Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation of Matrix Metalloproteinases (MMPs) and Their Tissue Inhibitors TIMPs and Effect of HCV Protease Inhibitors.
Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation of Matrix Metalloproteinases (MMPs) and Their Tissue Inhibitors TIMPs and Effect of HCV Protease Inhibitors.
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DOI：
10.3390/ijms17040455
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发表时间：
2016-03-26
影响因子：
5.6
通讯作者：
Liuzzi GM
中科院分区：
文献类型：
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作者：
Latronico T;Mascia C;Pati I;Zuccala P;Mengoni F;Marocco R;Tieghi T;Belvisi V;Lichtner M;Vullo V;Mastroianni CM;Liuzzi GM
基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）之间的失衡可能有助于丙型肝炎（HCV）感染患者的肝纤维化。我们测量了HCV单感染和HIV/HCV合并感染患者中不同MMP和TIMP的循环水平，并评估了抗HCV治疗调节HCV受试者MMP和TIMP水平的潜力。我们分析了83份血浆样本，来自16名接受双重或三重抗HCV治疗的HCV单感染患者，15名HIV/HCV合并感染患者，检测不到HIV载量，和10名健康供体（HD）。通过SearchLight多重免疫测定试剂盒测量MMP-1、MMP-2、MMP-3、MMP-8、MMP-9、MMP-10、TIMP-1和TIMP-2的水平。MMP-2和MMP-9是所有分析样本中表达最高的MMP，与HD相比，它们在HCV单感染和HIV/HCV共感染受试者中的水平显著升高。TIMP-1水平在HCV和HIV/HCV受试者中显著高于HD受试者，并与肝硬度相关。这些发现提高了使用循环TIMP-1作为HCV感染中肝纤维化的非侵入性标志物的可能性。一项纵向研究表明，在接受双重以及三重直接作用抗病毒药物（DAA）抗HCV治疗的患者中，MMP-9水平显著降低（较基线降低40%），对MMP-2、TIMP-1和TIMP-2无影响。由于MMP-2和MMP-9的失调可能反映肝脏中的炎症过程，因此HCV蛋白酶抑制剂治疗后MMP-9的降低表明对减轻肝脏炎症具有积极作用。
An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with hepatitis C (HCV) infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD). Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline) in patients receiving dual as well as triple direct-acting antivirals (DAA) anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation.