Using biomarkers to quantify problematic alcohol use
Direct biomarkers detect alcohol even in small amounts shortly after ingestion. But which one is nearly 100% specific for alcohol use?
PRACTICE RECOMMENDATIONS
› Use a quick screening instrument such as the single-question tool or the AUDIT 1-3 to objectively determine whether patients’ drinking is risky for themselves or for others. C
› Suspect alcoholic liver disease if the ratio of aspartate aminotransferase to alanine aminotransferase is > 3. C
› Consider using the PEth assay in high-risk patients to differentiate between heavy alcohol use and social drinking. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
To understand the utility of these direct biomarkers, it is helpful to look at the indirect biomarkers first.
Indirect biomarkers have limited sensitivity and specificity
When alcohol is consumed in large enough quantities over time, indirect biomarkers of alcohol can become abnormal.22 The major indirect biomarkers are the liver enzymes aspartate and alanine aminotransferase (AST and ALT), gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV) of red blood cells, and carbohydrate-deficient transferrin (CDT). Indirect biomarkers have limited sensitivity and specificity for AUD. (For specifics on sensitivity and specificity of indirect and direct biomarkers, see TABLE 2.23-31)
Liver enzymes. AST and ALT are also present in the heart, muscle, and kidneys. Elevated levels usually imply injury to hepatocytes, with ALT being more reflective of liver involvement than AST. Both AST and ALT are elevated in other common liver conditions including hepatitis C virus infection and fatty liver disease. In alcoholic liver disease (ALD), AST is elevated more than ALT; an AST-to-ALT ratio > 3 suggests ALD. An elevated GGT often indicates hepatic injury and is used to confirm that elevated alkaline phosphatase is of hepatic origin.3
MCV is the average volume of erythrocytes,33 and an elevated MCV is a potential indicator of excessive alcohol intake. Macrocytosis requires sustained alcohol use, and the test has low sensitivity. Other diseases such as vitamin B12 or folic acid deficiency, hypothyroidism, hematologic diseases (eg, cold agglutinin disease, multiple myeloma, amyloidosis), and certain medications can also increase MCV.34 Moreover, MCV responds slowly to alcohol use, abstinence, and relapse because red cells have a life span of 120 days.35
CDT. Transferrin is a glycoprotein produced in the liver. The level of transferrin with sialic acid chains increases with alcohol consumption as well as in the carbohydrate deficient glycoprotein syndrome, leading to so-called carbohydrate deficient transferrin.36 It is a sensitive marker for detecting alcohol relapse and monitoring sobriety. Moderate-to-heavy alcohol use, averaging ≥ 40 g of alcohol per day for 2 weeks,36 can decrease the amount of carbohydrate attached to transferrin. Two weeks after complete alcohol cessation, CDT levels will return to normal.37
Continue to: CDT is approved...
