Clinical cure strategies for chronic hepatitis B patients with hepatitis B virus surface antigen <100 IU/mL after treatment with nucleos（t）ide analogues

Among chronic hepatitis B patients undergoing long-term treatment with nucleos（t）ide analogues （NAs）， approximately 10%—20% can achieve a low level of <100 IU/mL for hepatitis B surface antigen （HBsAg）. These patients have the advantage to achieve clinical cure （HBsAg clearance） and are currently a key focus for treatment discontinuation and combination treatment strategies. As for the selection of clinical management strategies， the NAs discontinuation strategy， based on the “immune reactivation” hypothesis， may lead to HBsAg clearance in some patients， especially among Caucasians， but the risk of recurrence after discontinuation cannot be neglected. The treatment strategies based on pegylated interferon-α exhibit a higher potential for active HBsAg clearance， and some novel immunomodulators have also shown preliminary efficacy. Overall， for patients with HBsAg <100 IU/mL previously treated with NAs， treatment discontinuation or active combination treatment should be carefully assessed based on individual risk-benefit profiles. In the future， it is essential to incorporate more refined biomarkers for precise stratification and explore novel combination regimens with finite treatment courses that are safe and highly effective， in order to help more patients achieve clinical cure and reduce long-term risks of liver disease.