Korean J Hepatol.  2010 Jun;16(2):147-157. 10.3350/kjhep.2010.16.2.147.

Genotypic resistance to entecavir in chronic hepatitis B patients

• Kim BU
• Goo JC
• Park BC
• Kim SO
• Hong SP
• Jeong JI
• Chae HB
• Park SM
• Youn SJ

• KMID: 1792593
• DOI: http://doi.org/10.3350/kjhep.2010.16.2.147

Abstract

BACKGROUND/AIMS
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.
METHODS
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)-naive patients (n=38) and LAM experienced patients (n=38). NA-naive 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.
RESULTS
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-naive 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.
CONCLUSIONS
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.

Keyword

Entecavir; Virologic breakthrough; Non-response; Genotypic resistance

MeSH Terms

Adult
Antiviral Agents/*therapeutic use
Drug Resistance, Viral/genetics
Female
Genotype
Guanine/*analogs & derivatives/therapeutic use
Hepatitis B/genetics
Hepatitis B, Chronic/*drug therapy/virology
Humans
Lamivudine/therapeutic use
Male
Middle Aged
Mutation
Polymorphism, Restriction Fragment Length
RNA-Directed DNA Polymerase/genetics
Retrospective Studies