Clearance of hepatitis B surface antigen during long-term nucleot(s)ide analog treatment in chronic hepatitis B: results from a nine-year longitudinal study.
BACKGROUND
Clearance of hepatitis B surface antigen (HBsAg) is considered the ultimate goal in chronic hepatitis B treatment. One treatment option is long-term nucleot(s)ide analog (NA) therapy. We followed a group of long-term NA therapy patients to evaluate the efficacy of this treatment in promoting clearance and longitudinal declines of HBsAg.


METHODS
The study included 791 NA therapy patients who received lamivudine as their first drug. At the baseline, 442 patients were hepatitis B e antigen (HBeAg)+ and 349 were HBeAg-. All analyses were performed after separating the HBeAg+ and HBeAg- cohorts. Cox proportional hazards models were used to determine which factors were associated with HBsAg clearance.


RESULTS
HBsAg clearance was observed in 18 (4.1 %) of the HBeAg+ patients and 20 (5.7 %) of the HBeAg- patients at baseline, giving seroclearance rates of 6.4 and 6.9 %, respectively, over the nine-year study period. HBsAg clearance was influenced by several independent factors that varied according to HBeAg cohort. For HBeAg+ patients, these included previous interferon therapy, infection with hepatitis B virus (HBV) genotype A, a ≥0.5 log IU/mL decline in HBsAg level within six months, and clearance of HBeAg at six months. For HBeAg- patients, these included infection with HBV genotype A, decline in HBsAg at six months, and a baseline HBsAg level of <730 IU/mL.


CONCLUSIONS
This study suggests that both direct antiviral potential and host immune response are needed to achieve HBsAg clearance by NA therapy. Viral genotype strongly influenced HBsAg clearance during NA therapy.
Department of Hepatology, Toranomon Hospital, 2-2 Toranomon, Minato-ku, Tokyo, Japan. hosa-p@toranomon.gr.jp
Tetsuya
T
Hosaka
Fumitaka
F
Suzuki
Masahiro
M
Kobayashi
Yuya
Y
Seko
Yusuke
Y
Kawamura
Hitomi
H
Sezaki
Norio
N
Akuta
Yoshiyuki
Y
Suzuki
Satoshi
S
Saitoh
Yasuji
Y
Arase
Kenji
K
Ikeda
Mariko
M
Kobayashi
Hiromitsu
H
Kumada
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000008:administration & dosage / Q000627:therapeutic use; D009711:Nucleotides / Q000008:administration & dosage / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D009711:Nucleotides; D019259:Lamivudine