Alcohol Abuse

Clinical Background

Approximately 20% of primary care patients in the U.S. drink alcohol (ethanol) at levels harmful to health.

Epidemiology

• Incidence – 20-30% of hospital admissions and health-care costs are due to alcohol abuse
• Age – usually young adults
• Sex – M>F

Pathophysiology

• Alcohol consumption has toxic effects on the liver and hematologic system
  • Liver enzymes are induced by alcohol and may increase during the ensuing hepatocyte injury
  • Alcohol also suppresses albumin production by the liver
  • Alcohol is toxic to the hematologic precursor cells and may affect red-cell morphology
  • Patterns of alcohol consumption (CDC definitions)
    • Binge drinking
      • Women – ≥4 drinks on a single occasion
      • Men – ≥5 drinks on a single occasion
    • Heavy drinking
      • Women – >1 drink/day on average
      • Men – >2 drinks/day on average
• Carbohydrate deficient transferrin (CDT)
  • Transferrin (plasma iron transport protein) contains 2 N-linked glycan chains that differ in their degree of branching, showing bi-, tri-, and tetra-antennary structures
    • Each N-glycan chain branch terminates with a sialic acid molecule
  • The level of disialo-, monosialo-, and asialo-transferrin isoforms is normally low or undetectable; however, the level of these CDTs is markedly increased by alcohol abuse

Clinical Presentation

• May present with signs of acute intoxication – slurred speech, altered sense of consciousness, coma
• Other nonspecific signs in non-intoxicated patients – depression, anxiety
• Complications
  • Withdrawal signs and symptoms – tremor, tachycardia, nausea, anxiety, sweating, insomnia
    • Delirium tremens – clouding of consciousness, psychomotor agitation, fear, delusions, hallucinations
  • Wernicke-Korsakoff syndrome – caused by alcohol-induced thiamine deficiency
  • Impaired cognition and learning, confabulation, ataxia, nystagmus
  • Cirrhosis
  • Pancreatitis
  • Esophageal varices
  • Coagulopathy (vitamin K deficiency)
  • Ascites
  • Megaloblastic anemia (vitamin B12 and folate deficiency)

Diagnosis

Indications for Testing

• Suspicion of alcohol abuse – meets criteria for diagnosis from ICD-10 and Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV)
• Trauma-related injury
• Monitoring of patient in substance abuse treatment
• Follow-up testing to investigate abnormalities of other biomarkers suggestive of alcohol abuse
  • Gamma glutamyl transferase (GGT)
  • Mean corpuscular volume (MCV)
  • HDL cholesterol
  • Aspartate aminotransferase (AST)
  • Alanine aminotransferase (ALT)

Criteria for Diagnosis

• ICD-10 criteria for diagnosis of alcoholism

  • ICD-10 defines 1 unit of alcohol equal to 8-10 g (half-pint of beer, 1 glass (5 oz) of wine, 1 oz of hard liquor)
• DSM IV criteria for alcohol dependency
  • Three or more of the following for at least 1 month or repeatedly over the past 12 months
    • Strong desire or compulsion to drink
    • Difficulty in controlling drinking in terms of onset, termination or extent of use
    • Physiologic withdrawal when use is reduced (tremor, sweating, tachycardia, anxiety, insomnia) or drinking to avoid withdrawal state
    • Evidence of alcohol tolerance – increasing amount required to produce same effects
    • Progressive neglect of other interests
    • Persistent use despite awareness of harmful effects

Laboratory Testing

• CBC – MCV may show macrocytosis
  • More sensitive test in females; not specific for alcohol abuse
  • Reduced sensitivity in B12 and folate deficiencies, liver disease, concomitant tobacco abuse and hypothyroidism
  • Normalization of MCV may require 2-4 months of abstinence
• Liver function tests
  • AST and ALT
    • AST/ALT ratio >2 suggests alcoholic etiology
    • May not be elevated; not highly sensitive or specific
    • ALT is fairly specific for liver injury, whereas AST may also be elevated in skeletal muscle and cardiac muscle injury
  • GGT
    • Sensitive and inexpensive marker
    • Even moderate drinkers (<60 g/week), especially men, show higher levels than abstainers
    • May be a less-sensitive marker in young drinkers
    • Age dependent for older patients – levels increase with age even in abstinent patients
    • Not specific to alcohol abuse; may be elevated in nonalcoholic fatty liver disease, drug intoxication, or other liver disease
    • Normalization requires 2-3 weeks of abstinence
• Ethanol levels – blood, urine or breath samples
  • Normally used for patients with suspected acute alcohol intoxication
  • Levels >0.15 g/dL (>1.5%) without evidence of intoxication or >3.0 g/dL (>3.0%) without death indicates alcohol dependence
  • Finding of positive level during daytime hours also indicative of potential alcohol abuse
• CDT
  • >50 g/day for at least 2 weeks elevates CDT
  • >2.5% or 25 IU/L suggests active alcohol abuse
  • More sensitive test in men
  • May be a sensitive marker of relapse in chronic abusers
  • Testing with highest sensitivity may be combination of GGT and CDT and possibly MCV
• Ethyl glucuronide
  • Urine test
  • Detects recent ethanol exposure (1-7 days)
  • Aids in monitoring alcohol abstinence
  • Positive results may reflect use of ethanol-containing personal care products (eg, cough syrups, mouth wash, hand sanitizer)
• Other, less-specific, tests
  • Platelet count on CBC – thrombocytopenia present in about 30% of alcohol-abuse patients
    • Rapidly normalizes with abstinence
  • HDL – increases with regular consumption of only 3-5 drinks per day
    • Decreases within 1-2 weeks of abstinence
  • Ferritin – increases with low levels of alcohol consumption
  • Albumin – low if alcohol abuse is associated with severe liver disease
  • Urate – increases with low levels of alcohol consumption
  • Immunoglobulin A – increased in chronic alcoholic liver disease

Differential Diagnosis

• Acute alcohol intoxication
  • Metabolic encephalopathy
  • Cerebrovascular event
  • Sepsis
  • Drug overdose
• Chronic alcohol abuse
  • Chronic infectious hepatitis
    • Hepatitis B and hepatitis C
  • Non-alcoholic fatty liver disease
  • Metabolic liver disease (eg, Wilson disease)
  • Chronic pancreatitis
  • Seizure disorder

Screening

Monitoring

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
HDL Cholesterol 0020053 Method: Detergent Solubilization, Enzymatic
Albumin, Serum or Plasma by Spectrophotometry 0020030 Method: Spectrophotometry
Uric Acid, Urine 0020481 Method: Spectrophotometry
Immunoglobulin A, Serum 0050340 Method: Nephelometry
Alkaline Phosphatase, Serum or Plasma 0020005 Method: Enzymatic
Bilirubin, Total, Serum or Plasma 0020032 Method: Spectrophotometry
Aspartate Aminotransferase, Serum or Plasma 0020007 Method: Enzymatic
Alanine Aminotransferase, Serum or Plasma 0020008 Method: Enzymatic
Albumin, Serum by Nephelometry 0050671 Method: Nephelometry
Ferritin 0070065 Method: Chemiluminescent Immunoassay