Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
World J Gastroenterol. 2018 Dec 21;24(47):5297-5311. doi: 10.3748/wjg.v24.i47.5297.
Hepatitis C virus (HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanisms of HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.
丙型肝炎病毒 (HCV) 感染通常会导致进行性肝脏疾病，从慢性炎症恶化至纤维化、肝硬化，甚至发展为肝细胞癌。长期、持续和失控的炎症反应是这些疾病的特征，进一步导致肝损伤和更严重的疾病进展。炎症细胞因子和趋化因子的水平随感染和治疗状态而变化，因此，它们可能作为疾病进展和治疗效果的候选生物标志物。HCV 诱导的炎症机制涉及经典病原体模式识别、炎性小体激活、肝内炎症级联反应以及氧化和内质网应激。直接作用抗病毒药物 (DAA) 是有效消除 HCV 的首选治疗方法，但 DAA 本身不足以阻断 HCV 感染个体中不受控制的炎症和严重肝损伤。一些在 DAA 治疗后实现持续病毒学应答的患者在治疗后仍长期存在进展为肝硬化和肝细胞癌的风险。因此，在 DAA 治疗期间或之后联合具有抗 HCV 作用的抗炎/保肝药物是这些患者的一种有前途的治疗方案。在这篇综述中，我们讨论了炎症介质与 HCV 感染之间的关系，总结了 HCV 诱导炎症的机制，并描述了具有抗 HCV 活性的抗炎/保肝药物在治疗晚期 HCV 感染中的潜在作用。
