Alcohol Abuse

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
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)

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 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
  - Nonspecificity for alcohol abuse limits usefulness; may also 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
- Positive level during daytime hours also indicative of potential alcohol abuse
CDT
- >40 g/day for at least 2 weeks elevates CDT
- >1.6% is considered elevated and associated with active alcohol use
- More sensitive test in men (especially >40 years)
- 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 (hair and blood testing in development)
- Detects recent ethanol exposure (1-7 days)
- 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; stored >12 hours
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

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

CDT may be an excellent test for monitoring abstinence

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count

ARUP #: 0040002

Methodology: Automated Cell Count

Use:

Initial test to determine macrocytosis

Test name: Hepatic Function Panel

ARUP #: 0020416

Methodology: Refer to individual components.

Use:

Initial screen for acute hepatitis

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

Test name: Ethanol, Serum or Plasma - Medical

ARUP #: 0090120

Methodology: Quantitative Gas Chromatography or Enzymatic Assay

Use:

One of the screens used to identify acute alcohol use

Limitations:

Assay detection limit varies based on instrumentation

Test name: Alcohols

ARUP #: 0090131

Methodology: Quantitative Gas Chromatography

Use:

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

Acetone is also detected

Limitations:

Assay detection limit is 5 mg/dL

Test name: Drugs of Abuse Test, Alcohol, Urine - Screen with Reflex to Confirmation/Quantitation

ARUP #: 0092280

Methodology: Semi-Quantitative Alcohol Dehydrogenase/ Qualitative Gas Chromatography-Flame Ionization Detection

Use:

Identify acute alcohol use

Screen with reflex to confirmation

Limitations:

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

Positive cutoff 40 mg/dL

Test name: Gamma Glutamyl Transferase, Serum or Plasma

ARUP #: 0020009

Methodology: Quantitative Enzymatic

Use:

Determine if cause of enzyme elevation is hepatocellular pattern

Limitations:

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

Test name: Carbohydrate Deficient Transferrin for Alcohol Use

ARUP #: 0070412

Methodology: Quantitative Electrophoresis

Use:

Identify alcohol abuse or abuse relapse (will detect chronic ethanol use [>40 g/day for 2 weeks])

More sensitive in men

Limitations:

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

Test name: Ethyl Glucuronide, Urine - Screen with Reflex to Confirmation/Quantitation

ARUP #: 2003189

Methodology: Qualitative Enzyme Immunoassay (EIA)/Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Use:

Detect recent ethanol exposure; monitor alcohol abstinence

Additional Tests Available

Test name: Ethanol, Urine, Qualitative - Medical

ARUP #: 0090518

Methodology: Quantitative Enzymatic

Comments:

Test name: HDL Cholesterol

ARUP #: 0020053

Methodology: Detergent Solubilization, Enzymatic

Comments:

Test name: Albumin, Serum or Plasma by Spectrophotometry

ARUP #: 0020030

Methodology: Quantitative Spectrophotometry

Comments:

Test name: Uric Acid, Urine

ARUP #: 0020481

Methodology: Quantitative Spectrophotometry

Comments:

Test name: Immunoglobulin A

ARUP #: 0050340

Methodology: Quantitative Nephelometry

Comments:

Test name: Alkaline Phosphatase, Serum or Plasma

ARUP #: 0020005

Methodology: Quantitative Enzymatic

Comments:

Test name: Bilirubin, Total, Serum or Plasma

ARUP #: 0020032

Methodology: Spectrophotometry

Comments:

Test name: Aspartate Aminotransferase, Serum or Plasma

ARUP #: 0020007

Methodology: Quantitative Enzymatic

Comments:

Test name: Alanine Aminotransferase, Serum or Plasma

ARUP #: 0020008

Methodology: Quantitative Enzymatic

Comments:

Test name: Albumin, Serum by Nephelometry

ARUP #: 0050671

Methodology: Quantitative Nephelometry

Comments:

Test name: Ferritin

ARUP #: 0070065

Methodology: Quantitative Chemiluminescent Immunoassay

Comments:

Guidelines

General

Comprehensive Review: April 2011
Last Update: April 2011

Cirrhosis

Head and Neck Cancer

Hemochromatosis

Hepatocellular Carcinoma

Liver Disease Evaluation

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