Bade Neeharika, Hellman Diana A, Matye David J, Jiang Shaoning, Tryggestad Jeanie B, Yu Zhongxin, Short Kevin R, Palle Sirish K
Section of Gastroenterology, Hepatology, and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Section of Diabetes and Endocrinology, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
J Cell Mol Med. 2025 Aug;29(16):e70817. doi: 10.1111/jcmm.70817.
Several non-invasive biomarkers for paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported, but no prior studies directly compared multiple protein or microRNA (miRNA) markers of liver health in adolescents with and without MASLD and determined which serum markers are associated with liver histopathological features. We measured 6 serum protein and 4 miRNA candidates in 3 groups of participants: 23 with obesity and biopsy-proven MASLD, 24 controls with obesity (Ob) and 24 controls with normal weight (NW). The MASLD group had higher median values for cytokeratin 18 (CK-18, 8.5 and 5.6-fold higher than NW and Ob, respectively), CK-18 fragments (2.6- and 2.6-fold), collagen IV (0.9- and 0.6-fold), miR-122 (16.9- and 10.7-fold) and miR-192 (9.7- and 12.0-fold). YKL-40 and N-terminal propeptide of type III procollagen were only higher in the MASLD group compared to the NW group. Serum AST, CK-18, CK-18 fragments, miR-122 and miR-192 were positively correlated with liver fibrosis stage. Area under the receiver operating curve for identifying MASLD for CK-18 (0.962), miR-192 (0.945) and miR-122 (0.944) was higher than ALT (0.935). miR-122 in serum and liver was inversely correlated in MASLD patients but neither was associated with putative mRNA targets AGPAT1 and DGAT1. These results show that CK-18, miR-122 and miR-192 are marginally better predictors of MASLD than ALT and correlated with fibrosis in this cohort, supporting further work to confirm these findings.
已有多项关于儿童代谢功能障碍相关脂肪性肝病（MASLD）的非侵入性生物标志物的报道，但此前尚无研究直接比较有无MASLD的青少年肝脏健康的多种蛋白质或微小RNA（miRNA）标志物，并确定哪些血清标志物与肝脏组织病理学特征相关。我们在三组参与者中检测了6种血清蛋白和4种miRNA候选物：23例经活检证实患有肥胖症且患有MASLD的患者、24例肥胖症对照组（Ob）和24例体重正常对照组（NW）。MASLD组的细胞角蛋白18（CK-18，分别比NW组和Ob组高8.5倍和5.6倍）、CK-18片段（2.6倍和2.6倍）、IV型胶原（0.9倍和0.6倍）、miR-122（16.9倍和10.7倍）和miR-192（9.7倍和12.0倍）的中位数较高。与NW组相比，仅MASLD组的YKL-40和III型前胶原N端前肽较高。血清谷草转氨酶（AST）、CK-18、CK-18片段、miR-122和miR-192与肝纤维化分期呈正相关。CK-18（0.962）、miR-192（0.945）和miR-122（0.944）用于识别MASLD的受试者工作特征曲线下面积高于谷丙转氨酶（ALT，0.935）。在MASLD患者中，血清和肝脏中的miR-122呈负相关，但两者均与假定的mRNA靶标AGPAT1和DGAT1无关。这些结果表明，在该队列中，CK-18、miR-122和miR-192作为MASLD的预测指标略优于ALT，且与纤维化相关，支持进一步开展工作以证实这些发现。
