Early changes of hepatitis B virus quasispecies during lamivudine treatment and the correlation with antiviral efficacy

• Published in: Journal of hepatology 2009-05, Vol.50 (5), p.895-905
• Main Authors: Chen, Li, Zhang, Qian, Yu, De-min, Wan, Mo-bin, Zhang, Xin-xin
• Format: Article
• Language: English
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; DNA, Viral - genetics; Drug Resistance, Viral - genetics; Evolution; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Genetic heterogeneity; Hepatitis B - drug therapy; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Humans; Lamivudine; Lamivudine - pharmacology; Lamivudine - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Phylogeny; RNA-Directed DNA Polymerase - genetics; Treatment Outcome
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2008.12.018

Background/Aims To investigate dynamic changes of hepatitis B virus (HBV) quasispecies within the reverse transcriptase (RT) region during the early stage of lamivudine treatment and the correlation with antiviral efficacy. Methods Twenty-five chronic hepatitis B patients received lamivudine treatment for 48 weeks. Fourteen patients responded to lamivudine, while eleven patients were non-responders. HBV DNA was extracted from serum samples at baseline and week 4. The RT region of HBV was amplified, then cloned and sequenced. Quasispecies complexity and diversity within the RT region were analyzed at baseline and week 4, and viral nucleotide substitution rates during the first 4 weeks were calculated. Results The quasispecies complexity and diversity were not different between responders and non-responders at baseline ( p > 0.05). However, the quasispecies complexity and diversity of responders were significantly lower than those of non-responders at week 4 ( p < 0.01). Furthermore, the viral nucleotide substitution rate of responders was significantly higher than that of non-responders ( p < 0.05). Conclusions The dynamic changes of HBV quasispecies within the RT region showed distinct patterns between responders and non-responders during early stage of lamivudine treatment. The dynamic changes of quasispecies complexity and diversity during the first 4 weeks were correlated with lamivudine antiviral efficacy and antiviral resistance.