Identification and management of alcohol dependence and withdrawal in alcoholic liver disease


  • Jody B. Glance M.D.,

    1. Departments of Psychiatry and Surgery, School of Medicine, University of Pittsburgh, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • Andrea DiMartini M.D.

    Corresponding author
    1. Departments of Psychiatry and Surgery, School of Medicine, University of Pittsburgh, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
    • Departments of Psychiatry and Surgery, School of Medicine, University of Pittsburgh, Starzl Transplant Institute, University of Pittsburgh Medical Center, 3811 O'Hara Street, Pittsburgh, PA 15213
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  • Potential conflict of interest: Nothing to report.


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Excessive alcohol use is associated with many adverse effects, including the development of alcohol dependence, problems within family and social networks, and medical consequences such as alcoholic liver disease (ALD).1 Treating patients with ALD requires awareness that the psychiatric disorder of alcohol dependence is commonly comorbid with ALD. Hepatologists are in a unique position to make a significant impact on the alcohol-dependent patient's future, because they often see these patients in the context of alcohol-related health issues. Although managing a medical crisis can take precedence in the immediate stabilization of the patient, identifying and recommending treatment for alcohol dependence can be life-saving.

Identification of Alcohol Use Disorders

ALD may occur as a result of alcohol abuse, but more frequently it is due to alcohol dependence (Table 1). Both disorders are important to address clinically, especially if ALD has developed. However, alcohol-dependent patients are at higher risk of continuing to drink2 and require more intensive treatment. Although the diagnosis should be established by a mental health clinician, brief questionnaires such as the Alcohol Use Disorders Identification Test (AUDIT) (Table 2) can be incorporated easily into a clinical assessment to establish problematic patterns of alcohol use.3

Table 1. DSM-IV Criteria for Alcohol Dependence*
  • *

    Criteria A and B must both be met.

  • Abbreviation: DSM-IV, Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision.

  • Adapted with permission from Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. Copyright 2000, American Psychiatric Association.

Criterion A. A maladaptive pattern of alcohol use, leading to clinically significant impairment or distress, as manifested by three or more of the following, occurring at any time in the same 12-month period:
 1. Tolerance, as defined by a need for markedly increased amounts of alcohol to achieve intoxication or desired effect, or markedly diminished effect with continued use of the same amount of alcohol
 2. Withdrawal, as manifested by either the characteristic withdrawal syndrome for alcohol, or drinking alcohol (or using a related substance such as benzodiazepines) to relieve or avoid withdrawal symptoms
 3. Drinking alcohol in larger amounts or over a longer period than intended
 4. Persistent desire or one or more unsuccessful efforts to cut down or control drinking
 5. Important social, occupational, or recreational activities given up or reduced because of drinking
 6. A great deal of time spent in activities necessary to obtain, to use, or to recover from the effects of drinking
 7. Continued drinking despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to be caused or exacerbated by drinking
Criterion B. No duration criterion separately specified, but several dependence criteria must occur repeatedly as specified by duration qualifiers associated with criteria (e.g., “persistent,” “continued”).
Table 2. Alcohol Use Disorders Identification Test (AUDIT)
  1. A score of 8+ generally indicates harmful or hazardous drinking. Questions 1–8 = 0, 1, 2, 3, or 4 points. Questions 9 and 10 are scored 0, 2, or 4 only. Screening tools such as the AUDIT are relatively quick, easily scored, and can be self-administered. A questionnaire and manual with guidelines for use are available at

 1. How often do you have a drink containing alcohol?NeverMonthly or less2 to 4 times a month2 to 3 times a week4 or more times a week 
 2. How many drinks containing alcohol do you have on a typical day when you are drinking?1 or 23 or 45 or 67 to 9Daily or almost daily 
 3. How often do you have 5 or more drinks on one occasion?NeverLess than monthlyMonthlyWeeklyDaily or almost daily 
 4. How often during the last year have you found that you were not able to stop drinking once you had started?NeverLess than monthlyMonthlyWeeklyDaily or almost daily 
 5. How often during the last year have you failed to do what was normally expected of you because of drinking?NeverLess than monthlyMonthlyWeeklyDaily or almost daily 
 6. How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session?NeverLess than monthlyMonthlyWeeklyDaily or almost daily 
 7. How often during the last year have you had a feeling of guilt or remorse after drinking?NeverLess than monthlyMonthlyWeeklyDaily or almost daily 
 8. How often during the last year have you been unable to remember what happened the night before because of your drinking?NeverLess than monthlyMonthlyWeeklyDaily or almost daily 
 9. Have you or someone else been injured because of your drinking?No Yes, but not in the last year Yes, during the last year 
10. Has a relative, friend, doctor, or other health care worker been concerned about your drinking or suggested you cut down?No Yes, but not in the last year Yes, during the last year 

