血清中TGF-β1、MMP-1表达水平联合FibroScan对乙肝肝纤维化诊断价值

Evaluation of serum levels of TGF-β1 and MMP-1 combined with FibroScan in the diagnosis of liver fibrosis caused by hepatitis B

目的评估血清中转化生长因子-β1(TGF-β1)、基质金属蛋白酶-1(MMP-1)表达水平联合FibroScan对乙肝肝纤维化的诊断价值,为早期诊断肝纤维化提供新方案。方法选取2015-2018年河南中医药大学第一附属医院确诊的145例乙肝病毒感染患者作为研究对象,进行肝活检后判断病理分期;通过Spearman等级相关分析,探讨血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、TGF-β1、MMP-1水平和FibroScan评价指标肝组织硬度(LSM)与肝纤维化的关系;通过ROC曲线分别评价TGF-β1、MMP-1、FibroScan和3种指标联合对乙肝肝纤维化的影响。结果相较于无明显纤维化期患者,明显纤维化期患者AST、ALT、TGF-β1、白介素-10(IL-10)、基质金属蛋白酶抑制因子-1(TIMP-1)和LSM显著增加,但MMP-1显著下降,差异均有统计学意义(P<0.05);TGF-β1、LSM与病理分期呈正相关(r=0.717、0.861,P<0.005);MMP-1与病理分期呈负相关(r=-0.827,P=0.027);ROC曲线和效能评估检测发现,TGF-β1单独组、MMP-1单独组、LSM单独组和TGF-β1+MMP-1+LSM联合组曲线下面积(AUC)分别为0.721、0.763、0.803、0.909,特异度分别为69.5%、73.5%、77.1%、89.3%,灵敏度分别为73.8%、75.4%、83.2%、92.2%。四组对乙肝肝纤维化诊断均具有评估价值,其中TGF-β1+MMP-1+LSM联合的评估能力最高。结论 TGF-β1+MMP-1+LSM联合对乙肝肝纤维化具有较高诊断价值,值得临床推广。

Objective To evaluate the diagnostic value of serum levels of transforming growth factor-β1(TGF-β1),matrix metalloproteinase-1(MMP-1)and FibroScan in hepatitis B fibrosis,and provide a new method for early diagnosis of hepatic fibrosis. Methods 145 patients with confirmed hepatitis B virus infection from 2015 to 2018 were selected as the study subjects,and the pathological stages were judged after liver biopsy. The relationship between serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),TGF-β1,MMP-1 and fibroScan index of liver stiffness measurement(LSM)and liver fibrosis was evaluated by Spearman grade correlation analysis. The effects of TGF-β1,MMP-1,FibroScan,and the combination of three indicators on diagnosis of liver fibrosis in hepatitis B were evaluated by ROC curves. Results Compared with the patients without obvious fibrosis,the levels of AST,ALT,TGF-β1,IL-10,TIMP-1 and LSM in patients with obvious fibrosis were increased significantly,but MMP-1 was decreased significantly(P<0.05).TGF-β1 and LSM were positively correlated with pathological stage(r=0.717,0.861,P<0.05);MMP-1 was negatively correlated with pathological stage(r=-0.827,P=0.005). ROC curve and efficacy evaluation showed that the area under curve(AUC)of TGF-β1,MMP-1,LSM and TGF-β1+MMP-1+LSM were 0.721,0.763,0.803 and 0.909,respectively,with specificity of 69.5%,73.5%,77.1%,89.3% and sensitivity of 73.8%,75.4%,83.2% and 92.2%,respectively. Four groups have evaluation value in the diagnosis of hepatitis B fibrosis,and the combination of TGF-β1+MMP-1+LSM has the highest evaluation ability. Conclusion TGF-β1,MMP-1 and LSM have diagnostic value for hepatitis B fibrosis and are worthy of clinical promotion.