Tavaglione Federica, Díaz Luis Antonio, Ajmera Veeral, Madamba Egbert, Singh Seema, Bettencourt Ricki, Richards Lisa, Loomba Rohit
MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, United States.
MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, United States; Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
J Hepatol. 2025 Jun 13. doi: 10.1016/j.jhep.2025.05.030.
BACKGROUND & AIMS: The 2023 subclassification of steatotic liver disease (SLD) relies on self-reported alcohol use, which lacks diagnostic precision in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity. In this study, we aimed to estimate the prevalence of underreported alcohol use, identify its independent predictors, and enhance SLD subclassification using PEth in a large, population-based cohort of individuals with overweight/obesity and SLD from the US.
This is a cross-sectional analysis of a prospective study including 391 community-dwelling adults with overweight/obesity and SLD, as defined by MRI-derived proton density fat fraction ≥5%, residing in Southern California. Participants underwent a standardized clinical research visit, including MRI assessment and PEth testing.
In this cohort, the mean (SD) age and BMI were 51 (13) years and 33 (6) kg/m, respectively. As PEth levels increased, insulin resistance and hemoglobin A1c decreased, while blood pressure and high-density lipoprotein cholesterol increased. Of individuals with SLD, 15.9% (95% CI 12.2%-19.5%) underreported their alcohol consumption. Male sex, absence of type 2 diabetes, and White race were the strongest independent factors associated with alcohol underreporting in this population. The use of PEth in addition to self-reported alcohol use resulted in 4-fold and 3-fold increases in MetALD and ALD diagnoses, respectively. Male sex, aspartate aminotransferase, mean corpuscular volume, high-density lipoprotein cholesterol, and MRI-derived proton density fat fraction were the strongest independent factors associated with higher PEth. PEth and self-reported alcohol use showed a moderate positive correlation, while the agreement was low.
PEth may objectively quantify alcohol use and help identify SLD subcategories alongside clinical history, reducing diagnostic misclassification.
The current subclassification of steatotic liver disease (SLD) relies on self-reported alcohol use, which is frequently limited by patient underreporting, potentially leading to diagnostic misclassification. In this study of 391 community-dwelling adults with overweight/obesity and SLD assessed by advanced MRI methods, we found that 15.9% (95% CI 12.2%-19.5%) of individuals with SLD underreported alcohol use based on their phosphatidylethanol (PEth) levels. Male sex, absence of type 2 diabetes, and White race were the strongest independent factors associated with alcohol underreporting in this population. The incorporation of PEth alongside self-reported alcohol use resulted in a 4-fold increase in MetALD diagnoses and a 3-fold increase in ALD diagnoses. These findings support the clinical utility of PEth as a direct, quantitative, objective alcohol biomarker which may help clinicians identify SLD subcategories and differentiate between its metabolic and alcohol-related etiologies.
2023年脂肪性肝病（SLD）的亚分类依赖于自我报告的饮酒情况，这在常规临床实践中缺乏诊断准确性。磷脂酰乙醇（PEth）是一种定量、客观的酒精生物标志物，具有高敏感性和特异性。在本本研究中，我们旨在估计酒精使用报告不足的患病率，确定其独立预测因素，并在美国一个基于人群的大型超重/肥胖和SLD个体队列中使用PEth来改进SLD的亚分类。
这是一项对前瞻性研究的横断面分析，纳入了391名居住在南加州的社区成年超重/肥胖和SLD患者，其定义为磁共振成像（MRI）衍生的质子密度脂肪分数≥5%。参与者接受了标准化的临床研究访视，包括MRI评估和PEth检测。
在该队列中，平均（标准差）年龄和体重指数分别为51（13）岁和33（6）kg/m²。随着PEth水平升高，胰岛素抵抗和糖化血红蛋白降低，而血压和高密度脂蛋白胆固醇升高。在SLD患者中，15.9%（95%置信区间12.2%-19.5%）的人饮酒情况报告不足。男性、无2型糖尿病和白人种族是该人群中与酒精报告不足相关的最强独立因素。除自我报告的饮酒情况外，使用PEth使代谢相关脂肪性肝病（MetALD）和酒精性肝病（ALD）的诊断分别增加了4倍和3倍。男性、天冬氨酸转氨酶、平均红细胞体积、高密度脂蛋白胆固醇和MRI衍生的质子密度脂肪分数是与较高PEth相关的最强独立因素。PEth与自我报告的饮酒情况呈中度正相关，但一致性较低。
PEth可以客观地量化酒精使用情况，并有助于结合临床病史识别SLD亚类，减少诊断错误分类。
目前脂肪性肝病（SLD）的亚分类依赖于自我报告的饮酒情况，这常常因患者报告不足而受到限制，可能导致诊断错误分类。在这项对391名通过先进MRI方法评估的社区成年超重/肥胖和SLD患者的研究中，我们发现，基于磷脂酰乙醇（PEth）水平，15.9%（95%置信区间12.2%-19.5%）的SLD患者饮酒情况报告不足。男性、无2型糖尿病和白人种族是该人群中与酒精报告不足相关的最强独立因素。将PEth与自我报告的饮酒情况相结合，使MetALD诊断增加了4倍，ALD诊断增加了3倍。这些发现支持了PEth作为一种直接、定量、客观的酒精生物标志物的临床实用性，它可能有助于临床医生识别SLD亚类，并区分其代谢和酒精相关病因。
