Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil.
Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas Departamento de Medicina Clínica Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Brazil.
Dig Liver Dis. 2020 Oct;52(10):1170-1177. doi: 10.1016/j.dld.2020.05.004. Epub 2020 Jun 7.
Disturbances in matrix metalloproteinases (MMPs) and corresponding tissue inhibitors (TIMPs) contribute to hepatitis C virus (HCV)-induced fibrosis. This study aimed to determine MMP-9/TIMP-1 levels in addition to MMP-2 and -9 activities; correlating with the improvement of liver fibrosis in patients under direct-acting antiviral (DAA) therapy.
Clinical and laboratory follow-up were performed before treatment and after 12 weeks post-treatment, referred as sustained viral response (SVR). We evaluated liver function including non-invasive fibrosis measurements; MMP activity by zymography; and MMP-9/TIMP-1 complex, inflammatory and pro-fibrogenic mediators by immunoenzymatic assays.
Cohort included 33 patients (59.5 ± 9.3 years, 60.6% females) whose reached SVR and 11 control-paired subjects (42.5 ± 15 years, 54.5% females). Before treatment, HCV patients presented higher MMP-9/TIMP-1 levels (P < 0.05) when compared to controls, and the highest values were observed in patients with fibrosis (P < 0.05). In addition, MMP-9/TIMP-1 levels were significantly reduced after DAA therapy (P < 0.0001) and were associated with profibrogenic biomarkers. No differences were observed for MMP-2 and -9 activities; however, these biomarkers were significantly associated with inflammatory mediators.
Our data suggest that MMP-9/TIMP-1 complex can be a promising biomarker of active fibrogenesis, being able to identify the interruption of fibrosis progression after HCV eradication.
基质金属蛋白酶（MMPs）及其相应的组织抑制剂（TIMPs）的紊乱导致丙型肝炎病毒（HCV）诱导的纤维化。本研究旨在确定 MMP-9/TIMP-1 水平，以及 MMP-2 和 -9 的活性；并与直接作用抗病毒（DAA）治疗后患者肝纤维化的改善相关。
在治疗前和治疗后 12 周（称为持续病毒学应答[SVR]）进行临床和实验室随访。我们评估了肝功能，包括非侵入性纤维化测量；通过酶谱法评估 MMP 活性；以及通过免疫酶联测定法评估 MMP-9/TIMP-1 复合物、炎症和促纤维化介质。
该队列包括 33 名患者（59.5±9.3 岁，60.6%为女性），他们达到了 SVR，并且有 11 名配对对照受试者（42.5±15 岁，54.5%为女性）。在治疗前，与对照组相比，HCV 患者的 MMP-9/TIMP-1 水平更高（P<0.05），并且纤维化患者的水平最高（P<0.05）。此外，DAA 治疗后 MMP-9/TIMP-1 水平显著降低（P<0.0001），并与促纤维化生物标志物相关。MMP-2 和 -9 的活性没有差异；然而，这些生物标志物与炎症介质显著相关。
我们的数据表明，MMP-9/TIMP-1 复合物可能是活跃纤维化的有前途的生物标志物，能够识别 HCV 消除后纤维化进展的中断。
