Editorial A Rational Approach to Liver Transplantation for the Alcoholic Patient 'THOMAS P. BERESFORD, M.D., JEREMIAH G. TuRCOTIE, M.D., ROBERT MERION, M.D., GORDON BURTCH, M.D., FREDERIC C. BLOW, PH.D., DARRELL CAMPBELL, M.D., KIRK J. BROWER, M.D., KATHY COFFMAN, M.D., MICHAEL LUCEY, M.D.
Received May 17, 1989; revised September 27, 1989; accepted October 18, 1989. From the Departments of Psychiatry, Surgery, and Internal Medicine, University of Michigan Alcohol Research Center, Ann Arbor. Address reprint requests to Dr. Beresford, University of Michigan Alcohol Research Center, 400 East Eisenhower Parkway, Suite A, Ann Arbor, Michigan 48104. Copyright © 1990 The Academy of Psychosomatic Medicine.
VOLUME 31 • NUMBER 3 • SUMMER 1990
Organ transplant teams throughout the United States have begun only recently to face the difficult decisions of whether and when to provide hepatic transplantation procedures for alcoholic patients. This has resulted in inconsistent approaches to clinical decision making in the case of alcoholics with tenninalliver failure, approaches that reflect widely held, yet sometimes antagonistic, values. Few have wished to document their concerns in professional literature, fearing legal action, administrative responses from health insurance institutions, or public opprobrium. Likewise, despite the frequency of liver failure due to alcoholism, there has been little or no application of the knowledge gained from 40 years of alcoholism research to the problem of how to evaluate patients for transplant. This may have stemmed from a belief among physicians that alcoholism is a unifonnly unpredictable illness with an ultimately poor prognosis. According to this view, giving an alcoholic a new liver is, at best, a risky proposition and, at worst, a waste of a life-saving procedure for some other nonalcoholic patient. This seems to have been the view of the Consensus Development Panel of the National Institutes of Health in 1983 when they openly stated that alcoholic cirrhosis and alcoholic hepatitis should be viewed as indications of a need for liver transplant in "only a small proportion of cases. "I They listed two criteria for choosing which patients might be considered appropriate for liver transplantation: I) those with "established clinical indicators of fatal outcome" and 2) those who are "judged likely to abstain from alcohol." They did not include any other reference to alcoholism, nor did they offer any guidance on how to judge the likelihood of abstinence. Since that time, transplant centers have approached the question of orthotopic transplantation for the alcoholic with differing inclusion and exclusion requirements. For many teams, the chief prognostic criterion has been the length of time the patient has remained abstinent from alcohol prior to pretransplant evaluation. Generally used as an exclusion criterion, the required period has been as brief as one or two months and as long as two years. For many transplant centers the abstinence criterion is an infonnal one and does not appear to be based on any empirical studies of alcoholism prognosis with or without transplant. A recent court case in Michigan highlighted this point. An alcoholic patient sued the state Medicaid Board for refusing payment for a liver transplant operation because, in the Board's view, the patient had not been alcohol-free for a sufficient period of time. 2 In deciding in the patient's favor, the court noted that the Board had applied an overly strict criterion: it had required the patient to demonstrate a length of preoper241
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ative sobriety (two years) that was longer than the likely natural course of his fatal illness (alcoholic cirrhosis). At the same time. the court noted that the Board had failed to consult any experts in the field of alcoholism in order to establish more reasonable and less arbitrary standards of inclusion and exclusion. The court challenged transplant providers and experts in alcoholism to present a humane and reasonable set of criteria, based on present knowledge, that would guide those making the difficult decision as to whether or not to provide this treatment when no alternative intervention exists. Other pressures are beginning to affect the clinical decision process. Until recently, the low success rate of liver transplantation among patients suffering from alcoholic cirrhosis served to dampen enthusiasm for the procedure among patients and surgeons alike. In one series only 20% survived for three years postoperatively.' Much of this trend may be linked to the fact that the transplant procedure occurred in the setting of unstable cardiac function or decompensated cirrhosis, both of which are common in this group of patients. While this rate documents the high risk for severely ill alcoholic cirrhotic patients, one group of authors has pointed out that the survival rate is no lower than that seen in other causes of decompensated cirrhosis. 4 The largest reported series performed since the introduction of cyclosporine pays careful attention to intercurrent physical conditions that worsen prognosis, and it lists a 73% two-year survival rate for transplanted alcoholic cirrhotic patients. ~ This was no different from that for transplanted patients with non-alcohol-related liver failure. Increasingly successful liver transplantation will likely increase the demand for livers by persons with alcoholism. Our program already has seen a tripling of physician referrals for alcoholic patients wanting hepatic transplant. This pressure is very likely to increase because of the magnitude of the problem. Alcoholism is a disease of massive proportions, affecting some 7% to 10% of Americans. 6 Fifteen percent of those persons suffering from alcoholism will develop cirrhosis,? the most frequent cause of liver failure in the United States today. Translated into numbers, this means that about one to two million Americans suffer from alcoholic cirrhosis. An attempt to provide new organs for so many people would overwhelm current resources. Yet the alcoholic cirrhotic population is composed of specific subgroups that may lay special claim to the transplant procedure. For example, some studies suggest that alcoholic cirrhosis occurs disproportionately in women who drink heavily, compared with heavy-drinking men. 8 An argument could be made that, because of this gender difference, any restriction on the ability to provide liver transplantation would discriminate against women. 242
