A large population study of spontaneous HBeAg seroconversion and acute exacerbation of chronic hepatitis B infection: implications for antiviral therapy.
OBJECTIVE
Clinical data on spontaneous hepatitis B e antigen (HBeAg) seroconversion and acute exacerbation of chronic hepatitis B (CHB) virus infection from large population studies are lacking. In the present study we examined the clinical features and significance of HBeAg seroconversion and acute exacerbation in 3063 Chinese CHB patients.


METHODS
Clinical assessment, liver biochemistry, hepatitis B virus (HBV) serology and HBV DNA, time of HBeAg seroconversion, and acute exacerbation were monitored.


RESULTS
Median age at HBeAg seroconversion was 34.5 years. The cumulative HBeAg seroconversion rate significantly increased with alanine aminotransferase (ALT) levels on presentation (p<0.0001). For patients with ALT levels more than twice the upper limit of normal (ULN) on presentation, the HBeAg seroconversion rate at the fifth year of follow up was 72.4%. After HBeAg seroconversion, 65.2% (73/110) of patients had undetectable HBV DNA levels by the Digene Hybrid Capture assay. Of these, 78.1% still had HBV DNA levels detectable by the Amplicor HBV Monitor Test. We found that 37.5% antibody to HBeAg (anti-HBe) positive patients had undetectable HBV DNA levels by the Digene Hybrid Capture assay before acute exacerbation. Acute exacerbations of longer duration, with higher peak ALT, bilirubin, and alpha fetoprotein levels were associated with an increased HBeAg seroconversion rate (p<0.0001-0.045). Acute exacerbation with peak ALT levels more than five times the ULN carried a 46.4% chance of HBeAg seroconversion within three months. HBeAg seroreversion and mortality occurred in 2.7% and 0.7% of acute exacerbations, respectively.


CONCLUSIONS
In the present study we have provided information on HBeAg seroconversion and acute exacerbation, which are important in decision making for CHB treatment and in designing clinical trials.
Yuen
M-F
MF
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Yuan
H-J
HJ
Hui
C-K
CK
Wong
D K-H
DK
Wong
W-M
WM
Chan
A O-O
AO
Wong
B C-Y
BC
Lai
C-L
CL
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006510:Hepatitis B Antibodies / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged
D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase