国产化学发光试剂检测4项血清肝纤维化标志物对肝纤维化诊断的应用分析

目的探讨国产化学发光(CL)试剂检测血清肝纤维化标志物透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原氨基端肽(PⅢNP)、Ⅳ型胶原(CⅣ)对肝纤维化的诊断价值。方法采用CL法检测123例有病理诊断的慢性肝炎患者(病例组)及30例健康体检者(对照组)的血清HA、LN、PⅢNP、CⅣ,病例组按纤维化程度分为S0～S4期,评价4项指标对肝纤维化的诊断价值。结果病例组HA、LN、CⅣ明显高于对照组(4.47±0.86)vs.(2.02±0.23),P=0.000;(4.15±0.81)vs.(3.57±0.67),P=0.002;(3.49±0.89)vs.(2.15±0.81),P=0.000]。4项指标均呈现对照组S0,S1S2,S2S3,S4期HA与CⅣ下降、LN与PⅢNP升高。不同肝纤维化分期的患者中4项指标组间差异均有统计学意义(P0.01),4项指标的S0与S1期比较,差异无统计学意义(P0.05),而S0与S2期、S1与S2期比较,差异均有统计学意义(P0.05)。LN、PⅢNP、CⅣ3项指标与肝纤维化程度有正相关性(P均0.01)。诊断肝纤维化的受试者工作特征曲线(ROC曲线)下面积(AUC)依次为CⅣ(0.790)HA(0.775)LN(0.725)PⅢNP(0.644)。HA、HA+LN+CⅣ3项联合、4项联合对肝纤维化诊断的敏感性及准确率较高;综合诊断效能CⅣLNPⅢNP;单项及联合检测的阳性似然比为1～3。结论 4项指标对肝纤维化诊断均有一定价值,但对早期肝纤维化诊断的意义有限,当纤维化程度为S2期时,其意义最明显。随着肝纤维化程度加重,HA与CⅣ反呈下降趋势,可能与细胞外基质的分解降低有关。多指标联合适合在排除肝纤维化时应用;所有单项及联合检测对诊断肝纤维化的阳性似然比均较低,说明其诊断价值有限,不能替代肝组织活检。

Application analysis on detection of four serum indicators with a domestic chemiluminescence reagent in liver fibrosis diagnosis

Objective To investigate diagnostic value of liver fibrosis for detecting the serum indicators of hyaluronic acid(HA), laminin(LN), procollagen Ⅲ N-terminal peptide (PⅢNP) and collagen type Ⅳ(CⅣ)with domestic chemical luminescence (CL) reagent. Methods Serum indicators of HA, LN, PⅢNP and CⅣwere detected with CL reagent in 123 cases of chronic hepatitis patients by pathological diagnosis(case group) and 30 healthy control(control group). Case group were divided into S0~S4 stages and diagnostic value was evaluated. Results It showed that the HA、LN、CIV in the case group were significantly higher than in control group(4.47±0.86) vs. (2.02±0.23), P = 0.000;(4.15±0.81) vs. (3.57±0.67), P = 0.002; (3.49±0.89) vs. (2.15±0.81), P = 0.000]. All of the four serum indicators showed control group < S0, S1 < S2, S2 > S3, HA and CⅣ dropped, LN and PⅢNP rose in S4 phage. There was statistically significance of four serum indicators in different liver fibrosis stages (P < 0.01). It showed that there was significant difference between S0 and S2 group, S1 and S2 group (P < 0.05). The other 3 indicators except HA were significantly correlated with fibrosis stage (P < 0.01). Areas under receiver operating characteristic(ROC)curve (AUC) for diagnosis of liver fibrosis were CⅣ(0.790)>HA(0.775)> LN(0.725)>PⅢNP(0.644), successively. Multiple serum indicators showed high sensitivity and accuracy of HA , three combination of HA+LN+CⅣand four indicators combination in diagnosis of liver fibrosis. Comprehensive diagnosis efficiency was CⅣ>LN>PⅢNP. Positive likelihood ratio of single to combination detection was 1~3. Conclusions The four indicators have certain value for diagnosis of liver fibrosis, however, it is limited in diagnosis of early liver fibrosis. It has prominent significance in fibrosis S2 stage. With aggravation of liver fibrosis, HA and CⅣ reversely decline. It may be related with decomposition and reduction of extracellular matrix. It is suitable for application of multi-indicator combination to exclude liver fibrosis. Positive likelihood ratio of all single and combination detection to diagnose liver fibrosis is much lower. It indicates limited diagnosis value and can’t substitute liver biopsy.