Applied Evidence

Using biomarkers to quantify problematic alcohol use

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References

PEth. Use of the PEth assay has increased in recent years and its accuracy has had a transformative effect on the diagnosis of AUD.54 PEth is a phospholipid found in erythrocyte membranes, formed by an interaction between ethanol and phosphatidylcholine, catalyzed by phospholipase D.55,56 Major advantages of PEth include an unusually long half-life and specificity. Red cells lack enzymes to degrade PEth, therefore PEth accumulates in red cells and has a half-life of 4 to 10 days57,58 allowing for detection of significant ethanol consumption extending back 3 to 4 weeks.59 There is no evidence that PEth is formed in the absence of ethanol, making the test essentially 100% specific, particularly at higher cutoff values of ≥ 150 ng/mL.31,60

PEth is known to be formed only in the presence of ethanol, making the test virtually 100% specific.

PEth levels are not affected by age, gender, or underlying liver or renal disease.61 PEth can differentiate between heavy alcohol use and social drinking and can therefore identify chronic excessive use.62 With chronic excessive alcohol consumption, PEth is detectable in blood up to 28 days after sobriety.63 A correlation exists between PEth concentrations in blood and the amount of consumed ethanol. PEth has increased specificity and sensitivity for the detection of latent ethanol use compared with other direct biomarkers.21 It can identify recent heavy drinking earlier than indirect biomarkers, as it does not rely on hepatic injury.

Using a cutoff level of 20 ng/mL, PEth assays have a sensitivity of 73% for any alcohol use in the past month; at 80 ng/mL, the sensitivity is 91% for > 4 drinks/d.61 PEth is considered semi-quantitative. The World Health Organization defines acceptable social alcohol use at a PEth value < 40 ng/dL for men and < 20 ng/dL for women. Chronic excessive use is defined by a level > 60 ng/dL.55 The cutoff levels tend to be arbitrary and vary with different guidelines.

PEth may be a useful marker in difficult-toassess settings, or in confirming or invalidating self-reported alcohol consumption.

Although false-positive PEth test results may be possible, most experts believe that dishonesty in self-reporting by test subjects is more likely. That said, the true specificity of PEth remains unknown; a lower value detected should not be regarded as absolute proof of relapse or chronic alcoholism.

Studies have shown a positive correlation between the AUDIT-C score and PEth values combined with self-reported alcohol consumption, indicating that PEth may be a useful marker in difficult-to-assess settings, or in confirming or invalidating self-reported alcohol consumption.61,64,65 The PEth test is now widely available and, in the authors’ experience, usually costs $100 to $200. Analysis typically costs $40 to $100,66 and costs could decrease as the test becomes more widely used. Turnaround time for PEth is 5 to 10 days. It is now the recommended assay by transplant hepatologists for detecting alcohol use.67TABLE 322,68 explains the currently accepted ranges for various PEth results.

Table of PEth values and their significance

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