Since the launch of lamivudine in China in 1998, nucleoside analogues have been successfully used in the antiviral treatment of patients with chronic hepatitis B. However, with the prolonged use of nucleoside analogues, the “seven-year itch” has begun to appear in patients who are receiving them. However, as the use of nucleoside analogs extends, patients receiving nucleoside analogs begin to experience the “seven-year itch”. For example, more and more patients feel that they have been taking the drugs for years and that their disease is well controlled and that they can stop taking them. But doctors are not so optimistic. In response to this problem, our experts have formed an expert group for a seminar on the long-term treatment of chronic hepatitis B. They have published a treatment guide on the long-term treatment of chronic hepatitis B with nucleosides and nucleotides, emphasizing that nucleosides and nucleotides need long-term treatment and should not be discontinued at will. Nucleoside drugs require long-term treatment mainly because they are prone to relapse after discontinuation. According to the results of studies, the relapse rate of various nucleoside drugs is about 30%-90% at 1 year after discontinuation, and some studies also show that the relapse rate will continue to increase as the time of discontinuation increases. In other words, most patients will relapse after stopping the drug, and relapse will cause the disease to worsen and even threaten life. Nucleosides are prone to relapse after drug discontinuation mainly because, after HBV infection, covalent closed-loop DNA (cccDNA) will be formed in the nucleus of hepatocytes, and cccDNA persists in hepatocytes and serves as a template for HBV replication, and continues to produce offspring HBV to infect other hepatocytes; the reduction of cccDNA is mainly dependent on the host immune system, and nucleosides can temporarily improve the disease, but The reduction of cccDNA is mainly dependent on the host immune system, nucleoside drugs can temporarily improve the disease, but there is no direct immunomodulatory effect, so it is difficult to have a significant impact on cccDNA, and it is conceivable that HBV replication will return once the drug is stopped. Therefore, nucleoside analogs should not be discontinued at will, and once you choose this drug you should be prepared to adhere to long-term treatment. However, according to the latest research results, it is not hopeless to stop the drug. The results of a study suggest that for patients with stable disease and good response after nucleoside therapy, that is, those who have achieved virological conversion and e antigen clearance with relatively low surface antigen levels, switching to pegylated interferon alpha-2a therapy for 48 weeks can significantly increase the e antigen serological conversion rate and surface antigen clearance rate. This regimen has been recognized by an increasing number of experts and is worth trying.