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Differences of YMDD mutational patterns, precore/core promoter mutations, serum HBV DNA levels in lamivudine‐resistant hepatitis B genotypes B and C
Author(s) -
Pan X. P.,
Li L. J.,
Du W. B.,
Li M. W.,
Cao H. C.,
Sheng J. F.
Publication year - 2007
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2007.00869.x
Subject(s) - genotype , lamivudine , virology , hepatitis b virus , hbeag , biology , polymerase chain reaction , orthohepadnavirus , hepatitis b , hepadnaviridae , gene , virus , hbsag , genetics
Summary. 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.