Alcohol Abuse

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
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Indications for Testing

  • Suspicion of alcohol abuse – patient meets World Health Organization (WHO) criteria for diagnosis from the International Classification of Diseases 10th Revision (ICD-10) and the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
  • 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)
    • High-density lipoprotein (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-5 criteria for alcohol use disorder
    • Symptoms
      • Alcohol often taken in larger amounts or over a longer period than intended
      • Persistent desire or unsuccessful efforts to cut down or control alcohol use
      • Significant amount of time spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects
      • Craving, or strong desire or urge to use alcohol
      • Recurrent alcohol use resulting in failure to fulfill major role obligations at work, school, or home
      • Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol
      • Important social, occupational, or recreational activities given up or reduced because of alcohol use
      • Recurrent alcohol use in physically hazardous situation
      • Continued alcohol use despite knowledge of having persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol
      • Tolerance, as defined by either of the following
        • Need for markedly increased amounts of alcohol to achieve intoxication or desired effect
        • Markedly diminished effect with continued use of the same amount of alcohol
      • Withdrawal, as manifested by either of the following
        • Characteristic withdrawal syndrome for alcohol (eg, trouble sleeping, shakiness, restlessness, nausea)
        • Alcohol (or closely related substance, such as benzodiazepine) taken to relieve or avoid withdrawal symptoms
    • Grade of severity
      • Mild – presence of 2-3 symptoms over the past 12 months
      • Moderate – presence of 4-5 symptoms over the past 12 months
      • Severe – presence of ≥6 symptoms over the past 12 months

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 with 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 abstinence
    • Platelet count – thrombocytopenia present in ~30% of alcohol-abuse patients
      • Rapidly normalizes with abstinence
    • HDL
      • Increases with regular consumption of 3-5 drinks per day
      • Decreases within 1-2 weeks of abstinence
    • Ferritin – increases with low levels of alcohol consumption
    • Albumin  – low concentrations in chronic alcoholic liver disease
    • Urate – increases with low levels of alcohol consumption
    • Immunoglobulin A – increased in chronic alcoholic liver disease
    • Liver function tests
      • AST and ALT
        • May not be elevated – not highly sensitive or specific
        • AST:ALT ratio – >2 suggests alcoholic etiology for elevation
        • ALT is fairly specific for liver injury, although AST may also be elevated with skeletal muscle and cardiac muscle injury
      • 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
        • Nonspecificity for alcohol abuse limits usefulness – may also be elevated with nonalcoholic fatty liver disease, drug intoxication, obesity, diabetes, hepatobiliary disorders
        • Age dependent – levels increase with age, even in abstinent patients
        • Normalization requires 2-3 weeks of abstinence
  • Specific testing
    • Ethanol levels – serum, urine, or breath specimens
      • 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

Differential Diagnosis

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

Markers for Monitoring Ethanol Exposure

 

Carbohydrate Deficient Transferrin (CDT)

Ethyl Glucuronide (EtG)

Ethyl Sulfate (EtS)

Phosphatidylethanol  (PEth)

Metabolite of ethanol

Indirect

Direct minor metabolite (<0.1% of ethanol disposition)

Direct ethanol metabolite

Test description

Long term marker of heavy ethanol abuse or abuse relapse

Heavy ethanol abuse increases fractions of CDT; consumption of 50-80 g/day for 1-2 weeks elevates CDT above baseline

Detects chronic use (≥40 g/day ethanol consumption for 2 weeks) 

Reported as percent

  • ≥1.7% – supports alcohol use >40 g/day
  • <1.4% – does not support alcohol use >40 g/day over the prior 2 weeks
  • 1.4-1.6% – reported as inconclusive  

Most useful for long-term abstinence monitoring (up to 2 weeks)

Good marker of acute alcohol ingestion

Detects short term ethanol exposure – 1-4 days post ingestion (up to 80 hours in urine)

  • Ethanol intake may be as low as ≤0.25 g/kg for detection at day 1 testing or ≤0.5 g/kg for detection at day 2 testing
  • May be useful in short-term monitoring of abstinence – negative test confirms abstinence during ~2 previous days

Detects longer term exposure (up to 4 weeks)

Distinguishes between heavy (>60 g/day) and less heavy use – tool for chronic heavy drinking

Sensitivity/specificity

Moderately sensitive and specific for longer-term alcohol use

More sensitive in men especially >40 years

  • Sensitivity decreases with high BMI, female gender, and smoking

Relatively sensitive marker of relapse in chronic abusers

Highest sensitivity may be achieved in combination with one or all of the following

  • Gamma-glutamyl transferase  (GGT)
  • Mean corpuscular volume (MCV)
  • EtG

Highest in heavy drinkers

Sensitivity wanes after 24 hours and with lower doses (Nanau, 2015)

Results do not accurately correlate with amount or frequency of ethanol use

Correlates best with heavy drinking in last 1-4 days

Correlates well with EtG but not CDT or guanosine triphosphate (GTP)

Specimens

Serum

Urine – most available testing with quantitation

Hair – may be better indicator of long-term alcohol consumption

Blood – may be detected up to 36 hours (Nanau, 2015)

Whole blood

Limitations

Cannot be used in individuals suspected of having congenital glycosylation disorders

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

Interference in quantitation may be caused by

  • Severe icterus
  • Genetic variants of transferrin
  • Excess monoclonal or polyclonal immunoglobulins

