Effects of HBV gene variations on disease development and antiviral therapy for patients with chronic hepatitis B.
BACKGROUND
Viral variation may change pathogenicity, escape immunity, lead to persistence infection, and cause drug resistance against antiviral therapy. This study was undertaken to investigate the effects of HBV gene variation on the progression of disease and on the efficacy of antiviral therapy for patients with chronic hepatitis B(CHB).


METHODS
Hepatitis B virus(HBV) gene mutational sites were detected using gene chip in selected hepatitis B patients.


RESULTS
In the patients HBeAg did not show serologic conversion or HBeAg(-)/anti-HBe(+), but their HBV DNA remained positive 24 weeks after alpha-interferon therapy, which was associated with mutations of nt1896, nt1814, nt1762 and nt1764. In the patients, that HBV DNA levels decreased or were undetectable, but rebounded later after antiviral therapy by lamivudine was associated with mutations of aa528 and (or) aa552 (i.e. YMDD mutation),which resulted in lamivudine-resistance. YMDD mutation was prone to occur 52 weeks after lamivudine therapy in some chronic hepatitis B patients (26.4%). Nt1896 mutation was common in most chronic hepatitis B patients (68.5%). Chronic severe hepatitis, cirrhosis, and primary liver carcinoma were related to the mutations of nt1896, nt1762 and nt1764.


CONCLUSIONS
HBV gene mutations could aggravate patient's condition and affect the efficacy of antiviral therapy. The regular detection of HBV gene mutation is helpful for identification of disease prognosis and adjustment of therapeutic strategy.
Chen
Jin-Yu
JY
Shenzhen Eastlake Hospital, Shenzhen 518020, China.
Wang
Lu-Wen
LW
Sun
Xiao-Mei
XM
Gong
Zuo-Jiong
ZJ
D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index
D000998:Antiviral Agents; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine