Differences of YMDD mutational patterns, precore/core promoter mutations, serum HBV DNA levels in lamivudine-resistant hepatitis B genotypes B and C

Authors

  • X. P. Pan,

    1. 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
    Search for more papers by this author
  • L. J. Li,

    1. 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
    Search for more papers by this author
  • W. B. Du,

    1. 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
    Search for more papers by this author
  • M. W. Li,

    1. 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
    Search for more papers by this author
  • H. C. Cao,

    1. 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
    Search for more papers by this author
  • J. F. Sheng

    1. 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
    Search for more papers by this author

Lan Juan Li, Key Laboratory of Infectious Diseases, Ministry of Public Health, Department of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. E-mail: ljli@zjwst.gov.cn, xiaopingpan@sohu.com

Abstract

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.

Ancillary