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

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.