AIM:To determine the utility of connective tissue growth factor(CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus(HBV)-induced chronic liver diseases(CLD-B).METHODS:Enzyme-linked immunosorbent assay was u...AIM:To determine the utility of connective tissue growth factor(CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus(HBV)-induced chronic liver diseases(CLD-B).METHODS:Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B(CHB) and 39 patients with HBVinduced active liver cirrhosis and 30 healthy individuals.Liver samples from 31 patients with CHB,8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1(TGF-β1) or CCN2 mRNA levels by in situ hybridization,and computer image analysis was performed to measure integrated optimal density(IOD) of CCN2 mRNA-positive cells in liver tissues.Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.RESULTS:Serum CCN2 concentrations were,respectively,4.0-or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals(P < 0.01).There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues(r = 0.87,P < 0.01).The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B(r = 0.85,P < 0.01).Serum CCN2 was a reliable marker for the assessment of liver fibrosis,with areas under the receiver operating characteristic(ROC) curves(AUC) of 0.94 or 0.85 for,respectively,distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.CONCLUSION:Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.展开更多
目的 检测慢性乙型肝炎(CHB)感染患者血清结缔组织生长因子(CTGF)的水平变化,并分析其与肝纤维化、Th17/Treg平衡的关系。方法 收集2016年6月至2018年6月该院确诊的CHB患者146例(研究组),同期来院体检者90例(对照组)作为研究对象,采集...目的 检测慢性乙型肝炎(CHB)感染患者血清结缔组织生长因子(CTGF)的水平变化,并分析其与肝纤维化、Th17/Treg平衡的关系。方法 收集2016年6月至2018年6月该院确诊的CHB患者146例(研究组),同期来院体检者90例(对照组)作为研究对象,采集研究对象空腹静脉血,检测丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TB)水平,采用酶联免疫吸附法(ELISA)检测血清CTGF、白细胞介素-17(IL-17)水平,流式细胞仪检测辅助性T淋巴细胞17(Th17)、调节性T淋巴细胞(Treg)百分率。分析CTGF与Th17/Treg的相关性及其与肝功能指标的相关性,受试者工作特征曲线(ROC曲线)分析CTGF、Th17/Treg对CHB诊断价值。结果 研究组血清中肝功能指标ALT、AST、TB均高于对照组,差异有统计学意义( P <0.05);血清CTGF、IL-17水平、Th17百分率、Th17/Treg比值高于对照组( P <0.05),Treg百分率与对照组比较差异无统计学意义( P >0.05);随患者肝纤维化程度加深,血清CTGF、IL-17及Th17、Th17/Treg均显著升高( P <0.05),Treg百分率呈现下降的趋势( P <0.05)。Pearson相关性分析结果显示,CHB患者血清CTGF与Th17/Treg、IL-17、Th17呈正相关( r =0.670,0.603、0.618, P =0.000);Th17/Treg与IL-17、Th17呈正相关( r =0.703、0.645, P =0.000);Treg与CTGF、IL-17、Th17、Th17/Treg呈负相关( r =-0.609、-0.598、-0.624、-0.683, P =0.000)。CTGF、Th17/Treg的ROC曲线下的面积(AUC)分别为 0.695 、0.753,灵敏度分别为68.9%、77.8%,特异度分别为56.7%、67.8%。结论 血清CTGF、Th17/Treg比值异常升高与CHB密切相关,检测CTGF、Th17/Treg可间接判断患者病情发展,并且为疾病的治疗提供理论基础。展开更多
基金Supported by National Natural Scientific Foundation,No. 30872236,81070370(to Gao RP)NIH 5R01AA016003 to (Brigstock D)
文摘AIM:To determine the utility of connective tissue growth factor(CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus(HBV)-induced chronic liver diseases(CLD-B).METHODS:Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B(CHB) and 39 patients with HBVinduced active liver cirrhosis and 30 healthy individuals.Liver samples from 31 patients with CHB,8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1(TGF-β1) or CCN2 mRNA levels by in situ hybridization,and computer image analysis was performed to measure integrated optimal density(IOD) of CCN2 mRNA-positive cells in liver tissues.Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.RESULTS:Serum CCN2 concentrations were,respectively,4.0-or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals(P < 0.01).There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues(r = 0.87,P < 0.01).The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B(r = 0.85,P < 0.01).Serum CCN2 was a reliable marker for the assessment of liver fibrosis,with areas under the receiver operating characteristic(ROC) curves(AUC) of 0.94 or 0.85 for,respectively,distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.CONCLUSION:Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.
文摘目的 检测慢性乙型肝炎(CHB)感染患者血清结缔组织生长因子(CTGF)的水平变化,并分析其与肝纤维化、Th17/Treg平衡的关系。方法 收集2016年6月至2018年6月该院确诊的CHB患者146例(研究组),同期来院体检者90例(对照组)作为研究对象,采集研究对象空腹静脉血,检测丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TB)水平,采用酶联免疫吸附法(ELISA)检测血清CTGF、白细胞介素-17(IL-17)水平,流式细胞仪检测辅助性T淋巴细胞17(Th17)、调节性T淋巴细胞(Treg)百分率。分析CTGF与Th17/Treg的相关性及其与肝功能指标的相关性,受试者工作特征曲线(ROC曲线)分析CTGF、Th17/Treg对CHB诊断价值。结果 研究组血清中肝功能指标ALT、AST、TB均高于对照组,差异有统计学意义( P <0.05);血清CTGF、IL-17水平、Th17百分率、Th17/Treg比值高于对照组( P <0.05),Treg百分率与对照组比较差异无统计学意义( P >0.05);随患者肝纤维化程度加深,血清CTGF、IL-17及Th17、Th17/Treg均显著升高( P <0.05),Treg百分率呈现下降的趋势( P <0.05)。Pearson相关性分析结果显示,CHB患者血清CTGF与Th17/Treg、IL-17、Th17呈正相关( r =0.670,0.603、0.618, P =0.000);Th17/Treg与IL-17、Th17呈正相关( r =0.703、0.645, P =0.000);Treg与CTGF、IL-17、Th17、Th17/Treg呈负相关( r =-0.609、-0.598、-0.624、-0.683, P =0.000)。CTGF、Th17/Treg的ROC曲线下的面积(AUC)分别为 0.695 、0.753,灵敏度分别为68.9%、77.8%,特异度分别为56.7%、67.8%。结论 血清CTGF、Th17/Treg比值异常升高与CHB密切相关,检测CTGF、Th17/Treg可间接判断患者病情发展,并且为疾病的治疗提供理论基础。