慢性乙型肝炎免疫耐受期患者的临床试验思考

Clinical trials considerations for patients with immune-tolerant phase chronic hepatitis B

在慢性乙型肝炎病毒感染的早期阶段,大多数患者处于免疫耐受期。过去通常认为免疫耐受期患者无疾病进展或与肝损伤相关的事件,且其抗病毒疗效欠佳,所以目前国内外指南通常不推荐进行抗病毒治疗。然而越来越多的研究结果显示,免疫耐受期患者如不治疗,亦可进展为肝硬化和肝细胞癌,临床上具有迫切的治疗需求。而目前抑制核衣壳组装、调节免疫、降低表面抗原等新作用机制的药物正在研发,为这部分患者实现病毒抑制甚至功能性治愈提供了可能性。现主要综述免疫耐受期人群最新研究进展、人群特征、治疗需求,对该阶段患者新药临床试验设计策略进行讨论。

Most patients with early stage chronic hepatitis B virus infection are in the immune-tolerant phase.Therefore,previously been generally believed that there is no disease progression or liver injury-related events,and poor antiviral efficacy in patients with immune-tolerant phase.With that in mind,antiviral therapy is generally not recommended in current domestic and foreign guidelines.However,more and more studies have shown that patients in the immune-tolerant phase may develop liver cirrhosis and hepatocellular carcinoma without treatment,so clinical treatment is urgently needed.Currently,drugs based on nucleocapsid inhibitor,immune modulation,and other novel mechanisms for viral replication are being developed to reduce hepatitis B surface antigen,which offers the possibility to achieve viral suppression or even functional cure in these patients.This paper mainly reviews and discusses the latest research progress,population characteristics,treatment needs,and design strategies of clinical trials of new drug for immune-tolerant phase population.