Intrahepatic HBV DNA as a predictor of antivirus treatment efficacy in HBeAg-positive chronic hepatitis B patients

ArticleinWorld Journal of Gastroenterology 13(20):2878-82 · June 2007with12 Reads
Source: PubMed
Abstract
To evaluate the effect of antiviral agents on intrahepatic HBV DNA in HBeAg-positive chronic hepatitis B patients. Seventy-one patients received treatment with lamivudine, interferon alpha (IFN-alpha 2b) or sequential therapy with lamivudine-IFN-alpha 2b for 48 wk. All subjects were followed up for 24 wk. Serum and intrahepatic HBV DNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP. At the end of treatment, the intrahepatic HBV DNA level in 71 patients decreased from a mean of (6.1 +/- 1.0) log10 to (4.9 +/- 1.4) log10. Further, a larger decrease was seen in the intrahepatic HBV DNA level in patients with HBeAg seroconversion. Intrahepatic HBV DNA level (before and after treatment) was not significantly affected by the patients' HBV genotype, or by the probability of virological flare after treatment. Intrahepatic HBV DNA can be effectively lowered by antiviral agents and is a significant marker for monitoring antivirus treatment. Low intrahepatic HBV DNA level may achieve better efficacy of antivirus treatment.
  • [Show abstract] [Hide abstract] ABSTRACT: AIM: To investigate the safety of β-L-D4A on DNA polymerase α. METHODS: Ion exchange chromatography was used to separate DNA polymerase α from crude extract of human Hela cells. Detailed kinetic parameters were determined for β-L-D4A against DNA polymerase α. RESULTS: DNA polymerase α was purified with 4% yield and 31 000 units/mg specific activity. The Michaelis constant (Km = 3.22 μmol/L), 50% inhibition concentration (IC50 = 178.49 μmol/L) and inhibition constant (Ki = 126 μmol/L) of β-L-D4A were determined by kinetic analysis. CONCLUSION: β-L-D4A is a more safe nucleoside for hepatitis B virus (HBV) infection with a lower host toxicity.
    Article · Dec 2007
  • [Show abstract] [Hide abstract] ABSTRACT: To investigate the safety of beta-L-D4A on DNA polymerase alpha. Ion exchange chromatography was used to separate DNA polymerase alpha from crude extract of human Hela cells. Detailed kinetic parameters were determined for beta-L-D4A against DNA polymerase alpha. DNA polymerase alpha was purified with 4% yield and 31000 units/mg specific activity. The Michaelis constant (Km = 3.22 micromol/L), 50% inhibition concentration (IC50 = 178.49 micromol/L) and inhibition constant (Ki = 126 micromol/L) of beta-L-D4A were determined by kinetic analysis. beta-L-D4A is a more safe nucleoside for hepatitis B virus infection with a lower host toxicity.
    Article · Jan 2008
  • [Show abstract] [Hide abstract] ABSTRACT: AIM: To purify and characterize the DNA polymerase δ and investigate the side effects of β-L-D4A (a novel nucleoside analog) on human DNA polymerases β and δ. METHODS: Human DNA polymerase δ was separated from crude extract of human Hela cells by ion exchange chromatography. Detailed kinetic parameters were determined for β-L-D4A against DNA polymerases β and δ. RESULTS: Human DNA polymerase δ was purified and characterized with a yield of 15% and a specific activity of 1911 Ukat/mg. When β-L-D4A was used as an inhibitor, the kinetic parameters of human DNA polymerases β and δ were Km = 1.86 μmol/L and 2.45 μmol/L, IC50 = 25.21 μmol/L and 150.1 μmol/L, Ki = 24.03 μmol/L and 132.7 μmol/L, respectively, suggesting that the inhibitory effect of β-L-D4A on human DNA polymerases β and δ was less than that of lamivudine. CONCLUSION: β-L-D4A is a competitive inhibitor of DNA polymerases β and δ. Its toxic side effects on DNA polymerases β and δ are less than lamivudine. It can be expected to become a high efficient and low toxic anti-HBV agent.
    Article · Mar 2008
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