Serum metabolomic signatures discriminate early liver inflammation and fibrosis stages in patients with chronic hepatitis B.
Serum metabolomic signatures discriminate early liver inflammation and fibrosis stages in patients with chronic hepatitis B.
复制标题
血清代谢组学特征可区分慢性乙型肝炎患者的早期肝脏炎症和纤维化阶段
DOI：
10.1038/srep30853
复制
发表时间：
2016-08-08
影响因子：
4.6
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Huang H;Sun Z;Pan H;Chen M;Tong Y;Zhang J;Chen D;Su X;Li L
慢性乙型肝炎（CHB）感染的中度坏死性炎症和纤维化的患者建议接受抗病毒治疗。然而，除了肝活检，目前还缺乏敏感和特异性的客观方法来确定慢性乙型肝炎患者的坏死性炎症和纤维化阶段。本研究旨在确定与CHB患者组织学进展相关的独特血清代谢组学特征，并开发用于早期CHB检测和分层的新型代谢物生物标志物组。建立了一种综合代谢组学分析方法，用于比较健康供体（n = 67）、轻度（G < 2和S < 2，CHB 1，n = 52）或中度（G ≥ 2或S ≥ 2，CHB 2，n = 36）坏死性炎症和纤维化患者的血清样品。开发了多变量模型以区分CHB1和CHB2与对照。确定了一组CHB相关生物标志物，包括溶血磷脂酰胆碱、磷脂酰胆碱、磷脂酰肌醇、磷脂酰丝氨酸和胆汁酸代谢产物。CHB 1和CHB 2患者通过简单的逻辑指数分层，PIP指数基于磷脂酰肌醇（PI）和磷脂酰丝氨酸（PS），AUC为0.961，优于所有目前可用的标志物。已经鉴定了一组区分健康对照、CHB1和CHB2患者的血清代谢物。拟议的代谢组学生物签名有可能被用作CHB管理的抗病毒治疗的指标。
Chronic HBV (CHB) infected patients with intermediate necroinflammation and fibrosis are recommended to receive antiviral treatment. However, other than liver biopsy, there is a lack of sensitive and specific objective method to determine the necroinflammation and fibrosis stages in CHB patients. This study aims to identify unique serum metabolomic profile associated with histological progression in CHB patients and to develop novel metabolite biomarker panels for early CHB detection and stratification. A comprehensive metabolomic profiling method was established to compare serum samples collected from health donor (n = 67), patients with mild (G < 2 and S < 2, CHB1, n = 52) or intermediate (G ≥ 2 or S ≥ 2, CHB2, n = 36) necroinflammation and fibrosis. Multivariate models were developed to differentiate CHB1 and CHB2 from controls. A set of CHB-associated biomarkers was identified, including lysophosphatidylcholines, phosphatidylcholines, phosphatidylinositol, phosphatidylserine, and bile acid metabolism products. Stratification of CHB1 and CHB2 patients by a simple logistic index, the PIPSindex, based on phosphatidylinositol (PI) and phosphatidylserine (PS), was achieved with an AUC of 0.961, which outperformed all currently available markers. A panel of serum metabolites that differentiate health control, CHB1 and CHB2 patients has been identified. The proposed metabolomic biosignature has the potential to be used as indicator for antiviral treatment for CHB management.