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 HBsA g in those patients under nucleos(t)ide analogue(s) [ NA (s)] therapy for ≥12 months. Methods We included 99 HBeA g‐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 HBeA g‐negative CHB patients treated under entecavir or tenofovir for a mean of 30 months as the comparison group. Results Compared to baseline, HBsA g 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 HBsA g<100 IU/mL were 2%, 3%, 3%, 5%, 5% and 5%, and <1000 IU/mL 6%, 9%, 15%, 19%, 24% and 61% respectively. Baseline HBsA g levels were the only significant variable associated with the time to HBsA g drop <1000 IU/mL. HBsA g loss occurred in 3.0% of patients. The high‐genetic barrier NA s were not found to offer a greater or faster HBsA g decline. Conclusions In HBeA g‐negative CHB patients, long‐term therapy with low‐genetic barrier NA (s) decreases serum HBsA g levels, but the rate of decline is slow. Lower baseline HBsA g levels are significantly associated with on‐therapy HBsA g drop <1000 IU/mL. Serum HBsA g decline is similar during therapy with low‐ or high‐genetic barrier NA s.