Predicting response to peginterferon alfa-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B.
Bonino F, Marcellin P, Lau GK, Hadziyannis S, Jin R, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Brunetto M, Farci P, Popescu M, McCloud P.
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Italy.
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.