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The cost of the procedure is high, varying from approximately $100,000 to as much as $300,000 per episode, depending upon the number of postoperative complications. At the same time, the availability of suitable organs for transplantation is low, requiring judicious conservation of a precious resource. For some, this justifies a reluctance to provide alcoholics with new livers because they do not deserve them or cannot be trusted to take proper care of a new organ, having "willfully" destroyed the liver with which they were born. Others enthusiastically would offer a transplant procedure to alcoholic persons who had demonstrated some form of accomplishment in other areas of their life, despite their alcoholism. 9 While emotionally charged issues such as these argue for a more objective approach. 10 the concern about an alcoholic's ability to take care of a "new" liver is a universally valid one and must be addressed. Faced with present clinical dilemmas and the increasing pressures outlined above. we have approached the problem of the alcoholic through the application of current knowledge of those factors bearing on the prognosis for sustained recovery from alcoholism. From this, we hope to offer a useful means for assessing the suitability of alcoholics for liver transplant. viewed solely in the context of alcoholism as an addictive illness. Because alcoholism is a complex disease. no single inclusion or exclusion criterion. such as length of prior abstinence. will likely provide a simple answer to this problem. In what follows, therefore, we shall attempt three interrelated discussions: I) a brief review of prognostic indicators of both short- and long-term remission from alcoholism (abstinence from alcohol). 2) a presentation of our own experience in evaluating and following alcoholic patients who present for the liver transplant procedure. and 3) a discussion of the decisionmaking process itself. METHODS Applying Current Knowledge Prognostic dilemmas. How can we predict the likelihood of stable, long-term remission in an alcohol-dependent person after hepatic transplant? It must be said at the outset that we have no clear way of measuring or predicting this at the present time. At best, current knowledge offers a series of factors which, when present, offer evidence for the patient's maintaining a stable remission from alcoholism. From this it follows that careful assessment can offer I) a view of how much a patient has done to maximize his or her chances of establishing a long-term remission or 2) a set of goals for medical and VOLUME 31· NUMBER 3· SUMMER 1990
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psychosocial posttransplant intervention that will serve to maximize longevity and health. In our clinical experience, both factors have been necessary. Both, moreover, can be accomplished in the preferred situation, i.e., when a patient presents well in advance of transplant and affords the transplant team the time required for a thorough evaluation of alcohol use. Establishing a set of posttransplant goals may be the only option in the more exigent situation in which a patient near death presents with little or no leisure for detailed alcohol-use assessment. This is not to say that careful evaluation or efforts to contact the patient's family should not be attempted in the latter situation, but that the timing may not always be propitious. Nonetheless, it is always best to have a clear sense of the patient's pattern of alcohol use prior to transplant, especially in those cases in which recent behavior may contraindicate the procedure. It is always best to define the relevant clinical parameters as clearly as possible. Definitions and diagnoses. For the present discussion, "remission" is defined as total abstinence from alcohol. We realize that for some, such as the members of the Alcoholics Anonymous (AA) fellowship, abstinence alone falls far short of the stable social and spiritual adjustment meant by the term "sobriety." In the discussion that follows, we hope to make use of the forces and phenomena that sobriety entails as we discuss long-term prognosis, and we hope that these will be recognizable. For others, such as the behavioral psychologists, the concept of total abstinence may not be defensible in a condition in which relapse behavior is frequent. In the high-risk and high-gain medical setting of liver transplants, after which relapse may lead directly to death, we believe that total abstinence is the only workable definition. As to the length of remission, we define "short-term" as less than three years and "long-term" as greater than three years. Many persons familiar with alcoholism research will argue with this point since short-term outcome studies rarely chart progress beyond two years, and many focus only on a one-year follow-up. Our choice of this definition is based on Vaillant's landmark studies6 of prognostic factors, as discussed below. When considering an illness with a natural history that courses over decades, a three-year abstinence seems to us the minimum for any discussion of long-term abstinence. Finally, let us define two forms of "alcoholism" itself. While the presence of alcoholism may seem obvious in the face of proven alcoholic cirrhosis, the former is not a precondition for the latter. Alcoholic cirrhosis results from physiologic responses to prolonged toxic insults from ethanol. Alcohol dependence, by contrast, is an addictive disease with signs and 244
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symptoms common to other addictive diseases. The hallmarks of alcohol addiction include tolerance to ethanol, withdrawal symptoms upon abstinence, impaired control of usage once drinking begins, and impaired social functioning resulting from uncontrolled drinking. For a distinct subgroup, an intense craving for alcohol between drinking bouts may also be part of the constellation of symptoms. One need not be addicted to alcohol in order to imbibe quantities sufficient to injure one's liver. There are people within our clinical experience (see below) as well as in the experience of others (see Jellinek's discussion of beta alcoholism ll ), in whom heavy, but controlled, use of alcohol resulted in cirrhosis, despite the absence of addictive symptoms and signs. Patients who drink addictively must be separated from those who may drink heavily but who have not lost control of their ability to use alcohol. Nondependent persons appear much more likely to remain abstinent than those in whom the addictive process has been established. For the present discussion, we refer to the former group of patients as sufferers of alcohol abuse, not of alcohol dependence, the more serious diagnosis. This is consistent with others who have used the same terms. 12 . 13 For purposes of pretransplant evaluation, the DSM-III-R diagnostic criteria for alcohol dependence '3 are probably the best at hand, although they may not cover the entire spectrum of patients included by the term "alcoholism." The difficulties in establishing a clinical diagnosis of alcoholism have been well reviewed. 6 For present purposes, we have used the DSMIII-R criteria, but we also note that the symptomatic expression of alcoholism varies widely among individuals. Because of this, like the triage surgeon, we emphasize that in clinical practice the final alcoholism diagnostic assessment should be made by the clinician most experienced in diagnosing and treating alcoholism. In this study all but three of the evaluations were completed by a senior psychiatrist with over 12 years of experience in evaluating alcoholic patients in the general hospital. The remaining assessments were supervised by the same psychiatrist.
