A prospective study characterizing full-length hepatitis B virus genomes during acute exacerbation.
OBJECTIVE
Hepatitis B virus (HBV) evolves rapidly in patients with chronic hepatitis B, and HBV variation may trigger acute exacerbation. To study this relationship, we investigated full-length viral sequences before, during, and after exacerbation.


METHODS
We prospectively studied 14 patients with exacerbation of hepatitis B, either spontaneously (n = 4) or after receiving various medical interventions (n = 10), and measured their serum alanine aminotransferase (ALT) and HBV DNA levels monthly. Full-length HBV genomes at baseline, at the peak of serum viral load, at ALT peak, and after ALT peak were obtained by polymerase chain reaction, sequenced, and compared. Replication activities of serial HBV variants were assayed by in vitro transfection.


RESULTS
Serum viral load was increased in all exacerbations. Viral peak preceded ALT peak in 13 (93%) of the 14 patients. At virologic peak, 12 patients (86%) harbored viral genome identical to the corresponding baseline genome. At and after ALT peak, 9 (64%) and 7 (50%) of the viral genomes remained identical to baseline, respectively. Mean nucleotide change per genome was 0.2 at virologic peak but increased to 4.4 and 8.1 at and after ALT peak, respectively. The replication potential of the viral variant that emerged during or after exacerbation was equivalent to that at baseline.


CONCLUSIONS
Most exacerbations were preceded by an upsurge of serum HBV identical to the preexisting HBV strain. After exacerbation, about half of the patients were repopulated by a different viral variant, which was likely a result of immune selection.
Liu
Chun-Jen
CJ
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, 1 Chang-Te Street, Taipei 100, Taiwan. peijer@ha.mc.ntu.edu.tw
Chen
Pei-Jer
PJ
Lai
Ming-Yang
MY
Kao
Jia-Horng
JH
Chang
Ching-Fung
CF
Wu
Hui-Lin
HL
Shau
Wen-Yi
WY
Chen
Ding-Shinn
DS
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019943:Amino Acid Substitution; D001483:Base Sequence / Q000235:genetics; D002353:Carrier State; D005260:Female; D014644:Genetic Variation / Q000502:physiology; D016679:Genome, Viral; D006509:Hepatitis B / Q000097:blood / Q000503:physiopathology* / Q000821:virology; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019562:Viral Load; D014779:Virus Replication
D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase