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Quantitation of Hepatitis B Virus Covalently Closed Circular DNA in Chronic Hepatitis B Patients

Quantitation of Hepatitis B Virus Covalently Closed Circular DNA in Chronic Hepatitis B Patients


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About the Book

This dissertation, "Quantitation of Hepatitis B Virus Covalently Closed Circular DNA in Chronic Hepatitis B Patients" by Ka-ho, Danny, Wong, 王嘉豪, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract Wong DKH Abstract of thesis entitled "Quantitation of hepatitis B virus covalently closed circular DNA in chronic hepatitis B patients" Submitted by Danny Ka-Ho Wong for the degree of Doctor of Philosophy at the University of Hong Kong in July 2004 Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays an important role in the persistence of chronic hepatitis B infection. This thesis aimed to (1) develop and validate a specific assay for cccDNA quantitation; (2) study the dynamics of cccDNA in the different phases of chronic hepatitis B infection and in hepatocellular carcinoma (HCC); and (3) investigate the effect of nucleoside analogues on cccDNA. The Invader technology was implemented for the quantitation of total HBV DNA and cccDNA and validated in terms of specificity, accuracy and precision. Abstract Wong DKH HBeAg-positive patients (n = 16) had higher median intrahepatic total HBV DNA and cccDNA levels than anti-HBe-positive patients (n = 36) (94.0 vs. 12.8 copies/cell, respectively; P Low levels of intrahepatic cccDNA were detectable in 37.5% (6/16) of patients with HBsAg seroclearance, and the proportion of intrahepatic HBV DNA in the form of cccDNA was high (71.2% - 100%). HCC still occurred in 5.4% of these patients. In 21 patients with HBV-related HCC, tumor tissues had significantly higher median cccDNA levels (0.35 vs. 0.16 copies/cell, respectively; P = 0.030) and higher proportion of intrahepatic HBV DNA in the form of cccDNA (100% vs. 84%, respectively; P = 0.004) compared to non-tumor tissues. Liver biopsies at baseline and 48 weeks of treatment were obtained from 34 patients on an entecavir vs. lamivudine trial. After 48 weeks of treatment, there was a 1.9 and 1.0 logarithmic reduction in the intrahepatic total HBV DNA and cccDNA levels respectively. However the proportion of intrahepatic HBV DNA in the form of cccDNA increased from 5.5% to 81.3% (P Abstract Wong DKH cccDNA was detectable in serum of chronic hepatitis B patients. Serum and intrahepatic cccDNA levels correlated positively (r = 0.481, P = 0.002). Serum samples from 82 patients receiving lamivudine for one year were studied. Serum cccDNA was significantly reduced by a median of 2.12 log copies/mL at one year. 10 At week 52, the reduction of serum cccDNA in the 15 patients (18.3%) with rtM204V/I mutations was significantly less compared to the patients without mutations (0.80 vs. 2.35 log copies/mL, respectively; P In conclusion, cccDNA persisted into the late stages of chronic hepatitis B disease, where the majority of intrahepatic HBV DNA was in the form of cccDNA. cccDNA might also play a role in hepatocarcinogenesis. While cccDNA levels decreased during nucleoside analogue therapy, the proportion of intrahepatic HBV DNA in the form of cccDNA increased significantly. Antiviral therapy may need to be given for a longer period in order to suppress/eradicate cccDNA. In the future, it may be possible to monit


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Product Details
  • ISBN-13: 9781374726321
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 254
  • Weight: 880 gr
  • ISBN-10: 137472632X
  • Publisher Date: 27 Jan 2017
  • Binding: Hardback
  • Language: English
  • Spine Width: 16 mm
  • Width: 216 mm


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Quantitation of Hepatitis B Virus Covalently Closed Circular DNA in Chronic Hepatitis B Patients
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