Measures of the likelihood of abstinence. Once proper diagnosis has been established, the clinician must look to prognostic factors that will suggest the likelihood of a longterm remission from alcohol addiction. These factors appear in three main areas of functioning: 1) the extent to which alcohol dependence (alcoholism) is recognized by the patients and by their families. both as a present problem and as a condition that must be dealt with postoperatively, 2) the degree of present social stability. and 3) the nature and extent of changes in life-style conducive to long-term abstinence from ethanol. VOLUME 31· NUMBER 3· SUMMER 1990
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I. Patient andfamily recognition. The most salient question for the clinician is whether or not the patient understands and agrees with the diagnosis of alcoholism in a way that shows an unambivalent approach to remission of the disease. This presumes that the clinician has made a diagnosis of alcohol dependence. as noted above. and is sufficiently confident in that diagnosis to discuss it with the person. While the details of how to address this difficult point in the clinical situation are not appropriate here. the process itself focuses clinician. patient. and family on a life-threatening problem in such a way as to ally them. In our setting. we engage patient and family for three clinical reasons. First. a corroborating third party is always useful in establishing an alcohol-use history. Second, the clinician gains access to the network of social support that must sustain the patient not only through the transplant procedure, but through remission from alcoholism as well. If the persons who make up that network are unaware of the alcoholism or approach it in a destructive manner. the likelihood of relapse will increase for many patients. Third. the clinician must assess the family's understanding of alcoholism and their willingness both to set limits on the patient and to call for professional help should drinking resume. The willingness of the family to provide clear limits in tolerating drinking behavior appears to be a powerful prognostic indicator of remission from alcoholism. 14 2. Social stability. In earlier work. Strauss and Bacon 's established four measures of social functioning that consistently characterized alcoholic patients who were likely to remain in treatment over the short term. These assess permanence of work. of domicile, and of significant intimate relationships. While these indices are not exhaustive. and while they are not replacements for a careful social history. they offer a beginning point for measurement and follow-up. 3. Changes in style ofliving. Vaillant b.'4 presents. to our knowledge, the only prospective data carried beyond two years that focus specifically on the factors in an alcoholic person's life that promote abstinence. He distinguished "securely abstinent" (three years or more) as opposed to "ever abstinent" (more than two years) on the basis of the presence of two or more of the following in the clinical course: a substitute "dependency." a source of hope or self-esteem, acceptance by another human being, and a negative behavioral reinforcer. In Vaillant's study.b the "securely abstinent" group 246
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had two or more of the four prognostic factors in their favor. while the comparison "ever abstinent" group evidenced only one or none. These factors predated the extended periods of abstinence and represented changes in living made by those alcohol-dependent people who were most likely to find themselves in remission three years later. It is important for clinicians to understand that for most patients the decision to remain abstinent is most often a product of an internal struggle with an ambivalence toward alcohol use. For long-term abstinence to occur, the struggle must result in a decision not to drink. For many alcoholic people. this decision must be made daily. For some transplant candidates, the presence of a painful or life-threatening medical condition may assist in the decision not to drink. along with one or more of the positive life predictors that Vaillant identified. For this study. we combined all of the above factors into a prognostic scale. This research scale is available from the authors.
RESULTS The study subjects were patients referred for evaluation of alcohol and substance use as part of pretransplant assessment. Of the 37 total subjects, 20 (54%) were male. and 17 (46%) were female. The mean age for the total group was 41.6 years. The mean age for males (41.5 years) did not differ significantly from that for females (41.7 years). While the ages ranged from 13 to 63, most patients presented between ages 30 and 49 years (Figure I). FIG URE I. Age distribution of patients assessed for liver transplant (N=37)
m Male
... .
•r.a
'u c :>
~
Female All
10
U.
10·19
20·29
30-39
40-49
50·59
60-69
Age Group
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TABLE 1. Causes of liver failure in 37 patients Number with Diagnosis"
Disease
Alcoholic cirrhosis Chronic active hepatitis Non-A. non-B hepatitis Alpha-. anti-trypsin deficit Alcoholic hepatitis Cryptogenic cirrhosis Primary billiary cirrhosis Autoimmune hepatitis
26 4 2 2 I I
• I
"Total diagnoses exceed 37 since some patients had more than one diagnosis.
TABLE 2.
Diagnoses of 37 patients according to DSM·III·R
Diagnosis (DSM·III·R)
Number with Diagnosis
Alcohol dependence (303.90) 29 Alcohol abuse" (305.70) 4 Polydrug dependence (304.90) 6 Opioid dependence (304.00) I Amphetamine dependence (304.40)
I
Conduct disorder (3 12.90) No diagnosis (000.00)
• 3
"D5M-IIl crileria were used.
TABLE 3.
Length of preoperative sobriety in 34 patients
Length of Time 3 months but 6 months bUI < J year > I year but 3 ears
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Number of Patients 9 5 6 10 4
Table I lists the frequency of pathologic diagnoses responsible for liver failure. Each diagnosis was established by the referring internist and was confirmed by the transplant team physicians and surgeons. Most included a tissue diagnosis read by a pathologist. Twenty-six patients (70%) suffered from alcoholic cirrhosis. Four patients (11%) suffered from chronic hepatitis B infection; each of these patients presented a history of intravenous (iv) drug use, although none had been active in iv use within two years of the evaluation. Sixteen (62%) of the 26 patients with alcoholic cirrhosis were male, and 10 (38%) were female. The average age of the male alcohol cirrhotics was 41.5 years (range, 31 to 58 years), and the females averaged 43.0 years of age (range, 27 to 55 years); the difference in mean age was not significant. We list DSM-llI-R psychiatric diagnoses in Table 2. Twenty-nine patients (78%) fulfilled criteria for alcohol dependency, while four patients (II %) met the DSM-llI criteria for alcohol abuse without a history consistent with addictive signs of alcoholism. Eight patients (22%) described a history of past dependence on one or more drugs. Six of these (16% of the total) suffered at some time in their lives from dependence on two or more substances, one of which was alcohol; in all but one case use had ceased at least three years prior to evaluation. Of the 34 patients with a history of drug or alcohol dependence, 26 (76%) used alcohol alone, while eight (24%) used alcohol along with other substances at some point in their past. Only one patient (3%) in this group presented a non-substance-related psychiatric diagnosis. It is noteworthy that three patients (8%) gave no history of alcohol or drug dependence or abuse; in each case the lack ofdiagnosis was confirmed by one or more corroborating family members. Of the 34 patients with confirmed use of alcohol, preassessment lengths of abstinence varied from a few months to over three years; the longest was 10 years. We show these frequencies in Table 3. Twenty patients (59%) had been alcohol-free for less than one year. Only four (12%) had achieved long-term sobriety (defined by cessation of use) for more than three years. Interestingly, only seven of the patients (21 %) had been in any alcoholism treatment programs prior to the evaluation. As discussed below, the remaining 79% were "fresh" cases, a positive sign prognostically. We found no association of either length of sobriety or prior treatment with postoperative outcome, although we caution that the numbers of cases were too small for statistical confidence. Preoperative cognitive functioning was an important part of the assessment since it had an effect on postoperative care and subsequent compliance with the regimen of immunosuppressive medicines. As presented in Table 4, 13 patients (35%) PSYCHOSOMATICS