Incidental exposure from ethanol-containing products may be detected

False-positive results may be caused by microbial formation or fermentation, ethanol-containing products (eg, hand sanitizer, mouthwash)

False-negative results may be caused by bacterial degradation, >4 days since ethanol ingestion

Amount of ethanol consumed over last 7 days (most PEth resides in red blood cell membranes)

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 the hematologic system
    • Induces liver enzymes which may increase during the ensuing hepatocyte injury
    • Suppresses albumin production by the liver
    • Toxic to the hematologic precursor cells and may affect red blood cell morphology

Clinical Presentation

  • Signs of acute intoxication
    • Slurred speech
    • Altered sense of consciousness
    • Coma
  • 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 – due to alcohol-induced thiamine deficiency
    • Impaired cognition and learning, confabulation, ataxia, nystagmus
    • Cirrhosis
    • Pancreatitis
    • Esophageal varices
    • Coagulopathy – due to vitamin K deficiency
    • Ascites
    • Megaloblastic anemia – due to vitamin B12 and folate deficiency
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.

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

Limitations 

Limit of detection varies based on instrumentation

Ethanol, Urine, Qualitative - Medical 0090518
Method: Quantitative Enzymatic

Limitations 

For medical purposes only; not valid for forensic use

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

Limitations 

For medical purposes only; not valid for forensic use

Alcohols 0090131
Method: Quantitative Gas Chromatography

Alcohol, Urine, Quantitative 2010136
Method: Quantitative Gas Chromatography

Limitations 

For medical purposes only; not valid for forensic use

The absence of expected drug(s) and/or drug metabolite(s) may indicate inappropriate timing of specimen collection relative to drug administration, poor drug absorption, diluted/adulterated urine, or limitations of testing

Carbohydrate Deficient Transferrin for Alcohol Use 0070412
Method: Quantitative Electrophoresis

Limitations 

Not suitable for the evaluation of patients suspected of having congenital glycosylation disorders

Ethyl Glucuronide Screen Only, Urine 2012695
Method: Qualitative Enzyme Immuonassay

Limitations 

Results do not accurately correlate with amount or frequency of ethanol use

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

Limitations 

Results do not accurately correlate with amount or frequency of ethanol use

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

Limitations 

Results do not accurately correlate with amount or frequency of ethanol use

Phosphatidylethanol (PEth) 2012130
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Guidelines

O'Shea RS, Dasarathy S, McCullough AJ, Practice Guideline Committee of the American Association for the Study of Liver Diseases, Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease Hepatology. 2010; 51(1): 307-28. PubMed

General References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington: Virginia: Amer Psychiatric Pub Inc., 2013.

Bortolotti F, De Paoli G, Tagliaro F. Carbohydrate-deficient transferrin (CDT) as a marker of alcohol abuse: a critical review of the literature 2001-2005. J Chromatogr B Analyt Technol Biomed Life Sci. 2006; 841(1-2): 96-109. PubMed

Crunelle CL, Yegles M, van Nuijs AL, Covaci A, De Doncker M, Maudens KE, Sabbe B, Dom G, Lambert WE, Michielsen P, Neels H. Hair ethyl glucuronide levels as a marker for alcohol use and abuse: a review of the current state of the art. Drug Alcohol Depend. 2014; 134: 1-11. PubMed

Delanghe JR, De Buyzere ML. Carbohydrate deficient transferrin and forensic medicine. Clin Chim Acta. 2009; 406(1-2): 1-7. PubMed

Helander A, Böttcher M, Fehr C, Dahmen N, Beck O. Detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification. Alcohol Alcohol. 2009; 44(1): 55-61. PubMed

Ingall GB. Alcohol biomarkers. Clin Lab Med. 2012; 32(3): 391-406. PubMed

Lande G, Marin B, Chang AS. Clinical application of ethyl glucuronide testing in the U.S. Army. J Addict Dis. 2011; 30(1): 39-44. PubMed

Nanau RM, Neuman MG. Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions Biomolecules. 2015; 5(3): 1339-85. PubMed

Neels H, Yegles M, Dom G, Covaci A, Crunelle CL. Combining serum carbohydrate-deficient transferrin and hair ethyl glucuronide to provide optimal information on alcohol use. Clin Chem. 2014; 60(10): 1347-8. PubMed

Sterneck M, Yegles M, von GR, Staufer K, Vettorazzi E, Schulz K, Tobias N, Graeser C, Fischer L, Nashan B, Andresen-Streichert H. Determination of ethyl glucuronide in hair improves evaluation of long-term alcohol abstention in liver transplant candidates. Liver Int. 2014; 34(3): 469-76. PubMed

Waszkiewicz N, Szajda SD, Kępka A, Szulc A, Zwierz K. Glycoconjugates in the detection of alcohol abuse. Biochem Soc Trans. 2011; 39(1): 365-9. PubMed

Weykamp C, Wielders J, Helander A, Anton RF, Bianchi V, Jeppsson J, Siebelder C, Whitfield JB, Schellenberg F, IFCC Working Group on Standardization of Carbohydrate-Deficient Transferrin. Harmonization of measurement results of the alcohol biomarker carbohydrate-deficient transferrin by use of the toolbox of technical procedures of the International Consortium for Harmonization of Clinical Laboratory Results. Clin Chem. 2014; 60(7): 945-53. PubMed

Medical Reviewers

Last Update: April 2017