EASL Clinical Practice Guidelines

Management of alcohol abuse and alcohol dependence

A large number of European citizens drink alcohol. Europe has the highest per capita alcohol consumption (11 L of pure alcohol per year in population ⩾15 years old). Fifteen percent of Europeans (58 million citizens) drink excessively (>40 g per day in men, and >20 g per day in women), with a higher proportion among males and young people.

Alcohol abuse and alcohol dependence must be seen as different forms of the same disorder, as it is recognized in the new DSM-V draft. Alcohol abuse is not recognized as a disorder in the ICD-10, and in fact the WHO uses the terms hazardous and harmful alcohol use instead of alcohol abuse. The term 'risky drinker' is commonly used to define people who drink excessively.

Drinking habits of patients need to be routinely screened in patients with liver diseases, and this must be done with tools that have proven its reliability [16]. There is a common trend to measure alcohol intake in grams per day or grams per week. Calculations are usually made counting standard drink units [33]. The content of a standard drink may differ from country to country, but in Europe most of the countries have fixed their standard drink unit to an ethanol content of 8–10 g. Even though measurements in standard drinks may lose accuracy, they are reliable, save time, and are particularly useful in busy clinical settings.

Screening tools to detect alcohol abuse and dependence

Quantity-frequency questionnaires and retrospective diaries (time-line follow back) can be used to calculate patients' drinking habits. The former are usually preferred for their simplicity, but they must include data on both working and weekend days. A good alternative to quantity frequency questionnaires is the use of screening instruments to screen risky drinking and alcohol dependence. There are many tools that have been validated and translated into many languages, but the AUDIT (Alcohol Use Disorders Inventory Test) remains the 'gold standard'. Developed by the WHO in 1982, it has proven to have good sensitivity and specificity in clinical settings across different countries [34]. The AUDIT has 10 questions that explore consumption (1–3), dependence (4–6), and alcohol related problems (7–10) (Table 2). There are two cut-off points, one for dependence and one for risky drinking. Shorter versions have been developed. The AUDIT C includes just the first three questions of the AUDIT and is reliable for the screening of 'risky drinking' [[35], [36]]. The NIAAA (National Institute of Alcohol Abuse and Alcoholism) recommends using the third question of the AUDIT (How often do you have six or more drinks in one occasion?) as a single screening question, which should be followed by the whole AUDIT in case the answer is rated positive [16].

Table 2
AUDIT questionnaire [36]. To score the AUDIT questionnaire, sum the scores for each of the 10 questions. A total ⩾8 for men up to age 60, or ⩾4 for women, adolescents, or men over age 60 is considered a positive screening test.

Screening of patients with psychiatric disorders

Alcoholics have a high psychiatric co-morbidity. In general, population surveys of alcoholics show high prevalence of anxiety disorders, affective disorders, and schizophrenia [37]. Anxiety and affective disorders may be independent or concurrent with alcohol dependence. Independent disorders will need specific treatment, while concurrent disorders may disappear once the patient is weaned off alcohol.

Alcoholics have a higher risk of developing other addictions, including nicotine. Alcoholics tend to be heavier smokers and the treatment of nicotine dependence requires more intensive support [38]. Alcoholics who are polydrug users are difficult to manage and should be systematically referred to specialized treatment.

Data suggest that alcohol dependence appears within 5 years before the patient is referred to specialist treatment. Special attention should be paid to the coordination between hepatologists and addiction specialists (psychiatrists, psychologists, and social workers) in order to reduce the gap between the signs of alcohol dependence appearing and referral. Because cigarette smoking and alcohol abuse are synergistic in causing cardiovascular diseases and cancer, including HCC, hepatologists are encouraged to promote and assist smoking cessation among patients with ALD [39].

Management of alcohol withdrawal syndrome

Alcohol withdrawal syndrome (AWS) is a severe medical condition affecting alcohol-dependent patients who suddenly discontinue or decrease alcohol consumption. Light or moderate AWS usually develops within 6–24 h after the last drink and symptoms may include increase in blood pressure and pulse rate, tremors, hyperreflexia, irritability, anxiety, headache, nausea, and vomiting. These symptoms may progress to more severe forms of AWS, characterized by delirium tremens, seizures, coma, cardiac arrest, and death [40]. Severity scores for AWS are potentially useful in the management of patients. However, these scores are insufficiently validated at this time, especially in the setting of ALD.