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suffered from documented hepatic encephalopathy at some point in their clinical history. Only five (14%) patients fell below the cut-off score for the Hopkins Mini-Mental State examination l6 at the time of preoperative assessment. This improvement in mental state most likely reflected stabilized liver functioning through preoperative care. Five (33%) of the 15 patients who proceeded to transplant encountered postoperative delirium. Due to the small numbers of patients involved, we cannot suggest a relation between pre- and postoperative mental functioning at this time. We list the frequencies of patient and family acceptance of the patient's alcohol abuse or dependence in Table 5. Twenty-four (71 %) of the patients with DSM-III-R alcohol dependence or abuse both recognized and accepted their condition and were willing to enter some form of treatment. All but four were joined by their families in this acceptance. Ten patients (28%) did not initially recognize alcohol dependence as an illness. Three of the to died during the preoperative evaluation conducted in the intensive care unit to which they had been admitted prior to referral for hepatic transplant evaluation. A fourth patient underwent transplant but did not survive the procedure. One patient was deemed inappropriate for the procedure medically and psychiatrically. Two patients remain under consideration for transplant. The final three patients were referred to alcoholism treatment after stabilization oftheir liver failure. Two successfully completed treatment and are currently on the transplant list. In sum, five of these 10 patients suffered untoward outcomes at the time of this writing. By contrast, 14 of the 21 patients who accepted their dependence as a disease to be reckoned with underwent transplant; three died within three months. Five of the remaining seven are on the waiting list or are being followed medically. One patient was referred for alcoholism treatment, and the final patient was deemed inappropriate because of compliance difficulties with the preoperative evaluation. In total, four of the 21 patients (19%) who recognized their alcohol dependence at the pretransplant interview suffered untoward outcomes. The Strauss-Bacon social stability index, a commonly used measure of short-term compliance with alcoholism treatment, described these patients as a good prognosis group (Table 6). Fully 29 (85%) of the 34 patients scored three or four points on this index. Taken alone, however, this measure did not appear to differentiate outcome as well as it might in combination with the long-term prognostic factors. We list the frequencies of Vaillant's long-term factors in Table 7. The first three "positive" factors, suggesting life changes in the direction of health, occurred far more frequently than did the one "negative" factor suggesting behavioral modVOLUME 31' NUMBER 3· SUMMER 1990
TABLE 4.
Pre- and postoperative cognitive functioning in 37 patients
Cognitive Functioning
Number of Patients
Pre-op encephalopathy by history 13 present absent 24 Pre-op Mini-Mental State score ~4
32 5
$23 Post-op delirium present absent
5 13
TABLE S. Preoperative acceptance of alcohol dependence! abuse in 34 patients Points
Number of Patients
4 Patient and family acknowledge diagnosis 3 Patient only 2 Family only I Neither patient nor family
20 4 6 4
TABLE 6. Social stability of 34 patients based on the Strauss-Bacon index Points
Number of Patients·
4
19
3 2 I
10 4 I
Note: This index assigns one point for each of the following: presently married and living with spouse, living alone, stable address for the past 2 years, stable job for the past 3 years. a Alcohol-dependent and -abuse patients combined
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ification. Recalling Vaillant's original use of these factors-two or more suggesting TABLE 7. Long-term prognostic factors promoting absti· nence from alcohol a likelihood of abstinence of three years or more-24 (77%) of the patients in this n(%) Yes No Prognostic Factor sample exhibited two or more factors 26 (58) II Substitute activities 15 while seven (23%) showed one or none. 26 (69) 8 Source of hope 18 Considering the latter group, four patients 27 (81) 21 6 Social rehab relationship had untoward outcomes (two died 25 (12) 22 Negative consequencesa 3 posttransplant; two were deemed inapproaDoes not include terminal liver failure priate) and three did well (one is alive and well posttransplant; two entered alcoholism treatment and await transplant). TABLE 8. DSM·m·R diagnosis and outcome (1987-1988) Twelve of the good prognosis group are No. Who Are alive and well posttransplant while two Alive and Well (%) Diagnosis n died postoperatively; none were deemed 10(77%) Alcohol dependence 13 inappropriate for the procedure. At the 2 2 Alcohol abuse time of this report, the remaining patients I o Poly-drug abuse either have been listed for the procedure 2 2 None 14 (78%) or are continuing in the medical evaluation 18 Total process. Table 8 lists the outcome in relation to psychiatric diagnosis. These data suggest an outcome in the TABLE 9. Clinical decisions for treatment ofalcohol range of those reported by other transplant programs reporting abuser.Jdependen~a on their experience in this population. Table 9 summarizes our (1987-1988) experience in making clinical decisions in this complex setting. Decision N=34 As noted above, we make every effort to treat alcohol depen15 Received transplanl dence when this is possible. The most difficult decision, dis9 Put on waiting list or on hold cussed more fully below, is whether a transplant is too great a 4 In evaluation process risk for psychiatric reasons that might appear less objective 4 NOI treated than those encountered in more "concrete" aspects of medicine. Medical cOnlraindication 2 Based on our experience, we estimate that we are likely to 2 Noncompliance encounter that decision in about 10% of cases; we deemed two Died during evaluation 2 (6%) of 34 to be unacceptably high-risk patients solely on the aDiagnosed according (0 DSM-III-R basis of their preoperative behavior and efforts at compliance. Finally, Table 10 summarizes our experience with the social stability score, the TABLE 10. Decisions vs. predictive scales in 17 alcohol· dependent patien~ score on Vaillant's long-tenn prognostic factors, and the simple addition of the two Received Did Not Receive Transplant (Deceased) Transplant Scores as a combined score. While the frequenSocial stability cies are small, they suggest that the prog13 (4) 3 or 4 nostic factors score or the combined score lor 2 2 may offer better methods for further study Long-term score of this population than the measure of 12 (2) >6 o social stability alone. The clinical prob3 (2) 2 12 more complexity of assessment than we 3 (2)
Received May 17, 1989; revised September 27, 1989; accepted October 18, 1989. From the Departments of Psychiatry, Surgery, and Internal Medicine, University of Michigan Alcohol Research Center, Ann Arbor. Address reprint requests to Dr. Beresford, University of Michigan Alcohol Research Center, 400 East Eisenhower Parkway, Suite A, Ann Arbor, Michigan 48104. Copyright © 1990 The Academy of Psychosomatic Medicine.
