EDITORIAL

Addictive Behavior After Solid OrganTransplantation: What Do We Know Alreadyand What Do We Need To Know?Santiago Tome, Adnan Said, and Michael R. LuceySection of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School ofMedicine and Public Health, Madison, WI

Received August 1, 2007; accepted August 8, 2007.

See Article on Page 159

Transplantation of kidneys, livers, hearts, and lungshas changed from a last-hope effort to become part ofthe standard armamentarium of tertiary care through-out the first world. As part of this gradual evolution,liver transplantation in the United States has attainedmany of the markers of an established area of clinicalpractice, such as concentration on liver transplantationat the annual Liver Meeting of the American Associationfor the Study of Liver Diseases, a thriving journal, and,most recently, specific subspecialty training programsin Transplant Hepatology accredited by the Accredita-tion Council for Graduate Medical Education and acertifying examination in Transplant Hepatology underthe auspices of the American Board of Internal Medi-cine. At the same time, there has been a gradual evo-lution in how outcome after solid organ transplantationis assessed. Although organ survival and patient sur-vival remain crucial endpoints, as shown by the out-standing annual data reports published by the Scien-tific Registry of Transplant Recipients, as long-termsurvival has become commonplace, an increasing em-phasis is being placed on morbidity after solid organtransplantation.1,2 The recurrence of the original dis-ease, the development of new diseases, the morbid con-sequences of immunosuppression, and the psycholog-ical health of the transplant recipient all contribute to amore complete understanding of the lives of recipientsof solid organ transplants. As such, alcohol abuse anddrug abuse after transplantation are important areas ofinterest in assessing the quality of life after solid organtransplantation.

Unfortunately, there are many inherent barriers togetting accurate data about alcohol and/or illicit druguse by transplant recipients. Several of the most com-mon methods used to obtain information, such as self-reports, assessment by clinical findings, and collateralreports, are subject to many biases. In particular, thelack of an objective and reliable instrument to measurealcohol intake and the perceived risk to the recipientthat candor about drug or alcohol use could harm his orher chances of receiving further care from the trans-plant program tend to encourage underreporting.3 Ontop of this, the medical literature dealing with alcoholand drug use after transplant is replete with retrospec-tive data, whereas only a few studies have been per-formed in a prospective fashion.4 Finally, as a result ofour interaction with addiction specialists, an importantevolution in the understanding of addictive behaviorhas occurred within the transplant community asshown by the gradual change in the definition of alcoholrelapse used in liver transplant studies. Early publica-tions tended to define relapse as any alcohol use by thealcoholic patient.4 In contrast, recent retrospective andprospective studies have adopted the nomenclature ofaddictive medicine by distinguishing a transient re-lapse (a “slip”) from harmful drinking.5-7

Given these caveats, it is understandable that, de-spite the increased interest in posttransplant morbid-ity, it has been difficult to apply the tools of meta-analysis to the assessment of the frequency of addictivebehavior after transplantation. Consequently, Dew etal.8 are to be congratulated for their outstanding effortto analyze alcohol and other drug use after transplan-tation, which is published in this issue of Liver Trans-

Address reprint requests to Michael R. Lucey, M.D., Section of Gastroenterology and Hepatology, H6/515 CSC, University of Wisconsin Hospitaland Clinics, 600 Highland Avenue, Madison, WI 53711. Telephone: 608-263-7322; FAX: 608-265-5677; E-mail: mrl@medicine.wisc.edu

DOI 10.1002/lt.21311Published online in Wiley InterScience (www.interscience.wiley.com).

LIVER TRANSPLANTATION 14:127-129, 2008

© 2008 American Association for the Study of Liver Diseases.

plantation. Among the 54 papers that they identified asdealing with this topic, 50 were concerned with livertransplant recipients, 3 dealt with kidney recipients,and there was 1 on heart transplant recipients. Nopaper dealing with addiction in lung transplant pa-tients was found that met their entry criteria. The firstquestion posed by this review is why have so few studiesbeen directed to addictions in recipients of transplantsother than liver transplants. We do not know whetherthe disparity in the number of papers is a reflection of alack of concern that alcoholism or drug use occurs inthese populations. One explanation for a lesser degreeof interest could be that alcoholism and intravenousdrug use are primary drivers of many of the liver dis-eases that lead to liver transplantation, whereas theywould, when present, constitute a secondary problemin the kidney, heart, and lung transplant populations.Another possible factor is the different pattern of tran-sition of care in kidney transplant recipients, who arereturned to their community heath care providers,where the impact of addiction in this population maynot be as easily recognized. In any case, Dew et al.’sstudy is a call to clinical investigators in the kidney,heart, and lung transplant worlds that an opportunityawaits whoever wishes to document and analyze theproblem of addiction in these populations.

Thus, Dew et al.’s study8 concentrates almost exclu-sively on liver transplant recipients and seeks to dis-cover how frequently these patients’ addictions relapseafter transplantation. According to their meta-analysis,when alcoholic liver disease is the pretransplant diag-nosis, approximately 6 out of 100 recipients per yearwill use alcohol after transplantation, and less than 3will resume heavy alcohol use. The rate for illicit druguse is even lower. For the addiction specialist, the per-sistence of sobriety after transplantation is surprisingand unexplained.9 Among the possible explanations forthese findings are that they are a consequence of livertransplant recipients being a highly selected populationwith less craving for alcohol than typical alcoholics,that they are a result of potential therapeutic propertiesof transplantation on addictions, and that they repre-sent an underestimate because alcoholic transplant re-cipients hide their drinking.3,10

Another curious observation in Dew et al.’s study8 isthat the rate of alcoholic relapse, defined as either anyor heavy use, seems higher in Europe than in NorthAmerica, whereas the rate of nonadherence to immu-nosuppressives is higher in North America than Eu-rope. As the authors point out, the geographic diver-gence of alcohol relapse and nonadherence, althoughunexplained, shows that interpretation of these phe-nomena amounts to medical anthropology and needs totake into account such societal forces as attitudes toalcohol use and universal access to medical care.

