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Risk factors, scoring systems, and interventions for alcohol relapse after liver transplantation for alcoholic liver disease

2018; Lippincott Williams & Wilkins; Volume: 11; Issue: 5 Linguagem: Inglês

10.1002/cld.696

2046-2484

Jane Lim, Vinay Sundaram,

Liver Disease and Transplantation

Watch a video presentation of this article Watch the interview with the author Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT) in the United States.1 Transplantation for ALD can be controversial, partially because of concerns regarding alcohol relapse.1 In patients with ALD, rates of post-LT drinking approach 50%, with 20% of recipients returning to harmful drinking.2 Although overall survival rates posttransplantation for ALD are comparable with non-ALD,1, 3 clinical outcomes for those with "slips" are different from those who return to harmful drinking. A slip is defined as consumption of a limited amount of alcohol, followed by immediate procedures to reestablish abstinence, whereas harmful drinking is defined as consumption of four or more drinks in 1 day or drinking for 4 or more days consecutively.1 Occasional slips are not associated with graft loss or reduced overall survival,1, 4 but harmful drinking can increase risk for advanced allograft fibrosis, graft loss, recurrent alcoholic cirrhosis, and reduced survival.4, 5 Therefore, it is essential to identify factors associated with alcohol relapse, evaluate scoring systems for predicting relapse, and establish interventions to reduce the risk for relapse after transplantation. Several patient risk factors have been associated with alcohol relapse after transplantation (Table 1). Duration of abstinence is often an important consideration for transplant listing.1, 6 However, although certain transplant centers require a minimum of 6 months of abstinence to be listed for LT, there are conflicting findings whether this duration of sobriety predicts a lower risk for relapse.3, 6, 7 Therefore, the 6-month rule is not a reliable predictor of post-LT sobriety. Strong social support, such as a life companion or a support system of friends or family, is protective against drinking post-LT.8 Comorbid psychiatric illnesses including anxiety, depression, and personality disorders are associated with a higher risk for relapse.6, 9 In addition, cigarette smoking at time of LT evaluation was shown to be an independent predictor of alcohol use post-LT.8 Lastly, pretransplant noncompliance is strongly associated with an increased risk for relapse.9 In one prospective study, 75% of LT recipients with a single missed clinic appointment without notification, missed medication dose, or missed refill of prescriptions relapsed to drinking post-LT.9 Several scoring systems have been proposed to predict posttransplant alcohol relapse (Table 2). The High Risk Alcoholism Relapse scale (HRAR) assesses three variables: duration of heavy drinking, number of drinks per day, and number of prior alcoholism inpatient treatment experiences10 (Table 1). A few studies have evaluated the association between the HRAR score and post-LT alcohol relapse. In a prospective trial, an HRAR score ≥4 was associated with an increased risk for harmful drinking post-LT.6 Another retrospective study, however, did not find an association between HRAR score and alcohol use post-LT, although the study had limitations regarding sample size and generalizability of the study population.11 Therefore, further prospective studies are needed to validate the HRAR. One retrospective study found that groups ARRA III and IV had significantly greater rates of post-LT alcohol use8: • ARRA I: 0% • ARRA II: 8% • ARRA III: 57% • ARRA IV: 75% The Alcohol Relapse Risk Assessment (ARRA) assesses nine factors that were associated with post-LT alcohol use in a single-center retrospective study.8 Patients are categorized into four groups based on total number of points. Patients in groups ARRA III (4-6 points) and ARRA IV (7-9 points) had significantly higher rates of alcohol relapse.8 The ARRA scale has not been validated by other studies. The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a comprehensive tool that was developed to standardize pretransplant psychosocial evaluations.12 It has not been validated for predicting post-LT alcohol relapse, but it was found to be associated with increased rejection episodes, hospitalizations, infection rates, and psychiatric decompensations in a prospective study of heart, lung, liver, and kidney transplant recipients.12 The SIPAT may be a promising tool, and further prospective trials are needed to study its association with alcohol relapse. Lastly, the University of Michigan Alcoholism Prognosis Score (MAPS) was developed to stratify potential transplant candidates into low- and high-risk categories for alcohol relapse.13 It evaluates insight into alcoholism, social stability, and presence of factors that suggest a favorable sobriety prognosis. However, a single-center retrospective study found that there was no significant association between pre-LT MAPS and alcohol use post-LT.14 Few studies have evaluated specific psychosocial interventions to prevent alcohol relapse after LT. A randomized controlled trial (RCT) found that pre-LT motivational enhancement therapy (MET) combined with encouragement to attend Alcoholics Anonymous (AA) and case management meetings reduced drinks per day in the pretransplant period compared with "treatment as usual," which included referral for intensive outpatient therapy and AA or Narcotics Anonymous. The impact of MET on post-LT relapse was not determined because of the small number of patients who underwent LT.15 Being followed by an addiction psychiatrist integrated within the liver transplant center may also significantly lower rates of relapse.7 Participating in a structured addiction program before and after LT may reduce the risk for relapse by more than 50%.3 In regard to pharmacological interventions, baclofen is the only medication that has been studied in patients with alcoholic cirrhosis, and none has been studied after LT.16 In an RCT of 84 patients with alcohol dependence and cirrhosis, baclofen significantly improved abstinence and reduced relapse compared with placebo.16 Disulfiram and naltrexone are approved for alcohol dependence but carry a risk for hepatotoxicity.17 Topiramate and ondansetron are also promising agents due to reduced risk for hepatotoxicity, but they have not been studied in patients with advanced liver disease.17 Although no standardized psychosocial or pharmacological interventions are part of the LT protocol, the American Association for the Study of Liver Diseases guidelines for LT evaluation recommend early referral of patients with ALD to a transplant center to initiate psychosocial assessment and addiction treatment goals. Patients with ALD should ideally be evaluated by clinicians skilled in mental health and addiction experience.18 Identifying patient factors that are associated with alcohol relapse and establishing interventions to prevent relapse are important for improving outcomes in patients who underwent transplant for ALD. Although length of sobriety has an uncertain association with relapse risk, poor social support, psychiatric comorbidities, tobacco use, and noncompliance are all associated with increased risk for alcohol relapse. Scoring systems have been proposed to predict risk for alcohol relapse after LT, but validation studies are lacking. In addition, pharmacological interventions are limited for this population. Therefore, psychosocial interventions are the cornerstone for relapse prevention. There are a limited number of studies for specific psychosocial interventions; however, pre-LT MET was more effective than "treatment as usual" for reducing drinking in the pre-LT period. Pre- and post-LT structured addition management was associated with reduced alcohol relapse after LT. Lastly, follow-up with an addiction psychiatrist integrated within the transplant center was more efficacious than those not affiliated with a liver transplant center.