HBsAg loss is higher among caucasians compared to Asians after stopping nucleos(t)ide analogue therapy: results from a large, global, multi-ethnic cohort of patients with chronic hepatitis B (RETRACT-B study)

Abstract

Background: Despite several recent studies, the efficacy of finite nucleos(t)ide analogue (NA) therapy for CHB patients has not yet been well established due to contradictory findings and inadequate sample sizes. We aim to establish and describe a global, multi-center cohort of CHB patients who discontinued NA therapy, and evaluate outcomes following cessation of NA therapy. Methods: This is an on-going cohort study of CHB patients who discontinued NA therapy between 2000-2020 from 12 participating centers across North America, Europe and Asia. Patients coinfected with HIV, hepatitis C virus, hepatitis D virus, or those who received (peg)interferon treatment within a year prior to NA cessation were excluded. We analyzed retreatment and off-treatment HBsAg loss using multivariable logistic regression. Only HBeAg negative patients with undetectable HBV DNA at the time of NA cessation were included in this analysis. Results: Among 1,509 CHB patients who discontinued NA therapy (mean age 52.7±11.3 years, 72.4% male, 11.4% Caucasian, 86.5% Asian, 43.4% HBV genotype B), 70.5% were HBeAg negative, 16.8% were HBeAg positive, and 12.7% had unknown HBeAg status at start of NA therapy (SOT). Majority were treated with entecavir (ETV [51.7%]) or tenofovir disoproxil fumarate (TDF [28.6%]) prior to cessation. Total median follow-up time was 16.4 (IQR:6.9-31.6) months, median time to retreatment was 10.1 (IQR:5.6-19.8) months, and median time to HBsAg loss was 17.0 (IQR:11.4-32.0) months. Overall, 42.9% were retreated and 8.1% (n = 111) had HBsAg loss. Odds of retreatment were higher among Asians (vs. Caucasians: OR 1.7; 95% CI 1.1-2.6; p=0.03), and among those treated with ETV (vs. TDF: OR 1.5; 95% CI 1.1-1.9; p=0.006). Older age was also associated with higher odds of retreatment, and there were no significant differences in retreatment by SOT HBeAg status. Odds of HBsAg loss were higher among males (vs. females: OR 1.9; 95% CI 1.1-3.6; p=0.04), and among Caucasians (vs. Asians: OR 2.6; 95% CI 1.4-4.9; p=0.002). While not statistically significant, HBsAg loss was higher among SOT HBeAg positive patients, and among those treated with TDF (vs. ETV). There were 12 deaths during follow-up of which, 8 were liver-related. Conclusion: Odds of HBsAg loss after NA cessation were 2.6 times higher among Caucasians compared to Asians, and 1.9 times higher among males compared to females. There was also a trend towards higher HBsAg loss in those treated with TDF compared to those treated with ETV.