Quantitation of covalently closed circular hepatitis B virus DNA in chronic hepatitis B patients

✍ Scribed by Danny Ka-Ho Wong; Man-Fung Yuen; HeJun Yuan; Simon Siu-Man Sum; Chee-Kin Hui; Jeff Hall; Ching-Lung Lai

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 236 KB
• Volume: 40
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.20353

✦ Synopsis

This study examined a signal amplification assay, the Invader assay, for the quantitation of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in liver biopsies and sera. DNA was extracted from liver biopsy and serum samples were collected from 16 hepatitis B e antigen (HBeAg)-positive and 36 antibody-to-HBeAg-positive (anti-HBe-positive) chronic hepatitis B patients. The amount of total HBV DNA and cccDNA was measured using the Invader assay. Anti-HBe-positive patients had lower median total intrahepatic HBV DNA (P < .001) and intrahepatic cccDNA levels (P ‫؍‬ .001) than HBeAg-positive patients. Intrahepatic cccDNA correlated positively with the total intrahepatic HBV DNA (r ‫؍‬ 0.950, P < .001). However, the proportion of intrahepatic HBV DNA in the form of cccDNA was inversely related to the amount of total intrahepatic HBV DNA (r ‫؍‬ ؊0.822, P < .001). A small amount of cccDNA was detected in 39 of 52 (75%) serum samples. Anti-HBe-positive patients had lower median serum cccDNA levels than HBeAg-positive patients (P ‫؍‬ .002). Serum HBV DNA correlated positively with intrahepatic total HBV DNA (r ‫؍‬ 0.778, P < .001) and intrahepatic cccDNA (r ‫؍‬ 0.481, P ‫؍‬ .002). In conclusion, the Invader assay is a reliable assay for the quantitation of cccDNA. Serum and intrahepatic total HBV DNA and cccDNA levels become lower as the disease progresses from HBeAgpositive to anti-HBe-positive phase, with cccDNA becoming the predominant form of intrahepatic HBV DNA. (HEPATOLOGY 2004;40:727-737.