Laboratory Studies

Biomarkers

Alcohol biomarkers are physiological indicators of alcohol exposure or ingestion and may reflect the presence of an alcohol use disorder. These biomarkers are not meant to be a substitute for a comprehensive history and physical examination by an appropriate health professional. Instead, alcohol biomarkers should be a complement to self-reported measures of drinking.^[4]

In a population of psychiatric patients, research evidence has shown the usefulness of biological measures in the detection of alcohol use disorders when compared with patient self-report. A 2007 study of 486 consecutively admitted psychiatric patients showed a low correlation between self-reported consumption of alcohol and illicit drugs and biological measures; 52% of the patients underreported their consumption of illicit drugs when compared with urine toxicology screening results; 56% of patients underreported alcohol use as evaluated by carbohydrate-deficient transferrin (CDT), and 37% of patients underreported alcohol use as evaluated by CDT + gamma glutamyltransferase (GGT).^[39]Replication of such research in a primary care population is needed to show that biological measures aid the primary care clinician in detecting alcohol use disorders.

Alcohol biomarkers are generally divided into indirect and direct biomarkers.^[4]

Indirect alcohol biomarkers suggest heavy alcohol use by detecting the toxic effects that alcohol may have had on organ systems or body chemistry.^[4]

Indirect alcohol biomarkers include aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), mean corpuscular volume (MCV), and carbohydrate-deficient transferrin (CDT).^[4]
GGT, AST, and MCV are the most frequently used indirect biomarkers.^[5]As a screen for alcohol dependence, the sensitivity/specificity of CDT is generally higher than AST, ALT, GGT, or MCV.^{[4, 40, 6]}(See Table 2 below.) CDT is less sensitive/specific in women than men.^[41]
CDT is a collection of various isoforms of the iron transport protein transferrin.^[5]Alcohol consumption above 50-80 g/d for 2-3 weeks appears to increase serum concentrations of CDT.^{[6, 40]}CDT tends to distinguish chronic heavy drinkers from light social drinkers.^[5]A number of different ways are available to measure CDT; some may be better than others, depending on factors such as the type of alcohol consumption and gender.^[42]
The combination of GGT and CDT compared with GGT or CDT alone shows a higher diagnostic sensitivity, a higher diagnostic specificity, and a stronger correlation with the actual amounts of alcohol consumption (see Table 2 below).^{[40, 6]}Combination GGT/CDT values appear to increase after the daily alcohol consumption exceeds a threshold of 40 g.^[6]This approach is cost-effective, easy to manage in hospital laboratories, and should be suitable for routine clinical care.^[6]
Other indirect alcohol biomarkers of emerging interest include total serum sialic acid (TSA), 5-hydroxytryptophol (5-HTOL), N-acetyl-beta-hexosaminidase (Beta-Hex), plasma sialic acid index of apolipoprotein J (SIJ), and salsolinol.^[7]

Direct alcohol biomarkers are analytes of alcohol metabolism.^[4]

Direct alcohol biomarkers include alcohol itself and ethyl glucuronide (EtG).^[4]
A blood alcohol level might be helpful in the office if the patient appears intoxicated but is denying alcohol abuse. A blood alcohol level in excess of 300 mg/dL, a blood alcohol level of greater than 150 mg/dL without gross evidence of intoxication, or a blood alcohol level of greater than 100 mg/dL upon routine examination indicates alcoholism with a high degree of reliability. The short half-life of alcohol limits its use widely as a biomarker.^[6]As the blood alcohol level detects alcohol intake in the previous few hours, it is not necessarily a good indicator of chronic excessive drinking.^[5]
EtG is a minor, nonoxidative, water-soluble, stable, and direct metabolite of alcohol that is formed by the conjugation of ethanol with activated glucoronic acid.^{[40, 6, 5]}Shortly after alcohol intake, even in small amounts, EtG becomes positive.^[5]After complete cessation of alcohol intake, EtG can be detected in urine for up to 5 days after heavy binge drinking^{[7, 6]}, making EtG an important biomarker of recent alcohol consumption.^[5]A 2006 report by the Substance Abuse and Mental Health Services Administration states that the use of EtG should be considered as a potential valuable clinical tool, but the use of EtG in forensic settings is premature.^[4]
Other direct alcohol biomarkers of emerging interest include acetaldehyde, fatty acid ethyl esters (FAEE), Ethyl Sulfate (EtS), and Phosphatidylethanol (PEth).^{[4, 7]}

Table 2. Sensitivity and Specificity of Alcohol Biomarkers* (Open Table in a new window)

Biomarker	Sensitivity (%)	Specificity (%)
AST	15-69	47-68
ALT	18-58	50-57
GGT	34-85	11-95
MCV	34-89	26-95
CDT	39-94	82-100
CDT + GGT	90 †	98
Alcohol	0-100	0-100
EtG	76-91	77-92
*Values vary considerably according to gender, age, drinking pattern, prevalence of alcohol abuse/dependence, and prevalence of comorbidity, among other factors.^{[40, 6, 41, 43, 44]} † The sensitivity comes from one study in Finland, which uses a special formula. This study needs to be replicated.^[45]

Other Tests

The possibility of polysubstance abuse/dependence justifies performing a blood/urine toxicology screen for other substances of abuse.

Treatment & Management

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Media Gallery

Deaths while intoxicated. Data from the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

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Table 1. AUDIT Questions and Scoring System

Questions	0 Points	1 Point	2 Points	3 Points	4 Points
1. How often do you have a drink containing alcohol?	Never	Monthly or less	2-4 times a month	2-3 times a week	4 or more times a week
2. How many drinks containing alcohol do you have on a typical day when you are drinking?	1 or 2	3 or 4	5 or 6	7-9	10 or more
3. How often do you have 6 or more drinks on 1 occasion?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
4. How often during the past year have you found that you were not able to stop drinking once you had started?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
5. How often during the past year have you failed to do what was normally expected of you because of drinking?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
6. How often during the past year have you needed a first drink in the morning to get yourself going after a heavy drinking session?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
7. How often during the past year have you had a feeling of guilt or remorse after drinking?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
8. How often during the past year have you been unable to remember what happened the night before because you had been drinking?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
9. Have you or has someone else been injured as a result of your drinking?	No		Yes, but not in the past year		Yes, during the past year
10. Has a relative, friend, or a doctor or other health care worker been concerned about your drinking or suggested you cut down?	No		Yes, but not in the past year		Yes, during the past year

Table 2. Sensitivity and Specificity of Alcohol Biomarkers*

Biomarker	Sensitivity (%)	Specificity (%)
AST	15-69	47-68
ALT	18-58	50-57
GGT	34-85	11-95
MCV	34-89	26-95
CDT	39-94	82-100
CDT + GGT	90 †	98
Alcohol	0-100	0-100
EtG	76-91	77-92
*Values vary considerably according to gender, age, drinking pattern, prevalence of alcohol abuse/dependence, and prevalence of comorbidity, among other factors.^{[40, 6, 41, 43, 44]} † The sensitivity comes from one study in Finland, which uses a special formula. This study needs to be replicated.^[45]