Commentary: Alcohol and Alcoholism Special Issue on ‘Alcohol and Liver Transplantation’

Commentary: Alcohol and Alcoholism Special Issue on ‘Alcohol and Liver Transplantation’ ‘Bacchus has drowned more people than Neptun’ (Thomas Fuller, Gnomologia 1732) Alcoholic liver disease (ALD) is the number one liver disease in Europe and one of the leading liver diseases in the USA. In 2010, ~1 million Europeans died of cirrhosis of the liver with half of them of alcoholic liver cirrhosis (Blachier et al., 2013). Until now, the only cure for this disease is liver transplantation (LT). According to Blachier et al. (2013), 33% of all LTs were performed for end-stage ALD in Europe between 1988 and 2009. Thus, the end-stage ALD together with virus-related cirrhosis are the leading indications for LT. Since, Thomas Starzl’s first publication in 1990 (Starzl et al., 1988) on LT in end-stage ALD, this topic was controversially debated until now. Although, it was soon clear that the survival of patients following LT for ALD was comparable to or even better as survival for patients with other liver diseases, the introduction of the only cure for alcoholic cirrhosis was taken critically by the public as well as by the medical profession. The major argument for this was the opinion that alcoholism and ALD are self-induced diseases and it would be irresponsible to give a liver to somebody who destroyed his own liver by drinking too much especially when the availability of organs is limited. This opinion was further enhanced when the football star Georg Best continued drinking following LT and finally died due to cirrhosis in the new transplanted liver. However, as the time changes, opinions also change. ALD mostly occurs in patients with alcohol use disorders (AUDs), and AUD is a disease with ~60% genetic background. The son of a father with AUD has a significant higher risk for alcoholism. Thus, genetics are important components of alcoholism especially in males. Therefore, part of the disease is not self-induced. Similar considerations of personal responsibility apply to other liver diseases such as hepatitis C, non-alcoholic fatty liver disease (NAFLD) and sclerosing cholangitis with human immunodeficiency virus. Ethics require equitable organ allocations to all such patients. Alcoholism is difficult to treat with a high-relapse rate despite psychiatric therapy sometimes flanked by medication. Therefore, one has to face the critical question of relapse following LT. Would it not be a vast of organ when relapse occurs following LT? However, it is important to define relapse carefully which could be the consumption of any alcohol on one side and heavy drinking following LT on the other, which makes a great difference. It is noteworthy that recurrence of liver disease after LT also occurs in primary sclerosing cholangitis, autoimmune hepatitis and primary biliary cirrhosis. It also occurred in hepatitis C before the cure of hepatitis C virus became available. Thus, in conclusion recurrence after LT is common in various types of liver diseases, not only in ALD. As a long-term outcome survival and not relapse is of considerable importance. Unfortunately, worldwide no standardized procedures exist to predict the outcome in advance before LT. Relapse may jeopardize the liver according to relative recent data not within the first 5 years following LT but afterwards. Therefore, recurrence to drinking matters. Although relapse of alcoholism is relatively low following LT, it still exists. Therefore, it seems important to minimize the risk for relapse by evaluating the patient’s risk beforehand. As a ‘rule’ 6-month abstinence prior to LT has been generally accepted. However, the ‘6-month rule’ is based on an observation of 11 patients. In this paper by Kumar et al. (1990), 7 out of 11 patients survived (64%), while 4 died (36%) after LT with an abstinence interval of <6 months before LT. In contrast, if patients were abstinent between 6 and 24 months 86% survived and 16% died. From these results, it was concluded that 6 months would be a good abstinence interval. It was also found that the ‘6-month rule’ predicts relapse after LT since in one publication 50% of patients relapsed with <6-month abstinence prior to LT compared to 23% with 6–12 months abstinence (Foster et al., 1997). Indeed, pre-transplantation abstinence (6 months or more) is a good inclusion criterion (i.e. 88% sobriety post-transplant) but a poor exclusion criterion (i.e. with <6 months abstinence only 41% returned to drinking) (Foster et al., 1997). In a landmark study by Mathurin et al. (2011), it was shown for the first time that patients with acute alcoholic hepatitis transplanted without any abstinence before LT had a surprising low-relapse within the first 2 years. Thus, the ‘6-month rule’ has to be questioned especially since other predictors of relapse have to be taken into consideration such as young age, lack of social support, use of other illegal drugs, the presence of another family member with alcoholism and failure of prior rehabilitation. As a consequence, as suggested by Addolorato et al. (2013) and Mathurin et al. (2011), an expert psychosocial evaluation is of outstanding value and the integration of a psychiatrist or other addiction expert experienced in the diagnosis and treatment of alcoholism is mandatory. In this special issue of Alcohol and Alcoholism, world leading experts in the field of LT in general and of LT in ALD in particular summarize the present knowledge on this topic. Many of the questions raised above such as predictive values for post-transplant survival and relapse are addressed. The papers are grouped into three sections: (i) evaluation and selection of candidates (ii) post-transplant outcomes and (iii) consideration of special patient groups. While Beresford and Lucey focus on the essentials of psychiatric and behavioral evaluation for alcohol addicts referred for LT and offer clinical standardization across the transplant programs in various locales, Parker and Holt explain the new rules of the National Health System in UK for transplanting