Benzodiazepines are considered the 'gold standard' treatment for AWS, given their efficacy to reduce both withdrawal symptoms and the risk of seizures and/or delirium tremens [[41], [42]]. Long-acting benzodiazepines (e.g. diazepam, chlordiazepoxide) provide more protection against seizures and delirium, but short and intermediate-acting benzodiazepines (e.g. lorazepam, oxazepam) are safer in elderly patients and those with hepatic dysfunction [43]. In Europe, clomethiazole is also used to treat AWS [44].

Given the side-effects of benzodiazepines in patients with advanced liver disease and potential for abuse, preliminary research has been conducted to identify new medications for AWS, such as clonidine, atenolol, carbamazepine, valproic acid, gamma-hydroxybutyrate, topiramate, baclofen, gabapentin, and pregabalin [45]. Whilst sufficient evidence in favor of their use is lacking, topiramate and baclofen have promise given their potential to be used for AWS first [[46], [47]], and then to prevent relapse.

Medical therapy of alcohol dependence in patients with ALD

Alcohol abstinence represents a critical goal in patients with ALD since abstinence improves the clinical outcomes of all stages of ALD. In the past, disulfiram was the only drug available for alcoholism. Disulfiram represents an effective alcohol pharmacotherapy [48]; however, disulfiram should be avoided in patients with severe ALD because of possible hepatotoxicity [49]. More recently, the growing understanding of the neurobiology of alcoholism has led to the development of effective pharmacologic agents that can complement psychosocial treatments, in particular naltrexone [50]and acamprosate [51]. Both naltrexone and acamprosate are approved to treat alcoholism; however, these drugs have not been tested in patients with cirrhosis. The opioid antagonist naltrexone has been intensively evaluated, especially the oral formulation [52]. A large trial also showed the efficacy of an intramuscular formulation of naltrexone in alcoholism [53]. Given the potential for hepatotoxicity, naltrexone has not been tested in patients with ALD, and its use in this population is not recommended. Acamprosate is a modulator of the glutamatergic receptor system and a meta-analysis of 24 randomized controlled trials confirmed its efficacy as an alcohol pharmacotherapy [54]. Based on some clinical trials, gamma-hydroxybutyric acid was approved in some European countries (Italy and Austria) to treat alcoholism, but more research is needed, considering the risk of gamma-hydroxybutyric acid abuse [55].

Amongst other compounds, topiramate, ondansetron, and baclofen seem the most promising pharmacotherapies for alcoholism [56]. Topiramate is an anticonvulsant medication, which has demonstrated safety and efficacy in reducing heavy drinking [57]. There was also a decrease in liver enzyme levels in patients treated with topiramate [58]; however, topiramate has not been tested in patients with ALD. The 5-HT3 antagonist ondansetron has been shown to reduce drinking, but this effect was limited to 'early onset' alcoholics [59]. Some studies suggest that baclofen, a GABAB receptor agonist, increases abstinence rate and prevents relapse in alcohol-dependent patients [60]. Moreover, to date, baclofen represents the only alcohol pharmacotherapy tested in alcoholics with significant liver disease. Baclofen may represent a promising pharmacotherapy for alcohol-dependent patients with ALD. A clinical trial demonstrated the safety and efficacy of baclofen in promoting alcohol abstinence in alcoholic cirrhotics patients [61], but confirmatory studies in cirrhotic patients are warranted.

The effect of brief interventions

Brief interventions are often performed through motivational interviewing [62]. Motivational interviewing is a technique, which aims to be both non-judgmental and non-confrontational. Its success depends largely on the presentation of objective feedback based on information provided by the physician. The technique involves acknowledgement that individuals who attend a counseling session, assessment or prevention program may be at different levels of readiness to change their alcohol consumption patterns. The technique attempts to increase a patient's awareness of the potential problems caused, consequences experienced, and risks faced as a result of patterns of alcohol consumption. A meta-analysis found evidence for the positive impact of brief interventions on alcohol consumption and alcohol related morbidity and mortality [62]. The most recent Cochrane review shows that brief interventions are effective to reduce drinking by an average of 57 g per week in men [63]. Evidence is less conclusive in women and populations under 16 years of age. A brief intervention should at least have the components defined in the five As' model: Ask about use, Advice to quit or reduce, Assess willingness, Assist to quit or reduce and Arrange follow-up.

When a motivational component is added to brief interventions its efficacy improves [64]. Essential components of a motivational approach are an empathic attitude and a collaborative approach that respects the patients' autonomy and evoques from them ways to reach the goals agreed.

Recommendations

Suggestions for futures studies

  1. Collaborative studies by multidisciplinary teams composed of epidemiologists, addiction specialists, and hepatologists are strongly encouraged.
  2. The impact of brief interventions on the prognosis of advanced ALD should be evaluated.
  3. More studies testing anti-craving drugs in the setting of advanced ALD are required.