‘I’m sober, Doctor, really’: Best biomarkers for underreported alcohol use
When and how to use highly specific combinations to assess withdrawal risk.
Because patients with disorders unrelated to alcohol use can have elevated MCV, alone it is not a useful screening marker for alcohol abuse.10 Additionally, because macrocytosis can persist under strictly controlled alcohol abstinence, MCV is not a reliable clinical indicator of relapse.11
LFTs measure enzymes and proteins. ALT, AST, and GGT are the most relevant for detecting heavy drinking. An AST:ALT ratio >2:1 supports a suspicion of alcohol abuse.12 More than 90% of patients with an AST:ALT ratio of 2:1 have alcoholic liver disease. This increases to more than 96% if the ratio is 3:1.13
GGT is an enzyme concentrated in the liver, bile ducts, and kidneys; normal range is 0 to 45 U/L (for females) or 53 U/L (for males).14 GGT levels >30 U/L correlate with alcohol consumption of >4 drinks per day.15 GGT has a half-life of 14 to 26 days and remains elevated for 4 to 6 weeks after drinking cessation, which make it useful for monitoring abstinence in treatment programs.16 Sensitivity ranges from 37% to 85% and specificity is as high as 93% in nonmedical populations.17 Although nonalcoholic liver disease can elevate GGT in persons who do not abuse alcohol, 50% to 72% of GGT elevations can be explained by excessive alcohol consumption.18
CDT is a newer biomarker used to monitor alcohol consumption. The most accurate way to express CDT level is as a percentage of total transferrin concentration. This method accounts for individual variations in transferrin levels, thus minimizing false positives.18 In persons who consume >4 or 5 drinks per day for 2 weeks or more, CDT is >1.3% of total transferrin.19 Unfortunately, because it is expensive and requires sophisticated test methodology, CDT testing is not available at most hospitals.20
Combinations improve detection
Each biochemical measure has strengths and weaknesses as a marker for determining patients’ alcohol consumption (Table 2). CDT and GGT show the highest sensitivity for heavy drinking, and CDT has a higher specificity than GGT (Table 3).21,22 Relapse to alcohol use after abstinence may be best identified by a simultaneous 30% increase in CDT and GGT.5
Because GGT has a longer half-life than CDT, its diagnostic efficiency in detecting alcohol relapse may not develop until 4 weeks after alcohol detoxification, whereas CDT may become clinically useful for detecting relapse as early as 1 week after detoxification.23
Table 2
Biomarkers of alcohol use: Strengths and weaknesses
| Biomarker | Strengths | Weaknesses |
|---|---|---|
| CDT | High specificity for alcohol use; few factors cause false positives High sensitivity in distinguishing alcoholics from social drinkers Marker of relapse and abstinence from drinking Confirmatory test for patients suspected of alcohol abuse | Low sensitivity; more valuable to confirm than exclude heavy drinking Cost (average $30/assay) and low availability of testing Likely less sensitive for women and younger patients compared with men Poor screening tool for alcohol use in general population |
| GGT | Elevations precede alcohol-induced liver damage High specificity in patients with suspected alcohol abuse Effective marker for patients suspected of binge drinking Inexpensive ( | Can be falsely elevated by liver and biliary disease, smoking, obesity, and medications that induce microsomal enzymes Low sensitivity makes it a poor screening tool in general population Poor marker of relapse |
| AST:ALT >2:1 | Highly sensitive and specific for alcohol-induced liver damage | Enzyme elevations can be detected only after periods of heavy drinking Elevations secondary to liver damage at the hepatocellular level (after fatty changes) |
| MCV | Accuracy similar in male and female patients Elevations in suspected cases of alcohol use indicate chronicity of drinking Routine laboratory test | Poor biomarker for relapse False positives caused by liver disease, hemolysis, bleeding disorders, anemia, folate deficiency, and medications that reduce folate Low sensitivity and specificity for alcohol use make it a poor screening tool for alcohol abuse |
| AST: aspartate aminotransferase; ALT: alanine aminotransferase; CDT: carbohydrate deficient transferrin; GGT: gamma-glutamyl transferase; MCV: mean corpuscular volume | ||
Table 3
Interpreting diagnostic test performance
| Term | Definition | Applicability |
|---|---|---|
| Sensitivity | Percent of persons with disease who test positive | High value is desirable for ruling out disease (low false-negative rate) |
| Specificity | Percent of persons without disease who test negative | High value is desirable for ruling in disease (low false-positive rate) |
| Positive predictive value | Percent of positive test results that are true positives | Probability that a person with a positive test result has the disease |
| Negative predictive value | Percent of negative test results that are true negatives | Probability that a person with a negative test result is disease-free |
| Source: References 21,22 | ||
There is evidence that combining tests can improve alcohol use detection.24 For example, Dolman et al25 found that the ability of the AUDIT questionnaire to correctly predict which patients would experience alcohol withdrawal increases when it is used in combination with biochemical markers. Specifically, the positive predictive value of an AUDIT score ≥8 increased from 17% to 47% when found in combination with ≥2 abnormal biochemical marker levels; the study looked at GGT, ALT, AST, and MCV. Sensitivity was 94% and specificity was 98%.
