Differences of YMDD mutational patterns, precore/core promoter mutations, serum HBV DNA levels in lamivudine-resistant hepatitis B genotypes B and C.
The aims of this study were to investigate the viral differences among lamivudine-resistant hepatitis B virus (HBV) genotypes B and C in vivo. Fifty-three patients carrying lamivudine-resistant HBV were enrolled in this study. HBV genotypes, Levels of alanine aminotransferase (ALT), HBV DNA levels were monitored during therapy. The polymerase and precore/core promoter genes were amplified by polymerase chain reaction and their products were sequenced directly. Among 53 patients resistant HBV genotypes B and C accounted for 41.50% and 58.50%, respectively. The occurrence of reverse transcriptase rt204I mutants was lower in genotype B (36.36%) than that in genotype C (87.10%), whereas rt204V mutants was higher in genotype B (63.64%) than that in genotype C (12.90%). The occurrence of precore mutation (nt1896A) was higher in genotype B (77.27%) than that in genotype C (32.26%). Serum HBV DNA levels after emergence of lamivudine resistance were higher in genotype C (7.71 +/- 0.80 Log copies/mL) compared with genotype B (6.97 +/- 0.77 Log copies/mL). Multivariate analysis identified pretreatment HBV DNA levels, HBeAg status and HBV genotype as independent factors associated with a shorter time to lamivudine resistance(P = 0.035, P = 0.006 and P = 0.001, respectively). Multivariate analysis showed that HBV genotype (P = 0.004) and pretreatment ALT levels (P = 0.01) was independently associated with YMDD mutational patterns. The results showed that the YMDD mutational patterns, precore mutation and serum HBV DNA levels differ between lamivudine-resistant HBV genotypes B and C in vivo. It is valuable for treatment of lamivudine-resistant HBV in clinic.
Pan
X P
XP
Key Laboratory of Infectious Diseases, Ministry of Public Health, Department of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Li
L J
LJ
Du
W B
WB
Li
M W
MW
Cao
H C
HC
Sheng
J F
JF
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D020816:Amino Acid Motifs; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment
D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D000410:Alanine Transaminase