoholic liver disease,alcoholic hepatitis,alcoholic cirrhosis,alcoholism,liver transplantation,alcoholic recurrence,controversies,alcoholic abstinence,relapse,selection criteria

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