Alcohol use disorder: Recognition, testing, and initial management strategies

Abstract

Alcohol use is common around the world, and its use is growing, especially in the United States, where an epidemiological study found that rates of alcohol use, high-risk drinking (defined as 4 or more drinks on any day for women and 5 or more for men), and alcohol use disorder (AUD) had increased by 11.2%, 29.9%, and 49.4%, respectively, between 2001 and 2012 to 72.7% of respondents using alcohol, 12.6% partaking in high-risk drinking, and 12.7% meeting criteria for AUD.¹ Notably, these increases were greatest among women, older adults, and racial and ethnic minorities.¹ The harmful use of alcohol has resulted in ~3 million deaths and over 130 million disability-adjusted life years annually from various causes, including injury, cardiovascular disease, malignancy, and digestive diseases.² Excessive alcohol use is a significant cause of liver disease and a common indication for liver transplant in the United States. Studies have shown that AUD treatment with psychotherapy or medication decreases incidence of alcohol-associated liver disease (ALD) and lowers rates of decompensation in those with underlying cirrhosis.^3,4 Given this, hepatologists are uniquely positioned to help patients with harmful alcohol use; however, few feel adequately trained to do so.⁵

ALCOHOL USE DISORDER

AUD can be defined as a condition characterized by the inability to stop or control alcohol use despite adverse consequences. It is defined by behavioral and physical symptoms, including withdrawal, tolerance, and cravings.⁶ It is a spectrum that varies from mild to severe based on the number of criteria experienced, with a diagnosis of AUD being made if the patient has had 2 or more of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria shown in Table 1 in the last 12 months.⁶

TABLE 1.

DSM criteria for AUD

Alcohol intake in larger amounts or over a longer period than was intended

There is a persistent desire or unsuccessful efforts to cut down or control alcohol use

A great deal of time is spent in activities necessary to obtain alcohol, use alcohol or recover from its effects

Craving or a strong desire or urge to use alcohol

Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school, or home

Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused by or exacerbated by the effects of alcohol

Important social, occupational, or recreational activities are given up or reduced because of alcohol

Recurrent alcohol use in situations in which it is physically hazardous

Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol

Tolerance as defined by either a need for markedly increased amounts of alcohol to achieve intoxication or desired effect or a markedly diminished effect with continued use of the same amount of alcohol

Withdrawal as manifested by either the characteristic withdrawal syndrome for alcohol or is taken to relieve or avoid withdrawal symptoms.

Note: Severity: Mild (2–3 criteria); moderate (4–5 criteria); severe (6+ criteria).

SCREENING FOR AUD

Many patients in hepatology clinics may already have an established diagnosis of AUD; however, screening for AUD should be performed for patients with unclear underlying liver disease or chronic liver disease in general. There are 3 commonly used screening tools for AUD that have been validated for different populations:

1. Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)

2. CAGE

3. Single alcohol screening question (SASQ)

AUDIT-C

The AUDIT-C is a shortened version of the Alcohol Use Disorders Identification Test (AUDIT). The AUDIT, developed by the World Health Organization, consists of 10 questions with a score of up to 40, a sensitivity of up to 73%, and a specificity of up to 97% to detect unhealthy alcohol use.⁷ Although the AUDIT-C consists of only the first 3 questions addressing alcohol consumption (Table 2), it has been shown to have similar sensitivity and specificity.^7,8

TABLE 2.

AUDIT-C questionnaire for screening of AUD

How often did you have a drink containing alcohol in the past year?
Never = 0	Monthly or less = 1	Two to 4 times a month = 2	Two to 3 times a week = 3	Four or more times a week = 4
How many drinks did you have on a typical day when you were drinking in the past year?
None to 2=0	3 or 4 = 1	5 or 6 = 2	7–9 = 3	10 or more = 4
How often did you have 6 or more drinks on 1 occasion in the past year?
Never = 0	Less than monthly = 1	Monthly = 2	Weekly = 3	Daily or almost daily = 4

Note: AUDIT-C score of greater than or equal to 4 is considered positive for men and greater than or equal to 3 is considered positive for women.

CAGE

CAGE stands for Cut down, Annoyed, Guilty, and Eye-opener based on the questions of the screening test. This screening test has not been as well validated across ethnic groups as the AUDIT-C has been; however, its simplicity is helpful in a brief clinical encounter.⁹ The CAGE screening test is considered positive if the patient reports 2 or more of the following:

Have you ever felt you should “cut down” on your alcohol use?

Have people “annoyed” you by criticizing your alcohol use?

Have you felt bad or “guilty” about your alcohol use?

Have you ever used alcohol first thing in the morning (an “eye-opener”)?

A cutoff of 1 positive answer has been shown to have greater sensitivity though this decreases its specificity.

