Hepatitis B surface antigen seroclearance during nucleoside analogue therapy: surface antigen kinetics, outcomes, and durability

Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for nucleoside analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and durability of HBsAg seroclearance in NA-treated patients have not been well described. We compared the HBsAg kinetics and long-term serologic outcomes of 51 chronic hepatitis B patients achieving HBsAg seroclearance during NA therapy with those of 51 HBsAg-positive controls, matched for age, sex, hepatitis B e antigen status, NA type, and treatment duration. Viral profiles before and after HBsAg seroclearance during and after NA treatment cessation were determined. The median time to HBsAg seroclearance and the median follow-up duration after HBsAg seroclearance were 61.2 and 51.6 months respectively. Patients achieving HBsAg seroclearance maintained high median rates of HBsAg reduction throughout therapy (first 6 months, 0.40 IU/mL/year; after year 1, 0.39 IU/mL/year; p = 0.809). For controls, the median rate of HBsAg reduction was significantly slower with time (first 6 months and after year 1, 0.19 and 0.05 IU/mL/year; p = 0.006). The difference in the median HBsAg reduction rates after year 1 between the two groups was significant (p < 0.001). The cumulative rates of antibody to HBsAg development and HBsAg seroreversion 72 months after HBsAg seroclearance were 68.9 and 8.3 % (one patient receiving immunosuppressive therapy; one patient with pre-S/S variant), respectively. Among 22 patients who discontinued therapy after HBsAg seroclearance, 21 remained HBsAg negative with undetectable hepatitis B virus DNA and one patient with reactivation had the pre-S/S variant. NA-treated patients achieving HBsAg seroclearance uniquely maintained high rates of HBsAg reduction throughout treatment, with HBsAg seroclearance durable in most of the patients after treatment cessation.