Predicting response to peginterferon alfa-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B

Ferruccio Bonino ^1*, P Marcellin ², G KK Lau ³, S Hadziyannis ⁴, R Jin ⁵, T Piratvisuth ⁶, G Germanidis ⁷, C Yurdaydin ⁸, M Diago ⁹, S Gurel ¹⁰, M-Y Lai ¹¹, M Brunetto ¹², P Farci ¹³, M Popescu ¹⁴ and P McCloud ¹⁵

¹ Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Italy
² INSERM Unite 481, France
³ The University of Hong Kong, China
⁴ Henry Dunant Hospital, Greece
⁵ Beijing You An Hospital, China
⁶ Prince of Songkla University, Thailand
⁷ Papageorgiou General Hospital, Greece
⁸ University of Ankara, Turkey
⁹ Hospital General Universitario de Valencia, Spain
¹⁰ University of Uludag, Turkey
¹¹ National Taiwan University Hospital, Taiwan
¹² Azienda Ospedaliera Universitaria Pisana, Italy
¹³ Universita di Cagliari, Italy
¹⁴ Roche, Switzerland
¹⁵ Roche, Australia

^* To whom correspondence should be addressed. E-mail: bonino{at}med-club.com.

Accepted 10 October 2006

Abstract

Background and aims: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24-week post-treatment biochemical and virologic response rates with peginterferon alfa-2a ± lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses has been investigated.

Patients and methods: Multivariate analyses were performed using available data from 518 patients treated with peginterferon alfa-2a monotherapy ± lamivudine, or lamivudine monotherapy. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA <20,000 copies/mL.

Results: In logistic regression analyses across all treatment arms, peginterferon alfa-2a (± lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response 24 weeks post-treatment. In the peginterferon alfa-2a and lamivudine monotherapy arms, patients infected with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to combination than peginterferon alfa-2a monotherapy (p=0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for peginterferon alfa-2a, 19.0% for combination, and 10.0% for lamivudine-treatment groups, with genotypes B or C associated with a sustained combined response to peginterferon alfa-2a ±lamivudine therapy.

Conclusions: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response 24 weeks post-treatment, in patients treated with peginterferon alfa-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon alfa-2a ±lamivudine.

Keywords: antiviral agents, chronic hepatitis B, multivariate, post-treatment, predictor

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Digest

Robin Spiller and Emad El-Omar
Gut 2007 56: 601. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Shamliyan, T. A., MacDonald, R., Shaukat, A., Taylor, B. C., Yuan, J.-M., Johnson, J. R., Tacklind, J., Rutks, I., Kane, R. L., Wilt, T. J. (2009). Antiviral Therapy for Adults With Chronic Hepatitis B: A Systematic Review for a National Institutes of Health Consensus Development Conference. ANN INTERN MED 150: 111-124 [Abstract] [Full Text]  
• Dusheiko, G, Antonakopoulos, N (2008). Current treatment of hepatitis B. Gut 57: 105-124 [Full Text]