Virus-host interplay in chronic hepatitis B: Predicting response to immunomodulating antiviral therapy

It is of great importance to optimize pegylated interferon alfa (Peg-IFNα) based treatment strategies for patients with chronic Hepatitis B, as only a minority of patients achieves a favorable response. In Chapter 2, we describe a cohort of 92 patients with chronic Hepatitis B (44 HBeAg-positive and 48 HBeAg-negative) with HBV-DNA levels >100,000 copies/mL (>17,182 IU/mL) who were treated with a combination of Peg-IFNα and adefovir for 48 weeks. Two years after treatment ended a relatively high rate of HBsAg loss was observed in both HBeAg-positive (11%) and HBeAg-negative (17%) patients. In addition 41% of HBeAgpositive patients achieved HBeAg loss, and 25% of HBeAg-negative patients had a combined response (defined as HBeAg negativity, HBV-DNA levels ≤ 2,000 IU/mL and ALT normalization) at year 2.
Despite the relatively high response rates in this study, the majority of patients were still treated without achieving a satisfactory outcome. This stresses the need for predictive markers of therapy response. Previously identified factors, such as HBV genotype, lower HBV DNA and higher ALT level, explain only part of the variation in response to Peg-IFNα based therapy. This thesis focused on the identification of novel markers of response which may allow the selection of those patients most likely to respond to treatment with Peg-IFNα based therapy.