HIV/HCV合并感染肝硬化发生率高、进展快，相关性肝病已成为合并感染者主要死因。目前尚无有效抗HIV/HCV合并感染肝纤维化药物。Cenicriviroc（CVC）为CCR2和CCR5双受体拮抗剂，抗HIV新药。我们发现，活化型HSCs不仅表达HIV协同受体CCR5和CCR2，而且HIV gp120通过与CCR5作用促进肝纤维化发展；CVC具有调节HSCs、抑制gp120诱导的HSCs胶原蛋白I合成及抗肝脏炎症作用。本项目采用qRT-PCR、Western Blot、和流式细胞术等技术，通过CVC对单核细胞肝内迁移和KCs亚群和功能的调节，以及CVC调控 HSCs和抑制gp120促肝纤维化作用。从整体、细胞与分子水平检测CVC抗肝纤维化作用机制，探寻HIV/HCV合并感染快速肝纤维化治疗的新方法，同时为其他原因所致肝硬化防治新药研发提供新的思路和策略。

Progression of liver fibrosis is more rapid and development of cirrhosis more common among those with HIV/HCV coinfected, compared to HCV monoinfection. However, the mechanism by which HIV accelerate liver fibrosis progression in HCV-infected people remain unclear. At present there is no effective and accepted therapy for hepatic fibrosis. Liver disease is one of the leading causes of morbidity and mortality in indivisuals with HIV/HCV coinfected. Our previous studies have found that: 1) CCR2 and CCR5, HIV coreciptors , express in activated hepatic stellate cells(HSCs); 2) HIV gp120 increase extra cellul matrix (ECM) expression in HSCs in vitra via CCR5 mechanism. 3) CCL2 / CCR2 axis adjustment monocytes infiltrating the liver and affect liver damage and liver fibrosis process. 4) Gp120-induced HSCs synthesis of extracellular matrix was inhibited by Cenicriviroc (CVC) that is blocked by both CCR2 and CCR5 reciports. 5）CVC significantly reduce liver inflammation and liver fibrosis in rats thioacetamide (TAA) induced. This project will further study that mechanism of CVC regulate HSC, CVC inhibit HIV gp120-induced HSC biological functions and reduce the liver inflammation using ELISA, qRT-PCR, Western Blot and Zymographg methods.These findings not only clarify the anti-hepatofibrotic role and mechanism of CVC, but also provide a norval anti-fibrotic strategie.