Hepatitis B virus with the rtL80V/I mutation is associated with a poor response to adefovir dipivoxil therapy.
OBJECTIVE
Lamivudine (LAM) resistance is frequently associated with various types of genomic changes in hepatitis B virus (HBV)-DNA including YMDD mutations (rtM204V/I). We intended to examine the effects of these genotypic variants on the antiviral efficacy of adefovir dipivoxil (ADV) therapy.


METHODS
A total of 97 chronic hepatitis B (CHB) patients with YMDD mutants who had been treated with ADV for >12 months were analysed. Mutations of the entire polymerase domain of HBV were determined by direct sequencing.


RESULTS
All the 97 patients had genotype C HBV associated with rtM204V/I mutations; 63 (65%) rtM204I, 27 (28%) rtM204V and seven (7%) both. The rtL80V/I and rtL180M variants were identified in 66 (68%) and 67 (69%) patients respectively. The rtM204I and rtM204V variants were strongly associated with rtL80V/I and rtL180M respectively (P<0.01). There was no difference in antiviral response at 12 months after ADV therapy between patients in relation to the type of YMDD mutation or the presence of rtL180M. However, interestingly, after ADV therapy for 12 months, patients with rtL80V/I achieved a much smaller reduction in serum HBV-DNA titre than those without it (mean, -3.43 vs. -4.43 log(10) copies/ml; P=0.018). In addition, patients with rtL80V/I had lower rates of undetectable HBV-DNA (20 vs. 26%), alanine aminotransferase normalization (70 vs. 81%) and HBeAg loss (16 vs. 26%) than those without it, although none of these differences was statistically significant.


CONCLUSIONS
These results provide evidence that rtL80V/I variants of HBV may be associated with a poor antiviral response to ADV in CHB patients with YMDD mutants.
Lee
Yoon-Seon
YS
Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Chung
Young-Hwa
YH
Kim
Jeong A
JA
Kim
Sung Eun
SE
Shin
Jung Woo
JW
Kim
Kang Mo
KM
Lim
Young-Suk
YS
Park
Neung Hwa
NH
Lee
Han Chu
HC
Lee
Yung Sang
YS
Suh
Dong Jin
DJ