Lee Kwang Seob, Cho Yongin, Kim Hongkyung, Hwang Hyunkyeong, Cho Jin Won, Lee Yong-Ho, Lee Sang-Guk
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University School of Medicine, Incheon 22212, Korea.
Biomedicines. 2022 May 24;10(6):1216. doi: 10.3390/biomedicines10061216.
Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease, yet cost-effective and non-invasive diagnostic tools to monitor the severity of the disease are lacking. We aimed to investigate the metabolomic changes in NAFLD associated with therapeutic responses. It was conducted in 63 patients with NAFLD who received either ezetimibe plus rosuvastatin or rosuvastatin monotherapy. The treatment response was determined by MRI performed at baseline and week 24. The metabolites were measured at baseline and week 12. In the combination group, a relative decrease in xanthine was associated with a good response to liver fat decrease, while a relative increase in choline was associated with a good response to liver stiffness. In the monotherapy group, the relative decreases in triglyceride (TG) 20:5_36:2, TG 18:1_38:6, acetylcarnitine (C2), fatty acid (FA) 18:2, FA 18:1, and docosahexaenoic acid were associated with a decrease in liver fat, while hexosylceramide (d18:2/16:0) and hippuric acid were associated with a decrease in liver stiffness. Models using the metabolite changes showed an AUC of >0.75 in receiver operating curve analysis for predicting an improvement in liver fat and stiffness. This approach revealed the physiological impact of drugs, suggesting the mechanism underlying the development of this disease.
非酒精性脂肪性肝病（NAFLD）是慢性肝病的主要病因，但目前缺乏用于监测疾病严重程度的经济高效且非侵入性的诊断工具。我们旨在研究与治疗反应相关的NAFLD代谢组学变化。该研究对63例接受依泽替米贝加瑞舒伐他汀或瑞舒伐他汀单药治疗的NAFLD患者进行。治疗反应通过基线和第24周时进行的MRI确定。代谢物在基线和第12周时进行测量。在联合治疗组中，黄嘌呤相对减少与肝脏脂肪减少的良好反应相关，而胆碱相对增加与肝脏硬度降低的良好反应相关。在单药治疗组中，甘油三酯（TG）20:5_36:2、TG 18:1_38:6、乙酰肉碱（C2）、脂肪酸（FA）18:2、FA 18:1和二十二碳六烯酸的相对减少与肝脏脂肪减少相关，而己糖神经酰胺（d18:2/16:0）和马尿酸与肝脏硬度降低相关。使用代谢物变化的模型在预测肝脏脂肪和硬度改善的受试者操作曲线分析中显示曲线下面积（AUC）>0.75。这种方法揭示了药物的生理影响，提示了该疾病发生发展的潜在机制。
