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Deep sequencing analysis of HBV genotype shift and correlation with antiviral efficiency during adefovir dipivoxil therapy.

Wang Y, Shan X, Liang Z, Shan Y, Huang W, Zhang D, Zen A, Zhou X, Zhao Y, Gong X, Xu G, Zhang X, Chen J, Huang A - PLoS ONE (2015)

Bottom Line: Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy.Moreover, patients with dominant genotype C may have a better therapeutic effect.The genotype and genotype shift might be associated with antiviral efficiency.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China; Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.

ABSTRACT

Background: Viral genotype shift in chronic hepatitis B (CHB) patients during antiviral therapy has been reported, but the underlying mechanism remains elusive.

Methods: 38 CHB patients treated with ADV for one year were selected for studying genotype shift by both deep sequencing and Sanger sequencing method.

Results: Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy. In contrast, all 38 patients showed mixed genotype before ADV treatment by deep sequencing. 95.5% mixed genotype rate was also obtained from additional 200 treatment-naïve CHB patients. Of the 13 patients with genotype shift, the fraction of the minor genotype in 5 patients (38%) increased gradually during the course of ADV treatment. Furthermore, responses to ADV and HBeAg seroconversion were associated with the high rate of genotype shift, suggesting drug and immune pressure may be key factors to induce genotype shift. Interestingly, patients with genotype C had a significantly higher rate of genotype shift than genotype B. In genotype shift group, ADV treatment induced a marked enhancement of genotype B ratio accompanied by a reduction of genotype C ratio, suggesting genotype C may be more sensitive to ADV than genotype B. Moreover, patients with dominant genotype C may have a better therapeutic effect. Finally, genotype shifts was correlated with clinical improvement in terms of ALT.

Conclusions: Our findings provided a rational explanation for genotype shift among ADV-treated CHB patients. The genotype and genotype shift might be associated with antiviral efficiency.

No MeSH data available.


Related in: MedlinePlus

The correlation between genotype shift and clinical therapeutic parameters.(A) Left, change of ALT level after ADV treatment. Right, the decrease in ALT levels of the genotype shift (GS) group was significantly higher than group without genotype shift (NS) (p <0.05). (B) Left, comparison of HBeAg seroconversion after ADV treatment between the GS group and the NS group (p >0.05). Right, comparison of HBeAg seroclearance after ADV treatment between the GS group and the NS group(p >0.05). (C)Left, change of HBV DNA load after ADV treatment. Right, the reduction of HBV DNA load in GS group and NS group did not different significantly (p >0.05).
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pone.0131337.g004: The correlation between genotype shift and clinical therapeutic parameters.(A) Left, change of ALT level after ADV treatment. Right, the decrease in ALT levels of the genotype shift (GS) group was significantly higher than group without genotype shift (NS) (p <0.05). (B) Left, comparison of HBeAg seroconversion after ADV treatment between the GS group and the NS group (p >0.05). Right, comparison of HBeAg seroclearance after ADV treatment between the GS group and the NS group(p >0.05). (C)Left, change of HBV DNA load after ADV treatment. Right, the reduction of HBV DNA load in GS group and NS group did not different significantly (p >0.05).

Mentions: Three clinical parameters, including ALT, HBV DNA load and HBeAg level were used to assess clinical therapeutic effect. After ADV treatment, patients with genotype shift showed a more significant reduction of ALT (p = 0.0173) compared with patients without genotype shift (Fig 4A). However, the rate of HBeAg seroconversion or seroclearance and change of HBV DNA load in patients with and without genotype shift did not differ significantly (p>0.05) (Fig 4B and 4C). Together, these data suggested that genotype shift was correlated with clinical improvement in terms of ALT.


Deep sequencing analysis of HBV genotype shift and correlation with antiviral efficiency during adefovir dipivoxil therapy.

Wang Y, Shan X, Liang Z, Shan Y, Huang W, Zhang D, Zen A, Zhou X, Zhao Y, Gong X, Xu G, Zhang X, Chen J, Huang A - PLoS ONE (2015)

The correlation between genotype shift and clinical therapeutic parameters.(A) Left, change of ALT level after ADV treatment. Right, the decrease in ALT levels of the genotype shift (GS) group was significantly higher than group without genotype shift (NS) (p <0.05). (B) Left, comparison of HBeAg seroconversion after ADV treatment between the GS group and the NS group (p >0.05). Right, comparison of HBeAg seroclearance after ADV treatment between the GS group and the NS group(p >0.05). (C)Left, change of HBV DNA load after ADV treatment. Right, the reduction of HBV DNA load in GS group and NS group did not different significantly (p >0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482366&req=5

pone.0131337.g004: The correlation between genotype shift and clinical therapeutic parameters.(A) Left, change of ALT level after ADV treatment. Right, the decrease in ALT levels of the genotype shift (GS) group was significantly higher than group without genotype shift (NS) (p <0.05). (B) Left, comparison of HBeAg seroconversion after ADV treatment between the GS group and the NS group (p >0.05). Right, comparison of HBeAg seroclearance after ADV treatment between the GS group and the NS group(p >0.05). (C)Left, change of HBV DNA load after ADV treatment. Right, the reduction of HBV DNA load in GS group and NS group did not different significantly (p >0.05).
Mentions: Three clinical parameters, including ALT, HBV DNA load and HBeAg level were used to assess clinical therapeutic effect. After ADV treatment, patients with genotype shift showed a more significant reduction of ALT (p = 0.0173) compared with patients without genotype shift (Fig 4A). However, the rate of HBeAg seroconversion or seroclearance and change of HBV DNA load in patients with and without genotype shift did not differ significantly (p>0.05) (Fig 4B and 4C). Together, these data suggested that genotype shift was correlated with clinical improvement in terms of ALT.

Bottom Line: Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy.Moreover, patients with dominant genotype C may have a better therapeutic effect.The genotype and genotype shift might be associated with antiviral efficiency.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China; Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.

ABSTRACT

Background: Viral genotype shift in chronic hepatitis B (CHB) patients during antiviral therapy has been reported, but the underlying mechanism remains elusive.

Methods: 38 CHB patients treated with ADV for one year were selected for studying genotype shift by both deep sequencing and Sanger sequencing method.

Results: Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy. In contrast, all 38 patients showed mixed genotype before ADV treatment by deep sequencing. 95.5% mixed genotype rate was also obtained from additional 200 treatment-naïve CHB patients. Of the 13 patients with genotype shift, the fraction of the minor genotype in 5 patients (38%) increased gradually during the course of ADV treatment. Furthermore, responses to ADV and HBeAg seroconversion were associated with the high rate of genotype shift, suggesting drug and immune pressure may be key factors to induce genotype shift. Interestingly, patients with genotype C had a significantly higher rate of genotype shift than genotype B. In genotype shift group, ADV treatment induced a marked enhancement of genotype B ratio accompanied by a reduction of genotype C ratio, suggesting genotype C may be more sensitive to ADV than genotype B. Moreover, patients with dominant genotype C may have a better therapeutic effect. Finally, genotype shifts was correlated with clinical improvement in terms of ALT.

Conclusions: Our findings provided a rational explanation for genotype shift among ADV-treated CHB patients. The genotype and genotype shift might be associated with antiviral efficiency.

No MeSH data available.


Related in: MedlinePlus