Hepatitis B virus genotype B has an earlier emergence of lamivudine resistance than genotype C.
BACKGROUND
Hepatitis B virus (HBV) genotype B and C seem not to affect the therapeutic response to lamivudine (3TC). Whether a given genotype has an earlier emergence of 3TC resistance remains unclear. We thus conducted this study to elucidate the association of HBV genotype with the emergence of 3TC-resistant strains in Taiwanese patients.


METHODS
Forty chronic hepatitis B patients who developed resistance after 3TC therapy were retrospectively enrolled. HBV genotype, serum alanine aminotransferase (ALT) and HBV DNA levels were determined at baseline. The presence of 3TC-resistant mutations was confirmed by direct sequencing whenever biochemical breakthrough developed.


RESULTS
The distribution of HBV genotype B and C in 40 patients receiving 3TC therapy were 60% and 40%, respectively. The mean interval to detect 3TC-resistant strain was 19.6 +/-1.7 months. By using multivariate analysis, HBV genotype B and higher pre-treatment HBV DNA level were independently associated with earlier detection of 3TC-resistant strains. In addition, genotype B was significantly associated with development of 3TC resistance within the first 12 months of 3TC therapy compared with genotype C (odds ratio 8.27; P=0.004).


CONCLUSIONS
Compared with HBV genotype C, genotype B appears to have an earlier biochemical resistance to 3TC than genotype C. Therefore, more frequent monitoring of viral load or genotypical resistance might be needed for patients with HBV genotype B infection receiving 3TC therapy, especially during the first year.
Hsieh
Ting-Hui
TH
Division of Hepatology, Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA.
Tseng
Tai-Chung
TC
Liu
Chun-Jen
CJ
Lai
Ming-Yang
MY
Chen
Pei-Jer
PJ
Hsieh
Hsin-Ling
HL
Chen
Ding-Shinn
DS
Kao
Jia-Horng
JH
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification* / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D015999:Multivariate Analysis; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013624:Taiwan; D013997:Time Factors
D019380:Anti-HIV Agents; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine