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Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy.

Abstract：

BACKGROUND & AIMS:Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a unique episomal replicative intermediate responsible for persistent infection of hepatocytes. Technical constraints have hampered the direct study of cccDNA maintenance and clearance mechanisms in patients. The aim of this study was to develop a sensitive and specific assay for quantifying cccDNA in biopsy samples from chronic hepatitis B patients during different natural history phases and in patients undergoing antiviral therapy. METHODS:Intrahepatic cccDNA levels were quantified by a specific real-time PCR assay. Ninety-eight liver biopsy samples from patients in the major phases of the natural history of chronic hepatitis B and 32 pairs of samples from patients receiving adefovir dipivoxil (ADV) therapy were assessed. RESULTS:cccDNA was detected, at levels ranging over 3 orders of magnitude, in patients in different phases of the natural history of chronic hepatitis B. cccDNA levels were strongly correlated with levels of total intracellular HBV DNA and serum HBV DNA. Forty-eight weeks of ADV therapy resulted in a significant 0.8 log decrease in cccDNA copies/cell. Changes in cccDNA were correlated with a similar reduction in serum HBsAg titer but not with a decrease in the number of HBV antigen-positive cells during ADV treatment. CONCLUSIONS:cccDNA persists throughout the natural history of chronic hepatitis B, even in patients with serologic evidence of viral clearance. Long-term ADV therapy significantly decreased cccDNA levels by a primarily noncytolytic mechanism.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Werle-Lapostolle B,Bowden S,Locarnini S,Wursthorn K,Petersen J,Lau G,Trepo C,Marcellin P,Goodman Z,Delaney WE 4th,Xiong S,Brosgart CL,Chen SS,Gibbs CS,Zoulim F

doi

10.1053/j.gastro.2004.03.018

keywords:

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

1750-8

issue

7

eissn

0016-5085

issn

1528-0012

pii

S0016508504004482

journal_volume

126

pub_type

杂志文章

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