Liver Transplantation for Alcoholic Liver Disease: A Survey of Transplantation Programs in the United States James E. Everhart* and Thomas P. Beresford A lcoholic liver disease (ALD) is one of the most controversial and publicly discussed indications for liver transplantation. Every aspect of transplantation for alcoholic patients has come under scrutiny, including the selection of suitable candidates, the intensity of their evaluation, monitoring after transplantation, and prevention of relapse to drinking. Until now, liver transplantation programs have been relatively free to develop their own approaches to the special problems of liver transplantation for alcoholic patients. Consequently, it is not known how programs compare in their approaches to this common problem. To determine current practices regarding transplantation for patients with ALD, we performed a systematic survey of all liver transplantation programs in the United States. Methods Survey forms were mailed to each program in the United States using labels supplied by the United Network for Organ Sharing (UNOS). The survey was accompanied by a letter from one of the authors (T.P.B.) stating that the results would be presented at a conference on liver transplantation for the patient with ALD. Second requests and subsequent contacts were made to nonresponders. Responses were received from 69 programs that met the analysis criteria of reporting five or more initial adult liver transplants in 1995. From UNOS data it was estimated that these programs constituted 90% to 95% of all programs meeting the criteria. Survey forms were completed and returned between August and November of 1996. The survey form was constructed with the aid of the conference organizers. It comprised four pages divided into three sections of mostly multiple choice questions that focused primarily on the policies and practice of liver transplantation From the *Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, and the Veterans Affairs Medical Center, Denver, Colorado. Address reprint requests to James E. Everhart, MD, MPH, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, 45 Center Dr, Rm 6AN-12J, Bethesda, MD 20892-6600. Copyright r 1997 by the American Association for the Study of Liver Diseases 1074-3022/97/0303-0005$3.00/0 during the year 1995. The first section captured the characteristics of the center s program, such as the number of transplants done. The second and longest section concerned the pretransplant evaluation of the patient with ALD. The third section concerned posttransplantation monitoring and relapse prevention efforts. All data were entered and analyzed in SAS on a Microsoft Windows platform. 1 Comparisons of means were made by Student s t test and frequencies by exact tests. Nonparametric analysis of variance using the Kruskal-Wallis test was used to compare variables with multiple levels. Results Responses were obtained from 69 centers that reported performing initial liver transplants on five or more adult recipients during 1995. All analyses were based on the number of responses to each question, not all of which were answered by all respondents. Forms were completed by transplant surgeons (57%), hepatologists (20%), coordinators (15%), and persons familiar with the evaluation of alcoholism (8%). The distribution of transplants is shown according to the total number of transplants reported at each center, number of transplants for ALD, and percent of transplants for ALD in 1995 (Figs. 1-3). The 69 programs reported performing 3,517 initial liver transplants in adults during 1995 (mean per center, 51; range, 5-393). Only 59 centers provided information on the number of transplants performed for ALD or ALD with hepatitis C. The number of reported recipients of initial liver transplants for ALD was 849, with a range of 2 to 119 and a mean of 14. Among these 59 centers, 27.8% of transplants were reported as being for ALD. With increasing numbers of total transplants, there was a statistically nonsignificant trend toward a decreasing percentage of transplants for ALD (P 5.09). Only 5% of programs had become less restrictive in the last 5 years in listing patients with ALD, whereas 32% had become more restrictive and 63% were about the same. Fifty-one percent of respondents stated that they provide referring physicians with written criteria or guidelines on the 220 Liver Transplantation and Surgery, Vol 3, No 3 (May), 1997: pp 220-226
Survey of Transplantation Programs 221 Figure 1. Responses to question, How many adults received an initial transplant in 1995 at your center? clinical indications and exclusions for transplantation for patients with ALD. Evaluation Programs were asked which criteria were very important, less important, or not important in making the diagnosis of ALD during evaluation for transplantation (Table 1). Programs placed greatest emphasis on the evaluation by experts in alcoholism or by transplant physicians. Less emphasis was placed on the referral diagnosis and biochemical or histological evidence of ALD. All six criteria were considered very important by 12% of respondents; an additional 16% consider five of the criteria very important. Respondents that considered histology very useful in making the diagnosis of ALD were also more likely to consider biochemical tests very important (83% v 53% of other respondents; P 5.02). No other pairing of diagnostic modalities had a stronger association than expected by chance. Programs were asked about the contributions of a psychiatrist or other specialist in addiction medicine in the evaluation of patients with suspected ALD. All but two programs used at least one of these services, and 35% used all four (Table 2). Among patients with ALD, active alcohol use was considered an absolute contraindication to transplantation by 81% of programs and a relative contraindication by the remaining. The period of abstinence required before transplanting was re- Figure 2. Responses to question, How many transplants were performed for ALD or combined hepatitis C and ALD in 1995?
