直接抗病毒药物类抗丙型肝炎病毒药物的黑框警告及预防

丙型肝炎病毒（hepatitis C virus，HCV）是引起丙型肝炎的病原体，感染后极易慢性化并导致肝纤维化、肝硬化甚至肝癌。随着直接抗病毒药物（direct-acting antiviral agents，DAA）类抗HCV药物不断发展，临床上用其治疗后持续病毒学应答率逐渐提高，药品不良反应明显减少。但近年来，DAA类抗HCV药物在国外临床应用中出现了一些严重不良反应事件，因此美国食品药品管理局在这些药物的使用说明书中加入了黑框警告。国内今年已开始陆续上市了多个DAA类抗HCV药物，但尚未大规模应用。本文阐述了此类药物的黑框警告内容（包括引起严重皮肤反应、导致心动过缓、严重肝损伤和乙型肝炎病毒再激活）及其发生机制，并提出预防及解决措施，为我国临床合理用药提供参考。

Black box warnings of direct acting antiviral agents against hepatitis C virus and preventions of their adverse effects

Hepatitis C virus (HCV) is one of the major causes for chronic hepatitis and usually leads to liver fibrosis, cirrhosis and even hepatocellular carcinoma. With the research and development of direct-acting antiviral agents (DAAs), treatment of HCV-infected patients with DAAs in clinical practice increases the sustained virological response and decreases the adverse effects. However, in recent years some DAAs cause a number of serious adverse events in patients infected with HCV, and hence U.S. Food and Drug Administration (FDA) adds black boxed warnings to these drugs. Several DAAs against HCV have also been approved in China since this year without real-world clinical application. In this article, several black box warnings to those drugs are summarized, including the risks of leading to serious skin reactions, bradycardia, serious liver injury risk and hepatitis B reactivation, and the occurrence mechanisms of those adverse effects induced by DAAs and how to avoid these serious adverse effects are also discussed. It is helpful for reasonable treatment of HCV-infected patients by clinicians.