LIVER TRANSPLANTATION 14:1609-1613, 2008 ORIGINAL ARTICLE Detecting Lifetime Alcohol Problems in Individuals Referred for Liver Transplantation for Nonalcoholic Liver Failure Ed Day, 1 David Best, 1 Ruth Sweeting, 1 Rebecca Russell, 1 Kerry Webb, 2 George Georgiou, 3 and James Neuberger 2 1 University of Birmingham Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, Birmingham, United Kingdom; 2 Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; and 3 Birmingham and Solihull Mental Health National Health Service Trust, Birmingham, United Kingdom Transplantation for alcoholic liver disease is becoming increasingly common, and with adequate screening, short- to mediumterm outcomes are very good. However, while conducting a prospective study of the outcome of liver transplantation in Birmingham, United Kingdom, we observed that a research diagnosis of alcohol abuse or dependence was made in a number of cases in which no reference to alcohol problems had been made by the referring agency. This article explores the characteristics of these missed cases and highlights key patient characteristics that might prompt a more detailed assessment of alcohol consumption. Two hundred eight individuals completed the research interview, and 80 (39%) met Diagnostic and Statistical Manual of Mental Disorders IV criteria for a lifetime diagnosis of either alcohol abuse (n 29) or dependence (n 51). When the initial referral details were reviewed, the possibility of alcohol problems had not been raised in 10 (12.5%) of these cases. Hepatitis C was the most common primary diagnosis in the missed cases, but there was no difference between diagnosed and missed cases in terms of demographic factors, severity of liver disease, or the number or degree of lifetime problems associated with alcohol. However, members of the missed group were more likely to have drunk alcohol in the past 6 months and in a greater volume and were more likely to have used illicit drugs such as opiates, amphetamines, hallucinogens, and cannabis. These findings point to the need to take an adequate history of lifetime alcohol problems in all patients being considered for liver transplantation. Liver Transpl 14:1609-1613, 2008. 2008 AASLD. Received January 30, 2008; accepted April 12, 2008. See Editorial on Page 1559 Despite a recent harm reduction strategy for tackling alcohol problems in England, alcohol consumption in the United Kingdom is high and rising. The per capita consumption of alcohol has risen by 50% in the United Kingdom since 1970, whereas it has fallen in other European counties such as Italy and France, and about 7% of the adult population in England (2.9 million people) is dependent on alcohol. Such changes in per capita consumption are directly reflected in changes in harm, and between 1996 and 2000, 13.8% of all liver transplants in the United Kingdom were for alcoholic liver disease (ALD). Despite evidence of equivalent effectiveness for transplantation in those with and without a history of drinking problems, 1 concerns remain about the prognosis for former drinkers who may return to alcohol consumption postoperatively. 2 ALD is now a well-established reason for liver transplantation, and short-term outcomes of patients transplanted for alcoholic cirrhosis are comparable to or better than those of patients transplanted for other types of end-stage liver disease. 3 With adequate screen- Abbreviations: ALD, alcoholic liver disease; AUDIT, Alcohol Use Disorder Identification Test; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders IV; MAST, Michigan Alcohol Screening Test; MELD, Model for End-Stage Liver Disease; NS, not significant; SCL-90-R, Symptom Checklist-90-Revised; SD, standard deviation. This project was supported by 2 grants from the University Hospital Birmingham Charities Fund. Address reprint requests to Ed Day, Department of Psychiatry, University of Birmingham, The Barberry, 25 Vincent Drive, Birmingham, United Kingdom B15 2FG. Telephone: 0121 678 2356; FAX: 0121 678 2351; E-mail: e.j.day@bham.ac.uk DOI 10.1002/lt.21528 Published online in Wiley InterScience (www.interscience.wiley.com). 2008 American Association for the Study of Liver Diseases.
