Pennsylvania Hospital of University of Pennsylvania, Philadelphia (Drs. Chaudhari and Nunes); Henry Ford Hospital, Detroit, MI (Dr. Moonka) frederick.nunes@pennmedicine.upenn.edu
The authors reported no potential conflict of interest relevant to this article.
Direct biomarkers detect alcohol even in small amounts shortly after ingestion. But which one is nearly 100% specific for alcohol use?
› 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
References
CASEA 34-year-old woman presents with fatigue. She appears defensive when asked about her alcohol use. She answers No to all questions on the CAGE (cut down, annoyed, guilty, eye-opener) screening tool, but acknowledges drinking excessively on rare occasions. Her physician has a high suspicion for alcohol use disorder (AUD) and recommends further testing. The patient agrees but denies having used alcohol over the past several days. Which of the following is most likely to help support the suspicion of a heavy drinking pattern?
Routine lab tests (liver panel and complete blood count).
Blood or urine alcohol level.
Phosphatidylethanol (PEth) level in the blood.
Ethyl glucuronide (EtG) in the urine.
Carbohydrate-deficient transferrin (CDT) in the blood.
(See "Case answer.").
About 1 in 12 Americans have AUD,1 and 1 in 10 children live in a home with a parent who has a drinking problem.2 While the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) succinctly defines AUD with specific criteria,1 the term generally refers to an inability to control or stop drinking despite adverse social or health consequences. AUD is regarded as > 4 drinks per day for men and > 3 drinks per day for women.3 A “standard drink” would be a 12-oz bottle of beer, a 5-oz glass of wine, or 1.5 oz of distilled spirits. Effects of chronic alcohol use are vast and include malnutrition, alcohol withdrawal syndrome, alcoholic liver disease, pancreatitis/pancreatic cancer, cardiomyopathy, and stroke.4-6Alcohol use by a pregnant woman can lead to fetal alcohol syndrome in her child.7
AUD may be more prevalent in the wake of COVID-19.Primary care practitioners tend to miss a large fraction of patients with AUD in their practice, especially younger patients and those without somatic comorbidities.8 Systematic screening for AUD can identify many of these people.8 Particularly as the COVID-19 pandemic continues to unfold and increases stress for everyone, risk of worsening drinking increases both in individuals with current AUD and for those in remission.9 Contrary to common belief, patients visiting primary care favor screening for at-risk drinking.10 Thus, awareness of the prevalence of AUD and patient acceptance of screening should encourage wider testing.
Screening tools. The 2014 guidelines published by the Centers for Disease Control and Prevention recommend using quick screening tools—ie, single question or AUDIT 1-3 (TABLE 111-18)—as an objective means of determining whether patients’ drinking creates a risk for themselves or others.11 Excessive drinking identified using alcohol questionnaires can help reduce medical complications and health care costs.19 The questionnaires we review do not provide a diagnosis but help identify individuals who might benefit from more thorough assessment.20 Following up, as needed, by testing for alcohol biomarkers can provide quantitative insight into problematic alcohol use.2
Primary care practitioners tend to miss a large fraction of patients with alcohol use disorder in their practice. Systematic screening for AUD can identify many of these patients.
But before we discuss the utility of biomarkers, it’s important to quickly review how alcohol is eliminated from the body.
Alcohol elimination
The stomach and small intestine are the primary sites for alcohol absorption. Alcohol elimination from the body occurs through 3 pathways. The first involves oxidative metabolism, which eliminates most ethanol (95%) through the actions of alcohol dehydrogenase, cytochrome P4502E1, or catalase. A lesser amount of alcohol (2%-5%) is eliminated, unchanged, via the second pathway, which includes urine, sweat, and breath. Nonoxidative metabolism makes up the third pathway. Nonoxidative metabolism removes a very small amount (0.1%) of alcohol and involves the direct ethanol biomarkers PEth, EtG, ethyl sulfate (EtS), and fatty acid ethyl esters (FAEEs).21 Our emphasis in this article is on assays of direct metabolites of alcohol—particularly PEth.