patients with ALD. Since in UK, ALD increased steadily within the last years and reached epidemic proportions such new approaches seem necessary to handle the increasing demand for LT. The role of relapse rates following LT has been addressed by Rogal and colleagues as well as by Kodali and colleagues. While, the first reported prospective long-term medical and psychosocial outcomes, the latter performed a meta-analysis of seven studies with respect to drinking outcomes. Both studies show a relatively low-relapse rate for alcohol drinking following LT with ~20 and 26%, respectively. Interestingly, the annual alcohol relapse was found to be 4.7% for any alcohol use and 2.9% for heavy alcohol use in the meta-analysis. In addition, relapsers had a significant increase in graft injury and in post-transplant mortality. It is concluded that early identification of relapse may improve outcomes. Thus, close monitoring should already be performed during the first year following LT. It is noteworthy that relapse rates after LT are by far much lower as compared to conventional therapy of AUDs. Of great interest is the observation of Vassallo and colleagues who reported a higher rate of cancer development in patients with ALD following transplantation which was primarily associated with smoking. Indeed, cancer is another alcohol-associated disease, primarily cancer of the upper alimentary tract (oral cavity, larynx, pharynx, esophagus), the large intestine and the female breast. It is not surprising that the patients with ALD develop some of these cancers following LT, since ethanol-mediated DNA damage has occurred long before LT and it is only a question of time until tumors occur. Therefore, it seems mandatory to have a strict surveillance protocol after LT to diagnose these cancers as early as possible by endoscopy, otolaryngologists and gynecologists. Special subgroups of patients with ALD have been focused on by various authors. While, Mellinger and Volk discuss individualized assessments of alcohol use and risk of relapse, alongside standard medical and psychosocial criteria, they also emphasized the importance of fairness of allocating organs to patients with ALD by referring to recent data from patients transplanted for alcoholic hepatitis who did not have any abstinence before transplantation. In this context, a recent judgment was rendered by the Federal German Court that all patients with the need of LT had to be treated equally and fair. Another issue namely living donor LT for ALD has been discussed by Braun and Ascher. These authors performed a literature review and found only five publications from Asian transplant centers dealing with this topic. In summary, relapse rates ranged from 8 to 22% and pre-transplant abstinence did not affect post-transplant relapse. However, the data available are rather limited. Ursec-Bedoya and colleagues reported drinking behavior following LT in patients transplanted for other liver diseases, and the authors concluded that alcohol drinking should be monitored and information about potential harmful consumption should be addressed by an addiction specialist, since alcohol use after LT may jeopardize the graft. Similarly, as shown by Wieland and Everson attention needs to be drawn on the combined effect of ALD and hepatitis C infection. Both conditions may occur frequently with a severe negative effect of alcohol in hepatitis C. Although hepatitis C is now curable, alcohol consumption following LT may jeopardize the graft. This special issue of Alcohol and Alcoholism is closed by a remarkable observation on drinking behavior in experimental animals. Ronan and colleagues demonstrated that the peripheral and central injection of cyclosporine A to C57BL/6NHsd mice decreased alcohol consumption possibly through inhibition of calcineurin implicating neuroimmune mechanisms in the etiology of AUD. In summary, in 2018, LT for ALD is well established with an excellent survival. To guarantee long-term survival and a low-relapse rate for alcohol consumption following LT-standardized selection criteria are mandatory, the decision process has to be done in a team including close-related persons to the patient (the team on the ward), gastroenterologists, anesthesiologists and surgeons, but most importantly psychiatrists with experience in addiction. In addition, during post-transplantation, an early surveillance program may detect alcohol-associated cancers at a treatable stage. However, the aim of future is to reduce the number of LTs for ALD by reducing ALD. Prevention (higher taxation and reduced availability of alcoholic beverages together with clarification of facts to the public) and early detection of ALD (training programs for general practitioners to identify individuals on risk for ALD) may hereby foster this most important aim. CONFLICT OF INTEREST STATEMENT None declared. REFERENCES Addolorato G, Mirijello A, Leggio L, et al.  . ( 2013) Liver transplantation in alcoholic patients: impact of an alcohol addiction unit within a liver transplant center. Alcohol Clin Exp Res  37: 1601– 8. Google Scholar CrossRef Search ADS PubMed  Blachier M, Leleu H, Peck-Radosavljevic M, et al.  . ( 2013) The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol  58: 593– 608. Google Scholar CrossRef Search ADS PubMed  Foster PF, Fabrega F, Karademir S, et al.  . ( 1997) Prediction of abstinence from ethanol in alcoholic recipients following liver transplantation. Hepatology  25: 1469– 77. Google Scholar CrossRef Search ADS PubMed  Kumar S, Stauber RE, Gaaler JS, et al.  . ( 1990) Orthotopic liver transplantation for alcoholic liver disease. Hepatology  11: 159– 64. Google Scholar CrossRef Search ADS PubMed  Mathurin PH, Moreno PH, Didier S, et al.  . ( 2011) Early liver transplantation for severe alcoholic hepatitis. N Engl J Med  365: 1790– 800. Google Scholar CrossRef Search ADS PubMed  Starzl TE, Van Thiel D, Tzakis AG, et al.  . ( 1988) Orthotopic liver transplantation for alcoholic cirrhoses. JAMA  260: 2542– 4. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Alcohol and Alcoholism Oxford University Press