1610 DAY ET AL. TABLE 1. Lifetime DSM-IV Diagnosis by Referrer s Diagnosis of Alcohol-Related Problems Alcohol-Related Liver Disease Highlighted in the Initial Referral Alcohol Abuse (n 29) Alcohol Dependence (n 51) Yes 25 (86%) 45 (88%) No 4 (14%) 6 (12%) Abbreviation: DSM-IV, Diagnostic and Statistical Manual of Mental Disorders IV. DSM-IV Diagnosis Made at Baseline Assessment ing, short- to medium-term outcomes are very good. However, the resources available for screening for a history of alcohol problems are limited in the United Kingdom and vary considerably from center to center (Rees, unpublished data, 2005). A detailed assessment of alcohol consumption and the lifetime history of abuse or dependence is not always conducted for all cases being considered for liver transplantation, particularly if alcohol is not cited as a main cause of liver failure in the referral process. While conducting a prospective study of the outcome of liver transplantation, we observed that a research diagnosis of alcohol abuse or dependence was made in a number of cases for which no reference to alcohol problems had been made by the referring agency. This article explores the characteristics of these missed cases and highlights key patient characteristics that might prompt a more detailed assessment of alcohol consumption. PATIENTS AND METHODS Participants and Setting All patients 18 years old or older who were admitted for liver transplant assessment at the Birmingham Liver Unit between July 2004 and July 2007 were considered for the study. Patients referred for transplantation were usually first seen as outpatients and, if considered potential transplant candidates, were admitted for a week-long assessment process. Patients were eligible for the study if they could speak English adequately and were not encephalopathic to a degree that prevented them from providing informed consent to take part. An assessment interview was conducted during the inpatient stay that consisted of a mixture of semistructured research interviews and selfcomplete questionnaires, investigating variables in 4 broad areas: 1. Demographics, including age, gender, ethnicity, level of education, employment history, and relationship status. 2. Liver disease severity, which was scored with the Model for End-Stage Liver Disease. 3. Psychological symptoms, which were assessed with the Symptom Checklist-90-Revised. 4,5 This is a selfreport symptom inventory designed to reflect the psychological symptom patterns of community, medical, and psychiatric respondents. Each of the 90 items is rated on a 5-point scale of distress ranging from 0 (not at all) to 4 (extremely), and the results can be summarized in terms of the Global Severity Index. 5 4. Alcohol use history, which was obtained with a combination of the Brief Drinker Profile 6 and the Lifetime Drinking History. 7 All measures of amounts of alcohol were converted to English units to aid ease of comparison. Lifetime diagnoses of alcohol abuse or dependence were made with Chapter 11 of SCAN: Schedules for Clinical Assessment in Neuropsychiatry. 8 The study was approved by the local research ethics committee and the University Hospital National Health Service Foundation Trust. All participants gave fully informed, written consent. Data Analysis The collected data were analyzed with the SPSS Statistical Package, version 12.0. Initially, 1 sample Kolmogorov-Smirnov was used to test for normal distribution. Statistical significance was established with chi-square test categorical data, with Fisher s exact test being employed when necessary. For parametric, continuous data, 2-tailed independent sample t tests and Pearson s correlations were used appropriately. Mann-Whitney U tests and Spearman s rho were used when the data were nonparametric. A P value of less than 0.05 was considered to be significant. RESULTS Two hundred eight individuals completed the research interview and were medically assessed to determine suitability for liver transplantation. The research interview showed that 39% (n 80) of these cases met Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for a lifetime diagnosis of either alcohol abuse (14%) or dependence (25%). The initial referral materials were reviewed, and presumptive primary, secondary, and tertiary diagnoses were recorded. When the initial referral details were reviewed, the possibility of alcohol problems had not been raised in 10 (12.5%) of the cases for which a DSM-IV lifetime diagnosis of alcohol abuse or dependence was subsequently made (Table 1). There were no cases in which a diagnosis of ALD made by the referring clinician was
