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Korean J Hepatol > Volume 16(2); 2010 > Article
The Korean Journal of Hepatology 2010;16(2): 147-157.
doi: https://doi.org/10.3350/kjhep.2010.16.2.147
Genotypic resistance to entecavir in chronic hepatitis B patients
Byeong Uk Kim, M.D., Ja Chung Goo, M.D., Byeong Chul Park, M.D., Soo Ok Kim, Ph.D.1, Sun Pyo Hong, Ph.D.1, Jee In Jeong, M.D., Hee Bok Chae, M.D., Seon Mee Park, M.D., Sei Jin Youn, M.D.
Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea, 1GeneMatrix Inc., Yongin, Korea

The prevalence and clinical characteristics of entecavir (ETV) resistance is not well known. The aim of this study was to determine the frequency of genotypic resistance in nonresponders and virologic breakthrough (VBT) patients.
The medical records of 76 chronic hepatitis B patients treated for a least 6 months from October 2006 to October 2008 were reviewed retrospectively. We divided patients into two groups: nucleoside analogue (NA)-na?ve patients (n=38) and lAM experienced patients (n=38). NA-na?ve and lAM experienced patients received ETV at 0.5 and 1.0 mg/day, respectively. The virologic response and VBT were investigated in both groups. We used the multiplex restriction fragment mass polymorphism (RFMP) method to test genotypic resistance at the rtI169, rtT184, rtS202, rtM204, and rtM250 sites.
Age, gender, serum AlT, and HBV DNA level before treatment did not differ between the groups. Neither VBT nor nonresponse was observed in the NA-na?ve group, whereas VBT and nonresponse were observed in three patients each in the lamivudine (lAM)-experienced group, all six patients had YMDD mutation at study enrollment, all three patients with VBT had genotypic resistance to ETV, but the three nonresponse patients did not have genotypic resistance to ETV.
We suspect that VBT is mostly associated with genotypic resistance to ETV. However, nonresponse might be associated with the continuance or reselection of the YMDD mutant in lAM-experienced patients.
KeyWords: Entecavir, Virologic breakthrough, Non-response, Genotypic resistance
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