Novel HBV Biomarkers-Guided NAs Withdrawal Strategy Promotes HBsAg Clearance in Asian CHB Patients: A Randomized Controlled Trial.

BACKGROUND & AIMS: Nucleos(t)ide analogue (NAs) discontinuation promotes hepatitis B surface antigen (HBsAg) clearance among European patients with chronic hepatitis B virus (HBV) infection. The efficacy and safety of a novel HBV biomarker-guided NAs withdrawal strategy among Asian patients was evaluated in this multicenter randomized controlled trial.

METHODS

NAs-experienced patients achieving HBsAg <200 IU/mL and undetectable HBV DNA for ≥12 months with HBV RNA or hepatitis core-related antigen undetectable were randomized 2:1 to stop or continue NAs therapy. Ninety patients were included in final modified intention-to-treat analysis (60 in the NAs-Stop group and 30 in the NAs-Continue group). Cumulative rates of HBsAg loss and relapse were evaluated at week 144.

RESULTS

Patients enrolled were 45.9 ± 10.2 years of age, with a median 9.4 years (interquartile range, 6.0-13.0 years) of treatment. Baseline characteristics between the two groups were balanced, with a median HBsAg level of 1.7 and 1.8 log10 IU/mL in the NAs-Stop and NAs-Continue groups, respectively (P = .224). Compared with patients in the NAs-Continue group, NAs-stoppers showed an increased 144-week cumulative incidence of HBsAg clearance (25.9% vs 4.2%; P = .013) and more profound HBsAg decline during follow-up (0.90 log10 IU/mL vs 0.46 log10 IU/mL; P = .056). Cumulatively, 38.6% and 20.2% of patients experienced virological and clinical relapse after stopping NAs, with 16 patients retreated and no serious adverse events occurring. Subgroup analysis revealed that hepatitis B e antigen-negative patients with baseline HBsAg level <100 IU/mL had a more favorable response following NAs withdrawal, achieving an HBsAg loss rate of 40.0%.

CONCLUSIONS

Asian patients with long-term HBV suppression benefit from NAs discontinuation guided by novel HBV markers, which provides rationale for finite NAs treatment. ClincialTrials.gov, Number: NCT04519359.