Three pretransplant factors were found to assist inpredicting alcoholic relapse after transplantation: lackof social support, a family history of alcoholism, andless than 6 months of abstinence from alcohol. Bothsocial support and family history are in agreement withthe studies by Vaillant11 in nontransplant alcoholic

populations. The 6-month period of abstinence is amore questionable prognostic tool, and here, like theauthors, we must read between lines. As they point out,use of the 6-month rule to select alcoholic patients forliver transplantation is almost ubiquitous, and this ex-erts a profound bias on their meta-analysis because itmeans that the highest risk patients, those with lessthan 6 months of abstinence, are likely to have beenexcluded before the data could be collected. Data on thenatural history of alcoholism do not provide much sup-port for the 6-month abstinence concept. Valliant’s lon-gitudinal observational studies of a cohort of alcoholicsfound that 6 months of abstinence by itself was of littleprognostic significance.11 Indeed, at least 59% of re-lapsing patients had already achieved 6 months of ab-stinence, whereas 41% of patients who achieved 2 yearsof abstinence relapsed. More recently, the same authorhas extended the interval of observation in his prospec-tive cohorts to 60 years. The vast majority of relapses inhis study occurred before the seventh year of absti-nence, and by analogy to the concept of a cancer-freeperiod as a definition of cure, he concluded that a fol-low-up of 5 years rather than one of 1 or 2 years wouldbe necessary to determine stable recovery from alcohol-ism.12 Similarly, DiMartini et al.’s prospective study ofa cohort of transplanted alcoholics,6 albeit confoundedby the use of the 6-month rule, nevertheless indicatesthat it is a weak prognostic indicator at best. The ab-sence of a link between pretransplant rehabilitationtreatment and posttransplant alcoholic relapse is anunexpected finding in the present study. Rehabilitationsupport has been considered a good predictor of absti-nence outside transplant.11 In order to understandwhether rehabilitation has a positive or negative influ-ence, we need to better understand how a history ofrehabilitation treatment influenced selection for trans-plantation, something that is difficult to know from ananalysis of published, largely retrospective studies.

Therefore, on the basis of Dew et al.’s study,8 what wedo we know already about addictions after solid organtransplantation, and what do we need to know? First,we can conclude that addiction has been largely ig-nored in transplant recipients other than liver recipi-ents. There is a need for studies of addiction in kidney,heart, and lung recipients. These studies, like futurestudies in liver patients, would be best if they includeda prospective study design beginning before transplan-tation. Next, we know that relapse rates for alcoholismafter liver transplantation are quite low. However, thestudies included in the meta-analysis that led to thisconclusion have many biases and confounders. Weneed studies designed to limit these biases by usingstudy designs that recognize the difficulty of identifyingalcohol or drug relapse, especially because the patientsperceive that it is in their interest to conceal their be-havior. One such method is to separate the study per-sonnel from the transplant personnel and to keep rev-elations of alcohol or drug use confidential, that is,within the study. We know that predicting future alco-hol or drug relapse remains imperfect, as is well dem-onstrated by the still contentious status of the 6-month

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abstinence rule. We need future studies that confrontthe issue of the suitability for transplantation of pa-tients with duration of abstinence shorter than 6months.

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3. Weinrieb RM, Van Horn DH, McLellan AT, Lucey MR. In-terpreting the significance of drinking by alcohol-depen-dent liver transplant patients: fostering candor is the keyto recovery. Liver Transpl 2000;6:769-776.

4. Tome S, Lucey MR. Timing of liver transplantation in al-coholic cirrhosis. J Hepatol 2003;39:302-307.

5. Fuller RK. Definition and diagnosis of relapse to drinking.Liver Transpl Surg 1997;3:258-262.

6. DiMartini A, Day N, Dew MA, Javed L, Fitzgerald MG, JainA, et al. Alcohol consumption patterns and predictors of

use following liver transplantation for alcoholic liver dis-ease. Liver Transpl 2006;12:813-820.

7. Pfitzmann R, Schwenzer J, Rayes N, Seehofer D, NeuhausR, Nussler NC. Long-term survival and predictors of re-lapse after orthotopic liver transplantation for alcoholicliver disease. Liver Transpl 2007;13:197-205.

8. Dew MA, Di Martini A, Steel J, De Vito Dabbs A, Myas-covky L, Unruh M, Greenhouse J. Meta-analysis of risk forrelapse to substance use after transplantation of the liveror other solid organs. Liver Transpl 2008;14:159-172

9. Beresford TP. Probabilities of relapse and abstinenceamong liver transplant recipients Liver Transpl 2006;12:705-706.

10. Weinrieb RM, Van Horn DH, McLellan AT, Volpicelli JR,Calarco JS, Lucey MR. Drinking behavior and motivationfor treatment among alcohol-dependent liver transplantcandidates. J Addict Dis 2001;20:105-119.

11. Vaillant GE. The natural history of alcoholism and itsrelationship to liver transplantation. Liver Transpl Surg1997;3:304-310.

12. Vaillant GE. A 60-year follow-up of alcoholic men. Addic-tion 2003;98:1043-1051.

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