Phosphatidylethanol Outperforms Traditional Alcohol Biomarkers for Detecting MetALD

Phosphatidylethanol (PEth) may serve as a viable alcohol biomarker for detecting metabolic dysfunction and alcohol-associated liver disease (MetALD) and differentiating it from metabolic dysfunction-associated steatotic liver disease (MASLD), according to findings from a recent study.1

In the head-to-head study assessing diagnostic accuracy for MetALD, PEth outperformed several previously available blood-based indirect biomarkers, including the ALD/NAFLD index (ANI), mean corpuscular volume (MCV), gamma-glutamyl transferase (GGT), and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio.1

In June 2023, a multistakeholder effort led by the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asociación Latinoamericana para el Estudio del Hígado yielded new liver disease nomenclature to address concerns about the inaccurate and stigmatizing nature of the previous nomenclature. With this change came an entirely new category of steatotic liver disease (SLD), MetALD, to encompass patients with MASLD who consume greater amounts of alcohol per week.2

“Objective alcohol biomarkers to accurately measure alcohol use are urgently needed, not only for diagnosis but also for appropriately treating individuals with MASLD, MetALD, and ALD,” Rohit Loomba, MD, a professor of medicine, director of hepatology, and chief of the division of gastroenterology at the University of California at San Diego, and colleagues wrote.1 “To date, there is a paucity of studies using PEth to quantify alcohol use in the setting of SLD. Additionally, there are no studies using PEth to differentiate MetALD from MASLD and establishing specific PEth thresholds associated with a diagnosis of MetALD.”

To address this gap in research, investigators conducted a cross-sectional analysis of data from the San Diego Liver Study, which enrolled consecutive adults 40–75 years of age with overweight or obesity, defined as BMI ≥ 25 kg/m2, from the greater San Diego area, without other causes of liver disease other than metabolic dysfunction and excessive alcohol use. A total of 374 prospectively recruited participants with SLD and PEth testing from the San Diego Liver Study were included in the present analyses.1

Participants underwent a standardized clinical research visit, including medical history, physical examination, biochemical and PEth testing, standardized validated alcohol questionnaires, and advanced liver imaging using magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) as well as vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP) assessment.1

To assess alcohol use, participants completed standardized validated questionnaires at the time of the research visit, including the Lifetime Drinking History (LDH) questionnaire and the Alcohol Use Disorders Identification Test (AUDIT) questionnaire. Alcohol use was also assessed by the following direct and indirect blood-based alcohol biomarkers: PEth, AST/ALT ratio, GGT, MCV, and ANI.1

Investigators defined steatotic liver disease (SLD) as MRI-PDFF ≥ 5% or CAP ≥ 288 dB/m when MRI-PDFF was not available. The following definitions were used for SLD subclassifications:

• MASLD: SLD with ≥ 1 cardiometabolic risk factor and alcohol use < 20 g/day for women and < 30 g/day for men
• MetALD: SLD with ≥ 1 cardiometabolic risk factor and an average alcohol use of 20–50 g/day for women and 30–60 g/day for men
• ALD: SLD with ≥ 1 cardiometabolic risk factor and an average alcohol use of > 50 g/day for women and > 60 g/day for men

Among the cohort, the prevalence of MASLD, MetALD, and ALD was 90.1%, 6.4%, and 3.5%, respectively.1

Upon analysis, PEth showed a positive correlation with daily alcohol intake (rS = 0.54; P <.001) and AUDIT score (rS = 0.63; P <.001). Additionally, PEth showed a low positive correlation with GGT (rS = 0.11; P = .041), MCV (rS = 0.22; P <.001), and ANI (rS = 0.30; P <.001), whereas there was no correlation between PEth and AST/ALT ratio (rS = 0.03; P = .627).1

Investigators noted PEth had a robust diagnostic accuracy for detecting MetALD (AUROC, 0.81; 95% CI, 0.73–0.89) and the Youden cut-off was 25 ng/mL.1

Among 362 participants with complete data on alcohol biomarkers, PEth performance for MetALD was greater than ANI (AUROC, 0.66; 95% CI, 0.56–0.75; P = .018), MCV (AUROC, 0.60; 95% CI, 0.48–0.71; P <.001), GGT (AUROC, 0.60; 95% CI. 0.50–0.70; P = .001), and AST/ALT ratio (AUROC, 0.54; 95% CI, 0.43–0.64; P <.001).1

“PEth may be used clinically among individuals with SLD to assess the presence of MetALD,” investigators concluded.1 “Further studies are needed to validate these findings in other cohorts and clinical settings.”

References

1. Tavaglione F, Amangurbanova M, Yang AH, et al. Head-to-Head Comparison Between Phosphatidylethanol Versus Indirect Alcohol Biomarkers for Diagnosis of MetALD Versus MASLD: A Prospective Study. Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/apt.18506
2. Brooks A. From NAFLD to MASLD: 2023 Brings New Liver Disease Nomenclature. HCPLive. December 13, 2023. Accessed January 21, 2025. https://www.hcplive.com/view/from-nafld-to-masld-2023-new-liver-disease-nomenclature