There exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n = 324) from non-fibrosis (F0, n = 195), with an area under receiver operating characteristic curve (AUROC) at 0.775 (95% confidence interval [CI]: 0.735–0.816). Circulating sulfatides (SLs) emerged as central lipids distinctly associated with fibrosis pathogenesis in MASLD. Lipidomics analysis of lipoprotein fractions revealed a redistribution of circulating SLs from high-density lipoproteins (HDLs) onto low-density lipoproteins (LDLs) in MASLD fibrosis. We further verified that patient LDLs with reduced SL content triggered a smaller activation of type II natural killer T lymphocytes, compared with control LDLs. Our results suggest that hepatic crosstalk with systemic immunity mediated by lipoprotein metabolism underlies fibrosis progression at early-stage MASLD.

中文翻译：

---

MASLD 纤维化转变的无创脂质组强调了脂蛋白硫酸酯在肝脏免疫调节中的作用


迫切需要一种非侵入性面板来区分代谢功能障碍相关脂肪性肝病 （MASLD） 中的轻度纤维化和非纤维化。在这项工作中，我们对 PERSONS 队列的血清应用定量脂质组学和类固醇组学，并对肝脏病理进行基于活检的组织学评估。我们使用定量组学数据和临床变量训练了一个套索回归模型，得出了一个脂质和临床指标的组合面板，该组区分轻度纤维化 （>F1， n = 324） 和非纤维化 （F0， n = 195），受试者工作特征曲线下面积 （AUROC） 为 0.775 （95% 置信区间 [CI]： 0.735–0.816）。循环硫酸酯 （SLs） 作为中央脂质出现，与 MASLD 的纤维化发病机制明显相关。脂蛋白组分的脂质组学分析显示，在 MASLD 纤维化中，循环 SLs 从高密度脂蛋白 （HDL） 重新分布到低密度脂蛋白 （LDL）。我们进一步证实，与对照 LDL 相比，SL 含量降低的患者 LDL 触发的 II 型自然杀伤 T 淋巴细胞的激活较小。我们的结果表明，脂蛋白代谢介导的肝脏串扰与全身免疫是早期 MASLD 纤维化进展的基础。