Determinants of HBsAg Loss After Nucleos(t)ide Discontinuation in a Prospective Cohort of HBeAg-Negative Caucasian Patients

Abstract

Introduction: Nucleos(t)ide analogues (NAs) discontinuation in HBeAg-negative chronic hepatitis B (CHB) aims at increasing functional cure rates. However, clinical outcomes and predictive factors for HBsAg loss or re-treatment are affected by the heterogeneity of studies. We aimed to analyse baseline factors associated with outcomes after NAs discontinuation in a cohort with homogeneous re-treatment criteria. Methods: Prospective multicenter study of 149 HBeAg-negative CHB with complete viral suppression and absence of cirrhosis recruited from 2016 to 2021. Re-treatment criteria after NAs discontinuation were homogeneous based on liver tests and HBV-DNA levels. Results: In this predominantly Caucasian cohort, 71% received tenofovir with a median treatment duration of 10 (7-13) years. Forty patients (27%) achieved HBsAg loss after 44 (28-54) months. Lower qHBsAg at end of treatment (EOT) and longer treatment duration were independent predictors of HBsAg loss. Combining qHBsAg at EOT (1000 IU/mL) and month 3 after NA interruption (100 IU/mL) stratified patients into high (> 70%) or low (< 10%) likelihood of HBsAg loss. On the other hand, 43 (29%) patients were retreated; HBV-DNA < 100 IU/mL at month 3 was significantly associated with remaining off-therapy. Overall, safety was favourable, with mild or transient ALT flares occurring in 64 patients (43%). However, one patient (0.6%) developed a severe hepatitis and required liver transplantation. Conclusions: NA withdrawal results in functional cure rates exceeding 25%, particularly in patients with long-term antiviral treatment and low qHBsAg levels. Combining qHBsAg levels at EOT and at 3 months accurately stratifies patients according to the probability of HBsAg loss. Close monitoring to detect the need for treatment re-introduction is mandatory.