Commentary: Alcohol and Alcoholism Special Issue on ‘Alcohol and Liver Transplantation’

Loading next page...
 
/lp/ou_press/commentary-alcohol-and-alcoholism-special-issue-on-alcohol-and-liver-46H1WZSP6m
Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.
ISSN
0735-0414
eISSN
1464-3502
D.O.I.
10.1093/alcalc/agx117
Publisher site
See Article on Publisher Site

Abstract

‘Bacchus has drowned more people than Neptun’ (Thomas Fuller, Gnomologia 1732) Alcoholic liver disease (ALD) is the number one liver disease in Europe and one of the leading liver diseases in the USA. In 2010, ~1 million Europeans died of cirrhosis of the liver with half of them of alcoholic liver cirrhosis (Blachier et al., 2013). Until now, the only cure for this disease is liver transplantation (LT). According to Blachier et al. (2013), 33% of all LTs were performed for end-stage ALD in Europe between 1988 and 2009. Thus, the end-stage ALD together with virus-related cirrhosis are the leading indications for LT. Since, Thomas Starzl’s first publication in 1990 (Starzl et al., 1988) on LT in end-stage ALD, this topic was controversially debated until now. Although, it was soon clear that the survival of patients following LT for ALD was comparable to or even better as survival for patients with other liver diseases, the introduction of the only cure for alcoholic cirrhosis was taken critically by the public as well as by the medical profession. The major argument for this was the opinion that alcoholism and ALD are self-induced diseases and it would be irresponsible to give a liver to somebody who destroyed his own liver by drinking too much especially when the availability of organs is limited. This opinion was further enhanced when the football star Georg Best continued drinking following LT and finally died due to cirrhosis in the new transplanted liver. However, as the time changes, opinions also change. ALD mostly occurs in patients with alcohol use disorders (AUDs), and AUD is a disease with ~60% genetic background. The son of a father with AUD has a significant higher risk for alcoholism. Thus, genetics are important components of alcoholism especially in males. Therefore, part of the disease is not self-induced. Similar considerations of personal responsibility apply to other liver diseases such as hepatitis C, non-alcoholic fatty liver disease (NAFLD) and sclerosing cholangitis with human immunodeficiency virus. Ethics require equitable organ allocations to all such patients. Alcoholism is difficult to treat with a high-relapse rate despite psychiatric therapy sometimes flanked by medication. Therefore, one has to face the critical question of relapse following LT. Would it not be a vast of organ when relapse occurs following LT? However, it is important to define relapse carefully which could be the consumption of any alcohol on one side and heavy drinking following LT on the other, which makes a great difference. It is noteworthy that recurrence of liver disease after LT also occurs in primary sclerosing cholangitis, autoimmune hepatitis and primary biliary cirrhosis. It also occurred in hepatitis C before the cure of hepatitis C virus became available. Thus, in conclusion recurrence after LT is common in various types of liver diseases, not only in ALD. As a long-term outcome survival and not relapse is of considerable importance. Unfortunately, worldwide no standardized procedures exist to predict the outcome in advance before LT. Relapse may jeopardize the liver according to relative recent data not within the first 5 years following LT but afterwards. Therefore, recurrence to drinking matters. Although relapse of alcoholism is relatively low following LT, it still exists. Therefore, it seems important to minimize the risk for relapse by evaluating the patient’s risk beforehand. As a ‘rule’ 6-month abstinence prior to LT has been generally accepted. However, the ‘6-month rule’ is based on an observation of 11 patients. In this paper by Kumar et al. (1990), 7 out of 11 patients survived (64%), while 4 died (36%) after LT with an abstinence interval of <6 months before LT. In contrast, if patients were abstinent between 6 and 24 