Inquiring about alcohol consumption in a nonconfrontational, nonjudgmental manner is the most consistent, yet often overlooked, way to identify alcohol use. However, patients with alcohol use disorders may minimize or deny use. Of the biomarkers of alcohol use, testing directly for alcohol using blood alcohol levels or breath analyzers has been the clinical standard for detection and monitoring due to wide availability. Because of its rapid elimination, measurements of alcohol will only detect very recent use. Although not widely used in routine clinical practice, urinary ethyl glucuronide, a conjugated minor ethanol metabolite with a longer detection window than ethanol itself, can be detected even after serum ethanol levels are negative. Carbohydrate deficient transferrin (CDT) is an abnormal form of a liver protein resulting from sustained heavy alcohol use. CDT may be detected in the blood after several weeks of abstinence, but will not be positive with lesser amounts of consumption and can be elevated in patients with advanced liver disease, falsely suggesting alcohol use. Hair toxicology analyses, although not widely available, can identify alcohol and other drug use for up to 90 days. Although biomarkers may establish use, the pattern of use including quantity and frequency of use or establishing an alcohol use disorder requires further investigation.


alcoholic liver disease


carbohydrate deficient transferrin

Alcohol Withdrawal

An acute manifestation of alcohol dependence, alcohol withdrawal, is commonly observed in the inpatient setting, where a patient does not have access to alcohol. Because patients with alcohol dependence may minimize the amount of alcohol use, alcohol withdrawal symptoms (Table 3) may initially go unrecognized or symptoms may be incorrectly diagnosed as manifestations of psychiatric illness.4 However, correctly distinguishing between alcohol withdrawal or intoxication and hepatic encephalopathy is critical, as treating encephalopathy with benzodiazepines will worsen the delirium and could cause dangerous sedation. Onset of withdrawal is somewhat variable; some patients may develop symptoms even before their blood alcohol levels reach zero, whereas others may show no signs of withdrawal until several days of abstinence have passed. Tremulousness is usually the earliest sign of withdrawal. Seizures may occur shortly thereafter, and often without warning; thus, every patient admitted with liver disease must be monitored for signs of alcohol withdrawal. Delirium tremens may develop at any time during the first week following alcohol cessation, though the typical time course is 48 to 72 hours of abstinence. If symptoms of alcohol withdrawal are not recognized or are mistaken for another clinical condition, the results may be fatal. Patients with significant medical comorbidities such as pancreatitis, gastrointestinal bleeding, hepatic insufficiency, cardiac disease or hemodynamic instability, severe electrolyte disturbances, prior withdrawal seizures, or delirium may be considered for admission to an intensive care unit to monitor withdrawal.

Table 3. DSM-IV Criteria for Alcohol Withdrawal
  1. Abbreviation: DSM-IV, Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision.

  2. Adapted with permission from Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. Copyright 2000, American Psychiatric Association.

Criterion A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged.
Criterion B. Two (or more) of the following, developing within several hours to a few days after Criterion A:
 1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100)
 2. Increased hand tremor
 3. Insomnia
 4. Nausea or vomiting
 5. Transient visual, tactile, or auditory hallucinations or illusions
 6. Psychomotor agitation
 7. Anxiety
 8. Grand mal seizures
Criterion C. The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
Criterion D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

The use of oral ethyl alcohol to prevent or treat alcohol withdrawal is discouraged, because it contradicts efforts to encourage abstinence, is difficult to monitor clinically, and continues to damage the liver and overall health. Benzodiazepines are the mainstay of medication management of withdrawal.5 Glucuronidation is preserved in cirrhosis; therefore, a benzodiazepine that does not require phase I biotransformation is preferred (e.g., lorazepam or oxazepam). Care must be taken in advanced liver disease for although tolerance to alcohol may have developed, the response to benzodiazepines may be less predictable. A strategy of starting at a low dose and closely monitoring the response, giving additional dosages as symptoms emerge is preferred. However, under-treating and allowing significant withdrawal to develop can be dangerous. Clinical skill is required to balance these complex needs. Once an adequate dose is determined, a fixed-schedule taper may be used, decreasing the dosage by approximately 25% per day. However, a symptom-triggered protocol such as the CIWA-Ar (Table 4) is more sensitive to the specific treatment needs of the individual and can be used in addition to a fixed taper. Based on reassessment every 2 to 4 hours, the resulting score will identify breakthrough withdrawal symptoms requiring additional benzodiazepine administration.6 A continuous intravenous infusion of benzodiazepines or propofol may be necessary, but this is only appropriate in an intensive care setting, where the patient can be continuously monitored for any respiratory depression or other adverse events. In complex cases when intensive care is required, toxicology or addiction medicine services may be consulted to assist with management. Similarly, the use of anticonvulsants and barbiturates for withdrawal remains controversial, and specialists should be consulted for their use. Other medical considerations include adequate fluid and electrolyte replacement, parenteral thiamine, multivitamins, glucose, and adequate calorie support. Sarff and Gold7 provide an excellent review of current treatment options for alcohol withdrawal in an intensive care setting.

Table 4. Example of a Symptom-Triggered Alcohol Withdrawal Protocol
  1. Patients should be scored a minimum of every four hours, and more frequently if showing signs of active withdrawal. The maximum score is 67. A score of <10 does not usually require medication-assisted treatment of withdrawal.7 A score of 10–15 indicates moderate withdrawal that may require medication. A score of >15 suggests severe withdrawal requiring medication-assisted treatment.

