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Association of intrahepatic cccDNA reduction with the improvement of liver histology in chronic hepatitis B patients receiving oral antiviral agents.
- Source :
-
Journal of medical virology [J Med Virol] 2011 Apr; Vol. 83 (4), pp. 602-7. - Publication Year :
- 2011
-
Abstract
- Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is difficult to eradicate using current antiviral therapy. This study compares cccDNA reduction with relation to liver histology in nucleoside/nucleotide-naïve chronic hepatitis B patients receiving oral antiviral monotherapy (n=35), including entecavir (ETV, n=13), adefovir dipivoxil (ADV, n=22) or placebo (n=14). Serum HBV DNA, intrahepatic total HBV DNA and cccDNA are quantified. Histological hepatic examination is performed at baseline and at 48 weeks of treatment. Treatment with ETV or ADV shows significant median reduction in serum HBV DNA (-6.21 and -4.27 log(10) copies/mL) and intrahepatic total HBV DNA (-1.69 and -1.23 log(10) copies/cell). Intrahepatic cccDNA levels are reduced slightly in the ETV and the ADV groups, but do not differ statistically from the placebo group (-0.17 vs. -0.01 vs. 0.02 copies/cell). Only the level of intrahepatic cccDNA correlates with Knodell necroinflammation activity (r=0.527, P<0.001) and Ishak fibrosis severity (r=0.348, P=0.015) before treatment. Multivariate logistic regression analysis indicates that treatment-induced cccDNA reduction is associated with improved necroinflammation (P=0.041) and fibrosis (P=0.026). In conclusion, baseline intrahepatic cccDNA loads correlate with histologic activity. Although one-year ETV or ADV treatment is insufficient for cccDNA eradication, oral antiviral therapies may improve liver histology, probably by suppressing intrahepatic cccDNA.<br /> (Copyright © 2011 Wiley-Liss, Inc.)
- Subjects :
- Adenine administration & dosage
Adenine analogs & derivatives
Adult
Blood virology
Female
Guanine administration & dosage
Guanine analogs & derivatives
Hepatitis B, Chronic pathology
Histocytochemistry
Humans
Liver pathology
Male
Middle Aged
Organophosphonates administration & dosage
Placebos administration & dosage
Treatment Outcome
Viral Load
Antiviral Agents administration & dosage
DNA, Circular genetics
DNA, Viral genetics
Hepatitis B virus genetics
Hepatitis B, Chronic drug therapy
Hepatitis B, Chronic virology
Liver virology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9071
- Volume :
- 83
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 21328373
- Full Text :
- https://doi.org/10.1002/jmv.22014