八项肝纤维化血清标志物比较研究

The diagnostic value of eight serum indices for liver fibrosis

目的 比较血清血小板衍生生长因子-BB(PDGF-BB)、转化生长因子-β_1(TGF-β_1),基质金属蛋白酶抑制剂-1(TIMP-1)、基质金属蛋白酶-1(MMP-1),透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(C-Ⅳ)和层黏连蛋白(LN)及外周血单个核细胞(PBMC)内TIMP-1 mRNA、MMP-1 mRNA在肝纤维化中的诊断价值。方法 常规肝穿活检、组织病理学诊断;RT-PCR检测PBMCs中MMP-1 mRNA、TIMP-1 mRNA水平;酶标法检测血清PDGF-BB、TGF-β_1、TIMP-1和MMP-1含量;放射免疫法检测血清HA、PCⅢ、C-Ⅳ和LN含量。结果 经ROC曲线分析,血清PDGF-BB、TIMP-1、HA、PCⅢ、C-Ⅳ、LN和TIMP-1 mRNA的AUC分别为0.985、0.726、0.318、0.728、0.727、0.583、0.463、0.876,血清PDGF-BB和PBMCs中TIMP-1 mRNA的灵敏度和特异度分别为90％,95％,73.7％、100％;两者联合检测的灵敏度为97.4％,特异度为95.0％。结论 八项指标中,血清PDGF-BB的诊断价值最大。在筛选肝纤维化患者时,以血清PDGF-BB、PBMC中TIMP-1 mRNA联合检测最佳。

Objective Using receiver operating characteristic (ROC) curve to compare the value of platelet derived growth factor-BB (PDGF-BB), transforming growth factor- β1(TGF- β1), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA) , type ffl procollagen (PC Ⅲ) , type Ⅳ collagen (C- Ⅳ) and laminin (LN) in serum and message RNA (mRNA) expression of TIMP-1 and MMP-1 in peripheral blood mononucleocytes (PBMC) to diagnose liver fibrosis. Methods Serum samples from 60 chronic hepatitis B patients and 20 healthy blood donors were assayed for serum level of PDGF-BB, TGF- β1, MMP-1 and TIMP-1 with ELISA, and for serum level of HA, PC ffl, C- Ⅳ and LN, with RIA. The mRNA expression of TIMP-1 and MMP-1 in PBMC was detected by RT-PCR. Liver biopsy was performed in all those patients. The biopsy materials were examined histopathologically. Results Through the analysis by ROC curve, serum PDGF-BB is the most valuable marker, and its sensitivity was the highest among eight indices. The marker with the highest specificity was TIMP-1 mRNA in PBMCs. The area under the curve (AUC) of PDGF-BB, TIMP-1, HA, PC Ⅲ, C- Ⅳ, LN, TIMP-1 mRNA was 0.985, 0.726, 0.318, 0.728, 0.727, 0.583, 0.463, 0.876, respectively. The sensitivity and specificity of combination of PDGF-BB and TIMP-1 mRNA were 97.4%, 95.0%, respectively. Conclusions Serum PDGF-BB is the most potential index among eight markers. The combination of serum PDGF-BB and TIMP-1 mRNA in PBMC might be more efficient to screen liver fibrosis.