Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa.

Background & Aims: Therapy with pegylated interferon (PEG-IFN)-alfa results in sustained response in a minority of patients with chronic hepatitis B virus (HBV) infection and has considerable side effects. We analyzed data from the 2 largest global trials of hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B to determine which are most likely to respond to PEG-IFN-alfa therapy.

Methods: The study included 542 patients treated with PEG-IFN-alfa-2a (180 microg/wk, 48 wk) and 266 patients treated with PEG-IFN-alfa-2b (100 microg/wk, 52 wk). Eighty-seven patients were excluded, leaving 721 patients for analysis. A sustained response was defined as HBeAg loss and HBV-DNA level less than 2.0 x 10(3) IU/mL 6 months after treatment. Logistic regression analysis was used to identify predictors of sustained response and a multivariable model was constructed.

Results: HBV genotype, high levels of alanine aminotransferase (ALT; >or=2 x upper limit of normal), low levels of HBV DNA (<2.0 x 10(8) IU/mL), female sex, older age, and absence of previous IFN therapy predicted a sustained response. Genotype A patients with high ALT and/or low HBV-DNA levels had a high predicted probability (>30%) of a sustained response. The strongest predictors of response were a high level of ALT in genotype B patients and a low level of HBV DNA in genotype C patients. Genotype D patients had a low chance of sustained response, irrespective of ALT or HBV-DNA levels.

Conclusions: The best candidates for a sustained response to PEG-IFN-alfa are genotype A patients with high levels of ALT or low levels of HBV DNA, and genotypes B and C patients who have both high levels of ALT and low HBV DNA. Genotype D patients have a low chance of sustained response.