Basic research has made significant advances in virology and pathophysiology We are at a very critical time regarding the treatment of hepatitis B. The treatment of hepatitis B is a very important issue. There is an urgent need to improve anti-HBV efficacy, achieve HBsAg clearance, and ultimately achieve safe drug discontinuation. It is reassuring to know that we have made great progress in basic research, mainly in targeted therapies for the HBV viral life cycle as well as pathophysiology. Direct antiviral therapy Some studies have shown that cell entry inhibitors and assembly inhibitors targeting the cell entry and assembly process of HBV are very promising, and phase I clinical trials have already begun. The inability to completely remove cccDNA is the main reason for the persistence of HBV, so the treatment of cccDNA is still the main direction of research, specifically the following three pathways: ① inhibition of cccDNA synthesis signals in infected cells; ② when cccDNA synthesis, the use of epigenetic modification to inhibit its expression, silencing it, thereby reducing the expression of HBV antigen, and achieve immune recovery or reconstitution; ③ also what I talked about in the report – direct destruction of cccDNA, there have been several important research results in this regard in Science this year, i.e., interferon-α and lymphotoxin-β are able to induce cascade signaling in already infected cells, up-regulate APOBEC 3A and APOBEC 3B, both of which are cytosine deaminases, which can cause cccDNA to be mutated so that it can be recognized and degraded by DANase. This supports the concept that once cccDNA is synthesized, we can recognize it and remove it. Indirect antiviral therapy There are also several avenues for indirect antiviral agents: (i) targeting the immune response in patients with chronic hepatitis B in order to stimulate the innate immune system, for which TLR-7 agonists are in phase II clinical trials; and (ii) there are many exciting results in the area of acquired immunity, for example, with PD-1 blockers, vaccine therapies, and other approaches. To summarize, I think the prospects for new approaches to hepatitis B treatment are very promising. But for now, a cure for hepatitis B will require patience. What we can do now is to try different targets and conduct clinical trials to choose the best treatment program. However, it is still difficult to see which is the best way to fight HBV. cccDNA is the “holy grail” that we are longing for, and it will take time and effort to get it.