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

R.B. Takkenberg1,*, V. Terpstra4, H.L. Zaaijer3, C.J. Weegink1, M.G.W.

Dijkgraaf4, P.L.M. Jansen1, M.G.H.M. Beld5, H.W. Reesink1DOI:

10.1111/j.1440-1746.2011.06766.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell

Publishing Asia Pty Ltd

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Journal of Gastroenterology and Hepatology

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Publication History

Accepted manuscript online: 9 MAY 2011 06:56PM EST

Received date: 16-Dec-2010 , Accepted date: 27-Apr-2011

Abstract

Background: We investigated whether intrahepatic markers could predict response

in chronic hepatitis B patients treated with peg-IFN and adefovir for 48 weeks.

Methods: Intrahepatic cccDNA, total intrahepatic HBV DNA and the proportion of

HBsAg and HBcAg positive hepatocytes in 16 HBeAg positive and 24 HBeAg negative

patients were measured at baseline and at the end of treatment.

Results: Baseline intrahepatic markers were not associated with sustained

virological response (SVR) defined as HBV DNA <2,000 IU/mL and persistent normal

ALT levels at the end of follow-up (week 72). At the 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 the end of treatment (p

= 0.0009). Using HBsAg ≤ 7.5% as 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.