222 Everhart and Beresford Figure 3. Percentage of transplants for ALD in 1995, calculated from data in Figs. 1 and 2. ported as 6 months by 85% of centers. Other responses were 0 months (three centers), 3 months (four centers), and 12 months (three centers). Programs were asked whether they asked patients with ALD to sign an alcohol rehabilitation contract. Thirty-eight percent of programs always ask patients to sign a contract, 39% usually or sometimes ask patients, and 23% never ask patients. Centers were asked about the relative importance of six features in listing a patient with ALD Table 1. Responses to the Question, During Evaluation for Transplantation, How Do You Consider Each of the Following in Making a Diagnosis of Alcoholic Liver Disease? Criteria n Very Less Not Referral diagnosis 69 45 51 4 Liver histology 68 34 62 4 Biochemical evidence of alcohol dependence 68 63 25 12 Psychiatric evaluation 69 93 7 0 Transplant physician evaluation 69 80 20 0 Nonphysician evaluation 69 93 7 0 for liver transplantation (Table 3). Except for willingness to sign an alcohol rehabilitation contract, each of these features was considered very important by the majority of respondents. All six features were considered very important by 18% of centers; an additional 26% considered five features very important. Programs that always asked patients to sign an alcohol rehabilitation contract were also more likely to emphasize other criteria in deciding to list a patient with ALD (P 5.01). If drinking relapse occurred after listing, 10 centers (15%) would permanently remove the patient from the transplant list. Most centers would remove the patient from the list and reevaluate at a later time: five (7%) in 3 months, 32 (47%) in 6 Table 2. Responses to the Question, What Contributions Does a Psychiatrist or Other Expert in Addiction Medicine Make in the Evaluation of the Patient With ALD? (n 5 68) % Routinely sees each case 83 Offers a diagnosis or detailed case history 68 Actively participates in the decision to list 74 Treats alcoholism 45 None of the above 3 One contribution 23 Two contributions 10 Three contributions 29 All four contributions 35
Survey of Transplantation Programs 223 Table 3. Responses to the Question, How Is Each of the Following in Making the Decision to List a Patient With Alcoholic Liver Disease? Feature n Very Less Not Duration of abstinence 69 86 13 1 Previous failure at alcohol rehabilitation 69 59 39 1 Willingness to sign rehabilitation contract 69 45 23 32 Social or family support 69 91 9 0 Other substance abuse 69 79 21 0 Other psychiatric disorders (personality disorder, major mood disorder, or schizophrenia) 67 76 24 0 months, and 14 (21%) as clinically indicated. Only two (3%) of the centers would require counseling but not remove the patient from the list. Other centers used different periods for the time until reevaluation after relapse from 2 to 3 months to 1 to 2 years. No center would proceed to transplantation without at least counseling or reevaluation. Nine of 26 programs that always ask patients to sign a rehabilitation contract would permanently remove patients who relapsed to drinking, whereas only one of the other 43 programs would permanently remove patients who relapsed. The odds ratio for this association was 22, with a 95% confidence interval of 2.6 to 189. Forty-three percent of programs have had thirdparty payers refuse payment for transplantation for a patient with ALD because of failure to complete a set period of abstinence. Payment refusal for required counseling was reported by 26% of the respondents and refusal solely because of the diagnosis of ALD by only 12% of programs. No payment refusal for any of these reasons was reported by 40% of programs. After Transplantation All programs but one reported that they tell ALD patients not to drink any alcohol after transplantation. For patients who received transplants for other causes of liver disease, a high proportion (64%) of programs also tell patients