Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis.
Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis.
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DOI：
10.3748/wjg.v18.i18.2280
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发表时间：
2012-05
影响因子：
4.3
通讯作者：
Rongli Piao;D. Brigstock;Jie Zhu;Man-Li Zhang;R. Gao
中科院分区：
文献类型：
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作者：
Rongli Piao;D. Brigstock;Jie Zhu;Man-Li Zhang;R. Gao
目的探讨结缔组织生长因子（CCN2/CTGF）在乙型肝炎病毒（HBV）诱导的慢性肝病（CLD-B）患者肝纤维化评估中的作用。方法采用酶联免疫吸附法测定107例慢性乙型肝炎（CHB）患者、39例hbv诱导的活动性肝硬化患者和30例健康人血清中CCN2的含量。采用原位杂交法检测31例CHB患者、8例HBV诱导的肝硬化患者和8例肝脏组织学正常的HBV携带者的肝脏样本中转化生长因子β-1 （TGF-β1）或CCN2 mRNA水平，并通过计算机图像分析测量肝组织中CCN2 mRNA阳性细胞的综合最佳密度（IOD）。采用H、E染色及Van Gieson法观察组织学炎症分级及纤维化分期。结果慢性乙型肝炎患者和活动性肝硬化患者血清CCN2浓度分别比健康人高4.0倍或4.9倍（P < 0.01）。血清中CCN2水平与肝组织中CCN2 mRNA表达量具有较好的一致性（r = 0.87, P < 0.01）。CLD-B患者血清CCN2水平随着组织学纤维化分期的加重而升高（r = 0.85, P < 0.01）。血清CCN2是评估肝纤维化的可靠指标，其受试者工作特征曲线（ROC）下面积（AUC）分别为0.94和0.85，用于区分正常肝脏对照者和F1期肝纤维化患者，或区分轻度和重度纤维化。结论CLD-B患者血清CCN2检测对评估肝纤维化严重程度有临床意义。
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 HBV-induced 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.