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

  • Nonspecific testing
    • CBC
      • MCV
        • May show macrocytosis
        • More sensitive test in females – not specific for alcohol abuse
        • Limited as a screening test – reduced sensitivity in B12 and folate deficiencies, liver disease, concomitant tobacco abuse, and hypothyroidism
        • Not a suitable marker for following abstinence – normalization of MCV may require 2-4 months of abstinencea
      • 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
    • 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
        • Nonspecificity for alcohol abuse limits usefulness – may also be elevated in nonalcoholic fatty liver disease, drug intoxication, obesity, diabetes, hepatobiliary disorders
        • 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
        • Normalization requires 2-3 weeks of abstinence
  • Ethanol levels – blood, urine, or breath samples
    • Use for patients with suspected acute alcohol consumption
    • Suggestive of dependence
      • Levels >0.15 g/dL (>1.5%) without evidence of intoxication
      • >3.0 g/dL (>3.0%) without death
      • Positive level during daytime hours
  • Carbohydrate deficient transferrin (CDT)
    • Can detect ≥40 g/day ethanol consumption for ≥2 weeks
    • ≥1.6% – considered elevated and associated with active alcohol use
      • Levels between 1.4 and 1.6% 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
      • Highest sensitivity achieved by using combination of GGT and CDT – possibly add MCV to these tests
  • Ethyl glucuronide
    • Detects recent ethanol exposure – 1-4 days post ingestion
      • Dose may be as low as ≤0.25 g/kg at day 1 testing or ≤0.5 g/kg at day 2 testing
      • Aids in monitoring alcohol abstinence – negative test confirms ~2 previous days
    • Urine – most available testing with quantitation
    • False-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

Differential Diagnosis

Screening

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

Monitoring

  • Ethyl glucoronide – may be an excellent test for monitoring short term abstinence (1-4 days)
  • Carbohydrate deficient transferrin – may be an excellent test for monitoring longer abstinence (up to 2 weeks)

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
  • Ethyl glucuronide (EtG) and ethyl sulfate (EtS)
    • Direct metabolites of ethanol
    • Can be detected up to 80 hours in urine after ethanol ingestion
      • Good marker of acute alcohol ingestion
      • May be useful in short term monitoring for abstinence
  • 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
    • Level of disialo-, monosialo-, and asialo-transferrin isoforms – normally low or undetectable
      • Level of these CDTs – 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
Ethanol, Serum or Plasma - Medical 0090120
Method: Quantitative Gas Chromatography/Enzymatic
Use to identify acute alcohol ingestion

Assay detection limit – varies based on instrumentation

 
Alcohols 0090131
Method: Quantitative Gas Chromatography
Use to identify ethanol, methanol, acetone, or isopropanol ingestion

Assay detection limit – 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

Use to identify acute alcohol ingestion

Screen with reflex to confirmation

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

Positive cutoff 40 mg/dL

 
Drugs of Abuse - Confirmation/Quantitation - Alcohol, Urine 2010136
Method: Quantitative Gas Chromatography

Use to identify acute alcohol ingestion

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

Positive cutoff 5 mg/dL

 
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

Cannot be used in patient suspected of having congenital glycosylation disorders

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

 
Ethyl Glucuronide Screen with Reflex to Confirmation, Urine 2007912
Method: Qualitative Enzyme Immunoassay/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Identify recent ethanol exposure within 1-4 days after ingestion

Cutoff for positive screen – set at 500 ng/mL

False-positive results –microbial formation or fermentation, ethanol-containing products (eg, hand sanitizer, mouth wash)

False-negative results – bacterial degradation, >4 days since ethanol ingestion

 
Ethyl Glucuronide and Ethyl Sulfate Confirmation, Urine 2007909
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Identify recent ethanol exposure within 1-4 days after ingestion

Analytic sensitivity – limit of quantification is 100 ng/mL

Incidental exposure from ethanol containing products may be detected

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
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 chronic alcohol related hepatic injury

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

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

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