Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
J Lipid Res. 2024 Oct;65(10):100647. doi: 10.1016/j.jlr.2024.100647. Epub 2024 Sep 18.
There is a clinical need for a simple test implementable at the primary point of care to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) in the population. Blood plasma samples from adult patients with varying phenotypes of MASLD were used to identify a minimal set of lipid analytes reflective of underlying histologically confirmed MASLD. Samples were obtained from the NIDDK Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database prospective cohort study (MASLD group; N = 301). Samples of control subjects were obtained from cohort studies at the University of California San Diego (control group; N = 48). Plasma samples were utilized for targeted quantitation of circulating eicosanoids, related bioactive metabolites, and polyunsaturated fatty acids by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) lipidomics analysis. Bioinformatic approaches were used to discover a panel of bioactive lipids that can be used as a diagnostic tool to identify MASLD. The final panel of fifteen lipid metabolites consists of 12 eicosanoid metabolites and 3 free fatty acids that were identified to be predictive for MASLD by multivariate area under the receiver operating characteristics curve (AUROC) analysis. The panel was highly predictive for MASLD with an AUROC of 0.999 (95% CI = 0.986-1.0) with only one control misclassified. A validation study confirmed the resulting MASLD LIPIDOMICS SCORE, which may require a larger-scale prospective study to optimize. This predictive model should guide the development of a non-invasive "point-of-care" test to identify MASLD patients requiring further evaluation for the presence of metabolic dysfunction-associated steatohepatitis.
目前，临床上需要一种简单的检测方法，能够在初级医疗点识别出代谢功能障碍相关脂肪性肝病（MASLD）患者。本研究利用患有不同 MASLD 表型的成年患者的血浆样本，确定了一套能够反映潜在组织学证实的 MASLD 的最小脂质分析物集。这些样本取自 NIDDK 非酒精性脂肪性肝炎临床研究网络（NASH CRN）NAFLD 数据库前瞻性队列研究（MASLD 组；N=301）。对照组的样本来自加利福尼亚大学圣地亚哥分校的队列研究（对照组；N=48）。利用超高效液相色谱-质谱（UPLC-MS）脂质组学分析，对血浆样本中循环类二十烷酸、相关生物活性代谢物和多不饱和脂肪酸进行靶向定量。使用生物信息学方法发现了一组生物活性脂质，可作为一种诊断工具来识别 MASLD。最终确定的 15 种脂质代谢物由 12 种类二十烷酸代谢物和 3 种游离脂肪酸组成，通过多变量受试者工作特征曲线下面积（AUROC）分析，这些代谢物被鉴定为 MASLD 的预测因子。该模型对 MASLD 的预测能力很强，AUROC 为 0.999（95%CI=0.986-1.0），只有一个对照被错误分类。验证研究证实了由此产生的 MASLD 脂质组学评分，可能需要进行更大规模的前瞻性研究来优化。该预测模型应指导开发一种非侵入性的“即时”检测方法，以识别需要进一步评估代谢功能障碍相关脂肪性肝炎的 MASLD 患者。