VOLUME 31 • NUMBER 3 • SUMMER 1990
Organ transplant teams throughout the United States have begun only recently to face the difficult decisions of whether and when to provide hepatic transplantation procedures for alcoholic patients. This has resulted in inconsistent approaches to clinical decision making in the case of alcoholics with tenninalliver failure, approaches that reflect widely held, yet sometimes antagonistic, values. Few have wished to document their concerns in professional literature, fearing legal action, administrative responses from health insurance institutions, or public opprobrium. Likewise, despite the frequency of liver failure due to alcoholism, there has been little or no application of the knowledge gained from 40 years of alcoholism research to the problem of how to evaluate patients for transplant. This may have stemmed from a belief among physicians that alcoholism is a unifonnly unpredictable illness with an ultimately poor prognosis. According to this view, giving an alcoholic a new liver is, at best, a risky proposition and, at worst, a waste of a life-saving procedure for some other nonalcoholic patient. This seems to have been the view of the Consensus Development Panel of the National Institutes of Health in 1983 when they openly stated that alcoholic cirrhosis and alcoholic hepatitis should be viewed as indications of a need for liver transplant in "only a small proportion of cases. "I They listed two criteria for choosing which patients might be considered appropriate for liver transplantation: I) those with "established clinical indicators of fatal outcome" and 2) those who are "judged likely to abstain from alcohol." They did not include any other reference to alcoholism, nor did they offer any guidance on how to judge the likelihood of abstinence. Since that time, transplant centers have approached the question of orthotopic transplantation for the alcoholic with differing inclusion and exclusion requirements. For many teams, the chief prognostic criterion has been the length of time the patient has remained abstinent from alcohol prior to pretransplant evaluation. Generally used as an exclusion criterion, the required period has been as brief as one or two months and as long as two years. For many transplant centers the abstinence criterion is an infonnal one and does not appear to be based on any empirical studies of alcoholism prognosis with or without transplant. A recent court case in Michigan highlighted this point. An alcoholic patient sued the state Medicaid Board for refusing payment for a liver transplant operation because, in the Board's view, the patient had not been alcohol-free for a sufficient period of time. 2 In deciding in the patient's favor, the court noted that the Board had applied an overly strict criterion: it had required the patient to demonstrate a length of preoper241
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ative sobriety (two years) that was longer than the likely natural course of his fatal illness (alcoholic cirrhosis). At the same time. the court noted that the Board had failed to consult any experts in the field of alcoholism in order to establish more reasonable and less arbitrary standards of inclusion and exclusion. The court challenged transplant providers and experts in alcoholism to present a humane and reasonable set of criteria, based on present knowledge, that would guide those making the difficult decision as to whether or not to provide this treatment when no alternative intervention exists. Other pressures are beginning to affect the clinical decision process. Until recently, the low success rate of liver transplantation among patients suffering from alcoholic cirrhosis served to dampen enthusiasm for the procedure among patients and surgeons alike. In one series only 20% survived for three years postoperatively.' Much of this trend may be linked to the fact that the transplant procedure occurred in the setting of unstable cardiac function or decompensated cirrhosis, both of which are common in this group of patients. While this rate documents the high risk for severely ill alcoholic cirrhotic patients, one group of authors has pointed out that the survival rate is no lower than that seen in other causes of decompensated cirrhosis. 4 The largest reported series performed since the introduction of cyclosporine pays careful attention to intercurrent physical conditions that worsen prognosis, and it lists a 73% two-year survival rate for transplanted alcoholic cirrhotic patients. ~ This was no different from that for transplanted patients with non-alcohol-related liver failure. Increasingly successful liver transplantation will likely increase the demand for livers by persons with alcoholism. Our program already has seen a tripling of physician referrals for alcoholic patients wanting hepatic transplant. This pressure is very likely to increase because of the magnitude of the problem. Alcoholism is a disease of massive proportions, affecting some 7% to 10% of Americans. 6 Fifteen percent of those persons suffering from alcoholism will develop cirrhosis,? the most frequent cause of liver failure in the United States today. Translated into numbers, this means that about one to two million Americans suffer from alcoholic cirrhosis. An attempt to provide new organs for so many people would overwhelm current resources. Yet the alcoholic cirrhotic population is composed of specific subgroups that may lay special claim to the transplant procedure. For example, some studies suggest that alcoholic cirrhosis occurs disproportionately in women who drink heavily, compared with heavy-drinking men. 8 An argument could be made that, because of this gender difference, any restriction on the ability to provide liver transplantation would discriminate against women. 242
