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Impact of viral replication inhibition by entecavir on peripheral T lymphocyte subpopulations in chronic hepatitis B patients.

You J, Sriplung H, Geater A, Chongsuvivatwong V, Zhuang L, Li YL, Lei H, Liu J, Chen HY, Tang BZ, Huang JH - BMC Infect. Dis. (2008)

Bottom Line: Using pre-therapy level as the reference, a significant decrease in CD8+ T cells and increase in CD4+ T cells were found from week 12.Both parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks.After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by 0.51.

View Article: PubMed Central - HTML - PubMed

Affiliation: Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Thailand. jingyoukm@126.com

ABSTRACT

Background: To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.

Methods: Fifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1-12, 13-24 and 24-48, respectively. Multilevel modelling was used to analyse the relationship between these variables.

Results: Of the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 10(7) copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8+ T cells and increase in CD4+ T cells were found from week 12. Both parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4-48 week). After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by 0.51.

Conclusion: T-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.

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Related in: MedlinePlus

Dynamic fluctuations of serum levels of viral load and ALT and peripheral T-lymphocyte subpopulations during entecavir treatment over time. Note: The thick lines are the mean values.
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Figure 1: Dynamic fluctuations of serum levels of viral load and ALT and peripheral T-lymphocyte subpopulations during entecavir treatment over time. Note: The thick lines are the mean values.

Mentions: HBV DNA levels declined sharply by around 3 log10 copies/mL during the first two weeks, with a highly significant reduction (p < 0.0001) at week 2 and thereafter, as compared to those at baseline (Table 2 and Fig. 1); 31%, 51% and 78% of the patients had undetectable serum HBV DNA levels at week 12, 24 and 48 respectively. The magnitude of HBV DNA reduction was up to 63% of the baseline level at the end of the study. The mean reduction in the serum HBV DNA levels at week 48 was 5 log10 copies per milliliter. At the end of week 24 and 48, the proportion of subjects losing HBeAg and converting to HBeAb positive were 6/55 (11%) and 9/55 (16%), and 4/55 (7.3%) and 9/55 (14.5%), respectively. Highly significantly decreasing serum aminotransferase and total bilirubin (ALT, AST and TBil) (p < 0.0001) occurred during the first 2 weeks of the study (Table 2 and Fig. 1). At week 48, ALT levels were normalized in 84% of the patients. At the end of 24th and 48th weeks, complete response (ALT normalization and HBV DNA and HBeAg loss) was observed in 11% and 15%, respectively. There was no evidence of drug resistance or adverse effect in CHB patients treated for up to 48 weeks.


Impact of viral replication inhibition by entecavir on peripheral T lymphocyte subpopulations in chronic hepatitis B patients.

You J, Sriplung H, Geater A, Chongsuvivatwong V, Zhuang L, Li YL, Lei H, Liu J, Chen HY, Tang BZ, Huang JH - BMC Infect. Dis. (2008)

Dynamic fluctuations of serum levels of viral load and ALT and peripheral T-lymphocyte subpopulations during entecavir treatment over time. Note: The thick lines are the mean values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570678&req=5

Figure 1: Dynamic fluctuations of serum levels of viral load and ALT and peripheral T-lymphocyte subpopulations during entecavir treatment over time. Note: The thick lines are the mean values.
Mentions: HBV DNA levels declined sharply by around 3 log10 copies/mL during the first two weeks, with a highly significant reduction (p < 0.0001) at week 2 and thereafter, as compared to those at baseline (Table 2 and Fig. 1); 31%, 51% and 78% of the patients had undetectable serum HBV DNA levels at week 12, 24 and 48 respectively. The magnitude of HBV DNA reduction was up to 63% of the baseline level at the end of the study. The mean reduction in the serum HBV DNA levels at week 48 was 5 log10 copies per milliliter. At the end of week 24 and 48, the proportion of subjects losing HBeAg and converting to HBeAb positive were 6/55 (11%) and 9/55 (16%), and 4/55 (7.3%) and 9/55 (14.5%), respectively. Highly significantly decreasing serum aminotransferase and total bilirubin (ALT, AST and TBil) (p < 0.0001) occurred during the first 2 weeks of the study (Table 2 and Fig. 1). At week 48, ALT levels were normalized in 84% of the patients. At the end of 24th and 48th weeks, complete response (ALT normalization and HBV DNA and HBeAg loss) was observed in 11% and 15%, respectively. There was no evidence of drug resistance or adverse effect in CHB patients treated for up to 48 weeks.

Bottom Line: Using pre-therapy level as the reference, a significant decrease in CD8+ T cells and increase in CD4+ T cells were found from week 12.Both parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks.After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by 0.51.

View Article: PubMed Central - HTML - PubMed

Affiliation: Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Thailand. jingyoukm@126.com

ABSTRACT

Background: To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.

Methods: Fifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1-12, 13-24 and 24-48, respectively. Multilevel modelling was used to analyse the relationship between these variables.

Results: Of the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 10(7) copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8+ T cells and increase in CD4+ T cells were found from week 12. Both parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4-48 week). After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by 0.51.

Conclusion: T-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.

Show MeSH
Related in: MedlinePlus