Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis.
Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis.
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DOI：
10.1053/j.gastro.2012.04.031
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发表时间：
2012-08
期刊：
影响因子：
29.4
通讯作者：
Schuppan D
中科院分区：
文献类型：
--
作者：
Kornek M;Lynch M;Mehta SH;Lai M;Exley M;Afdhal NH;Schuppan D
在慢性丙型肝炎(CHC)患者中，通过组织学分析确定，CD4+和CD8+T细胞激活或凋亡时释放的微小颗粒与炎症有关。非酒精性脂肪肝(NAFL)或非酒精性脂肪性肝炎(NASH)患者可以根据肝脏中不同免疫细胞的激活情况与CHC患者区分开来。我们用流式细胞术比较了67例NAFL和NASH患者和42例CHC患者的循环微粒谱，并与健康人(对照组)进行了比较；根据组织学分析，这些谱与炎症分级和纤维化分期相关。我们在血清学和组织学分析的基础上，评估了这些档案确定炎症和纤维化严重程度的能力。慢性丙型肝炎患者的CD4+和CD8+T细胞微粒水平升高；根据组织学分析和丙氨酸氨基转移酶(ALT)水平，这种水平与疾病严重程度相关。NAFL或NASH患者外周血中不变自然杀伤T细胞(INKT)和巨噬细胞/单核细胞(CD14+)微粒子数量显著增加，参与了NASH的发病过程。CD14+和iNKT细胞的微粒与ALT水平和NASH严重程度(基于组织学)相关。NAFL或NASH患者与CHC患者，或任一组患者与对照组(受试者工作特征曲线下面积0.56~0.99)之间的微粒子水平有明显差异。血清免疫细胞微粒的定量检测可用于评估慢性肝病患者肝脏炎症的程度和特征。
Microparticles released into the bloodstream upon activation or apoptosis of CD4+ and CD8+ T cells correlate with inflammation, determined by histologic analysis, in patients with chronic hepatitis C (CHC). Patients with nonalcoholic fatter liver (NAFL) or nonalcoholic steatohepatitis (NASH) can be differentiated from those with CHC based on activation of distinct sets of immune cells in the liver. We compared profiles of circulating microparticles from patients with NAFL and NASH (n=67) to those with CHC (n=42), compared with healthy individuals (controls) using flow cytometry; the profiles were correlated with inflammation grade and fibrosis stage, based on histologic analyses. We assessed the ability of the profiles determine the severity of inflammation and fibrosis, based on serologic and histologic analyses. Patients with CHC had increased levels of microparticles from CD4+ and CD8+ T cells; the levels correlated with disease severity, based on histologic analysis and levels of alanine aminotransferase (ALT). Patients with NAFL or NASH had significant increases in numbers of microparticles from invariant natural killer T (iNKT) cells and macrophages/monocytes (CD14+), which mediate pathogenesis of NASH. Microparticles from CD14+ and iNKT cells correlated with levels of ALT and severity of NASH (based on histology). Levels of microparticles could differentiate between patients with NAFL or NASH and those with CHC, or either group of patients and controls (area under the receiver operating characteristic curves ranging from 0.56 to 0.99). Quantification of immune cell microparticles from serum samples can be used to assess the extent and characteristics of hepatic inflammation in patients with chronic liver disease.
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DOI：
10.1056/nejmoa0907929
发表时间：
2010-05-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sanyal AJ;Chalasani N;Kowdley KV;McCullough A;Diehl AM;Bass NM;Neuschwander-Tetri BA;Lavine JE;Tonascia J;Unalp A;Van Natta M;Clark J;Brunt EM;Kleiner DE;Hoofnagle JH;Robuck PR;NASH CRN
通讯作者：
NASH CRN
影响因子：
29.4
作者：
Day, CP
通讯作者：
Day, CP
影响因子：
9.8
作者：
Regev, A;Berho, M;Schiff, ER
通讯作者：
Schiff, ER
影响因子：
4.4
作者：
Durante-Mangoni, E;Wang, RJ;Exley, MA
通讯作者：
Exley, MA
影响因子：
13.5
作者：
Park, Ogyi;Jeong, Won-Il;Wang, Lei;Wang, Hua;Lian, Zhe-Xiong;Gershwin, M. Eric;Gao, Bin
通讯作者：
Gao, Bin