With the in-depth research on the antiviral treatment of chronic hepatitis B (referred to as chronic hepatitis B), as well as the accumulation of clinical experience in the treatment of chronic hepatitis B, more and more patients in China have received antiviral treatment. However, there are still many problems to be solved in the clinic, among which the treatment of patients treated with nucleoside (acid) analogs has become a hot spot of clinical concern. Discontinuation of nucleoside (acid) analogs after treatment is an important issue that has been troubling doctors and patients for a long time. According to the results of a recent large-scale patient survey organized by Wu Jieping Foundation, more than 90% of patients are eager to obtain the opportunity to safely discontinue the drug through a limited course of treatment, and as many as 63% of patients hope that they can safely discontinue the drug through a course of treatment of 1-2 years. However, the clinical reality is in stark contrast to patients’ expectations. For example, a significant proportion of patients being treated with nucleoside (acid) analogs still do not achieve a complete response or therapeutic endpoint, or relapse occurs after stopping the drug. How to realize the expectation of discontinuation in such patients by adjusting the treatment regimen is a difficult and hot issue in the antiviral treatment of chronic hepatitis B. In recent years, advances in the study of the natural history of chronic hepatitis B have provided new ideas to address this problem. The natural history of chronic hepatitis B suggests that patients in the immune control phase, i.e., inactive carrier phase, have a good long-term prognosis. Nucleoside (acid) analogs, on the other hand, because of their strong viral suppression, if they fail to achieve durable immune control, relapse is inevitable when they are discontinued. Polyethylene glycol interferon (PEGI), another antiviral therapy, has both immunomodulatory and antiviral mechanisms of action, which is more advantageous for achieving durable immune control after drug withdrawal. Some research data show that for patients taking nucleoside (acid) analogs who have achieved HBV-DNA negative, HBeAg clearance, and HBsAg << span=""> 1,500IU/ml, sequential long-acting interferon alpha-2a therapy can have a 25% chance of HBsAg conversion, while the continued nucleoside analogs therapy group has an almost zero chance of HBsAg conversion. At the same time, if this group of patients had a more significant decrease in surface antigen (<< span=""> 200 IU/ml) at 24 weeks after treatment with long-acting interferon alpha-2a, the percentage of them obtaining surface antigen clearance would be about 50%. This would essentially have achieved clinical cure. Moreover, from the mechanism of action of long-acting interferon α-2a and previous data, it can be seen that the chances of relapse of long-acting interferon α-2a at the end of the treatment and after stopping the drug are much smaller than that of nucleoside (acid) analogs, and 86% of the patients can achieve a durable response at the end of the treatment; and with the prolongation of the time, the greater the chances of their HBsAg clearance. At the same time, long-acting interferon alpha-2a therapy significantly reduces the incidence of hepatocellular carcinoma. Therefore, as written in the new Slow Hepatitis B Guidelines, for patients taking nucleoside (acid) analogs who do not wish to take the medication for a long period of time, sequential long-acting interferon alpha-2a therapy can be tried to increase the likelihood of achieving HBsAg negativity.