De Gottardi A, Spahr L, Gelez P, Morard I, Mentha G, Guillaud O, et al. A simple score for predicting alcohol relapse after liver transplantation. Results from 387 patients over 15 years. Arch Intern Med 2007;167:1183-1188. (Reprinted by permission.)
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Background: Alcohol relapse can negatively influence the outcome after liver transplantation (LT). The aim of our study was to identify factors that could be associated with the recurrence of harmful alcohol consumption after LT. Methods: A total of 387 consecutive patients (23.8% women) who underwent LT for alcoholic cirrhosis in Geneva, Switzerland, and Lyon, France, between 1989 and 2005 were evaluated. Mean ± SD age was 51.3 ±7.5 years. Follow-up time was 61.2 ± 47.5 months. Alcohol consumption relapse and potential factors associated with it were studied. Results: The relapse rate of harmful alcohol consumption after LT was 11.9%. In univariate analysis, alcohol relapse was significantly associated with age greater than 50 years (P = .04), year of LT 1995 or earlier (P<.05), duration of abstinence less than 6 months (P = .02), presence of psychiatric comorbidities (P<.001), presence of a life partner (P<.05), and a high score on the High-Risk Alcoholism Relapse (HRAR) scale (P<.001). Multivariate logistic regression disclosed the following independent factors of relapse: duration of abstinence of less than 6 months (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.2-9.3) (P = .02); presence of psychiatric comorbidities (OR, 7.8; 95% CI, 3.1-20.0) (P<.001); and HRAR score higher than 3 (OR, 10.7; 95% CI, 3.8-30.0) (P = .001). In patients with none of these factors, alcohol relapse was 5%, while the presence of 1, 2, or 3 factors was associated with relapse rates of 18%, 64%, and 100% of the patients, respectively. Conclusions: In a large cohort of patients undergoing LT for alcoholic cirrhosis, a duration of abstinence of less than 6 months before wait-listing for LT, the presence of psychiatric comorbidities, or an HRAR score higher than 3 was associated with relapse into harmful drinking. The presence of more than 1 factor dramatically increased this risk over 50%. In the pre-LT evaluation in this setting, these factors should be accurately determined.
Alcoholic liver disease (ALD) is second only to chronic viral hepatitis as a leading indication for liver transplantation. It is now widely accepted that the overall clinical outcomes of liver transplantation for carefully selected patients with alcoholic liver disease are similar to those of other forms of liver disease.1, 2 However, relapse to harmful use of alcohol after transplant remains a concern and can lead to a range of problems for the affected individual including recurrent alcoholic liver disease,3 other alcohol-related disorders, noncompliance with immunosuppression leading to graft failure and increased mortality.3–8 Recurrent drinking may also undermine the already low public standing of transplantation for alcoholic liver disease9 with the concern that the rate of organ donation, the rate limiting factor for transplantation, may fall.
In this light, it is critical to select candidates who are likely to experience the maximum sustained benefit. It is also ethically important to identify an objective selection method because only 5% of those with end-stage alcoholic liver disease will receive a transplant. Several groups have sought to define pretransplant predictors of relapse to drinking with mixed results.8, 10, 11 In the largest study of this type to date, Gottardi and colleagues (2007) retrospectively analyzed outcomes of 387 transplants for alcoholic cirrhosis.12 The average follow-up was just on 5 years and 12% of the patients returned to harmful drinking. They report that consideration of three factors strongly predicted harmful alcohol consumption after liver transplantation. Harmful consumption was defined as consumption of at least 40gms per day plus a physical or mental health effect. This is an important point as most studies simply report any alcohol intake as the endpoint variable.13 Kelly et al. also used harmful intake as the endpoint defined as medical or social harm or consumption above 20gms/day.11 Standardization of such definitions are clearly required to make cross study comparisons.
Gottardi et al. showed that the High-Risk Alcoholism Relapse scale (HRAR), which has been shown to predict readmission rates for alcoholism treatment in male U.S. Veterans,14 was strongly predictive of relapse to harmful drinking after liver transplantation. The scale has three items (duration of heavy drinking, number of daily drinks and number of prior inpatient treatments), each rated from 0-2, yielding a total score from 0-6. After multivariate regression, an HRAR score of ≥4 (OR: 10.7), the presence of psychiatric comorbidity (OR: 7.8) and a duration of abstinence of ≤6 months at the time of listing (OR: 3.3) were each independently predictive of harmful consumption. Although pretransplant abstinence of at least 3 months was required in the participating liver centers, it should be noted that only 43 patients actually were transplanted with less than 6 months abstinence and the mean duration of pretransplant abstinence was 20 months. The most impressive finding was that those with 2 or 3 of these risk factors were at very high relapse risk, whereas the absence of all factors was associated with a relapse risk of only 5% (Table 1).
|Number of Risk Factors Present||Relapse Risk||%|
The strengths of this study are that the measures used are simple, relatively objective and do not require specialist assessment. The magnitude of the associations was impressive. The key limitations of the study are that it was a retrospective analysis of a cohort of patients who all underwent liver transplantation. Selection for transplantation was based on traditional multidisciplinary assessment and those considered at high risk of relapse did not undergo transplantation. Moreover, very few candidates had more than one risk factor (only 25 of 387 cases), with only 3 patients in the highest risk group, and 13 of 46 (28%) relapse events occurred in individuals with none of these risk factors. Nonetheless, 33 of 46 (72%) of relapse events were predicted by this simple measure. The authors conclude that these measures should be incorporated into pretransplant assessment and those with 2 or 3 risk factors considered as being of high risk of relapse.
These methods represent an advance on previous assessment which typically relied on a minimal period of 6 months pretransplant abstinence from alcohol coupled with a multidisciplinary assessment. The “six month rule” has been criticized as being arbitrary, and unfair to those with lower life expectancy at presentation. In addition, the pretransplantation duration of abstinence is a poor predictor of outcome in several studies.7, 15, 16 The multidisciplinary assessment suffers from lack of objectivity and susceptibility to bias on cultural or other grounds, or at least the perception that such bias might occur. DiMartini et al. and more recently Kelly et al. reported that factors associated with relapse in addictions outside the transplant context were also predictive of relapse to drinking after liver transplantation.10, 11 Prognostic factors included insight into the role of alcohol in liver disease, presence of psychiatric comorbidity, stability of relationships, housing and employment, maintenance of abstinence while physically well enough to drink, and expansion of social role with abstinence. Overall, these studies indicate progress toward accurate and objective assessment for this most complex treatment. These measures remain a work in progress as we currently have much more data concerning those who receive transplants than those who do not. Unsurprisingly, there are no randomized trials in this field. Finally, the identification of adverse prognostic factors can also be seen as a challenge to develop interventions capable of addressing relapse risk such that patients at high risk could be helped, not merely identified and excluded from transplantation.