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The cost of the procedure is high, varying from approximately $100,000 to as much as $300,000 per episode, depending upon the number of postoperative complications. At the same time, the availability of suitable organs for transplantation is low, requiring judicious conservation of a precious resource. For some, this justifies a reluctance to provide alcoholics with new livers because they do not deserve them or cannot be trusted to take proper care of a new organ, having "willfully" destroyed the liver with which they were born. Others enthusiastically would offer a transplant procedure to alcoholic persons who had demonstrated some form of accomplishment in other areas of their life, despite their alcoholism. 9 While emotionally charged issues such as these argue for a more objective approach. 10 the concern about an alcoholic's ability to take care of a "new" liver is a universally valid one and must be addressed. Faced with present clinical dilemmas and the increasing pressures outlined above. we have approached the problem of the alcoholic through the application of current knowledge of those factors bearing on the prognosis for sustained recovery from alcoholism. From this, we hope to offer a useful means for assessing the suitability of alcoholics for liver transplant. viewed solely in the context of alcoholism as an addictive illness. Because alcoholism is a complex disease. no single inclusion or exclusion criterion. such as length of prior abstinence. will likely provide a simple answer to this problem. In what follows, therefore, we shall attempt three interrelated discussions: I) a brief review of prognostic indicators of both short- and long-term remission from alcoholism (abstinence from alcohol). 2) a presentation of our own experience in evaluating and following alcoholic patients who present for the liver transplant procedure. and 3) a discussion of the decisionmaking process itself. METHODS Applying Current Knowledge Prognostic dilemmas. How can we predict the likelihood of stable, long-term remission in an alcohol-dependent person after hepatic transplant? It must be said at the outset that we have no clear way of measuring or predicting this at the present time. At best, current knowledge offers a series of factors which, when present, offer evidence for the patient's maintaining a stable remission from alcoholism. From this it follows that careful assessment can offer I) a view of how much a patient has done to maximize his or her chances of establishing a long-term remission or 2) a set of goals for medical and VOLUME 31· NUMBER 3· SUMMER 1990
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psychosocial posttransplant intervention that will serve to maximize longevity and health. In our clinical experience, both factors have been necessary. Both, moreover, can be accomplished in the preferred situation, i.e., when a patient presents well in advance of transplant and affords the transplant team the time required for a thorough evaluation of alcohol use. Establishing a set of posttransplant goals may be the only option in the more exigent situation in which a patient near death presents with little or no leisure for detailed alcohol-use assessment. This is not to say that careful evaluation or efforts to contact the patient's family should not be attempted in the latter situation, but that the timing may not always be propitious. Nonetheless, it is always best to have a clear sense of the patient's pattern of alcohol use prior to transplant, especially in those cases in which recent behavior may contraindicate the procedure. It is always best to define the relevant clinical parameters as clearly as possible. Definitions and diagnoses. For the present discussion, "remission" is defined as total abstinence from alcohol. We realize that for some, such as the members of the Alcoholics Anonymous (AA) fellowship, abstinence alone falls far short of the stable social and spiritual adjustment meant by the term "sobriety." In the discussion that follows, we hope to make use of the forces and phenomena that sobriety entails as we discuss long-term prognosis, and we hope that these will be recognizable. For others, such as the behavioral psychologists, the concept of total abstinence may not be defensible in a condition in which relapse behavior is frequent. In the high-risk and high-gain medical setting of liver transplants, after which relapse may lead directly to death, we believe that total abstinence is the only workable definition. As to the length of remission, we define "short-term" as less than three years and "long-term" as greater than three years. Many persons familiar with alcoholism research will argue with this point since short-term outcome studies rarely chart progress beyond two years, and many focus only on a one-year follow-up. Our choice of this definition is based on Vaillant's landmark studies6 of prognostic factors, as discussed below. When considering an illness with a natural history that courses over decades, a three-year abstinence seems to us the minimum for any discussion of long-term abstinence. Finally, let us define two forms of "alcoholism" itself. While the presence of alcoholism may seem obvious in the face of proven alcoholic cirrhosis, the former is not a precondition for the latter. Alcoholic cirrhosis results from physiologic responses to prolonged toxic insults from ethanol. Alcohol dependence, by contrast, is an addictive disease with signs and 244
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symptoms common to other addictive diseases. The hallmarks of alcohol addiction include tolerance to ethanol, withdrawal symptoms upon abstinence, impaired control of usage once drinking begins, and impaired social functioning resulting from uncontrolled drinking. For a distinct subgroup, an intense craving for alcohol between drinking bouts may also be part of the constellation of symptoms. One need not be addicted to alcohol in order to imbibe quantities sufficient to injure one's liver. There are people within our clinical experience (see below) as well as in the experience of others (see Jellinek's discussion of beta alcoholism ll ), in whom heavy, but controlled, use of alcohol resulted in cirrhosis, despite the absence of addictive symptoms and signs. Patients who drink addictively must be separated from those who may drink heavily but who have not lost control of their ability to use alcohol. Nondependent persons appear much more likely to remain abstinent than those in whom the addictive process has been established. For the present discussion, we refer to the former group of patients as sufferers of alcohol abuse, not of alcohol dependence, the more serious diagnosis. This is consistent with others who have used the same terms. 12 . 13 For purposes of pretransplant evaluation, the DSM-III-R diagnostic criteria for alcohol dependence '3 are probably the best at hand, although they may not cover the entire spectrum of patients included by the term "alcoholism." The difficulties in establishing a clinical diagnosis of alcoholism have been well reviewed. 6 For present purposes, we have used the DSMIII-R criteria, but we also note that the symptomatic expression of alcoholism varies widely among individuals. Because of this, like the triage surgeon, we emphasize that in clinical practice the final alcoholism diagnostic assessment should be made by the clinician most experienced in diagnosing and treating alcoholism. In this study all but three of the evaluations were completed by a senior psychiatrist with over 12 years of experience in evaluating alcoholic patients in the general hospital. The remaining assessments were supervised by the same psychiatrist.
