Natural YMDD Motif Mutations of HBV Polymerase in the Chronic Hepatitis B Virus Infected Patients

Korean J Hepatol > Volume 9(1); 2003 > Article

The Korean Journal of Hepatology 2003;9(1): 1-9.

Natural YMDD Motif Mutations of HBV Polymerase in the Chronic Hepatitis B Virus Infected Patients

Young Min Shin, M.D., Jeong Heo, M.D., Gwang Ha Kim, M.D., Dae Hwan Kang, M.D., Geun Am Song, M.D., Mong Cho, M.D., Ung Suk Yang, M.D., Cheol Min Kim, M.D.1, Hee Kyung Park,1 and Hyun Jung Jang2

Department of Internal Medicine, and Biochemistry1, Pusan National University College of Medicine, Busan, Korea Department of Microbiology2, Pusan National University College of Natural Science, Busan, Korea

ABSTRACT

Background/Aims
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℃. 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.(Korean J Hepatol 2003;9:1-9)

KeyWords: Hepatitis/Viral/Chronic hepatitis B, YMDD mutation