Nucleoside analogs are one of the most important anti-hepatitis B virus drugs, which have the advantage of faster viral suppression and improvement of the condition, as well as being easy to take and easily accepted by patients. However, nucleoside analogs also have prominent disadvantages, that is, high relapse rate after stopping the drug, and need long-term medication. Some patients even have the experience of repeated relapses, known as the image of “good on bad off”. How to break the nightmare of drug withdrawal and relapse of nucleosides? Achieving clinical cure is undoubtedly the best way. Authoritative guidelines have clearly pointed out that the ideal endpoint of chronic hepatitis B treatment is to achieve HBsAg (surface antigen) clearance, that is, clinical cure. Numerous studies have confirmed that patients who achieve this endpoint have a low risk of cirrhosis and hepatocellular carcinoma, and long-term disease remission. The next best thing is to achieve durable serologic conversion of HBeAg (e antigen), an efficacy that can also help with long-term disease remission, achieve safe discontinuation of the drug, and also induce HBsAg clearance. However, the mechanism of action of nucleoside analogs is mainly direct antiviral, and although virologic suppression can be achieved relatively quickly, treatment to obtain HBeAg serologic conversion rate and HBsAg clearance are low, and various nucleoside (acid) analogs treatments for 2-5 years of HBeAg serologic conversion rate of no more than 30%, and the rate of HBsAg clearance is close to the natural clearance rate. For patients treated with nucleoside analogs, it is necessary to find other drugs to help achieve safe discontinuation. Interferon therapy achieves higher HBeAg serologic conversion and HBsAg clearance rates compared to nucleoside analogs. This is mainly because polyethylene glycol interferon (long-acting interferon) not only has a certain antiviral effect like nucleosides, but also helps the host to achieve immune control of hepatitis B virus through immunomodulation, and can achieve long-lasting HBeAg serological conversion and even HBsAg clearance. It is on the basis of such characteristics that pegylated interferon has been able to achieve truly successful treatment of chronic hepatitis B – clinical cure – with a limited course of treatment, eventually leading to the possibility of safe discontinuation of the drug in some populations. Results from a large clinical study (the OSST study) have already shown that nucleoside-treated patients treated with pegylated interferon alpha-2a have a nearly 2-fold increased chance of achieving HBeAg serologic conversion within 1 year than if they had continued on nucleoside therapy. In particular, the chance of achieving HBsAg clearance can be as high as 25% in patients who have already cleared HBeAg and have low HBsAg levels. In conclusion, nucleoside analog therapy is “good up but not good down”, in the case of nucleoside therapy, if the condition is stable, especially when the quantitative level of HBsAg is low, you can try to shorten the course of treatment through polyethylene glycol interferon, and strive for the serological conversion of HBeAg or even the clearance of HBsAg.