The vast majority of nucleoside analogs will relapse after stopping the drug, and some patients have the risk of acute exacerbation of the disease. However, after long-term treatment, many patients think that the disease is cured when some of the test data are normal, and they will always stop taking the drugs on their own; and some patients even face relapse after the doctor confirms that they can stop taking the drugs after the “major triple positive” has changed to “minor triple positive”. Why is this so? Nucleoside analogs treatment of chronic hepatitis B why relapse? It is said that chronic hepatitis B is a difficult disease to treat, and a very important point is because it is easy to relapse. Once the chronic hepatitis B virus invades the liver, the long strand of viral DNA forms a tight structure of circular tightly closed duplexes (cccDNA), settles in the nucleus of the liver cell, and continuously replicates the virus. Nucleoside analogs have a direct antiviral effect and can be effective very quickly, but unfortunately the treatment removes only the replicating progeny of the virus, so it is easy to relapse after stopping the drug. How to minimize relapse? Standardized treatment is an important solution to reduce recurrence. According to the current guideline, the treatment should be continued for 2 years or more after the conversion of “major triple positive” to “minor triple positive” before stopping the treatment. However, since the chances of achieving this with nucleoside therapy are relatively slim, patients who wish to safely discontinue their therapy can try a different strategy: interferon therapy. Compared with oral antivirals, interferon has an additional immunomodulatory effect, which strengthens immunity against the hepatitis B virus, and this immunity persists after discontinuation of the drug, resulting in long-lasting efficacy. In first-treatment patients, because of the improved immune function, the efficacy of interferon is long-lasting in more than 80% of those who stop taking the drug. Some studies have demonstrated that interferon treatment of patients receiving oral antivirals can shorten the course of treatment, lead to safe discontinuation, and reduce relapses. For example, in one study, the e-antigen conversion rate was less than 10% after 1 year of entecavir treatment followed by 1 year of continued treatment, whereas those treated with interferon after 1 year of entecavir therapy had more than a two-fold increase in the e-antigen conversion rate, and surface antigen clearance was achieved in some patients. In conclusion, nucleoside therapy is easy to relapse after stopping, if you are receiving nucleoside therapy, do not arbitrarily stop, for patients who expect to stop, you can try interferon therapy, strive to shorten the course of treatment, as soon as possible to realize the e antigen conversion, to achieve the safety of drug withdrawal.