title: A prospective study characterizing full-length hepatitis B virus genomes during acute exacerbation.
abstract: 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.
authors.affiliation: 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
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lai
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.forename: Ching-Fung
authors.initials: CF
authors.lastname: Chang
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Wu
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Shau
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
mesh_terms: 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
chemical_list: D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase