Lack of interferon sensitivity-determining region in the genome of hepatitis B virus genotype Ba.
OBJECTIVE
In chronic hepatitis B, both host and viral factors may predict the response to interferon (IFN) treatment. Whether IFN sensitivity-determining regions exist within the hepatitis B virus (HBV) genomic background remains largely unknown. We therefore performed full-length viral genomic comparison between HBVs obtained from IFN responders and non-responders.


METHODS
We enrolled 18 HBV genotype Ba patients who had received 24-week IFN 5 MU three times weekly and were followed monthly for 12 months post-treatment. There were 10 responders and eight non-responders. Pretreatment full-length viral nucleotide consensus sequence was obtained. In six non-responders and four responders, post-treatment viral nucleotide sequence was further compared with their corresponding pre-treatment specimens. In addition, the average number of nucleotide substitutions of the HBV quasispecies was compared between three responders and three non-responders.


RESULTS
HBV nucleotide consensus sequence was identical between responders and non-responders. We found 0-15 (mean 7.7) nucleotide substitutions in the post-treatment HBV genome in the six non-responders and 0-14 (mean 3.8) nucleotide substitutions in the four responders, respectively. Genetic complexity of HBV quasispecies was comparable between responders and non-responders.


CONCLUSIONS
Our results suggest that an IFN sensitivity-determining region might not exist within the genome of HBV genotype Ba. Host factors and virus-host interactions may be more important in determining the response to IFN treatment.
Liu
Chun-Jen
CJ
Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Chen
Pei-Jer
PJ
Lai
Ming-Yang
MY
Chen
Ting-Chih
TC
Wang
Hurng-Yi
HY
Huang
Wen-Ling
WL
Kao
Jia-Horng
JH
Chen
Ding-Shinn
DS
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D015678:Viral Structural Proteins / Q000235:genetics
D000998:Antiviral Agents; D016898:Interferon-alpha; D015678:Viral Structural Proteins