Interferons, especially long-acting interferons with a limited course of therapy, can achieve high rates of e antigen conversion and surface antigen clearance, and have a durable response after drug discontinuation, and are recommended by authoritative guidelines, such as the 2015 Asia-Pacific Liver Institute guidelines, as the first-line drug to achieve a durable response after drug discontinuation. However, in clinical practice, there are still some patients who have poor efficacy with long-acting interferon therapy, and in such cases, one should analyze and summarize the situation after a period of application to find the cause of the poor efficacy, either to exclude the problem and continue the application, or to change the regimen to combine with other drugs, or to stop the application, all of which should be discussed with the doctor and then decided. A common problem that causes poor efficacy of long-acting interferon is the inability to follow medical advice on the use of the drug, excluding reasons such as omissions, mainly because of adverse reactions affecting the application. If such problems exist, you should communicate with your doctor and ask him/her to give targeted treatment, and generally after treatment patients are able to adhere to the treatment. Based on the results of these studies, it is recommended that the efficacy of long-acting interferon should be evaluated at 24 weeks of treatment and that patients with different efficacy should be treated differently: if the surface antigen quantification decreases to ≤1500 IU/ml at 24 weeks of interferon treatment in HBeAg-positive patients, continue treatment until 48 weeks. For patients with e antigen serological conversion at 48 weeks and a sustained and significant decrease in surface antigen quantification to less than 250 IU/ml, treatment can be extended to 72 weeks or longer to achieve surface antigen clearance; for patients who have not experienced e antigen serological conversion at 48 weeks, treatment can be extended to 72 weeks.