not to drink alcohol; of the remainder, 19 (29%) recommended no more than one to two drinks per week. All programs reported that they monitor for drinking relapse after transplantation (Table 4). Except for the use of screening questionnaires and histology, each of the six methods was used by a majority of programs. Other approaches mentioned were asking the Alcoholics Anonymous sponsor, monitoring in a posttransplant support group, and using random breath tests. Efforts to prevent relapse after transplantation were made by all but two respondents (Table 5). Programs were asked to estimate the rate of relapse to drinking of any type at 2 years (Fig. 4). The rate of relapse was 0% (two programs) to 30% (mean, 14%), but the rate of relapse to addictive or uncontrolled drinking (drinking resulting in social or medical problems) was much lower, with a mean of 5% (Fig. 5). No single monitoring or prevention technique and no combination of techniques was associated with a higher rate of reported relapse to any drinking or to addictive drinking (P..10 for all comparisons). Interestingly, programs that would Table 4. Responses to the Question, How Do You Monitor Patients for Drinking Relapse After Transplantation? (n 5 69) % Ask patient 91 Ask family members 75 Through screening questions (such as CAGE or MAST questions) 17 Blood or serum tests (such as hepatic enzymes) 83 Blood or urine ethanol concentrations 64 Liver histology 42 One of the above methods 7 Two methods 9 Three methods 23 Four methods 32 Five methods 22 All six methods 7 Abbreviations: MAST, Michigan Alcoholism Screening Test.
224 Everhart and Beresford Table 5. Responses to the Question, What Efforts Does Your Program Make to Prevent Drinking Relapse After Transplantation for Alcoholic Liver Disease? (n 5 69) % Structured monitoring 55 Reinforcement of rehabilitation contract 42 Individual counseling 75 Alcoholics Anonymous or other support program 87 None of the above methods 3 One method 16 Two methods 26 Three methods 29 Four methods 26 permanently remove patients who relapse from the transplant list were also more likely to report a higher relapse rate to any alcohol drinking within 2 years of transplant (P 5.03). Stratified Analysis Responses to questions were stratified as follows: total number of transplants (5-49 or 50 or more), percent of transplants for ALD (,33% or $33%), and program restrictiveness (more restrictive in past 5 years or not more restrictive in past 5 years) to determine if these characteristics influenced treatment of the ALD patient before or after transplantation. Few of the subsequent answers were associated with these variables. Programs with at least 50 transplants were less likely to use a referral diagnosis of ALD than smaller programs (P 5.008). Both the larger programs and programs in which one third or more of transplants were for ALD were more likely than other programs to tell non-ald patients not to drink after transplantation (P 5.04 for each comparison). In addition, the larger programs were twice as likely as smaller programs to report drinking of any type 2 years after transplantation (53% v 26%; P 5.05). No other answers were associated with the stratification variables. There was no association between increasing restrictiveness in listing ALD patients for transplantation and either third-party payment refusal or rate of return to drinking. Validity The total number of adults receiving initial transplants in 1995 reported by the 69 centers was 3,517, whereas the UNOS tabulation for all US centers was 2,967. Likewise, the total number of transplants for ALD of 849 was overreported in this survey because the preliminary UNOS tabulation was no more than 765 for all centers (S. Belle, personal communication). Nevertheless, there was close agreement between the percent of transplants for ALD reported in the survey (27.8%) and by UNOS (25.8%). Figure 4. Responses to question, What is the rate of return to any drinking 2 years after transplant?
