HEPATITIS

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

F Bonino¹, P Marcellin², G K K Lau³, S Hadziyannis⁴, R Jin⁵, T Piratvisuth⁶, G Germanidis⁷, C Yurdaydin⁸, M Diago⁹, S Gurel¹⁰, M-Y Lai¹¹, M R Brunetto¹², P Farci¹³, M Popescu¹⁴, P McCloud¹⁵ for the Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group

¹ University of Pisa and Foundation IRCCS, Policlinico di Milano, Milan, Italy
² Service d’Hépatologie, INSERM Unite 481 and Centre de Recherches Claude Bernard sur les Hépatite Virales, Hôpital Beaujon, Clichy, France
³ Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
⁴ Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece
⁵ Digestive Disease Department, Beijing You An Hospital, Beijing, China
⁶ Department of Medicine, Prince of Songkla University, Songkla, Thailand
⁷ Pathology Clinic, Papageorgiou General Hospital, Thessalonika, Greece
⁸ Faculty of Medicine, University of Ankara, Ankara, Turkey
⁹ Hospital General Universitario de Valencia, Valencia, Spain
¹⁰ University of Uludag, Faculty of Medicine, Bursa, Turkey
¹¹ Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC
¹² Azienda Ospedaliera Universitaria Pisana, Pisa, Italy
¹³ Universita di Cagliari, Cagliari, Italy
¹⁴ Roche, Basel, Switzerland
¹⁵ Roche, Dee Why, Australia

Correspondence to:
Professor F Bonino
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico, Via Francesco Sforza 28, 20122 Milano, Italy; bonino{at}med-club.com

Objective: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24 week post-treatment biochemical and virological response rates with peginterferon -2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses was investigated.

Methods: Multivariate analyses were performed using available data from 518 patients treated with peginterferon -2a with or without lamivudine, or with lamivudine alone. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20 000 copies/ml.

Results: In logistic regression analyses across all treatment arms, peginterferon -2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post-treatment. In the peginterferon -2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon -2a monotherapy (p = 0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for the peginterferon -2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon -2a with or without lamivudine therapy.

Conclusions: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post-treatment, in patients treated with peginterferon -2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon -2a with or without lamivudine.

Abbreviations: ALT, alanine aminotransferase; CHB, chronic hepatitis B; HAI, Histological Activity Index; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B s antigen; HBV, hepatitis B virus; ITT, intention-to-treat; ULN, upper limit of normal

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

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