Letter to the Editor Regarding Afshar et al. (2017): Cut‐Point Levels of Phosphatidylethanol to Identify Alcohol Misuse in a Mixed Cohort Including Critically Ill Patients

Abstract

I N THIS LETTER, we briefly discuss the findings by Afshar and colleagues (2017) regarding the use of the alcohol biomarker phosphatidylethanol (PEth) to identify alcohol misuse in a mixed cohort of individuals, particularly in critically ill patients from an intensive care unit (ICU). This particular patient group as highlighted by the authors is a difficult cohort to test for the presence of an alcohol use disorder and has therefore been underresearched. We commend the authors for providing insights into the utility of PEth for identifying alcohol misuse in these patients. However, the aim of this letter was to raise awareness of a potential issue for comparing PEth results between very distinct populations and considerations for future reporting of this test.In this study by Afshar and colleagues (2017), a cohort of 122 individuals was recruited. This included: 38 healthy volunteers, 51 patients undergoing alcohol detoxification, and 38 patients from the ICU. The 10-question Alcohol Use Disorders Identification Test (AUDIT) and abbreviated AUDIT-C focusing on quantifying alcohol consumption were used to identify any alcohol misuse and severe alcohol misuse. The AUDIT score definitions used were based on ≥5 for females and ≥8 for males for any alcohol misuse and ≥13 and ≥16, respectively, for severe misuse. For the AUDIT-C, the score applied was ≥3 and ≥4 (any alcohol misuse) and ≥6 and ≥8 (severe alcohol misuse) for females and males, respectively. To summarize their findings briefly, the authors found that PEth displayed both high sensitivity and specificity for the identification of any alcohol misuse at a cutoff concentration of 250 ng/ml and for severe alcohol misuse a cutoff point set at 400 ng/ml. The authors applied these findings to both the mixed cohort (healthy volunteers and detox patients) and the critically ill patients from the ICU. These cutoffs were significantly higher than a previous study by Stewart and colleagues (2014) in patients with liver disease, who found that a concentration of 80 ng/ml provided optimal sensitivity and specificity for quantifying alcohol consumption of at least 4 drinks a day. These cutoffs were also higher than Swedish recommendations of 210 ng/ml for identifying heavy drinking (Helander and Hansson, 2013). More recently, a study by Schr€ ock and colleagues (2017) implemented a cutoff concentration of 112 ng/ml based on AUDIT-C scores of ≥4 (women) and ≥5 (men) for distinguishing between excessive and moderate alcohol consumption in healthy volunteers.We have previously highlighted the potential challenges facing PEth analysis in patients with advanced liver disease (Nguyen et al., 2018). In addition, other sources for PEth variation, such as the concentration of phosphatidylcholine species (the precursor molecule), concentration and activity of enzymes catalyzing the formation (phospholipase D) and degradation (phosphatidylcholine phospholipase C) of PEth, and the differing rates of ethanol absorption, have been discussed more extensively in previous reviews (Hah...

Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta‐analysis

“…We found that the odds of PEth sensitivity were lower for those with higher BMI, consistent with two prior studies (Hahn et al, 2012; Wang et al, 2017). In addition, since PEth is formed on the surface of red blood cells, it has been suggested that red blood cell depletion may reduce PEth (Nguyen & Seth, 2018); thus, we examined hemoglobin levels. We found increased odds of PEth sensitivity with higher levels of hemoglobin.…”

“…A handful of small studies have examined factors that might influence PEth sensitivity, including sex (Hahn et al, 2012;Stewart et al, 2014;Wurst et al, 2010), age (Cherrier et al, 2020;Hahn et al, 2012Hahn et al, , 2016b, body mass index (BMI; Wang et al, 2017), and hemoglobin level (Beck et al, 2018;Nguyen & Seth, 2018), and liver disease (Cherrier et al, 2020); we are aware of none that examined race/ethnicity, or HIV infection status. Lastly, examination of PEth sensitivity in venous versus finger-prick blood collection is needed, due to the increased risk for hemolysis and variability in blood volume and hematocrit from finger-prick blood collection (Beck et al, 2018;De Kesel et al, 2013;Kummer et al, 2016aKummer et al, , 2016b.…”