DETECTING LIFETIME ALCOHOL PROBLEMS 1611 TABLE 2. Comparison Between Cases in Which Lifetime Alcohol Problems Were Detected and Cases in Which They Were Missed Alcohol Problems Not Detected (n 10) Alcohol Problems Detected (n 70) Statistical Test Mean age in years SD 46.9 12.9 52.06 7.5 NS Male (%) 8 (80) 55 (79) NS Living with a partner (%) 5 (50) 45 (65) NS University degree or above (%) 2 (20) 9 (13) NS Employed (%) 2 (20) 9 (13) NS Mean MELD score SD 13.1 2.3 14.7 5.3 NS Ever seen by psychiatrist for emotional difficulties (%) 1 (10) 3 (4) NS Mean SCL-90-R Global Severity Index score ( SD) 60.9 10.7 64.0 11.6 NS Mean lifetime duration of drinking in years SD 28.6 12.1 31.5 9.1 NS Mean units of alcohol consumed per drinking day 4.4 3.2 6.4 5.1 NS SD Lifetime diagnosis of alcohol dependence (%) 6 (60) 45 (64) NS Mean MAST score for previous 6 months 2.5 1.1 2.8 4.2 NS Mean lifetime MAST score SD 19.4 13.0 19.1 11.7 NS Ever arrested due to alcohol (%) 4 (40) 10 (14) NS Ever arrested for drink driving (%) 4 (40) 17 (24) NS Ever received help for alcohol problems 6 (60) 29 (41) NS Drank alcohol in past 6 months (%) 5 (50) 8 (11) 2 9.76, P 0.01 Mean number of days since last alcoholic drink SD 420.8 437.9 882.3 1161.4 U 233, P 0.08 Mean weekly consumption of alcohol in the past 6 4.2 8.9 0.32 2.0 U 288, P 0.02 months in units SD Mean total consumption of alcohol in the past 6 112.8 232.7 13.58 58.0 U 209, P 0.001 months in units SD Current drinking goal given as total abstinence (%) 5 (50) 68 (97) 2 20.00, P 0.001 Currently smoking tobacco (%) 5 (50) 22 (31) NS Ever used illicit drugs (%) 7 (70) 21 (30) 2 5.81, P 0.03 Opiates 4 (40) 6 (9) 2 8.06 P 0.02 Cocaine 3 (30) 8 (11) NS Amphetamines 4 (40) 9 (13) 2 4.86, P 0.05 Barbiturates 2 (20) 4 (6) NS Hallucinogens 4 (40) 6 (9) 2 8.06, P 0.02 Cannabis 6 (60) 17 (24) 2 5.61, P 0.03 Abbreviations: MAST, Michigan Alcohol Screening Test; MELD, Model for End-Stage Liver Disease; NS, not significant; SCL-90-R, Symptom Checklist-90-Revised; SD, standard deviation. not confirmed by the research assessment (that is, false positives). Further analysis was carried out on the characteristics of the 10 cases for which alcohol problems had not been detected to determine if any common themes existed. Four had a primary diagnosis of hepatitis C infection, 3 had cryptogenic cirrhosis, 2 had metabolic cirrhosis (Wilson s disease and hemochromatosis), and 1 had primary biliary cirrhosis. The decision was made before the study was started that the researcher conducting the interviews about alcohol consumption would be completely independent of the transplant team in an attempt to increase the respondents candor. No information about the research findings was passed on to the transplant team. However, all the cases included in the study were screened by an addiction nurse specialist and/or a consultant addiction psychiatrist as part of the routine transplant program. This approach was given approval by the local research ethics committee. Seven were ultimately placed on the transplant waiting list and subsequently received liver transplants. Of the 3 not transplant-listed, 1 was too well, 1 was refused because of concerns about alcohol consumption, and 1 was refused on the basis of anesthetic risk. Table 2 shows a comparison between the cases for which the alcohol problem was not detected and those for which it was. There was no difference in terms of demographic factors, severity of liver disease, psychological morbidity, or the number or degree of lifetime problems associated with alcohol. However, members of the missed group were more likely to have drunk alcohol in the past 6 months and in a greater volume. When asked about drinking alcohol in the future, they were also less likely than the correctly diagnosed group to give total abstinence from alcohol as a goal. Finally, members of the group for which the diagnosis was missed were more likely to have used illicit drugs such as opiates, amphetamines, hallucinogens, and cannabis.
