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Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome

文献类型：期刊论文

作者Gao, Hong1; Ruan, Jianqing Q.6; Chen, Jie1; Li, Na6; Ke, Changqiang Q.5; Ye, Yang3,4,5; Lin, Ge3,4,6; Wang, Jiyao Y.1,2
刊名DRUG DESIGN DEVELOPMENT AND THERAPY
出版日期2015
卷号9页码:4861-4868
关键词drug-induced liver injury herb blood protein adducts prognostic marker
ISSN号1177-8881
DOI10.2147/DDDT.S87858
文献子类Article
英文摘要Background: The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS) induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrroleprotein adducts (PPAs) as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS. Methods: Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients' age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis. Results: Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23 patients with pyrrolizidine alkaloid-associated HSOS, ten recovered, four developed chronic disease, eight died, and one underwent liver transplantation within 6 months after onset. Blood PPAs were detectable in 24 of 40 patients with concentrations from 0.05 to 74.4 nM. Sensitivity and specificity of the test for diagnosis of pyrrolizidine alkaloid-associated HSOS were 100% (23/23) and 94.1% (23/24), respectively. The positive predictive value was 95.8% and the negative predictive value was 100%, whereas the positive likelihood ratio was 23.81. The level of blood PPAs in the severe group (died or received liver transplantation) was significantly higher than that in the recovery/chronicity group (P=0.004). Conclusion: Blood PPAs measured by ultra-performance liquid chromatography-tandem mass spectrometry are highly sensitive and specific for pyrrolizidine alkaloid-associated HSOS. The blood PPA concentration is related to the severity and clinical outcome of pyrrolizidine alkaloid-associated HSOS.
WOS关键词VENOOCCLUSIVE DISEASE ; MARROW TRANSPLANTATION ; LIVER ; HEPATOTOXICITY ; PATHOGENESIS ; TOXICITY ; ARTICLE
资助项目Shanghai Committee of Science and Technology, People's Republic of China[12401907400] ; Research Grant Council of Hong Kong SAR (GRF grant)[471013] ; Research Grant Council of Hong Kong SAR (GRF grant)[469712]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000360056500002
出版者DOVE MEDICAL PRESS LTD
源URL[http://119.78.100.183/handle/2S10ELR8/276711]  
专题天然药物化学研究室
通讯作者Wang, Jiyao Y.
作者单位1.Fudan Univ, Zhongshan Hosp, Dept Gastroenterol, Shanghai 200032, Peoples R China;
2.Fudan Univ, Ctr Evidence Based Med, Shanghai 200032, Peoples R China
3.Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China;
4.Shanghai Inst Mat Med, Joint Res Lab Promoting Globalizat Tradit Chinese, Hong Kong, Hong Kong, Peoples R China;
5.Shanghai Inst Mat Med, Shanghai, Peoples R China;
6.Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China;
推荐引用方式
GB/T 7714		 Gao, Hong,Ruan, Jianqing Q.,Chen, Jie,et al. Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2015,9:4861-4868.
APA Gao, Hong.,Ruan, Jianqing Q..,Chen, Jie.,Li, Na.,Ke, Changqiang Q..,...&Wang, Jiyao Y..(2015).Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome.DRUG DESIGN DEVELOPMENT AND THERAPY,9,4861-4868.
MLA Gao, Hong,et al."Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome".DRUG DESIGN DEVELOPMENT AND THERAPY 9(2015):4861-4868.

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来源：上海药物研究所

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