  2. Adapted with permission from Addiction Research Foundation Clinical Institute for Withdrawal Assessment of Alcohol, Revised (CIWA-Ar).

Nausea/Vomiting0–70 = none; 7 = constant nausea/vomiting
Tremor0–70 = none; 7 = severe
Paroxsymal sweats0–70 = none visible; 7 = drenching sweats
Anxiety0–70 = none; 7 = severe acute panic
Agitation0–70 = normal; 7 = constant pacing
Tactile disturbances0–70 = none; 7 = continuous hallucinations
Auditory disturbances0–70 = none; 7 = continuous hallucinations
Visual disturbances0–70 = none; 7 = continuous hallucinations
Headache/Fullness in head0–70 = none; 7 = extremely severe
Orientation/Clouding of sensorium0–40 = none; 4 = disoriented to place and/or person

Referral and Treatment Strategies

Successful abstinence depends on active recovery, and merely telling a patient with alcohol dependence to stop drinking, or even that continuing to drink will be fatal, is rarely helpful without also providing structure and support to achieve this goal. Relapses are common, even after life-threatening complications such as variceal hemorrhage.8 Every encounter with medical personnel is an opportunity to assess readiness for change (Fig. 1) and recommend appropriate treatment. A few minutes spent listening to the patient and then appropriately matching the recommendations to the level of readiness to change can improve the interaction and outcome. Addressing ambivalence and linking patients to specialty addiction treatment can greatly increase their chances for sustained sobriety. Motivational interviewing principles as developed by Miller and Rollnick9 to address ambivalence could be an intervention delivered by a therapist trained in the technique and includes developing discrepancy, avoiding argumentation, rolling with resistance, expressing empathy, and supporting self-efficacy to increase a patient's motivation to change harmful behaviors. However, even a few brief minutes of counseling by a health care provider can be effective in motivating an individual to reduce alcohol use.10

Figure 1.

Stages of change model. Adapted with permission from Kern MF. Copyright 2008, Nehemiah Family Services.

Ambivalence is the norm and even highly motivated individuals may require several attempts at sobriety and/or rehabilitation before abstinence is achieved. Following detoxification and hospital discharge, the patient may benefit from admission to a residential addiction rehabilitation program to provide appropriate treatment and remove the patient from an environment where alcohol is readily available. Some may benefit from day treatment programs such as partial hospitalization or intensive outpatient programs. Following successful completion, ongoing long-term maintenance therapy (e.g., individual therapy sessions, group therapy, or 12-step programs such as Alcoholics Anonymous) is strongly encouraged. Mutual support programs offer an excellent opportunity for the patient to engage in active recovery and learn how others have managed to stay sober and change their lives in positive ways.

Medications to treat alcohol dependence have modest effects in decreasing the risk for relapse and reducing cravings (Table 5). They are primarily adjuncts to psychosocial treatments and should be prescribed and monitored by physicians skilled in the treatment of addiction and liver disease due to the complexities of drug metabolism and effects. It has also been suggested that concurrent treatment of co-occurring psychiatric disorders may also help decrease the risk for relapse.11 As many patients with alcohol dependence are not offered medication treatment, they could be encouraged to discuss this with their addiction treatment providers.

Table 5. Medication-Assisted Treatment of Alcohol Dependence
MedicationMechanism of ActionPrecautions
  1. Four medications have been approved by the US Food and Drug Administration for the treatment of alcohol dependence. Other medications such as topiramate and ondansetron are sometimes used by addiction specialists as off-label treatments.

  2. Abbreviation: GABA, gamma-aminobutyric acid.

Disulfiram (Antabuse)Inhibits alcohol metabolism, thus causing acetaldehyde accumulation leading to flushing, palpitations, nausea, headache, thirst, vertigo, and hypotensionHigh risk of hepatotoxicity; not recommended for use in patients with advanced liver disease
Risk of cardiovascular effects (e.g., chest pain, arrhythmia, hemodynamic instability)
Acamprosate (Campral)Modulates glutamate and GABA systems, thus decreasing cravingsRenally excreted; use with caution in patients with renal insufficiency; contraindicated if creatinine clearance <30 mL/minute
Naltrexone (ReVia [daily oral medication]; Vivitrol [long-acting injectable medication given once monthly])Mu-opioid receptor antagonist that counteracts the reward/reinforcing effects of alcohol and reduces cravingsPotential risk of hepatotoxicity at high doses (particularly >300 mg/day; typical dose is 50 mg/day)
Contraindicated in patients taking concomitant opioid analgesics or opioid maintenance therapy (i.e., methadone, buprenorphine)

Alcohol dependence is a chronic, relapsing, and remitting illness with physiological, psychological, and social components, all of which must be addressed if treatment is to be successful. Because the majority of patients with alcohol dependence do not seek help independently, care providers who identify and intervene in the medical setting will address a major problem that is often missed or inadequately treated. Active interventions by medical care providers, including alcohol detoxification and referral to addiction treatment, can provide patients with the structure and support necessary to maintain sobriety and prevent an early demise from liver failure.