1612 DAY ET AL. DISCUSSION Although outcomes for liver transplantation for ALD are good, this is most likely due to the careful assessment and screening process that precedes acceptance onto a transplant list. 9 Alcohol consumption post-transplantation puts the individual at risk of a relapse to dependent drinking and may compromise the graft either through direct toxicity or through associated nonadherence with immunosuppressant or other treatment regimes. In this study, a diagnostic research interview conducted during transplantation assessment detected 80 cases of lifetime alcohol abuse or dependence. In 70 of these cases, alcohol was considered by the referring agency to be a causative factor for cirrhosis, but in 10 cases, it was not highlighted as a factor. The missed cases had not drunk significantly less alcohol throughout their life and were no less likely to have experienced alcohol problems. Furthermore, they were more likely to have drunk alcohol in the past 6 months and less likely to commit to future abstinence from alcohol. Much research effort has gone into elucidating predictive factors for relapse to alcohol consumption posttransplantation. A shorter length of sobriety, lack of attendance at rehabilitation treatment, a diagnosis of alcohol dependence (as opposed to alcohol abuse), and other substance use have all been suggested as likely risk factors for a return to problematic drinking. 3 This analysis suggests that members of the group for which a diagnosis of alcohol problems was missed were more likely to have at least 2 of these risk factors than the group for which it was made. So why were these 10 cases of alcohol abuse or dependence not highlighted at the point of referral? There are at least 2 possible answers. First, the assessment process adopted by the referring agency may have been insufficient, and the drinking history was missed. As ALD is essentially diagnosed by exclusion of other causes married to a credible history of alcohol misuse, 9 it may have been easier not to look for other potential problems when another diagnosis explaining the liver failure was present. There are many potential difficulties with screening for alcohol problems in a transplant assessment population. Biochemical markers are unreliable in patients with severe liver impairment. A better alternative may be brief self-report screening tools such as the Alcohol Use Disorder Identification Test (AUDIT), which are easy to administer by nonspecialist personnel and provide a measure of multiple dimensions of alcohol use disorders, including alcohol consumption, alcohol-related problems, and symptoms of dependence. 10,11 However, the sensitivity and specificity of the AUDIT questionnaire is untested in liver transplant assessment populations, and a more fundamental problem is that the AUDIT focuses on use in the past year and so misses problems early in the patient s life. This is significant as many potential transplant candidates will have stopped drinking for at least 6 months prior to referral. This study was able to detect problems earlier in life by using the DSM-IV framework for lifetime diagnoses and by harnessing the systematic approach to recording lifetime drinking patterns used in the Lifetime Drinking History instrument. A second potential reason for the 10 missed cases is nondisclosure by the patient themselves. As Weinrieb et al. pointed out, 12 most patients are aware that candor about drug or alcohol use could harm their chances of receiving a liver transplant. Many liver transplant programs in North America and Europe require alcoholics to attain abstinence from alcohol for 6 months to a year as a condition of eligibility for liver transplantation. 13 Although prospective studies of predictors for relapse to alcohol consumption post-transplantation suggest that the 6-month rule is a weak prognostic indicator at best, 3 rigid adherence to it will almost certainly encourage underreporting of alcohol consumption. Therefore, all transplant clinicians need to remember to ask about alcohol consumption across a patient s lifetime and where possible establish a establish a diagnosis of alcohol abuse or dependence. If time is limited in the clinical setting, arranging for assessment by a suitably trained psychiatrist, nurse, or social worker can help this process. In a comparative study of different methods for assessing alcohol consumption posttransplantation (interview with a caregiver, interview by the transplant team psychiatrist, and biochemical markers), DiMartini et al. 14 concluded that clinical interviews obtained by the transplant psychiatrist were the most successful method for identifying alcohol use. This was in the context of maintaining a good rapport with patients and also allowed an opportunity for continued education on the dangers of alcohol consumption and recommendations for appropriate treatment. The assessment system may be further refined by the use of structured questionnaires and could also be targeted toward particular diagnoses. For example, the diagnosis of cirrhosis secondary to hepatitis C infection was overrepresented in this group of missed heavy drinkers. 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