[Multiple-site analysis of HBV drug-resistant mutations in 340 patients with chronic hepatitis B].
OBJECTIVE
To analyze HBV drug-resistant mutations against nucleos(t)ide analogues at 12 reported sites in 340 patients with chronic hepatitis B.


METHODS
Serum HBV DNA was extracted and a nested PCR assay was employed for the reverse transcriptase (RT) gene amplification. Direct sequencing of PCR product was performed. The significance of detected mutations was analyzed in view of clinical data of the patients.


RESULTS
Drug-resistant mutations were detected in 68 patients taking lamivudine (LAM), 10 taking adefovir (ADV), 8 taking entecavir, and 1 taking telbivudine (LdT). M204V and M204I were the most common LAM-resistant mutations. The former usually emerged with L180M while the latter often emerged alone. N236T +/- A181 substitution was the most frequently seen ADV-resistant mutation. ETV-resistant mutations occurred on the basis of LAM-resistant mutations and T184 change was the most common form. LdT-resistance was observed as M204I. Interestingly, these drug-resistant mutations were detected in a few patients who had not been treated with nucleos(t)ide analogues.


CONCLUSIONS
Detection of HBV drug-resistant mutations at multiple sites of the viral RT gene is valuable for discovering and verifying drug resistance and thus is very helpful in planning anti-HBV therapy.
Xu
Dong-ping
DP
Viral Hepatitis Research Laboratory, Institute of Infectious Diseases, 302 Hospital of PLA, Beijing 100039, China.
Liu
Yan
Y
Cheng
Jun
J
Li
Xiao-dong
XD
Dai
Jiu-zeng
JZ
Li
Le
L
Liang
Zhao-ling
ZL
Bai
Li
L
Zhong
Yan-wei
YW
Xu
Zhi-hui
ZH
Ren
Xiao-qiang
XQ
Zhang
Ling-xia
LX
D000328:Adult; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
D004279:DNA, Viral