Measures of the likelihood of abstinence. Once proper diagnosis has been established, the clinician must look to prognostic factors that will suggest the likelihood of a longterm remission from alcohol addiction. These factors appear in three main areas of functioning: 1) the extent to which alcohol dependence (alcoholism) is recognized by the patients and by their families. both as a present problem and as a condition that must be dealt with postoperatively, 2) the degree of present social stability. and 3) the nature and extent of changes in life-style conducive to long-term abstinence from ethanol. VOLUME 31· NUMBER 3· SUMMER 1990
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I. Patient andfamily recognition. The most salient question for the clinician is whether or not the patient understands and agrees with the diagnosis of alcoholism in a way that shows an unambivalent approach to remission of the disease. This presumes that the clinician has made a diagnosis of alcohol dependence. as noted above. and is sufficiently confident in that diagnosis to discuss it with the person. While the details of how to address this difficult point in the clinical situation are not appropriate here. the process itself focuses clinician. patient. and family on a life-threatening problem in such a way as to ally them. In our setting. we engage patient and family for three clinical reasons. First. a corroborating third party is always useful in establishing an alcohol-use history. Second, the clinician gains access to the network of social support that must sustain the patient not only through the transplant procedure, but through remission from alcoholism as well. If the persons who make up that network are unaware of the alcoholism or approach it in a destructive manner. the likelihood of relapse will increase for many patients. Third. the clinician must assess the family's understanding of alcoholism and their willingness both to set limits on the patient and to call for professional help should drinking resume. The willingness of the family to provide clear limits in tolerating drinking behavior appears to be a powerful prognostic indicator of remission from alcoholism. 14 2. Social stability. In earlier work. Strauss and Bacon 's established four measures of social functioning that consistently characterized alcoholic patients who were likely to remain in treatment over the short term. These assess permanence of work. of domicile, and of significant intimate relationships. While these indices are not exhaustive. and while they are not replacements for a careful social history. they offer a beginning point for measurement and follow-up. 3. Changes in style ofliving. Vaillant b.'4 presents. to our knowledge, the only prospective data carried beyond two years that focus specifically on the factors in an alcoholic person's life that promote abstinence. He distinguished "securely abstinent" (three years or more) as opposed to "ever abstinent" (more than two years) on the basis of the presence of two or more of the following in the clinical course: a substitute "dependency." a source of hope or self-esteem, acceptance by another human being, and a negative behavioral reinforcer. In Vaillant's study.b the "securely abstinent" group 246
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had two or more of the four prognostic factors in their favor. while the comparison "ever abstinent" group evidenced only one or none. These factors predated the extended periods of abstinence and represented changes in living made by those alcohol-dependent people who were most likely to find themselves in remission three years later. It is important for clinicians to understand that for most patients the decision to remain abstinent is most often a product of an internal struggle with an ambivalence toward alcohol use. For long-term abstinence to occur, the struggle must result in a decision not to drink. For many alcoholic people. this decision must be made daily. For some transplant candidates, the presence of a painful or life-threatening medical condition may assist in the decision not to drink. along with one or more of the positive life predictors that Vaillant identified. For this study. we combined all of the above factors into a prognostic scale. This research scale is available from the authors.
RESULTS The study subjects were patients referred for evaluation of alcohol and substance use as part of pretransplant assessment. Of the 37 total subjects, 20 (54%) were male. and 17 (46%) were female. The mean age for the total group was 41.6 years. The mean age for males (41.5 years) did not differ significantly from that for females (41.7 years). While the ages ranged from 13 to 63, most patients presented between ages 30 and 49 years (Figure I). FIG URE I. Age distribution of patients assessed for liver transplant (N=37)
m Male
... .
•r.a
'u c :>
~
Female All
10
U.
10·19
20·29
30-39
40-49
50·59
60-69
Age Group
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TABLE 1. Causes of liver failure in 37 patients Number with Diagnosis"
Disease
Alcoholic cirrhosis Chronic active hepatitis Non-A. non-B hepatitis Alpha-. anti-trypsin deficit Alcoholic hepatitis Cryptogenic cirrhosis Primary billiary cirrhosis Autoimmune hepatitis
26 4 2 2 I I
• I
"Total diagnoses exceed 37 since some patients had more than one diagnosis.
TABLE 2.
Diagnoses of 37 patients according to DSM·III·R
Diagnosis (DSM·III·R)
Number with Diagnosis
Alcohol dependence (303.90) 29 Alcohol abuse" (305.70) 4 Polydrug dependence (304.90) 6 Opioid dependence (304.00) I Amphetamine dependence (304.40)
I
Conduct disorder (3 12.90) No diagnosis (000.00)
• 3
"D5M-IIl crileria were used.
TABLE 3.
Length of preoperative sobriety in 34 patients
Length of Time 3 months but 6 months bUI < J year > I year but 3 ears
248
Number of Patients 9 5 6 10 4
Table I lists the frequency of pathologic diagnoses responsible for liver failure. Each diagnosis was established by the referring internist and was confirmed by the transplant team physicians and surgeons. Most included a tissue diagnosis read by a pathologist. Twenty-six patients (70%) suffered from alcoholic cirrhosis. Four patients (11%) suffered from chronic hepatitis B infection; each of these patients presented a history of intravenous (iv) drug use, although none had been active in iv use within two years of the evaluation. Sixteen (62%) of the 26 patients with alcoholic cirrhosis were male, and 10 (38%) were female. The average age of the male alcohol cirrhotics was 41.5 years (range, 31 to 58 years), and the females averaged 43.0 years of age (range, 27 to 55 years); the difference in mean age was not significant. We list DSM-llI-R psychiatric diagnoses in Table 2. Twenty-nine patients (78%) fulfilled criteria for alcohol dependency, while four patients (II %) met the DSM-llI criteria for alcohol abuse without a history consistent with addictive signs of alcoholism. Eight patients (22%) described a history of past dependence on one or more drugs. Six of these (16% of the total) suffered at some time in their lives from dependence on two or more substances, one of which was alcohol; in all but one case use had ceased at least three years prior to evaluation. Of the 34 patients with a history of drug or alcohol dependence, 26 (76%) used alcohol alone, while eight (24%) used alcohol along with other substances at some point in their past. Only one patient (3%) in this group presented a non-substance-related psychiatric diagnosis. It is noteworthy that three patients (8%) gave no history of alcohol or drug dependence or abuse; in each case the lack ofdiagnosis was confirmed by one or more corroborating family members. Of the 34 patients with confirmed use of alcohol, preassessment lengths of abstinence varied from a few months to over three years; the longest was 10 years. We show these frequencies in Table 3. Twenty patients (59%) had been alcohol-free for less than one year. Only four (12%) had achieved long-term sobriety (defined by cessation of use) for more than three years. Interestingly, only seven of the patients (21 %) had been in any alcoholism treatment programs prior to the evaluation. As discussed below, the remaining 79% were "fresh" cases, a positive sign prognostically. We found no association of either length of sobriety or prior treatment with postoperative outcome, although we caution that the numbers of cases were too small for statistical confidence. Preoperative cognitive functioning was an important part of the assessment since it had an effect on postoperative care and subsequent compliance with the regimen of immunosuppressive medicines. As presented in Table 4, 13 patients (35%) PSYCHOSOMATICS
