Hepatitis B s antigen kinetics during treatment with nucleos(t)ides analogues in patients with hepatitis B e antigen‐negative chronic hepatitis B

BACKGROUND/AIMS: Serum hepatitis B s antigen (HBsAg) levels might be used as a predictor of virological breakthrough or of sustained off-treatment virological response in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. We evaluated the changes of HBsAg in those patients under nucleos(t)ide analogue(s) [NA(s)] therapy for ≥12 months. METHODS: We included 99 HBeAg-negative CHB patients treated with low-genetic barrier NA(s) for a mean of 66 months (lamivudine: 66, adefovir: 6, lamivudine plus adefovir: 11 and telbivudine: 16) and 86 HBeAg-negative CHB patients treated under entecavir or tenofovir for a mean of 30 months as the comparison group. RESULTS: Compared to baseline, HBsAg levels decreased by a median of 162, 1525, 943, 1545, 2163 and 3859 IU/mL at 6, 12, 24, 36, 48 and 60 months of therapy with low-genetic barrier NA(s) respectively. The 6-, 12-, 24-, 36-, 48- and 60-month cumulative rates of HBsAg<100 IU/mL were 2%, 3%, 3%, 5%, 5% and 5%, and <1000 IU/mL 6%, 9%, 15%, 19%, 24% and 61% respectively. Baseline HBsAg levels were the only significant variable associated with the time to HBsAg drop <1000 IU/mL. HBsAg loss occurred in 3.0% of patients. The high-genetic barrier NAs were not found to offer a greater or faster HBsAg decline. CONCLUSIONS: In HBeAg-negative CHB patients, long-term therapy with low-genetic barrier NA(s) decreases serum HBsAg levels, but the rate of decline is slow. Lower baseline HBsAg levels are significantly associated with on-therapy HBsAg drop <1000 IU/mL. Serum HBsAg decline is similar during therapy with low- or high-genetic barrier NAs.