Survey of Transplantation Programs 225 Figure 5. Responses to question, What is the rate of return to addictive or uncontrolled drinking 2 years after transplant? Separate responses by two individuals were provided from six centers. Paired responses showed no greater than chance agreement for questions regarding evaluation (64% agreement; 72% expected). The 80% agreement in responses to questions on posttransplantation management was better (expected agreement, 61%; k5.49). These six centers performed an average of 85 transplants, and the paired responses differed by an average of only 9 patients. The estimated 2-year relapse rate was 15% for the six programs, whereas the paired responses differed by an average of 3%. This lack of agreement cannot necessarily be generalized to the entire survey. The fact that two responses came from the same center may indicate disagreement between transplant personnel at that particular center. Discussion Generalizations can be made about areas of strong agreement among programs that responded to the survey. First, programs have not become more lenient in listing patients with ALD for transplantation: 95% of responders are at least as restrictive now as 5 years ago. Second, most programs (85%) require 6 months of abstinence before transplantation. The agreement on 6 months is striking because this was a short-answer question without forced choices. Third, virtually all programs consider active alcohol use a contraindication to liver transplantation, and 62% would remove a relapsed patient from the transplant list permanently or for at least 6 months. Fourth, nearly all programs consider the psychiatric evaluation or opinion of alcoholism experts very important in the diagnosis of ALD. A large majority of programs ask a psychiatrist or other addiction specialist to see each patient, to offer a diagnosis or case description, and to participate actively in the decision to offer transplantation. Fifth, programs were in strong agreement on the need for social or family support in listing the ALD patient for transplantation. They also reported substance abuse other than alcohol and the presence of other severe psychiatric disorders very important deterrents to transplantation. Thus there are reasons other than history of drinking and severity of illness that determine transplantation for the patient with ALD. Most programs tell alcoholic patients not to drink after transplantation. It was somewhat surprising that two thirds of programs also tell patients receiving transplants for other reasons not to drink any alcoholic beverages after transplantation. This approach is probably considered prudent, even though little information is available on the effect of alcohol consumption in the nonalcoholic patient after transplantation. All programs monitor alcoholics for drinking after liver transplantation, most commonly by asking the patient and the patient s family. Nearly all programs also conduct prevention efforts, most often through counseling,
226 Everhart and Beresford either on an individual basis or through a support program such as Alcoholics Anonymous. Results of an earlier survey of psychosocial aspects of heart, renal, and liver transplantation were similar to those of the current study. 2 In that survey, the majority of liver candidates were interviewed by mental health professionals, most of whom were psychiatrists or social workers. Active schizophrenia, current addictive drug usage, and current heavy ethanol use were considered absolute contraindications by a large majority of both cardiac and liver programs. Noncurrent ethanol abuse was much less of a deterrent to transplant. A recent survey of six of the seven Canadian adult liver transplantation centers found that behavioral problems related to alcoholism, drug addiction, and noncompliance had a negative influence on the decision to place patients on the waiting list for liver transplantation. 3 The responses to our survey may not be an accurate representation of each transplant program s practices and policies. Some programs overstated the number of transplants performed, resulting in at least a 20% overestimation of transplants. Thus, some inaccuracy in categorizing programs according to size may have occurred. More importantly, there were numerous discrepancies in the responses from programs that completed two questionnaires. Such differences may represent true disagreements, difficulty in answering the questions, or difficulty in forcing categorization of a complex social and clinical problem. Responders to the form may have been reflecting how individual patients were treated or even how they believe patients with ALD should be treated. In addition, many programs may not yet have policies for a number of the issues raised in this survey. Nevertheless, we believe the responses overall represent a fair current reflection of liver transplantation in the United States for the patient with ALD. This survey may best be viewed as a summation of opinions of transplant experts on the appropriate approaches to treatment of patients with ALD. Acknowledgments We thank all the individuals who completed the form. We also thank the United Network Organ Sharing for providing mailing labels and Blanca Bonilla for data entry and manuscript preparation. References 1. SAS Institute Inc. SAS companion for the Microsoft Windows environment, version 6 (ed 1). Cary, NC: SAS Institute, 1993. 2. Levenson JL, Olbrisch ME. Psychosocial evaluation of organ transplant candidates: A comparative survey of process, criteria, and outcomes in heart, liver, and kidney transplantation. Psychosomatics 1993;34:314-323. 3. Mullen MA, Kohut N, Sam M, Blendis L, Singer PA. Access to adult liver transplantation in Canada: a survey and ethical analysis. Can Med Assoc J 1996;154:337-342.