Watt J, Morley K C, Haber P S, Seth D, Volovets A
Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Edith Collins Centre (Translational Research in Alcohol Drugs and Toxicology), Drug Health Services, Sydney, New South Wales, Australia.
Alcohol Clin Exp Res (Hoboken). 2025 Sep;49(9):2013-2024. doi: 10.1111/acer.70133. Epub 2025 Aug 13.
Phosphatidylethanol (PEth), ethyl glucuronide (EtG), and ethyl sulphate (EtS) are highly sensitive and specific biomarkers of alcohol intake. This study investigated their application and relationship to traditional self-report measures in a mixed cohort of liver disease patients to guide decision making in liver transplant populations.
We recruited 183 participants (mean age 49.2 years, 62% male), with N = 99 liver disease (88% alcohol-associated liver disease [ALD]), N = 35 alcohol use disorder (AUD), and N = 49 healthy volunteers. Patient-reported alcohol intake and AUDIT score served as references and were compared to traditional biomarkers, PEth and serum EtG/EtS. Receiver operating characteristic (ROC) analysis and a range of biomarker cutoffs were examined to determine optimal test characteristics. A subset of blood samples modified to a standardized hematocrit analyzed the relationship between hematocrit and PEth.
Compared to traditional biomarkers, both PEth and EtG were sensitive and specific for alcohol intake. At the limit of detection (LOD), PEth was 95% sensitive at detecting any drinking. PEth cutoff of 300 μg/L was 86% sensitive and 92% specific for "heavy drinking," and 600 μg/L was 88% sensitive and specific for "very heavy drinking." PEth displayed superior test characteristics (sensitivity, specificity, PPV, NPV, and AUC) to all measured traditional biomarkers over two-day and one-month time frames. A subset of participants suspected of drinking but reporting abstinence had positive PEth tests (35%), suggestive of unreported drinking. PEth was positively correlated with hematocrit (r = 0.83, p < 0.01) and correction to a standardized median resulted in increases in PEth concentration in most cases.
PEth is clinically useful as an alcohol biomarker in patients with liver disease and is superior to traditional biomarkers, providing good test characteristics for "heavy" and "very heavy" drinking using stepwise cutoffs. PEth detected a subset of patients underreporting their alcohol use, with implications for the management of patients in liver transplant clinics.
磷脂酰乙醇（PEth）、葡萄糖醛酸乙酯（EtG）和硫酸乙酯（EtS）是酒精摄入的高敏感性和特异性生物标志物。本研究调查了它们在一组混合的肝病患者中的应用及其与传统自我报告测量方法的关系，以指导肝移植人群的决策。
我们招募了183名参与者（平均年龄49.2岁，62%为男性），其中N = 99名肝病患者（88%为酒精性肝病[ALD]），N = 35名酒精使用障碍（AUD）患者，以及N = 49名健康志愿者。患者报告的酒精摄入量和酒精使用障碍识别测试（AUDIT）评分作为参考，并与传统生物标志物PEth和血清EtG/EtS进行比较。采用受试者工作特征（ROC）分析和一系列生物标志物临界值来确定最佳测试特征。对一部分调整为标准化血细胞比容的血样分析了血细胞比容与PEth之间的关系。
与传统生物标志物相比，PEth和EtG对酒精摄入均具有敏感性和特异性。在检测限（LOD）时，PEth检测任何饮酒情况的敏感性为95%。PEth临界值为300μg/L时，对“重度饮酒”的敏感性为86%，特异性为92%；临界值为600μg/L时，对“极重度饮酒”的敏感性和特异性均为88%。在两天和一个月的时间范围内，PEth在所有测量的传统生物标志物中显示出更优的测试特征（敏感性、特异性、阳性预测值、阴性预测值和曲线下面积[AUC]）。一部分疑似饮酒但报告戒酒的参与者PEth检测呈阳性（35%），提示存在未报告的饮酒情况。PEth与血细胞比容呈正相关（r = 0.83，p < 0.01），在大多数情况下，校正至标准化中位数会导致PEth浓度升高。
PEth作为肝病患者的酒精生物标志物具有临床应用价值，优于传统生物标志物，使用逐步临界值可为“重度”和“极重度”饮酒提供良好的测试特征。PEth检测出了一部分少报酒精使用情况的患者，这对肝移植诊所患者的管理具有重要意义。
