膜微粒在非酒精性脂肪性肝炎中的诊断价值

陈俊; 李良平; 付万智

doi:10.3969/j.issn.1001-5256.2019.09.028

膜微粒在非酒精性脂肪性肝炎中的诊断价值

DOI: 10.3969/j.issn.1001-5256.2019.09.028

1. 简阳市人民医院感染科
2. 四川省人民医院消化内科

详细信息

中图分类号: R575.5
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出版历程
- 收稿日期: 2019-04-24
- 出版日期: 2019-09-20

Value of microparticles in the diagnosis of nonalcoholic steatohepatitis

Department of Infectious Diseases, The People's Hospital of Jianyang City

摘要

摘要:
目的探讨血浆中CD14+细胞群和恒定自然杀伤T淋巴细胞（iNKT）源性膜微粒（MP）水平在非酒精性脂肪性肝炎（NASH）中的诊断价值。方法纳入2015年3月-2015年11月四川省人民医院消化内科、肝胆外科接受肝活组织检查的非酒精性脂肪性肝病（NAFLD）患者（36例）,根据NAFLD活动度积分（NAS）和肝纤维化分期,分为NASH组（n=22）和非NASH组（n=14）。对照组为年龄、性别等因素匹配的健康体检者（n=15）。采用流式细胞术检测受试者血浆CD14+细胞和iNKT细胞的MP水平。符合正态分布的计量资料2组间比较采用t检验;多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验;非正态分布的计量资料2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ2检验,两变量相关采用Pearson相关性分析。应用受试者工作特征曲线（ROC曲线）评价MP的诊断价值。结果 NAFLD组血浆CD14+细胞MP水平高于对照组[（5. 92±0. 62）个/μl vs （4. 52±0. 42）个/μl,t=7. 160,P <0. 001]、iNKT细胞MP水...
- 非酒精性脂肪性肝炎 /
- 膜微粒 /
- 诊断
Abstract:
Objective To investigate the value of plasma levels of microparticles ( MPs) derived from CD14+cells and invariant natural killer T ( iNKT) cells in the diagnosis of nonalcoholic steatohepatitis ( NASH) . Methods A total of 36 patients with nonalcoholic fatty liver disease ( NAFLD) who underwent liver biopsy in Department of Gastroenterology and Department of Hepatobiliary Surgery, Sichuan Provincial People's Hospital, from March to November 2015, were enrolled, and according to the activity score of NAFLD and fibrosis stage, the patients were divided into NASH group with 22 patients and non-NASH group with 14 patients. A total of 15 individuals, matched for age and sex, who underwent physical examination were enrolled as control group. Flow cytometry was used to measure the plasma levels of MPs derived from CD14+cells and iNKT cells in all subjects. The t-test was used for comparison of normally distributed continuous data between groups; the t-test was used for comparison of non-normally distributed continuous data which became normally distributed after logarithmic transformation between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The chi-square test was used for comparison of categorical data between two groups. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Pearson correlation analysis was used to investigate the correlation between two variables, and the receiver operating characteristic ( ROC) curve was used to evaluate the diagnostic value of MP. Results Compared with the control group, the NAFLD group had significantly higher plasma levels of MPs from CD14+cells ( 5. 92 ± 0. 62 cells/μl vs 4. 52 ± 0. 42 cells/μl, t =7. 160, P < 0. 001) and MPs from iNKT cells ( 4. 38 ± 0. 51 cells/μl vs 3. 79 ± 0. 28 cells/μl, t = 3. 966, P < 0. 001) . Compared with thenon-NASH group, the NASH group had significantly higher plasma levels of MPs from CD14+cells ( 6. 25 ± 0. 48 cells/μl vs 5. 44 ± 0. 49 cells/μl, t = 4. 773, P < 0. 001) and MPs from iNKT cells ( 4. 70 ± 0. 39 cells/μl vs 3. 96 ± 0. 26 cells/μl, t = 6. 544, P < 0. 001) . There were significant differences in the plasma levels of MPs from CD14+cells and iNKT cells between the three groups ( F = 61. 039 and42. 285, both P < 0. 05) ; the NASH group had significantly higher plasma levels of MPs than the non-NASH group and the control group, and the non-NASH group had significantly higher plasma levels of MPs than the control group ( all P < 0. 05) . The plasma levels of MPs from CD14+cells and iNKT cells were positively correlated with NAFLD activity score ( r = 0. 697 and 0. 793, both P < 0. 001) . MPs from CD14+cells had an area under the ROC curve ( AUC) of 0. 886 ( 95% confidence interval [CI]: 0. 750-1. 000, P < 0. 001) in the diagnosis of NASH, with a sensitivity of 90. 9% and a specificity of 85. 6%; MPs from iNKT cells had an AUC of 0. 935 ( 95% CI: 0. 822-1. 000, P < 0. 001) , with a sensitivity of 81. 8% and a specificity of 92. 9%. Conclusion There are increases in the plasma levels of MPs from CD14+cells and iNKT cells in patients with NASH, which are positively correlated with the degree of liver inflammation, and therefore, they can be used as potential noninvasive indices for liver inflammation.
- nonalcoholic steatohepatitis /
- microparicles /
- diagnosis

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参考文献(28)

[1] FAZEL Y, KOENIG AB, SAYINER M, et al. Epidemiology and natural history of non-alcoholic fatty liver disease[J]. Metabolism, 2016, 65 (8) :1017-1025.

[2] Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese medical Association. Guidelines for management of non-alcoholic fatty liver disease[J]. J Clin Hepatol, 2010, 26 (2) :120-124. (in Chinese) 中华医学会肝脏病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南[J].临床肝胆病杂志, 2010, 26 (2) :120-124.

[3] KHAN FZ, PERUMPAIL RB, WONG RJ, et al. Advances in hepatocellular carcinoma:Nonalcoholic steatohepatitis-related hepatocellular carcinoma[J]. World J Hepatol, 2015, 7 (18) :2155-2161.

[4] SERFATY L, LEMOINE M. Definition and natural history of metabolic steatosis:Clinical aspects of NAFLD, NASH and cirrhosis[J]. Diabetes Metab, 2008, 34 (6 Pt 2) :634-637.

[5] GOH GB, CHANG PE, TAN CK. Changing epidemiology of hepatocellular carcinoma in Asia[J]. Best Pract Res Clin Gastroenterol, 2015, 29 (6) :919-928.

[6] WONG VW, WONG GL, CHOI PC, et al. Disease progression of non-alcoholic fatty liver disease:A prospective study with paired liver biopsies at 3 years[J]. Gut, 2010, 59 (7) :969-974.

[7] BAN LA, SHACKEL NA, MCLENNAN SV. Extracellular vesicles:A new frontier in biomarker discovery for non-alcoholic fatty liver disease[J]. Int J Mol Sci, 2016, 17 (3) :1-14.

[8] CHAN WK, STHANESHWER P, NIK MN, et al. Limited utility of plasma M30 in discriminating non-alcoholic steatohepatitis from steatosis-a comparison with routine biochemical markers[J]. PLo S One, 2014, 9 (9) :e105903.

[9] OROZCO AF, LEWIS DE. Flow cytometric analysis of circulating microparticles in plasma[J]. Cytometry A, 2010, 77 (6) :502-514.

[10] PATZ S, TRATTNIG C, GRUNBACHER G, et al. More than cell dust:Microparticles isolated from cerebrospinal fluid of brain injured patients are messengers carrying mRNAs, miRNAs, and proteins[J]. J Neurotrauma, 2013, 30 (14) :1232-1242.

[11] EL AS, MAGER I, BREAKEFIELD XO, et al. Extracellular vesicles:Biology and emerging therapeutic opportunities[J]. Nat Rev Drug Discov, 2013, 12 (5) :347-357.

[12] BEYER C, PISETSKY DS. The role of microparticles in the pathogenesis of rheumatic diseases[J]. Nat Rev Rheumatol, 2010, 6 (1) :21-29.

[13] WU ZH, JI CL, LI H, et al. Membrane microparticles and diseases[J]. Eur Rev Med Pharmacol Sci, 2013, 17 (18) :2420-2427.

[14] BARTENEVA NS, FASLER-KAN E, BERNIMOULIN M, et al.Circulating microparticles:Square the circle[J]. BMC Cell Biol, 2013, 14:23.

[15] FRITZSCHING B, SCHWER B, KARTENBECK J, et al. Release and intercellular transfer of cell surface CD81 via microparticles[J]. J Immunol, 2002, 169 (10) :5531-5537.

[16] ROZMYSLOWICZ T, MAJKA M, KIJOWSKI J, et al. Plateletand megakaryocyte-derived microparticles transfer CXCR4receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV[J]. AIDS, 2003, 17 (1) :33-42.

[17] EGUCHI A, MULYA A, LAZIC M, et al. Microparticles release by adipocytes act as “find-me”signals to promote macrophage migration[J]. PLo S One, 2015, 10 (4) :e123110.

[18] KORNEK M, POPOV Y, LIBERMANN T A, et al. Human T cell microparticles circulate in blood of hepatitis patients and induce fibrolytic activation of hepatic stellate cells[J]. Hepatology, 2011, 53 (1) :230-242.

[19] SUTTI S, BRUZZI S, ALBANO E. The role of immune mechanisms in alcoholic and nonalcoholic steatohepatitis:A 2015 update[J]. Expert Rev Gastroenterol Hepatol, 2016, 10 (2) :243-253.

[20] KLEINER DE, BRUNT EM, VAN NM, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease[J]. Hepatology, 2005, 41 (6) :1313-1321.

[21] STEPIEN E, GRUSZCZYNSKI K, KAPUSTA P, et al. Plasma centrifugation does not influence thrombin-antithrombin and plasmin-antiplasmin levels but determines platelet microparticles count[J]. Biochem Med (Zagreb) , 2015, 25 (2) :222-229.

[22] JEEN YM, JIN SY. Pathology of nonalcoholic steatohepatitis[J]. Korean J Hepatol, 2009, 15 (2) :122-130.

[23] ZHANG ZL, HUANG YS, FAN YD, et al. Effect of Xuezhikang on hepatitis and oxidative stress in rats with nonalcoholic fatty liver diseases[J]. Chin J Med Offic, 2018, 46 (6) :605-609. (in Chinese) 张子龙, 黄樱硕, 范煜东, 等.血脂康对非酒精性脂肪性肝病大鼠肝炎症及氧化应激影响[J].临床军医杂志, 2018, 46 (6) :605-609.

[24] SA R, ZHANG W, GE J, et al. Discovering a critical transition state from nonalcoholic hepatosteatosis to nonalcoholic steatohepatitis by lipidomics and dynamical network biomarkers[J].J Mol Cell Biol, 2016, 8 (3) :195-206.

[25] KORNEK M, POPOV Y, LIBERMANN TA, et al. Human T cell microparticles circulate in blood of hepatitis patients and induce fibrolytic activation of hepatic stellate cells[J]. Hepatology, 2011, 53 (1) :230-242.

[26] POVERO D, EGUCHI A, NIESMAN IR, et al. Lipid-induced toxicity stimulates hepatocytes to release angiogenic microparticles that require Vanin-1 for uptake by endothelial cells[J].Sci Signal, 2013, 6 (296) :1897-1904.

[27] POVERO D, EGUCHI A, LI H, et al. Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease[J]. PLo S One, 2014, 9 (12) :e113651.

[28] WITEK RP, YANG L, LIU R, et al. Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells[J]. Gastroenterology, 2009, 136 (1) :320-330.

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