months 86% survived and 16% died. From these results, it was concluded that 6 months would be a good abstinence interval. It was also found that the ‘6-month rule’ predicts relapse after LT since in one publication 50% of patients relapsed with <6-month abstinence prior to LT compared to 23% with 6–12 months abstinence (Foster et al., 1997). Indeed, pre-transplantation abstinence (6 months or more) is a good inclusion criterion (i.e. 88% sobriety post-transplant) but a poor exclusion criterion (i.e. with <6 months abstinence only 41% returned to drinking) (Foster et al., 1997). In a landmark study by Mathurin et al. (2011), it was shown for the first time that patients with acute alcoholic hepatitis transplanted without any abstinence before LT had a surprising low-relapse within the first 2 years. Thus, the ‘6-month rule’ has to be questioned especially since other predictors of relapse have to be taken into consideration such as young age, lack of social support, use of other illegal drugs, the presence of another family member with alcoholism and failure of prior rehabilitation. As a consequence, as suggested by Addolorato et al. (2013) and Mathurin et al. (2011), an expert psychosocial evaluation is of outstanding value and the integration of a psychiatrist or other addiction expert experienced in the diagnosis and treatment of alcoholism is mandatory. In this special issue of Alcohol and Alcoholism, world leading experts in the field of LT in general and of LT in ALD in particular summarize the present knowledge on this topic. Many of the questions raised above such as predictive values for post-transplant survival and relapse are addressed. The papers are grouped into three sections: (i) evaluation and selection of candidates (ii) post-transplant outcomes and (iii) consideration of special patient groups. While Beresford and Lucey focus on the essentials of psychiatric and behavioral evaluation for alcohol addicts referred for LT and offer clinical standardization across the transplant programs in various locales, Parker and Holt explain the new rules of the National Health System in UK for transplanting patients with ALD. Since in UK, ALD increased steadily within the last years and reached epidemic proportions such new approaches seem necessary to handle the increasing demand for LT. The role of relapse rates following LT has been addressed by Rogal and colleagues as well as by Kodali and colleagues. While, the first reported prospective long-term medical and psychosocial outcomes, the latter performed a meta-analysis of seven studies with respect to drinking outcomes. Both studies show a relatively low-relapse rate for alcohol drinking following LT with ~20 and 26%, respectively. Interestingly, the annual alcohol relapse was found to be 4.7% for any alcohol use and 2.9% for heavy alcohol use in the meta-analysis. In addition, relapsers had a significant increase in graft injury and in post-transplant mortality. It is concluded that early identification of relapse may improve outcomes. Thus, close monitoring should already be performed during the first year following LT. It is noteworthy that relapse rates after LT are by far much lower as compared to conventional therapy of AUDs. Of great interest is the observation of Vassallo and colleagues who reported a higher rate of cancer development in patients with ALD following transplantation which was primarily associated with smoking. Indeed, cancer is another alcohol-associated disease, primarily cancer of the upper alimentary tract (oral cavity, larynx, pharynx, esophagus), the large intestine and the female breast. It is not surprising that the patients with ALD develop some of these cancers following LT, since ethanol-mediated DNA damage has occurred long before LT and it is only a question of time until tumors occur. Therefore, it seems mandatory to have a strict surveillance protocol after LT to diagnose these cancers as early as possible by endoscopy, otolaryngologists and gynecologists. Special subgroups of patients with ALD have been focused on by various authors. While, Mellinger and Volk discuss individualized assessments of alcohol use and risk of