How to deal with relapse of oral antivirals for slow hepatitis B? Since the first nucleoside (acid) analogue, lamivudine, was used to treat slow hepatitis B, the use of these drugs has developed rapidly, with good clinical results. These drugs are taken orally and are often collectively referred to as oral antivirals for slow hepatitis B. They are able to inhibit viral replication relatively quickly, and in particular, entecavir and tenofovir medications are more potent and less resistant. However, with the increase of application, some problems of oral antivirals have also received attention, of which the problem of relapse of discontinuation is more prominent in recent years. More and more patients receiving oral antivirals with good efficacy wish to discontinue them, which has prompted the issue of discontinuation of oral antivirals to become a research direction in the field of chronic hepatitis B. Currently, major domestic and international guidelines are also exploring the criteria for discontinuation of oral antivirals, and the more consistent recommendation is that patients with major triplets should consider discontinuation after a longer period of consolidation therapy following e antigen seroconversion. The 2015 edition of the Guidelines for the Prevention and Treatment of Chronic Hepatitis B for patients with HBeAg-positive CHB, recommendation 6: The total course of NAs is recommended to be at least 4 years, and those who remain unchanged after achieving HBVDNA below the lower limit of detection, ALT normalization, and HBeAg serologic conversion, and then consolidation therapy for at least 3 years (reviewed every 6 months), may be considered for discontinuation, but a longer course of therapy may reduce relapse. For patients with HBeAg-negative CHB, recommendation 9: NAs treatment is recommended to reach the disappearance of HBsAg and undetectable HBVDNA, and then consider discontinuing the drug when it remains unchanged after 1.5 years of consolidation therapy (after at least 3 retests, each at 6 months interval). Unfortunately, however, the percentage of oral NAs drugs meeting the discontinuation criteria is low. In particular, it is very difficult to achieve disappearance of HBsAg in HBeAg-negative patients, and very few of them are converted to negative. The relapse rate of some patients who discontinued their drugs on their own because they failed to meet the guideline recommended discontinuation criteria was high. In the face of high relapse after discontinuation of oral antivirals, there are two responses: one is to adhere to long-term treatment to avoid relapse after discontinuation. The main reason for relapse after discontinuation of oral antiviral drugs is that these drugs can only inhibit viral replication without direct immunomodulatory effect, so it is difficult to completely remove the virus, and viral replication naturally resurfaces after discontinuation of drugs, and relapse is inevitable. Obviously, to avoid relapse, the drugs should not be stopped easily. Of course, in long-term treatment, we must also pay attention to maintaining good medication compliance, that is, we must adhere to the standardized medication, and at the same time adhere to follow-up, timely detection and treatment of drug resistance problems and safety issues, in order to ensure that the efficacy of treatment continues. The other is to consider adjusting the treatment regimen for safe discontinuation. In contrast to oral antivirals, long-acting interferon has both antiviral and immunomodulatory effects, and medical studies have found that for patients with good oral antiviral efficacy, receiving long-acting interferon can result in higher e antigen conversion and surface antigen clearance rates, and shorten the course of treatment for safe discontinuation. For example, results from the OSST study showed that patients with negative virologic conversion, e antigen clearance and low surface antigen levels after entecavir treatment had a surface antigen clearance rate of 25% after 48 weeks of treatment with long-acting interferon alpha-2a; in the NEWSWITCH study, a similar population had a surface antigen clearance rate of 31% after 48 weeks of treatment with long-acting interferon alpha-2a. Patients should take this issue seriously and should not stop taking oral antivirals at will, understanding that long-term adherence to standardized therapy is an important safeguard for maintaining efficacy. For patients who do expect to stop taking their medication, they can receive long-acting interferon therapy at the right time under the guidance of an experienced physician and strive for safe discontinuation.