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 μg/wk, 48 wk) and 266 patients treated with PEG-IFN-alfa-2b (100 μg/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 × 103IU/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; ≥2 × upper limit of normal), low levels of HBV DNA (<2.0 × 108IU/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.,
Erasmus MC: University Medical Center Rotterdam

Buster, E.H.C.J, Hansen, B.E, Lau, G.K.K, Piratvisuth, T, Zeuzem, S, Steyerberg, E.W, & Janssen, H.L.A. (2009). Factors That Predict Response of Patients With Hepatitis B e Antigen-Positive Chronic Hepatitis B to Peginterferon-Alfa. Gastroenterology, 137(6), 2002–2009. doi:10.1053/j.gastro.2009.08.061