血清肝纤维化指标与肝纤维化病理改变的相关性研究

目的：研究血清中透明质酸（HA）、层粘连蛋白（LN）、三型前胶原N端肽（PⅢNP）及Ⅳ型胶原（CⅣ）等肝纤维化指标的水平与肝纤维化分期的相关性，探讨其在乙型肝炎患者肝纤维化非创伤性诊断中的临床应用价值。方法采用放射免疫分析法检测172例乙型病毒性肝炎患者血清中HA、LN、PⅢNP和CⅣ的含量，以肝组织活检作为“金标准”，评价肝纤维化指标与肝纤维化分期的相关性及其用于鉴别明显肝纤维化的诊断价值。结果血清中肝纤维化指标的含量与肝纤维化分期呈正相关，相关系数由高至低分别为HA（r =0.687）、PⅢNP（r =0.490）、CⅣ（r =0.406）和LN（r =0.392）；自S2期开始，以上4项指标的水平均显著升高，与S0、S1期比较差异具有统计学意义（P ＜0.05）；轻度肝纤维化（S0～S1）和明显肝纤维化（S2～S4）两组间4项指标的差异均有统计学意义（P ＜0.05）；ROC曲线显示：单项指标预测明显肝纤维化时，AUC由高至低分别为HA（0.846）、PⅢNP（0.786）、CⅣ（0.747）和LN（0.638）；敏感性分别为LN（Se =80.57%）、HA（Se =75.16%）、CⅣ（Se =73.38%）和PⅢNP（Se =69.54%），特异性分别为HA（Spe =90.25%）、PⅢNP（Spe =81.89%）、CⅣ（Spe =71.51%）和LN（Spe =65.50%），准确性分别为HA（83.18%）、PⅢNP（75.74%）、LN（68.46%）和CⅣ（62.53%）。4项指标联合检查，诊断的敏感性降低（Se =68.85%），特异性提高（Spe =92.96%），诊断准确率提高至86.44%。结论单个指标检查中，HA是诊断肝纤维化最有价值的一项，4项指标联合检查可提高诊断的特异性和准确度。

Correlation between serum markers of liver fibrosis and liver pathological changes

Objective To explore the relationships between levels of liver fibrosis markers hyaluronic acid （HA）, laminin （LN）, procollagen type Ⅲ N-terminal endopeptidase （PⅢNP） and collagen type Ⅳ （CⅣ） in the serum and liver pathological changes, and study on the clinical application value of serum markers for non-traumatic liver fibrosis diagnosis in patients with hepatitis B. Methods The serum levels of HA, LN, PⅢNP and CⅣ were measured by radiommunoassay （RIA） in 172 patients with hepatitis B and liver biopsy was used as the gold standard, the correlation between the four serum markers and liver fibrosis were investigated and the diagnostic accuracy of four serum markers for obvious liver fibrosis was evaluated. Results There was a positive correlation between lvier fibrosis stage and these four serum markers. The correlation coefficient of HA, PⅢNP, CⅣ and LN were 0.687, 0.490, 0.406 and 0.392, respectively, without significant differences （P 〉 0.05） in serum levels of these four markers between S0 and S1. The serum levels of these four markers increased obviously from S2 to S4 which were significantly different compared with S1 （P 〈 0.05）. Also, there were significant differences in serum levels of these four markers between patients with no significant fibrosis （S0-S1） and significant fibrosis （S2-S4） （P 〈 0.05）. The area under receiver operating characteristic （ROC） curve of HA, PⅢNP, CⅣ and LN were 0.846, 0.786, 0.747 and 0.638, respectively. The sensitivities of HA, LN, PⅢNP and CⅣ for predicting significant fibrosis were 75.16%, 80.57%, 69.54% and 73.38%, respectively. While the specificities were 90.25%, 65.50%, 81.89% and 71.51%; the accuracies were 83.18%, 68.46%, 75.74% and 62.53%, respectively. When these four markers were all used for a combined assay, the specificity of diagnosis was increased to 92.96% and the accuracy was increased to 86.44%, while the sensitivity of diagnosis was reduced to 68.85%. Conclusions HA is the best serum marker for diagnosis of liver fibrosis. The specificity and accuracy would be increased with combined assay. The assay of these four serum markers were proved particularly effective in the diagnosis of hepatic fibrosis in patients with hepatitis B.