Exploring Phosphatidylethanol Cutoffs for Self‐Reported Unhealthy Alcohol Use: An International Multi‐Site Analysis
Pamela M. Murnane, Fan Xia, Majid Afshar, Jennifer L. Brown, Gabriel Chamie, Robert L. Cook, Marie Claude Couture, Ralph J. DiClemente, Robin Fatch, Tekeda Ferguson, Joel M. Francis, Jessica E. Haberer, Karen R. Jacobson, Amy C. Justice, Saidi Kapiga, Theresa W. Kim, Evgeny Krupitsky, Gregory M. Marcus, Patricia E. Molina, Winnie R. Muyindike, Bronwyn Myers, Kimberly Page, Shane A. Phillips, Mariann R. Piano, Veronica L. Richards, Kaku So‐Armah, Scott Stewart, Mark S. Sulkowski, Phyllis C. Tien, Sarah Woolf‐King, Judith A. HahnABSTRACT
Background
Unhealthy alcohol use is a preventable cause of morbidity and mortality, yet screening is hampered by inaccurate reporting. Phosphatidylethanol (PEth) is a biomarker that quantifies total drinking over the past 2–4 weeks, but PEth cutoffs for unhealthy drinking have not been well‐examined.
Methods
We pooled data from 22 studies (11,088 persons globally) that previously collected PEth and self‐reported alcohol use. Within a 90% training set, we calculated PEth cutoffs per Youden's J in 1000 bootstrapped samples and explored differences by region, age, sex, race/ethnicity, body mass index (BMI), HIV status, hemoglobin level, and an indirect serum marker of liver fibrosis, FIB‐4. For each cutoff, we estimated sensitivity, specificity, and positive and negative predictive values in a 10% validation dataset. We used two definitions for self‐reported unhealthy drinking per Alcohol Use Disorders Identification Test Consumption (AUDIT‐C) and National Institute on Alcohol Abuse and Alcoholism (NIAAA).
Results
Optimal PEth cutoffs using self‐reported alcohol use as the reference standard differed substantially by region. The cutoff for AUDIT‐C‐measured unhealthy alcohol use in studies from the United States (US) was 14.0 ng/mL (95% CI: 12.3–18.6) with 73.0% sensitivity (95% CI: 67.3–79.1) and 77.4% specificity (95% CI: 73.2–81.4); and was 65.7 ng/mL (95% CI 19.3–90.7) in studies from Africa, with 71.7% sensitivity (95% CI: 64.4–78.7) and 65.2% specificity (95% CI: 58.1–72.7). Cutoffs for AUDIT‐C did not differ between subgroups in the US, but within Africa, cutoffs were higher for men and lower for those with BMI ≥ 25 kg/m 2 . Cutoffs for NIAAA defined unhealthy alcohol use were similar to those using the AUDIT‐C.
Conclusions
Using self‐report as the reference standard, PEth cutoffs differed substantially by region and by some other characteristics, which may be attributable to differences in PEth formation, elimination and/or reporting bias. Further work using objective gold‐standard measures of alcohol consumption is needed for more definitive conclusions.