In late 2014, the results of a study by our medical doctors were published in the world-renowned journal Hepatology (The Liver). This study was named the OSST study, and its main objective was to analyze the efficacy of switching to long-acting interferon alpha-2a in patients with chronic hepatitis B treated with entecavir. The results of the study showed that patients who converted to long-acting interferon alpha-2a treatment after 48 weeks of virological conversion and e antigen clearance after entecavir treatment had significantly higher rates of e antigen conversion and surface antigen clearance compared to continuing entecavir treatment. This article by Chinese scholars is the first study published internationally for patients treated with nucleoside (acid) analogs, also known as oral antivirals, and therefore has attracted greater attention. Following the publication of this article, the journal Hepatology published several more reviews addressing this study in 2015. Most of these reviews endorsed the strategy of treating patients with oral antiviral therapy with long-acting interferon as a novel treatment idea that could help patients shorten their treatment course and aim for a durable response after drug discontinuation. The OSST study used sequential therapy, a direct replacement of entecavir with long-acting interferon, and showed a 3-fold increase in e antigen conversion and a zero breakthrough in surface antigen in patients treated with entecavir who were virologically negative and cleared of e antigen. This is certainly an exciting research result. However, some experts believe that oral antivirals and long-acting interferons have different mechanisms of action, and that the combined application of complementary mechanisms can achieve better efficacy, and at the same time, the combined treatment also helps to avoid the risk of virological rebound after discontinuation of oral drugs, so it is more reasonable to use the protocol of adding long-acting interferons instead of converting long-acting interferons for patients treated with oral drugs. This theory is supported by another study by our experts, which showed that for entecavir virologic responders, the 48-week e-conversion rate with the addition of long-acting interferon was 44%, seven times higher than with continued entecavir therapy. However, this study did not directly compare the two regimens of add-on and conversion to long-acting interferon, so it is still too early to draw conclusions. Although the specific regimen of switching from oral antivirals to long-acting interferon is still open to speculation, this treatment concept has been well accepted and is mentioned in the 2015 update of the Chinese guidelines for the prevention and treatment of chronic hepatitis B. This option brings a new strategy to achieve better efficacy and a new way of thinking to address the long-term treatment of oral drugs.