基质金属蛋白酶抑制剂-1在肝纤维化诊断中的临床应用

目的 评估血清基质金属蛋白酶抑制剂-1 (TIMP-1)在在肝纤维化诊断中的临床价值.方法 285例慢性乙型肝炎(CHB)患者,根据肝穿刺病理诊断结果分为无明显纤维化组(S0-S1)和明显纤维化组(S2-S4).将病理诊断结果作为金标准,使用ROC曲线评估TIMP-1诊断肝纤维化的敏感度、特异性和符合率,并和肝纤维化标记物HA、PCⅢ、CⅣ、LN比较其诊断性能,结果 对照组、S0-S1组、S2-S4组TIMP-1血清浓度分别为146,6±29.2、161.2±43.2、221.6±93.8 μg/L,对照组和S2-S4组及S0-S1组和S2-S4组间差异有统计学意义(t分别为5.32、4.98,P均小于0.01).TIMP-1区分慢性乙肝明显纤维化和轻度纤维化的ROC曲线下面积(AUC)为0.841(95％CI:0.762～0.920),TIMP-1在临界值为170.3 μg/L时,其敏感度、特异度分别为71.5％、82.4％,高于HA(75.6％、72.5％)、PCⅢ(70.5％、76.5％)、CⅣ(63.6％、78.4％)、LN(79.5％、64.7％).结论 血清TIMP-1诊断肝纤维化有较高的敏感度和特异性,血清TIMP-1可能是预测肝纤维化分期一个较好的指标.

Clinical application of tissue inhibitor of metalloproteinases-1 in assessment of liver fibrosis

Objective To evaluate the clinical value of TIMP~I in diagnosis of liver fibrosis. Methods Patients with CHB were divided into mild liver fibrosis group（ S0-S1,175 ） and significant liver fibrosis group（S2-S4,110 ）, accord- ing to pathological diagnosis. The diagnostic capacity of CTGF was assessed by comparing the area under receiver operating characteristic（AUC） with a panel of fibrosis markers. Results Serum level of TIMP-1 in control group, S0-S1 ,$2-$4 was 146.6±29.2,161.2±43.2,221.6±93.8 μg/L,respectively. The level of TIMP-1 in S2-S4 group was significantly higher than that of S0-S1 group （t= 5.32, P〈0. 01） and that of control group（t= 4. 98, P〈0.01 ）. The area ROC of TIMP-1 was 0.841（95% confidence interval, 0. 762 -0. 920） in distinguishing mild fibrosis from significant fibrosis, which was highest among five markers. When cutoff value of TIMP-1 was 10.3 μg/L, the sensi- tivity and specification was 70.5%,82.4% which were higher than that of HA（75.6%,72.5%）,PCIII （70. 5%, 76.5 % ） ,CIV （63.6%, 78. 4% ）, LN （79.5%, 64.7% ）, APRI （ 86.3%, 66.1% ） for assessing liver fibrosis. Conclusions Serum TIMP-1 has higher sensitivity, specificity in assessment of liver fibrosis, which may be a valuable marker for assessing liver fibrosis.