Alcohol Abuse

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
      • 8 oz of beer, 5 oz of wine, 1 oz of hard liquor
  • CDC – patterns of alcohol consumption
    • 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
  • DSM IV criteria for alcohol dependency
    • Three or more of the following for ≥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
      • 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
  • Liver function tests
    • Aspartate transaminase (AST) and alanine transaminase (ALT)
      • AST/ALT ratio – >2 suggests alcoholic etiology
      • May not be elevated – not highly sensitive or specific
      • ALT is fairly specific for liver injury, although AST may also be elevated in skeletal muscle and cardiac muscle injury
    • Gamma glutamyl transferase (GGT)
      • Sensitive and inexpensive indirect marker of alcohol consumption
      • 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
      • Nonspecificity for alcohol abuse limits usefulness – may also be elevated in nonalcoholic fatty liver disease, drug intoxication, obesity, diabetes, hepatobiliary disorders
      • Normalization requires 2-3 weeks of abstinence
  • Ethanol levels – blood, urine, or breath samples
    • Use 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
    • Positive level during daytime hours also indicative of potential alcohol abuse
  • Carbohydrate deficient transferrin (CDT)
    • Detects ≥40 g/day ethanol consumption for ≥2 weeks
    • ≥1.3% – considered elevated and associated with active alcohol use
      • Levels between 1.2 and 1.4% should be retested in 3-4 weeks
    • Sensitivity
      • Moderately sensitive and specific for longer-term alcohol use
      • More sensitive test in men – especially >40 years
      • May be a sensitive marker of relapse in chronic abusers
      • Testing with highest sensitivity – combination of GGT and CDT; possibly add MCV to these tests
  • Ethyl glucuronide
    • Detects recent ethanol exposure – 1-7 days
      • Dose may be as low as ≤0.25 g/kg at day 1 testing or ≤0.5 g/kg at day 2 testing
    • Urine test – current testing platform
      • Hair and blood testing in development
    • Aids in monitoring alcohol abstinence – negative test confirms ~2 previous days of abstinence
    • Positive results
      • May reflect use of ethanol-containing personal care products (eg, cough syrups, mouth wash, hand sanitizer)
      • Urine with high glucose level from diabetics
      • Storage of specimen >12 hours
    • Not widely available
  • Other, less-specific, tests
    • Platelet count – thrombocytopenia present in ~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 in association with chronic alcoholic liver disease
      • Urate – increases with low levels of alcohol consumption
      • Immunoglobulin A – increased in chronic alcoholic liver disease

Differential Diagnosis

Screening

  • Ethanol (serum, breath, or urine) – best screen for acute alcohol intoxication

Monitoring

  • Carbohydrate deficient transferrin may be an excellent test for monitoring abstinence

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
    • Suppresses albumin production by the liver
    • Toxic to the hematologic precursor cells and may affect red-cell morphology
  • 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
    • Considered an indirect marker of alcohol exposure – reflects toxic effects of ethanol on biochemical pathways

Clinical Presentation

  • May present with signs of acute intoxication – slurred speech, altered sense of consciousness, coma
  • Other nonspecific signs in nonintoxicated 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

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
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count 0040002
Method: Automated Cell Count

Initial test to determine macrocytosis

   
Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Initial screen for suspected alcohol related hepatic injury

Panel includes albumin, alkaline phosphatase, AST, ALT, direct bilirubin, total protein, and total bilirubin

   
Ethanol, Serum or Plasma - Medical 0090120
Method: Quantitative Gas Chromatography/Enzymatic

One of the screens used to identify acute alcohol use

Assay detection limit varies based on instrumentation

 
Alcohols 0090131
Method: Quantitative Gas Chromatography

Best test to identify acute use of ethanol, methanol, or isopropanol

Acetone is also detected

Assay detection limit is 5 mg/dL

 
Drugs of Abuse Test, Alcohol, Urine - Screen with Reflex to Confirmation/Quantitation 0092280
Method: Semi-Quantitative Alcohol Dehydrogenase/ Qualitative Gas Chromatography-Flame Ionization Detection

Identify acute alcohol use

Screen with reflex to confirmation

Sensitivity and specificity with urine are relatively poor; not valid for forensic use

Positive cutoff 40 mg/dL

 
Gamma Glutamyl Transferase, Serum or Plasma 0020009
Method: Quantitative Enzymatic
Use as indirect marker of alcohol consumption

May be less sensitive marker in young drinkers

Not specific for alcohol abuse; may be elevated in nonalcoholic fatty liver disease, drug intoxication, or other liver diseases

 
Carbohydrate Deficient Transferrin for Alcohol Use 0070412
Method: Quantitative Electrophoresis

Identify alcohol abuse or abuse relapse; will detect chronic ethanol use (≥40 g/day for 2 weeks)

More sensitive in men

Rare transferrin genetic variants may interfere with analysis

Advanced liver damage (including severe chronic viral hepatitis) and anti-epileptic drug therapy can increase CDT levels

Not recommended for general population screening

 
Ethyl Glucuronide, Urine - Screen with Reflex to Confirmation/Quantitation 2003189
Method: Qualitative Enzyme Immunoassay/Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Detect recent ethanol exposure; monitor alcohol abstinence (1-7 days)

Most sensitive 1-2 days after exposure

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Ethanol, Urine, Qualitative - Medical 0090518
Method: Quantitative Enzymatic
HDL Cholesterol 0020053
Method: Detergent Solubilization/Enzymatic
Albumin, Serum or Plasma by Spectrophotometry 0020030
Method: Quantitative Spectrophotometry
Uric Acid, Urine 0020481
Method: Quantitative Spectrophotometry
Immunoglobulin A 0050340
Method: Quantitative Nephelometry
Alkaline Phosphatase, Serum or Plasma 0020005
Method: Quantitative Enzymatic
Bilirubin, Total, Serum or Plasma 0020032
Method: Spectrophotometry
Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic
Alanine Aminotransferase, Serum or Plasma 0020008
Method: Quantitative Enzymatic
Albumin by Nephelometry 0050671
Method: Quantitative Nephelometry
Ferritin 0070065
Method: Quantitative Chemiluminescent Immunoassay