relapse, alongside standard medical and psychosocial criteria, they also emphasized the importance of fairness of allocating organs to patients with ALD by referring to recent data from patients transplanted for alcoholic hepatitis who did not have any abstinence before transplantation. In this context, a recent judgment was rendered by the Federal German Court that all patients with the need of LT had to be treated equally and fair. Another issue namely living donor LT for ALD has been discussed by Braun and Ascher. These authors performed a literature review and found only five publications from Asian transplant centers dealing with this topic. In summary, relapse rates ranged from 8 to 22% and pre-transplant abstinence did not affect post-transplant relapse. However, the data available are rather limited. Ursec-Bedoya and colleagues reported drinking behavior following LT in patients transplanted for other liver diseases, and the authors concluded that alcohol drinking should be monitored and information about potential harmful consumption should be addressed by an addiction specialist, since alcohol use after LT may jeopardize the graft. Similarly, as shown by Wieland and Everson attention needs to be drawn on the combined effect of ALD and hepatitis C infection. Both conditions may occur frequently with a severe negative effect of alcohol in hepatitis C. Although hepatitis C is now curable, alcohol consumption following LT may jeopardize the graft. This special issue of Alcohol and Alcoholism is closed by a remarkable observation on drinking behavior in experimental animals. Ronan and colleagues demonstrated that the peripheral and central injection of cyclosporine A to C57BL/6NHsd mice decreased alcohol consumption possibly through inhibition of calcineurin implicating neuroimmune mechanisms in the etiology of AUD. In summary, in 2018, LT for ALD is well established with an excellent survival. To guarantee long-term survival and a low-relapse rate for alcohol consumption following LT-standardized selection criteria are mandatory, the decision process has to be done in a team including close-related persons to the patient (the team on the ward), gastroenterologists, anesthesiologists and surgeons, but most importantly psychiatrists with experience in addiction. In addition, during post-transplantation, an early surveillance program may detect alcohol-associated cancers at a treatable stage. However, the aim of future is to reduce the number of LTs for ALD by reducing ALD. Prevention (higher taxation and reduced availability of alcoholic beverages together with clarification of facts to the public) and early detection of ALD (training programs for general practitioners to identify individuals on risk for ALD) may hereby foster this most important aim. CONFLICT OF INTEREST STATEMENT None declared. REFERENCES Addolorato G, Mirijello A, Leggio L, et al.  . ( 2013) Liver transplantation in alcoholic patients: impact of an alcohol addiction unit within a liver transplant center. Alcohol Clin Exp Res  37: 1601– 8. Google Scholar CrossRef Search ADS PubMed  Blachier M, Leleu H, Peck-Radosavljevic M, et al.  . ( 2013) The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol  58: 593– 608. Google Scholar CrossRef Search ADS PubMed  Foster PF, Fabrega F, Karademir S, et al.  . ( 1997) Prediction of abstinence from ethanol in alcoholic recipients following liver transplantation. Hepatology  25: 1469– 77. Google Scholar CrossRef Search ADS PubMed  Kumar S, Stauber RE, Gaaler JS, et al.  . ( 1990) Orthotopic liver transplantation for alcoholic liver disease. Hepatology  11: 159– 64. Google Scholar CrossRef Search ADS PubMed  Mathurin PH, Moreno PH, Didier S, et al.  . ( 2011) Early liver transplantation for severe alcoholic hepatitis. N Engl J Med  365: 1790– 800. Google Scholar CrossRef Search ADS PubMed  Starzl TE, Van Thiel D, Tzakis AG, et al.  . ( 1988) Orthotopic liver transplantation for alcoholic cirrhoses. JAMA  260: 2542– 4. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Journal

Alcohol and AlcoholismOxford University Press

Published: Mar 1, 2018

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial