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血管紧张素Ⅱ、血管紧张素(1-7)水平与HBV感染者肝硬化程度的相关性
Correlation of the levels of angiotensin II and angiotensin (1-7) with the degree of chronic hepatitis B liver fibrosis
文章发布日期:2019年09月29日  来源:  作者:俞冲, 顾玉玲, 李民, 等  点击次数:232次  下载次数:51次

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【摘要】: 目的 探讨慢性HBV感染者肝硬化患者不同阶段血浆血管紧张素Ⅱ(AngⅡ)、血管紧张素(1-7)[Ang(1-7)]的差异,及其在肝硬化发病过程中的意义。方法 前瞻性选取本院2017年3月-2019年3月就诊的HBV感染者86例,分为慢性乙型肝炎(CHB)组(A组,n=25)、乙型肝炎肝硬化代偿期组(B组,n=31)及乙型肝炎肝硬化失代偿期组(C组,n=30)。应用双抗体夹心法检测患者血浆AngⅡ、Ang(1-7)水平,同时采用FibroTouch进行肝脏硬度检测(LSM)。计量资料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;计数资料组间比较使用χ2检验。采用Pearson相关分析血浆AngⅡ、Ang(1-7)水平与LSM值的相关性;采用Spearman等级相关分析评价血浆AngⅡ、Ang(1-7)水平与乙型肝炎肝硬化程度的相关性;logistic回归分析评价AngⅡ、Ang(1-7)水平、LSM值对乙型肝炎肝硬化的预测价值。结果 随肝硬化进展,A、B、C 3组患者病程逐渐延长[(5.2±1.3)年vs (7.8±1.6)年vs (10.1±1.5)年,F=4.266,P=0.002],抗病毒治疗比率逐渐下降[76.00% vs 64.52% vs 53.33%,χ2=5.544,P=0.001],AngⅡ[(51.01±8.68) pg/ml vs (74.38±10.05) pg/ml vs (102.78±13.22)pg/ml,F=520.26,P<0.001]、AngⅡ/Ang(1-7)[(1.06±0.41) vs (2.32±0.23) vs (5.82±1.24),F=18.860,P<0.001]及FibroTouch LSM 值[(6.85±1.26)kPa、(18.25±3.22)kPa、(26.84±7.57)kPa,F=93.260,P<0.001]逐渐升高,而Ang(1-7)[(45.93±10.24)pg/ml vs (31.52±9.62)pg/ml vs (16.55±9.48)pg/ml,F=209.860,P<0.001]则逐渐下降;随着FibroTouch LSM值的升高,AngⅡ、AngⅡ/Ang(1-7)同步升高,呈正相关(Pearson相关系数分别为0.623、0.813,P值均<0.01),而Ang(1-7)与FibroTouch肝脏硬度呈负相关(Pearson相关系数为-0.677,P<0.01);随肝硬化进展,AngⅡ、AngⅡ/Ang(1-7)及FibroTouch LSM值逐渐升高,三者与肝硬化程度呈正相关(Spearman相关系数分别为0.639、0.886和0.712,P值均<0.01),而Ang(1-7)与肝硬化进展呈负相关(Spearman相关系数为-0.653,P<0.01);AngⅡ/ Ang(1-7)、FibroTouch LSM值对HBV感染者出现肝硬化有预警效能(比值比分别为1.884、2.015,P值均<0.01)。结论 对于HBV感染者,随着肝硬化程度加重,AngⅡ、AngⅡ/Ang(1-7)水平逐渐升高,而Ang(1-7)则逐渐下降,动态监测血浆AngⅡ、Ang(1-7)水平,可为肝硬化的实时评估及临床诊疗决策提供参考。
【Abstract】: Objective To investigate the differences in the plasma levels of angiotensin II (Ang II) and angiotensin (1-7) [Ang(1-7)] in different stages among patients with chronic hepatitis B (CHB) liver fibrosis and their significance in the pathogenesis of liver fibrosis. Methods A prospective study was performed. A total of 86 patients with hepatitis B virus (HBV) infection who attended our hospital from March 2017 to March 2019 were enrolled and divided into CHB group (group A) with 25 patients, compensated hepatitis B cirrhosis group (group B) with 31 patients, and decompensated hepatitis B cirrhosis group (group C) with 30 patients. The double-antibody sandwich method was used to measure the plasma levels of Ang II and Ang(1-7), and FibroTouch scan was used for liver stiffness measurement (LSM). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. A binary linear correlation analysis was used to investigate the correlation of the plasma levels of Ang II and Ang(1-7) with LSM; a Spearman rank correlation analysis was used to investigate the correlation of the plasma levels of Ang II and Ang(1-7) with the progression of CHB liver fibrosis; a logistic regression analysis was used to evaluate the value of Ang II, Ang(1-7), and LSM in predicting hepatitis B cirrhosis. Results With the progression of liver fibrosis from group A to group C, there was a significant increase in course of disease (5.2±1.3 years vs 7.8±1.6 years vs 10.1±1.5 years, F=4.266, P=0.002), a significant reduction in the proportion of patients receiving antiviral therapy (76.00% vs 64.52% vs 53.33%, χ2=5.544, P<0.001), significant increases in Ang II (51.01±8.68 pg/ml vs 74.38±10.05 pg/ml vs 102.78±13.22 pg/ml, F=520.260, P<0.001), Ang II/Ang(1-7) ratio (1.06±0.41 vs 2.32±0.23 vs 5.82±1.24, F=18.860, P<0.001), and LSM (6.85±1.26 kPa vs 18.25±3.22 kPa vs 26.84±7.57 kPa, F=93.260, P<0.001), and a significant reduction in Ang(1-7) (45.93±10.24 pg/ml vs 31.52±9.62 pg/ml vs 16.55±9.48 pg/ml, F=209.860, P<0.001). Ang II and Ang II/Ang(1-7) ratio were positively correlated with LSM (r=0.623 and 0.813, both P<0.01), while Ang(1-7) was negatively correlated with LSM (r=-0.677, P<0.01). Ang II, Ang II/Ang(1-7) ratio, and LSM gradually increased with the progression of liver fibrosis (r=0.639, 0.886, and 0.712, all P<0.01), while Ang(1-7) was negatively correlated with the progression of liver fibrosis (r=-0.653, P<0.01). Ang II/Ang(1-7) ratio and LSM had an early warning effect for liver cirrhosis in patients with HBV infection (odds ratio=1.884 and 2.015, both P<0.01). Conclusion In patients with HBV infection, there are gradual increases in Ang II and Ang II/Ang(1-7) ratio and a gradual reduction in Ang(1-7) with the aggravation of liver fibrosis. Dynamic monitoring of the plasma levels of Ang II and Ang(1-7) can provide a reference for real-time assessment of liver fibrosis and decision-making in clinical diagnosis and treatment.
【关键字】:乙型肝炎, 慢性;肝硬化;血管紧张素类
【Key words】:hepatitis B, chronic;liver cirrhosis;angiotensins
【引证本文】:YU C, GU YL, LI M, et al. Correlation of the levels of angiotensin II and angiotensin (1-7) with the degree of chronic hepatitis B liver fibrosis[J]. J Clin Hepatol, 2019, 35(11): 2461-2465. (in Chinese)
俞冲, 顾玉玲, 李民, 等. 血管紧张素Ⅱ、血管紧张素(1-7)水平与HBV感染者肝硬化程度的相关性[J]. 临床肝胆病杂志, 2019, 35(11): 2461-2465.

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