血清胶原酶对判断慢性乙型肝炎肝纤维化及炎症程度的意义被引量：15

The relationship of serum metalloproteinase with the severity of liver fibrosis and inflammation

导出

摘要目的观察慢性乙型肝炎患者血清基质金属蛋白酶(MMPs)及金属蛋白酶组织抑制因子(TIMPs)水平与肝纤维化及炎症程度的相关性,寻找新的判定肝纤维化程度的血清学指标。方法慢性乙型肝炎患者88例,间隔半年行两次肝穿刺活检,病理组织进行炎症活动度及纤维化程度半定量计分;检测血清TIMP1、TIMP2、MMP1、MMP2、MMP9、Ⅳ型胶原、层黏连蛋白、Ⅲ型前胶原N端肽、透明质酸水平。结果血清TIMP1(γ=0.540,P<0.001)、MMP2(γ=0.314,N=0.003)、TIMP1/MMP1(γ=0.269,P<0.001)与纤维化分级成正相关,MMP 1与纤维化分级成负相关(γ=-0.495,P<0.001),且与血清Ⅲ型前胶原N端肽、透明质酸相关;根据受试者工作特性曲线(ROC)下面积计算,MMP 1以13.96(ng/ml)为临界值,判别S2及S2以上纤维化的敏感性为90.5％,特异性为52.0％;TIMP1以76.84(ng/ml)为临界值,敏感性为91.6％,特异性为64.0％。MMP1以6.86(ng/ml)为临界值,判别肝硬化(S4)期敏感性为70.7％,特异性为80.9％;TIMP1以210.04(ng/ml)为临界值,其敏感性60.5％,特异性92.3％。MMP1、TIMP1与炎症分级及计分均有相关性,而TIMP1与碎屑坏死、桥接坏死相关性最好(r=0.43 5,P<0.001),TIMP2与MMP9与炎症没有明显相关性。结论血清TIMP1、MMP1、MMP2水平、TIMP1/MMP1比值可作评估肝? Objective To investigate the relationship of serum metalloproteinase with the severity of liver fibrosis and inflammation. Methods A total of 88 patients with HBV-related liver fibrosis and early cirrhosis were enrolled from six hospitals. Serum fibrosis markers including hyaluronic acid (HA), Ⅳ collagen (Ⅳ-C), aminoterminal propeptide of type Ⅲprocollagen (PⅢP), laminin (LN), matrix metalloproteinases (MMP)1, 2, 9 and tissue inhibitors of metalloproteinase (TIMP)1, 2 levels were determined. Liver biopsies were assessed according to a modified Scheuer and Chevallier'sscoring system. Results Serum TIMP1 (r = 0.540) and MMP2 (r = 0.314) were correlated positively with the degree of hepatic fibrosis, whereas serum MMP1 (r = -0.495) was correlated negatively. By receiver operating curve analysis (ROC), the sensitivity to distinguish the fibrosis stage 2 from stage 1 was 90.5% and the specificity was 52.0% if the cut-off value of MMP1 was 13.96 ng/ml, and the sensitivity was 91.6% and the specificity was 64.0% if the cut-off value of TIMP1 was 76.84 ng/ml. The sensitivity to distinguish cirrhosis (stage 4). from fibrosis (stage 3) was 70.7% and specificity was 80.9% if the cut-off value of MMP1 was 6.86 ng/ml, and the sensitivity was 60.5% and the specificity was 92.3% if the cut-off value of TIMP1 was 210.04 ng/ml. Conclusion Serum TIMP1, MMP1, MMP2 levels and TIMP1/ MMP1 ratio could be used as serum fibrosis markers.

作者尹珊珊李新民王宝恩王泰龄贾继东钱林学

机构地区首都医科大学附属北京友谊医院中日友好医院

出处《中华肝脏病杂志》 CAS CSCD 2004年第11期666-668,共3页 Chinese Journal of Hepatology

关键词血清胶原酶慢性乙型肝炎肝纤维化炎症程度基质金属蛋白酶金属蛋白酶组织抑制因子 Liver fibrosis Extracellular matrix Metalloproteinases

分类号 R512.62 [医药卫生—内科学] R575 [医药卫生—消化系统]

引文网络
相关文献

参考文献7

1Benyon RC, Arthur MJ. Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis, 2001, 21: 373-384.
2Watanabe T, Niioka M, Hozawa S, et al. Gene expression of interstitial collagenase in both progressive and recovery phase of rat liver fibrosis induced by carbon tetrachloride. J Hepatol, 2000, 33: 224-235.
3Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol, 1991, 13: 372-374.
4Chevallier M, Guerret S, Chossegros P, et al. A histological semiqunatative scoring system for evaluation of hepatic fibrosis in needle liver biopsy specimens: comparison with morphonetric studies.Hepatology, 1994, 20: 349-355.
5Korner T, Kropf J, Gressner AM. Serum laminin and hyalnronan in liver cirrhosis: markers of progression with high prognostic value. J Hepatol, 1996, 25: 684-688.
6Ueno T, Tamaki S, Sugawara H, et al. Significance of serum tissue inhibitor of metalloproteinases-1 in various liver diseases. J Hepatol,1996, 24: 177-184.
7Kasahara A, Hayashi N, Mochizuki K, et al. Circulating matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as serum makers of fibrosis in patients with chronic hepatitis C. Relationship to interferon response. J Hepatol, 1997, 26: 574-5