Alcohol Abuse

Clinical Background

Approximately 20% of primary care patients in the U.S. drink alcohol at levels that are harmful to their 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 ethanol and may increase during the ensuing hepatocyte injury
Ethanol also suppresses the production of albumin by the liver
Ethanol is toxic to the hematologic precursor cells and may affect red-cell morphology
Carbohydrate deficient transferrin (CDT)
- Transferrin, the iron transport protein in plasma, contains 2 N-linked glycan chains that differ in their degree of branching, showing bi-, tri-, and tetra-antennary structures
  - Each branch of the N-glycan chains terminates with a sialic acid molecule
- The relative abundance of the disialo, monosialo, and asialo transferrin isoforms is normally low or undetectable
- Ethanol abuse markedly increases the concentrations of the asialo-, monosialo-, and disialo-transferrin isoforms (CDT)

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 thiamine deficiency
- Impaired cognition, confabulation, ataxia, nystagmus, impaired learning
- Cirrhosis
- Esophageal varices
- Coagulopathy
- Ascites

Diagnosis

Indications for testing
- Suspicion of alcohol abuse (criteria met for ICD-10 diagnosis of alcoholism)
  - 1 unit of alcohol is equal to 8-10 g of alcohol (a half pint of beer, 1 glass of wine or 1 oz of hard liquor)
- Trauma related injury; substance abuse treatment monitoring
- Follow-up testing to investigate abnormalities of other biomarkers suggestive of alcohol abuse such as gamma glutamyl transferase (GGT), mean corpuscular volume (MCV), HDL cholesterol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT)
- Use of Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) criteria to help define alcohol dependence
- Three or more of the following for at least one month or repeatedly over the past 12 months:
  - A strong desire or sense of compulsion to drink
  - Difficulty in controlling drinking in terms of onset, termination or extent of use
  - Physiologic withdrawal (tremor, sweating, tachycardia, anxiety, insomnia) when use is reduced or drinking to avoid withdrawal state
  - Evidence of 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 ethanol abuse
  - Reduced sensitivity in B12 and folate deficiencies, liver disease, concomitant tobacco abuse and hypothyroidism
  - Normalization of MCV may take 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 in abstinent patients
    - Not a specific marker and may be elevated in nonalcoholic fatty liver disease, drug intoxication, other liver disease
    - Normalization after abstinence occurs in 2-3 weeks
- Ethanol levels – blood, urine or breath samples
  - Normally used for patients with suspected acute ethanol 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 ethanol abuse
- CDT
  - >50 g/day for at least 2 weeks elevates CDT
  - >2.5% or 25 IU/L suggests active substance abuse
  - More sensitive test in men
  - May be a sensitive marker of relapse in chronic abusers
  - Most sensitivity for testing may be combination of GGT and CDT and possibly MCV
- Other, less-specific, tests
  - Platelet count on CBC – thrombocytopenia present in about 30% of alcohol abuse patients
    - Rapidly normalizes with abstinence
  - HDL – increases with only 3-5 drinks per day regularly, 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 ethanol intoxication
- Metabolic encephalopathy
- Cerebrovascular event
- Sepsis
- Drug overdose
Chronic alcohol abuse
- Chronic infectious hepatitis
- Non-alcoholic fatty liver disease
- Metabolic liver disease (eg, Wilson disease)
- Seizure disorder

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
CBC with Platelet Count 0040002 Method: Automated Cell Count	Initial testing to determine if macrocytosis is present
Ethanol, Serum or Plasma - Medical 0090120 Method: Gas Chromatography or Enzymatic	Best test to identify acute use of ethanol	Assay detection limits may vary
Ethanol, Urine, Qualitative - Medical 0090518 Method: Enzymatic	Screen only; to identify acute alcohol consumption	Cutoffs for positivity vary
Alcohols 0090131 Method: 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: Alcohol Dehydrogenase/Gas Chromatography-Flame Ionization Detection	Screen with reflex to confirmation test to identify acute ethanol consumption	Sensitivity and specificity of test results are relatively poor with urine Positive cutoff 40 mg/dL
Hepatic Function Panel 0020416 Method: Refer to individual components.	Initial screening test for hepatobiliary problems This panel includes testing for albumin (serum or plasma), alkaline phosphatase (serum or plasma), aspartate aminotransferase (serum or plasma), alanine aminotransferase (serum or plasma), bilirubin, direct (serum or plasma), protein, total (plasma or serum), and bilirubin, total (serum or plasma)
Gamma Glutamyl Transferase, Serum or Plasma 0020009 Method: Enzymatic	Determine if enzyme elevation is due to hepatocellular pattern
Carbohydrate Deficient Transferrin for Alcohol Use 0070412 Method: Electrophoresis	Determine excessive alcohol use or alcohol abuse relapse	Not suitable for the evaluation of patients suspected of having congenital disorders of glycosylation. For this purpose, Carbohydrate-Deficient Transferrin for Congenital Glycosylation Disorders (0092453) should be utilized Rare genetic variants of transferrin may interfere with analysis Advanced liver damage (including severe chronic viral hepatitis) and antiepileptic drug therapy can increase CDT levels Not recommended for general population screening

Additional Tests Available

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