[The concept of a fountional cure for hepatitis B keeps pace with the times]

Hepatitis B surface antigen (HBsAg) seroclearance, or s-loss, has traditionally been regarded as a key indicator of hepatitis B virus (HBV) functional cure. However, growing insights into HBV pathogenesis and treatment strategies have reshaped our understanding of the relationship between s-loss and functional cure. While an HBsAg level below 100 IU/mL is often used to define partial cure, it primarily reflects a therapeutic milestone that facilitates eventual s-loss rather than a definitive endpoint. New biomarkers such as serum HBV RNA and hepatitis B core-related antigen are promising but, due to limitations in sensitivity, are not yet adequate substitutes for s-loss in defining functional cure. Importantly, achieving s-loss alone does not guarantee functional cure. Other factors-such as HBeAg seroclearance, the durability of s-loss, and whether single timepoint of rebound ("Blips") are permissible-must be considered in evaluating functional cure. These evolving perspectives underscore the importance of consolidation therapy. Further researches are needed to elucidate the mechanisms between different therapies induced s-loss, the implications of lower detection limits for HBsAg, and the role of hepatitis B surface antibodies in seeking functional cure.