In 2012, the authoritative chronic hepatitis B guideline European Academy of Hepatology (EASL) guidelines identified durable response after drug discontinuation as a treatment endpoint for chronic hepatitis B, while emphasizing that the ideal treatment endpoint should be durable HBsAg clearance after drug discontinuation. What is HBsAg? How is it harmful to patients with chronic hepatitis B? HBsAg is the surface antigen of the hepatitis B virus, or the familiar Australian antibody, which is actually the outer coat of the hepatitis B virus (HBV). HBV must rely on HBsAg to attach to and invade liver cells, without which HBV would not be able to enter the liver cells to reproduce or replicate. In addition, HBsAg can also make HBV evade the body’s immune function to pursue and long-term presence in the body and not cleared to cause harm. A large number of studies have found that patients with positive HBsAg have a high incidence of cirrhosis and hepatocellular carcinoma. At the same time, it has also been proven that patients who have achieved HBsAg clearance have significantly improved liver inflammation and fibrosis and reduced mortality. It can be said that HBsAg clearance is a “hat off” for patients, a complete escape from slow hepatitis B. In addition, the earlier the clearance of HBsAg, the better. If HBsAg clearance occurs before the age of 45, the incidence of cirrhosis, liver cancer and death is almost zero, but if HBsAg clearance occurs after the age of 45, even if HBsAg is cleared, there is still a risk of cirrhosis and liver cancer. The 2012 EASL guidelines emphasize that the ideal treatment endpoint for chronic hepatitis B is to achieve durable HBsAg clearance after drug discontinuation. Which treatment approach can be used to clear HBsAg as soon as possible to achieve the desired goal of treatment and ultimately remove the hepatitis B “cap”? Unfortunately, less than 1% of people are able to clear HBsAg spontaneously, and therefore rely primarily on drug therapy. Among the available drugs, oral nucleoside analogs induce a similar rate of HBsAg clearance as spontaneous clearance. Fortunately, pegylated interferon, with its dual mode of action of antiviral and immunomodulation, can help patients “remove their caps” by inducing an immune response that effectively clears infected hepatocytes and achieves a high HBsAg clearance rate. The results of the study showed that pegylated interferon treatment for HBeAg-positive chronic hepatitis B patients achieved an HBsAg clearance rate of 11% at 3 years after discontinuation of the drug, and HBeAg-negative chronic hepatitis B patients achieved an HBsAg clearance rate of 12%. In particular, HBsAg clearance is higher in those patients who respond well, such as patients with HBeAg seroconversion six months after pegylated interferon discontinuation, with HBsAg clearance close to 30% 3 years after discontinuation. HBsAg clearance is the ideal goal for the treatment of chronic hepatitis B. Of course, achieving this goal is bound to be an arduous journey, and under the guidance of a physician who is firm in his goals and chooses the correct and standardized treatment, it is expected that this goal will be achieved as soon as possible and long-term remission of the disease will be achieved.