Can interferon and nucleoside analogs be interchanged? Interferons and nucleosides are the two main classes of medications used in the antiviral treatment of chronic hepatitis B. They are different in nature. Nucleosides usually require long-term therapy, while interferon is a fixed course of therapy. Many patients start treatment with nucleoside drugs and then regret switching to interferon when they know they need long-term treatment. Is it too late? Can these two types of drugs be interchanged? Can I switch to interferon when I am already taking nucleosides? The development of chronic hepatitis B is closely related to the interaction between the chronic hepatitis B virus and the body’s immune system. Nucleoside drugs work directly against the virus, and because of the lack of immune effect, the effect of the drug disappears after stopping, and the hepatitis B virus will replicate again and the disease will relapse. So is the initial choice of nucleoside the only way to face long-term medication? Can I switch to long-acting interferon if I want to stop taking the drug? In order to maximize the patient’s chances of achieving a durable response after discontinuation, initial treatment with long-acting interferon is a more appropriate option. Some authoritative foreign guidelines recommend that the first line of treatment for chronic hepatitis B should be long-acting interferon therapy. However, studies have now shown that patients with chronic hepatitis B who are taking nucleoside analogs can shorten their course of treatment with long-acting interferon therapy and achieve a durable response after discontinuation of the drug. There are two options for switching to long-acting interferon: one is to add interferon to the original nucleoside analog therapy, and the other is to directly switch from the original nucleoside analog to interferon therapy. Nucleoside treated patients receiving interferon therapy may be considered for discontinuation if e antigen conversion has occurred and after consolidation of therapy. When is the time to switch to interferon? According to current studies, patients who have responded well to nucleoside therapy, especially those with viral conversion and e antigen clearance, have a better outcome when switching to long-acting interferon therapy, for example, the NEW SWITCH study showed that after 1 year of switching to long-acting interferon therapy, the surface antigen clearance rate was close to 20% and the rate of low surface antigen levels (<1000 IU/ml) was close to These patients have a very high chance of durable response after drug discontinuation. The efficacy of interferon in these patients has been described as the "icing on the cake". In other patients, such as those who are resistant to nucleoside therapy and those who have relapsed after discontinuation, the effect of interferon is more like a "blessing in disguise", although studies are limited and efficacy remains to be proven. In conclusion, there is a growing body of research confirming that long-acting interferon therapy in nucleoside treated patients can help improve outcomes, especially in terms of shortening the duration of therapy and achieving a durable response after drug discontinuation. Even if the desired efficacy is not achieved, patients can still continue with their original regimens without harm.