Sustained off-treatment viral control is associated with high Hepatitis B Surface Antigen seroclearance rates in Caucasian patients with Nucleos(t)ide Analogue induced HBeAg seroconversion.

Nucleos(t)ide Analogue withdrawal has been described to result in significant Hepatitis B surface antigen (HBsAg) loss rates in patients with long-term viral suppression and negative HBeAg at the start of treatment. In these patients off-treatment HBsAg loss is often preceded by viral rebound with concomitant Alanine Aminotransferase flares. In the present study, we investigated off-treatment HBsAg loss in a multicentric, international observational cohort of patients with Nucleos(t)ide Analogue induced HBeAg seroconversion. Ninety eight mono-infected, predominantly male (74.4%) chronic hepatitis B patients of mixed ethnicity (43.9% Asians, 49.0% Caucasians) who stopped treatment at a median of 11.4 (6.1-18.0) months after HBeAg seroconversion were included. A total of 16 patients experienced Hepatitis B surface Antigen loss during a median follow-up of 42.8 (22.7-83.2) months after treatment cessation: 14 off-treatment and 2 after retreatment initiation with subsequent long-term viral suppression. All patients with off-treatment HBsAg loss showed persistently low ALT (<1.5xULN) and HBV DNA (<2000 IU/mL) levels after HBeAg seroconversion. Persistent viral control was associated with significantly higher annual HBsAg seroclearance rates (8.4%) than relapse with (1.5%; p=0.008) or without (0.0%; p=0.009) subsequent retreatment. In addition, Caucasian patients with sustained off-treatment viral control had >6-fold higher annual HBsAg loss rates compared to non-Caucasian patients (14.8% vs 2.3% respectively; p=0.004).Persistent viral control after treatment cessation following NA induced HBeAg seroconversion was associated with high HBsAg loss rates in Caucasian patients.