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

Abstract

Background Objective measurement of alcohol consumption is important for clinical care and research. Adjusting for self‐reported alcohol use, we conducted an individual participant data (IPD) meta‐analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self‐reporting unhealthy alcohol consumption. Methods We identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test—Consumption (AUDIT‐C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1‐step IPD meta‐analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index—BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger‐prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self‐reported alcohol use using the AUDIT‐C score. Results One third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT‐C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables. Conclusions Among people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

Associations Between Patterns of Alcohol Use and Viral Load Suppression Amongst Women Living with HIV in South Africa

“…Social desirability bias may have led to over-reporting of adherence and under-reporting of alcohol use leading to the misclassification of participants into adherence and alcohol use categories. However, studies comparing alcohol self-report and biomarker data for South African women and people on ART have noted low rates of alcohol under-reporting [47,48]. Nonetheless, future studies should include biological indicators of alcohol use and ART adherence to validate self-report data.…”

Correlates of high phosphatidylethanol (PEth) levels and their concordance with self‐reported heavy alcohol consumption among men who have sex with men who binge drink alcohol

“…Moreover, our data were taken from participants' baseline visits, subsequent to the determination of eligibility. Thus, it is more likely that this observed discordance is due to decreased sensitivity of PEth in detecting unhealthy alcohol use for people living with HIV compared with HIV‐negative individuals (aOR = 0.77; 95% Cl: 0.66 to 0.89, p < 0.001), a finding that was demonstrated in a recent meta‐analysis (Hahn et al, 2021). The literature regarding HIV and alcohol metabolism is limited and mixed.…”

“…While PEth is highly specific in detecting any recent alcohol use (Hahn et al, 2012), determinations of suitable cutoff levels for PEth to discriminate between moderate and heavy drinking have been inconsistent, in part due to distinct sample characteristics and classifications of harmful use (Afshar et al, 2017; Schröck et al, 2017b; Stewart et al, 2014). Thus, heterogeneous cutoffs, ranging from 20 to 210 ng/ml, have been recommended or used in the literature to identify unhealthy consumption (Eyawo et al, 2020; Hahn et al, 2016; Ulwelling & Smith, 2018), though some studies have still observed low PEth sensitivity among certain subgroups who engage in heavy drinking (Hahn et al, 2021). To the best of our knowledge, only one study conducted in Peru has reported on the relationship between PEth and self‐reported alcohol use measures among MSM (Herrera et al, 2017), so little is known about the utility of PEth as an objective marker for MSM who binge drink.…”

Monitoring the use of alcohol—A critical overview of the state‐of‐the‐art biomarkers

“…As PEth concentrations decrease as a function of abstinence length, PEth sensitivity is as low as 67% after 14 days of abstinence and 43% after 28 days of abstinence (Moore et al, 2018). Nevertheless, it has been shown that, based on the expected degradation of PEth, evaluation of abstinence is possible, even when two consecutive PEth results are still above the threshold for abstinence (McDonell et al, 2017; Van Uytfanghe, Heughebaert, et al, 2022), While blood PEth levels seem not to be influenced by age, sex, kidney diseases, or drug intake (Andresen‐Streichert et al, 2017), a more recent study, however, suggests that sensitivity is reduced for persons with, for example, anemia or a high BMI (Hahn et al, 2021).…”