What blood markers are used to assess alcohol intake?

Blood Markers for Alcohol Intake

Direct alcohol biomarkers—specifically urinary ethyl glucuronide (EtG), phosphatidylethanol (PEth), and hair EtG—should be prioritized over traditional indirect markers for assessing alcohol intake due to their superior specificity and sensitivity. 1

Direct Alcohol Biomarkers (Preferred)

Urinary Ethyl Glucuronide (uEtG)

• Urinary EtG demonstrates 89% sensitivity and 99% specificity for detecting alcohol consumption, outperforming all indirect markers including GGT, AST, ALT, MCV, and CDT. 1
• Detection window extends up to 80 hours after alcohol intake, depending on consumption level. 1
• Remains accurate even in patients with compensated or decompensated cirrhosis, unlike many indirect markers. 1
• Use immunoassay for initial screening with liquid chromatography-tandem spectrometry confirmation for positive results. 1
• Cut-off of 0.1 mg/L detects very small amounts (<5g alcohol), which may capture accidental intake from foods or mouthwash; higher cut-offs reduce false positives while maintaining high sensitivity. 1

Hair Ethyl Glucuronide (hEtG)

• Monitors long-term abstinence over 6 months, with each 1 cm hair segment reflecting approximately one month of consumption. 1
• Established cut-offs: <7 pg/mg indicates abstinence, 7-30 pg/mg suggests social drinking, >30 pg/mg indicates chronic excessive consumption (>60g ethanol/day). 1
• Interpret cautiously with hair samples <3 cm or >6 cm in length. 1
• Hair treatments (dyeing, perming, bleaching) may reduce EtG concentrations in long hair. 1
• Short hair may show false positives from EtG incorporation via sweat after recent consumption. 1

Phosphatidylethanol (PEth)

• Direct metabolite of ethanol with high specificity for alcohol consumption. 1
• Longer detection window than urinary markers. 1
• Measured in serum or dried blood spots. 1

Ethyl Sulfate (EtS)

• Urinary detection with 76-82% sensitivity and 86-93% specificity for drinking within 3 days. 1
• Detection times prolonged in renal failure, creating longer positive windows in kidney disease patients. 1

Indirect Alcohol Biomarkers (Limited Utility)

Gamma-Glutamyl Transferase (GGT)

• GGT has greater sensitivity than AST for heavy drinking but lacks specificity for alcohol use alone. 1
• Loses specificity in advanced liver disease as it elevates with extensive fibrosis regardless of cause. 1
• Elevated in multiple non-alcoholic conditions including obesity, diabetes, smoking, and medication use. 1
• Normalizes after alcohol cessation but timeframe varies. 1

Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)

• AST elevation observed in all forms of alcohol-related liver disease with 50% sensitivity and 80% specificity. 1
• AST levels rarely exceed 300 U/ml in alcohol-related liver disease; levels above this suggest alternative causes. 1
• AST/ALT ratio typically >1 in alcohol-related liver disease, but this is neither specific nor sensitive, particularly in cirrhotic patients. 1
• ALT levels commonly lower than AST in alcohol-related conditions. 1

Carbohydrate-Deficient Transferrin (CDT)

• Requires daily intake of 50-80g ethanol over 1-2 weeks for positive result, limiting detection to heavy consumption only. 1
• Sensitivity ranges only 25-50% with significant false-negative rates in cirrhotic patients. 1
• Half-life of 2-3 weeks; normalizes within this timeframe after cessation. 1
• Should be expressed as %CDT (percentage of total transferrin) to account for individual transferrin variations. 1
• Measure only the disialotransferrin glycoform via high-performance liquid chromatography for optimal accuracy. 1
• More accurate post-transplant due to improved liver function. 1

Mean Corpuscular Volume (MCV)

• Indicates macrocytic anemia associated with alcohol use but has low sensitivity and specificity. 1
• Cannot establish alcohol use in alcohol-related liver disease when used alone. 1

Clinical Application Algorithm

For Recent Alcohol Use Detection (Past 3-5 Days)

1. Order urinary EtG as first-line test with sensitivity 89% and specificity 99%. 1
2. Consider urinary EtS as complementary marker if available. 1
3. Account for renal function when interpreting results. 1

For Chronic/Long-Term Monitoring (Weeks to Months)

1. Obtain hair EtG for 3-6 month retrospective assessment. 1
2. Measure PEth in blood for intermediate-term detection. 1
3. Combine with indirect markers only as adjunctive information. 1

For Heavy Drinking Confirmation

1. Measure CDT (as %CDT) if heavy consumption (>50-80g/day) suspected for ≥2 weeks. 1
2. Combine GGT with CDT to improve diagnostic accuracy (gamma-CDT formula: 0.8 × ln(GGT) + 1.3 × ln(CDT)). 2, 3
3. Recognize that CDT has limited value in cirrhotic patients. 1

Comprehensive Assessment Strategy

• Combine multiple biomarkers rather than relying on single tests, as each has limitations. 1
• Integrate biomarker results with clinical interview, physical examination, and validated screening tools (AUDIT, CAGE). 1
• Use biomarkers as aids to diagnosis and catalysts for patient discussion, not as punitive tools. 1
• Discuss biomarker testing with patients before ordering to maintain therapeutic alliance. 1

Critical Pitfalls to Avoid

• Never use indirect markers (GGT, AST, ALT, MCV, CDT) alone to confirm or refute alcohol use—they lack sufficient sensitivity and specificity. 1
• Do not assume normal liver enzymes exclude significant alcohol use or liver disease. 1
• Avoid relying on AST/ALT ratio in cirrhotic patients where it loses diagnostic value. 1
• Do not use CDT as screening tool in general populations due to low sensitivity. 1
• Remember that GGT elevation has multiple non-alcoholic causes and cannot differentiate liver disease etiologies. 1
• Consider that very low uEtG cut-offs may detect accidental alcohol exposure from non-beverage sources. 1