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suffered from documented hepatic encephalopathy at some point in their clinical history. Only five (14%) patients fell below the cut-off score for the Hopkins Mini-Mental State examination l6 at the time of preoperative assessment. This improvement in mental state most likely reflected stabilized liver functioning through preoperative care. Five (33%) of the 15 patients who proceeded to transplant encountered postoperative delirium. Due to the small numbers of patients involved, we cannot suggest a relation between pre- and postoperative mental functioning at this time. We list the frequencies of patient and family acceptance of the patient's alcohol abuse or dependence in Table 5. Twenty-four (71 %) of the patients with DSM-III-R alcohol dependence or abuse both recognized and accepted their condition and were willing to enter some form of treatment. All but four were joined by their families in this acceptance. Ten patients (28%) did not initially recognize alcohol dependence as an illness. Three of the to died during the preoperative evaluation conducted in the intensive care unit to which they had been admitted prior to referral for hepatic transplant evaluation. A fourth patient underwent transplant but did not survive the procedure. One patient was deemed inappropriate for the procedure medically and psychiatrically. Two patients remain under consideration for transplant. The final three patients were referred to alcoholism treatment after stabilization oftheir liver failure. Two successfully completed treatment and are currently on the transplant list. In sum, five of these 10 patients suffered untoward outcomes at the time of this writing. By contrast, 14 of the 21 patients who accepted their dependence as a disease to be reckoned with underwent transplant; three died within three months. Five of the remaining seven are on the waiting list or are being followed medically. One patient was referred for alcoholism treatment, and the final patient was deemed inappropriate because of compliance difficulties with the preoperative evaluation. In total, four of the 21 patients (19%) who recognized their alcohol dependence at the pretransplant interview suffered untoward outcomes. The Strauss-Bacon social stability index, a commonly used measure of short-term compliance with alcoholism treatment, described these patients as a good prognosis group (Table 6). Fully 29 (85%) of the 34 patients scored three or four points on this index. Taken alone, however, this measure did not appear to differentiate outcome as well as it might in combination with the long-term prognostic factors. We list the frequencies of Vaillant's long-term factors in Table 7. The first three "positive" factors, suggesting life changes in the direction of health, occurred far more frequently than did the one "negative" factor suggesting behavioral modVOLUME 31' NUMBER 3· SUMMER 1990
TABLE 4.
Pre- and postoperative cognitive functioning in 37 patients
Cognitive Functioning
Number of Patients
Pre-op encephalopathy by history 13 present absent 24 Pre-op Mini-Mental State score ~4
32 5
$23 Post-op delirium present absent
5 13
TABLE S. Preoperative acceptance of alcohol dependence! abuse in 34 patients Points
Number of Patients
4 Patient and family acknowledge diagnosis 3 Patient only 2 Family only I Neither patient nor family
20 4 6 4
TABLE 6. Social stability of 34 patients based on the Strauss-Bacon index Points
Number of Patients·
4
19
3 2 I
10 4 I
Note: This index assigns one point for each of the following: presently married and living with spouse, living alone, stable address for the past 2 years, stable job for the past 3 years. a Alcohol-dependent and -abuse patients combined
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ification. Recalling Vaillant's original use of these factors-two or more suggesting TABLE 7. Long-term prognostic factors promoting absti· nence from alcohol a likelihood of abstinence of three years or more-24 (77%) of the patients in this n(%) Yes No Prognostic Factor sample exhibited two or more factors 26 (58) II Substitute activities 15 while seven (23%) showed one or none. 26 (69) 8 Source of hope 18 Considering the latter group, four patients 27 (81) 21 6 Social rehab relationship had untoward outcomes (two died 25 (12) 22 Negative consequencesa 3 posttransplant; two were deemed inapproaDoes not include terminal liver failure priate) and three did well (one is alive and well posttransplant; two entered alcoholism treatment and await transplant). TABLE 8. DSM·m·R diagnosis and outcome (1987-1988) Twelve of the good prognosis group are No. Who Are alive and well posttransplant while two Alive and Well (%) Diagnosis n died postoperatively; none were deemed 10(77%) Alcohol dependence 13 inappropriate for the procedure. At the 2 2 Alcohol abuse time of this report, the remaining patients I o Poly-drug abuse either have been listed for the procedure 2 2 None 14 (78%) or are continuing in the medical evaluation 18 Total process. Table 8 lists the outcome in relation to psychiatric diagnosis. These data suggest an outcome in the TABLE 9. Clinical decisions for treatment ofalcohol range of those reported by other transplant programs reporting abuser.Jdependen~a on their experience in this population. Table 9 summarizes our (1987-1988) experience in making clinical decisions in this complex setting. Decision N=34 As noted above, we make every effort to treat alcohol depen15 Received transplanl dence when this is possible. The most difficult decision, dis9 Put on waiting list or on hold cussed more fully below, is whether a transplant is too great a 4 In evaluation process risk for psychiatric reasons that might appear less objective 4 NOI treated than those encountered in more "concrete" aspects of medicine. Medical cOnlraindication 2 Based on our experience, we estimate that we are likely to 2 Noncompliance encounter that decision in about 10% of cases; we deemed two Died during evaluation 2 (6%) of 34 to be unacceptably high-risk patients solely on the aDiagnosed according (0 DSM-III-R basis of their preoperative behavior and efforts at compliance. Finally, Table 10 summarizes our experience with the social stability score, the TABLE 10. Decisions vs. predictive scales in 17 alcohol· dependent patien~ score on Vaillant's long-tenn prognostic factors, and the simple addition of the two Received Did Not Receive Transplant (Deceased) Transplant Scores as a combined score. While the frequenSocial stability cies are small, they suggest that the prog13 (4) 3 or 4 nostic factors score or the combined score lor 2 2 may offer better methods for further study Long-term score of this population than the measure of 12 (2) >6 o social stability alone. The clinical prob3 (2) 2 12 more complexity of assessment than we 3 (2)
