[Natural YMDD motif mutations of HBV polymerase in the chronic hepatitis B virus infected patients].
OBJECTIVE
Lamivudine, a nucleoside analogue has been widely used as an effective antiviral agent for the treatment of patients with chronic hepatitis B infection. However, the YMDD motif mutation of HBV polymerase resistant to lamivudine very frequently occurs after long-term use of lamivudine. It is well known that the mutation is selected by the lamivudine. We hypothesized that a few mutant strains of YMDD motif are present as quasispacies before the lamivudine treatment, are selected by the treatment, and breakthrough during treatment. We investigated the prevalence of the YMDD motif mutants in patients with chronic hepatitis B infection who had not been treated by antiviral agents before.


METHODS
The study included the serums of 40 patients with chronic heptitis B infection, which stored at -70 degrees C. Thirty-four patients had chronic hepatitis and 6 patients had cirrhosis. Thirty-one patients were diagnosed by liver biopsy. The average age and range were 29 years and 13-57 years respectively. None had taken any antiviral agents before. To detect YMDD mutants, YVDD (M552V), and YIDD (M552I), we used direct sequencing and the restriction fragment length polymorphism (RFLP) method.


RESULTS
The YMDD mutant was detected by RFLP method in 7.5% (3/40) of the patients with chronic hepatitis B infection, in two patients with chronic hepatitis and one with cirrhosis. All were YMDD+ YIDD mutants.


CONCLUSIONS
The YMDD motif mutation occurs spontaneously without antiviral therapy in patients with chronic hepatitis B infection.
Shin
Young Min
YM
Department of Internal Medicine, Pusan National University College of Medicine, Busan, Korea.
Heo
Jeong
J
Kim
Gwang Ha
GH
Kang
Dae Hwan
DH
Song
Geun Am
GA
Cho
Mong
M
Yang
Ung Suk
US
Kim
Cheol Min
CM
Park
Hee Kyung
HK
Jang
Hyun Jung
HJ
D000293:Adolescent; D000328:Adult; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015684:Gene Products, pol / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length
D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus