Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir
Article first published online: 22 SEP 2011
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 26, Issue 10, pages 1527–1535, October 2011
How to Cite
Takkenberg, B., Terpstra, V., Zaaijer, H., Weegink, C., Dijkgraaf, M., Jansen, P., Beld, M. and Reesink, H. (2011), Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir. Journal of Gastroenterology and Hepatology, 26: 1527–1535. doi: 10.1111/j.1440-1746.2011.06766.x
- Issue published online: 22 SEP 2011
- Article first published online: 22 SEP 2011
- Accepted manuscript online: 9 MAY 2011 06:56PM EST
- Accepted for publication 27 April 2011.
- antiviral therapy;
- clinical hepatology;
- hepatitis B virus;
Background and Aim: We investigated whether intrahepatic markers could predict response in chronic hepatitis B virus (HBV) patients treated with peg-interferon and adefovir for 48 weeks.
Methods: Intrahepatic covalently closed circular DNA (cccDNA), total intrahepatic HBV DNA and the proportion of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) positive hepatocytes in 16 hepatitis B e antigen (HBeAg) positive and 24 HBeAg negative patients were measured at baseline and at end of treatment.
Results: Baseline intrahepatic markers were not associated with sustained virological response (SVR) defined as HBV DNA < 2000 IU/mL and persistent normal alanine aminotransferase levels at the end of follow-up (week 72). At end of treatment, intrahepatic cccDNA and total intrahepatic HBV DNA in HBeAg positive patients were significantly lower in patients with HBeAg seroconversion (P = 0.016 and P = 0.010) with positive predictive values (PPV) for SVR of 80% and 80%, respectively. In HBeAg negative patients, intrahepatic cccDNA and total intrahepatic HBV DNA had declined significantly at end of treatment (P = 0.035 and P = 0.041) and corresponding PPV for SVR was 73% and 82%. In HBeAg positive patients, median proportion of HBcAg positive hepatocytes declined significantly (P = 0.002) at end of treatment. In HBeAg negative patients, the proportion of HBsAg positive hepatocytes had declined significantly at end of treatment (P = 0.0009). Using HBsAg ≤ 7.5% as a limit, PPV for SVR in HBeAg negative patients was 83%.
Conclusions: At end of treatment in HBeAg positive patients, intrahepatic cccDNA and total intrahepatic HBV DNA were predictive for SVR. In HBeAg negative patients a proportion of < 7.5% HBsAg positive hepatocytes at end of treatment was a strong predictor for SVR.