Single alcohol screening question

The National Institute of Alcohol Abuse and Alcoholism’s (NIAAA) SASQ of “How many times in the last year have you had more than 4 drinks (for women) or 5 drinks (for men) in 1 day ?” with a positive response being once or more, has been shown to have acceptable sensitivity (73%–88%) and specificity (74%–100%) for screening for unhealthy alcohol use.⁷

If patients screen positive on any screening test, providers should have a further discussion regarding the patient’s alcohol use and refer for further evaluation and treatment as necessary.⁷

TREATMENT OF AUD

There have been many studies on the various interventions and treatments to help reduce or eliminate alcohol use; however, there is no “one size fits all” treatment, and multiple methods may need to be tried. Treatments can be separated into psychosocial/behavioral interventions and medication assistance. A review on psychotherapy in patients with chronic liver disease suggests that a combination of therapy (such as cognitive behavioral therapy and motivational interviewing) is better than one single type alone.¹⁰

Behavioral interventions

Mutual support groups

Twelve-step programs such as Alcoholics Anonymous (AA) or non–faith-based organizations such as SMART Recovery offer community support to prevent relapse.⁸ These programs differ from others listed here, as they are not led by health care professionals but are typically led by other community members.

Screening, brief intervention, and referral to treatment

Screening, brief intervention, and referral to treatment are meant to be applied universally to all patients regardless of the complaint. It typically takes about 5–10 minutes and may be completed with any of the previously mentioned screening tools. The screening then identifies a specific behavioral characteristic that should be addressed during the intervention/treatment.¹¹ Interventions may occur anywhere from 1 to 5 times with the goal of educating patients on the harms of their alcohol use and increasing motivation to reduce their alcohol intake.⁷ Brief treatments are recommended for patients who screen high risk and may involve more sessions with the goal of changing the current behaviors and to link with long-term care.

Cognitive behavioral therapy

Cognitive behavioral therapy, led by a trained professional, focuses on identifying triggers and behaviors that lead to alcohol use. It challenges disordered thoughts and beliefs and encourages changing coping mechanisms from using alcohol to activities without alcohol use.¹¹

Motivational enhancement therapy and motivational interviewing

Motivational enhancement therapy and motivational interviewing are forms of therapy that help patients explore and resolve their lack of motivation toward changing their alcohol use. It can help examine the gaps between current actions and desired health outcomes and help motivate patients to make changes.^8,11

Regardless of the type of therapy, psychotherapy for patients with AUD has been found to decrease the progression ALD and lower rates of decompensation for those with underlying cirrhosis.³ The NIAAA provides additional information online for patients and families looking for more information and assistance in obtaining these resources (https://alcoholtreatment.niaaa.nih.gov/).

Medications

There are currently only 3 Food and Drug Administration (FDA) approved drugs to treat AUD: acamprosate, naltrexone, and disulfiram. Despite their approval for the treatment of AUD, their use has not been extensively studied in populations with liver disease.

Acamprosate

Acamprosate is thought to affect the glutamine pathways, but its exact mechanism of action is not known. It has been demonstrated to reduce cravings and return to drinking. It is considered the first-line therapy by the American Psychiatric Association (APA) for moderate-severe AUD as soon as abstinence is obtained.¹² Doses of 666 mg tid are typically used, though given its renal metabolism, the dose may need to be adjusted or discontinued in patients with renal impairment. Acamprosate does not undergo hepatic metabolism and does not have a history of hepatotoxicity, making it a favorable medication in the chronic liver disease population.¹² Although no specific studies have been done in patients with chronic liver disease, a recent descriptive study of 48 patients with cirrhosis receiving acamprosate found that it was associated with a reduced chance of unplanned hospital admissions as compared with baclofen, which has been demonstrated to be safe in patients with AUD and cirrhosis (see Baclofen section below).¹³ A meta-analysis of treatments for AUD found the number needed to treat to prevent 1 person from returning to drinking was only 12.¹⁴

Naltrexone

Naltrexone is a mu-opioid receptor antagonist and has been found to be effective in the treatment of AUD by decreasing the pleasurable effects associated with alcohol use, with a number needed to treat of only 20 to prevent 1 person from returning to drinking.¹⁴ It is hepatically metabolized and previously had an FDA black box warning against the use in patients with liver disease though this warning has since been removed after insufficient evidence of liver injury attributable to the drug was found in further studies.^11,12 Previously, naltrexone had not been studied in patients with ALD; however, a recent retrospective review of naltrexone use in patients with AUD with and without ALD demonstrated lower aminotransferase and bilirubin levels during and after naltrexone use in patients with liver disease, including those with cirrhosis.¹⁵ Cumulative survival was similar between those with ALD (with and without cirrhosis) as compared with patients with AUD without ALD. Although patients with cirrhosis (compensated and decompensated) had higher alcohol-associated hospitalizations than those without ALD, none were related to naltrexone use.¹⁵ This study supports the idea that naltrexone is likely safe for the treatment of AUD in patients with ALD with close monitoring, though further safety data are needed for those with decompensated or Child-Pugh C cirrhosis¹¹ or acute hepatitis.¹² Naltrexone is typically started at 50 mg per day or lower in patients with cirrhosis, and if effective, a long-acting monthly injectable form is also available.¹² Given the convenience of a long-acting form, naltrexone may be a good option for patients after liver transplant as well.

