Objective To investigate the change in HBsAg quantification after HBV DNA negative conversion in chronic hepatitis B ( CHB) patients treated with nucleos ( t) ide analogues ( NAs) . Methods The CHB patients who were treated with NAs in Department of Infectious Diseases, 922 Hospital of PLA & Xiangnan Hospital Affiliated to Hunan Normal University, from January 2016 to November 2018 were enrolled. HBsAg quantitation and HBV DNA quantitation were measured. The chi-square test was used to investigate the difference in the distribution of HBsAg quantitation after HBV DNA negative conversion over the time of treatment. Results A total of 560 HBsAg quantification results were obtained from 275 patients. After 2, 3, 4, 5, and > 5 years of antiviral treatment, the proportion of patients with HBsAg< 20 IU/ml was 1. 2%, 4. 0%, 3. 7%, 4. 3%, and 9. 4%, respectively ( χ2= 11. 186, P = 0. 025) ; the proportion of patients with HBsAg < 200 IU/ml was 9. 9%, 13. 6%, 17. 1%, 23. 4%, and 30. 2%, respectively ( χ2= 21. 449, P < 0. 001) ; the proportion of patients with HBsAg < 1000 IU/ml was 40. 7%, 38. 8%, 56. 1%, 70. 2%, and 67. 9%, respectively ( χ2= 36. 341, P < 0. 001) ; the proportion of patients with HBsAg < 1500 IU/ml was 59. 3%, 64. 8%, 73. 2%, 76. 6%, and 79. 2%, respectively ( χ2= 27. 123, P < 0. 001) .Within 2 years of treatment, the HBeAg-negative patients had a significantly higher proportion of patients with HBsAg < 1000 IU/ml or <1500 IU/ml than the HBeAg-positive patients ( 45. 3%/64. 5% vs 22. 0%/38. 0%, χ2= 9. 039 and 11. 700, P = 0. 003 and 0. 001) . In the third year of treatment, the HBeAg-negative patients had a significantly higher proportion of patients with HBsAg < 1000 IU/ml or <1500 IU/ml than the HBeAg-positive patients ( 52. 6%/71. 1% vs 28. 6%/42. 9%, χ2= 5. 024 and 7. 617, P = 0. 025 and 0. 006) . Among the 162 patients who had multiple HBsAg quantitation tests, 66 had a gradual reduction in HBsAg quantitation, 47 had a gradual increase, and 49 had fluctuations in HBsAg quantitation, among whom 30 had a reduction in HBsAg quantitation from the first test to the last test and 19 had an increase in HBsAg quantitation. Conclusion After achieving virologic response to NAs, most CHB patients can reach the ideal threshold for combined or sequential interferon therapy by prolonged treatment, and some patients can even reach the ideal threshold for drug withdrawal; however, there are still some patients who may not reach the ideal endpoint even if the treatment is extended.
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