Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir

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http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06766.x/abstract

Intrahepatic response markers in chronic hepatitis B patients treated with

peginterferon alpha-2a and adefovir

Bart Takkenberg1,*, Valeska Terpstra2, Hans Zaaijer3, Weegink1, Marcel

Dijkgraaf4, Jansen1, Marcel Beld5, Hendrik Reesink1

Article first published online: 22 SEP 2011

DOI: 10.1111/j.1440-1746.2011.06766.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Volume 26, Issue 10, pages 1527–1535, October 2011

Abstract

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.