Immune Checkpoint Inhibitors in Chronic Hepatitis B: Accelerating a Predetermined Outcome or Altering the Trajectory of Cure?

Immune checkpoint inhibitors (ICIs) are assessed for functional cure in chronic hepatitis B (CHB) patients with low baseline HBsAg, particularly those with cancer. While ICIs may accelerate serum hepatitis B surface antigen (HBsAg) clearance, overall rates show no significant advantage over other treatments. This questions whether ICIs fundamentally alter cure trajectories or merely hasten predetermined outcomes, rather than fundamentally altering the cure trajectory for a broader population. Given ICI side effects, costs, and the lack of predictive biomarkers, their clinical benefit for solely accelerating clearance is uncertain. Future research should clarify ICI mechanisms and identify robust biomarkers beyond HBsAg levels to guide patient selection and optimize therapy, emphasizing shared decision-making, especially for low HBsAg patients.