Schenker Rachel B, Ramirez Cuauhtemoc B, Jang Cholsoon, Allayee Hooman, Zhao Xueheng, Setchell Kenneth D R, Kohli Rohit, Goran Michael I
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California, USA.
Department of Biologic Chemistry, University of California Irvine School of Medicine, Irvine, California, USA.
J Pediatr Gastroenterol Nutr. 2025 Jan;80(1):174-181. doi: 10.1002/jpn3.12420. Epub 2024 Nov 25.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common pediatric liver disease and can progress to liver fibrosis. Latino adolescents have increased MASLD and fibrosis risk. While fibrosis is diagnosed by biopsy or imaging, more accessible, noninvasive, and economical screening methods are needed. We aimed to use plasma metabolomics/lipidomics to identify potential fibrosis biomarkers in Latino adolescents with obesity.
Liver stiffness (LS) was measured in 93 Latino adolescents with obesity using magnetic resonance elastography. Metabolites and lipids were extracted from plasma and identified on Compound Discoverer. Associations between metabolites/lipids and fibrosis (LS > 2.73 kPa) were determined using linear regression models after covariate adjustment. False discovery rate (FDR) adjusted Pearson's correlations were performed. Analytes yielding significant FDR-adjusted correlations were examined further by receiver operator curve analysis.
Mean (±standard deviation) alanine transaminase (ALT) was 45.7(±65.2) IU/L, hepatic fat fraction was 12.7(±9.1)%, and LS was 2.4(±0.3) kPa. We identified 795 metabolites and 413 lipids in plasma, but only one single metabolite, dihydroxyacetone phosphate (DHAP), a marker of triglyceride synthesis, was significantly associated with fibrosis after FDR adjustment (p < 0.05). In terms of predicting fibrosis, ALT had an area under the curve (AUC) of 0.79, and DHAP had an AUC of 0.79. When combined, ALT + DHAP had an AUC of 0.89.
The combination of ALT + DHAP may have the potential as an accurate, noninvasive test for liver fibrosis. Our data are limited to Latino children with obesity, and a larger cohort should be examined to further validate this novel biomarker.
代谢功能障碍相关脂肪性肝病（MASLD）是最常见的儿科肝脏疾病，可进展为肝纤维化。拉丁裔青少年患MASLD和纤维化的风险增加。虽然纤维化通过活检或影像学诊断，但需要更易获得、非侵入性且经济的筛查方法。我们旨在利用血浆代谢组学/脂质组学来识别肥胖拉丁裔青少年潜在的纤维化生物标志物。
使用磁共振弹性成像技术对93名肥胖拉丁裔青少年测量肝脏硬度（LS）。从血浆中提取代谢物和脂质，并在Compound Discoverer上进行鉴定。在协变量调整后，使用线性回归模型确定代谢物/脂质与纤维化（LS＞2.73 kPa）之间的关联。进行错误发现率（FDR）调整后的Pearson相关性分析。通过受试者工作特征曲线分析进一步检查产生显著FDR调整后相关性的分析物。
平均（±标准差）丙氨酸转氨酶（ALT）为45.7（±65.2）IU/L，肝脂肪分数为12.7（±9.1）%，LS为2.4（±0.3）kPa。我们在血浆中鉴定出795种代谢物和413种脂质，但在FDR调整后，只有一种单一代谢物磷酸二羟丙酮（DHAP），即甘油三酯合成的标志物，与纤维化显著相关（p＜0.05）。在预测纤维化方面，ALT的曲线下面积（AUC）为0.79，DHAP的AUC为0.79。当两者结合时，ALT + DHAP的AUC为0.89。
ALT + DHAP的组合可能有潜力作为一种准确的肝纤维化非侵入性检测方法。我们的数据仅限于肥胖的拉丁裔儿童，应检查更大的队列以进一步验证这种新型生物标志物。