Disulfiram

Disulfiram is an aldehyde dehydrogenase inhibitor. Aldehyde dehydrogenase is the enzyme that breaks down ethanol byproducts, so disulfiram leads to their accumulation in the body. The use of alcohol while taking disulfiram leads to an unpleasant reaction, including flushing, nausea, and vomiting,¹² leading to avoidance of alcohol intake. Although FDA approved for AUD, it has been demonstrated to cause severe liver injury and should be avoided in all patients with liver disease.¹²

In addition to the 3 FDA-approved drugs for AUD, there are other medications that have been found to be efficacious in treating AUD though they have not been FDA approved for this indication.

Baclofen

Baclofen is a GABA_B receptor agonist that is given at starting doses of 10 mg tid and may be increased if tolerated.⁸ Baclofen is the only medication that has been studied in a randomized manner for AUD in ALD patients, though the study excluded patients with HCC or HE. The study demonstrated that when compared with placebo, baclofen led to higher rates and longer duration of abstinence without increased side effects.¹⁶

Gabapentin

The APA recommends the use of gabapentin in patients with moderate to severe AUD who have not responded or did not tolerate the first-line therapy (naltrexone and acamprosate).¹² Gabapentin also modulates GABA receptors and, when given at doses of 900–1800 mg/d, has been shown in a randomized controlled trial to increase rates of abstinence and decrease heavy drinking days.¹² Gabapentin is not metabolized by the liver and as such, has fewer concerns for use in patients with underlying liver disease.

Topiramate

Topiramate is thought to decrease alcohol use through the limbic system and modification of GABA pathways.¹⁷ It is recommended for second-line treatment by the APA, similar to gabapentin.¹² It has been shown to decrease heavy drinking days in a randomized placebo-controlled trial.¹⁸ It has never been studied specifically in patients with ALD, and given the increase in side effects, such as difficulty concentrating¹⁸ and cognitive dysfunction,¹² caution should be used in patients with a history of encephalopathy.

Other medications, such as ondansetron or varenicline, have shown some efficacy though their use for the treatment of AUD in patients with ALD has not yet been proven.^8,11 Table 3 summarizes the mechanisms, dosing, and contraindications of medications reviewed here.

Table 3.

Medications for treatment of AUD in patients with ALD

Medication	Dose	Mechanism of action	Metabolism	Contraindication	APA recommendation in AUD
FDA approved for treatment of AUD
Acamprosate	333 mg tid × 5–7 d, up titrated to 666 mg tid	Unknown, possibly glutamine pathways	No metabolism, renal excretion	Dose adjustment needed for renal dysfunction	First line
Naltrexone	25–50 mg starting dose	Opioid receptor antagonist	Primarily hepatic metabolism	Severe hepatic dysfunction (Child-Pugh B or C or severe hepatitis)	First line
Disulfiram	—	—	—	Should not be used in patients with underlying liver disease	—
Off label use for treatment of AUD
Baclofen	10 mg tid starting dose	GABAB receptor agonist	Primarily renal metabolism (15% hepatic metabolism)	Dose adjustment needed for renal dysfunction	No recommendation
Gabapentin	900–1800 mg per day in divided doses	GABA modulation	No metabolism, renal excretion	Dose adjustment needed for renal dysfunction	Second line
Topiramate	300 mg daily	Effects GABA pathways	Minimal hepatic metabolism, renal excretion	Dose adjustment needed for renal dysfunction	Second line

Abbreviations: AUD, alcohol use disorder; ALD, alcohol-associated liver disease; APA, American Psychiatric Association; FDA, Food and Drug Administration; GABA, gamma-aminobutryic acid; tid, 3 times a day.

CONCLUSIONS

AUD is typically a relapsing and remitting disease with significant consequences, including ALD. Decreasing alcohol use can not only improve liver function and the need for transplant, but alcohol use after liver transplant can lead to significant graft impairment and loss. Ideally, patients with AUD would be treated with a multidisciplinary team, including hepatologists, psychologists/psychiatrists, addiction medicine specialists, and social workers, as the combination of behavior therapy and medication has been shown to be most effective.¹⁹ However, many patients may not be identified or referred for care. This places the hepatologist in a unique position to help manage a patient’s AUD while also managing their underlying liver disease.