Abstract
BackgroundTo investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.MethodsFifty-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.ResultsOf the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 107 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.ConclusionT-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.
Highlights
To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy
All patients had presence of hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen (HBeAg) in the serum for at least 12 months; positive serum tests for Hepatitis B virus (HBV) hepatitis B virus DNA (DNA) with high viral load more than 105 copies/mL, documented on at least two occasions, at least 3 months apart, during the 12 months before entry; aminotransferase levels higher than 2 times the upper normal limit for at least 12 months; and liver biopsy taken within 12 months before enrollment showing chronic hepatitis [23]
The signs of the interaction term were negative for CD3+ and CD4+, and positive for CD8+ indicating that in the later period, the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities
Summary
To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy. An efficient antiviral T cell response can be restored transiently by lamivudine treatment in patients with chronic hepatitis B (CHB) concurrently with reduction of viremia This indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients [1113]. Understanding of the immune response upon HBV infection and the mechanisms responsible for T-cell failure may help identify rational therapeutic strategies to restore Tcell failure, allowing successful stimulation of antiviral T cell responses for obtaining long-lasting viral suppression and disease remission. This may offer us a possibility to better individualize HBV treatment based on the patient's immune condition and viral profile
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