Response Prediction in Modified Treatment of Chronic Hepatitis B

Treatment of chronic HBV infection leads to functional cure (HBsAg loss) in only a minority of patients. Over the last decades, multiple strategies aiming to optimize the effect of the available therapeutic agents have been examined. New therapeutic agents are being developed, but while awaiting those, biomarkers may be used in order to optimize the effect of currently available treatment options. Also, registered therapeutic agents may be combined.

This thesis describes the efficacy of several peginterferon-based treatment strategies. Adding peginterferon to ongoing nucleos(t)ide analogue treatment (‘add-on strategy’) is one of the strategies that has been studied over the last years. We found that this strategy may especially be beneficial for patients who were never treated with peginterferon in the past, and in patients with low baseline levels of HBV DNA, HBV RNA and quantitative HBsAg. In addition, this thesis shows on-treatment dynamics of well-known biomarkers HBV DNA, quantitative HBsAg and quantitative HBeAg, and new biomarkers hepatitis B core-related antigen (HBcrAg) and HBV RNA. By studying these biomarkers during different treatment strategies for both HBeAg-positive and HBeAg-negative chronic hepatitis B, we were able to identify patient groups who have a higher probability of achieving treatment response than others. In particular, patients with the highest chance of response had a strong early on-treatment decline of all biomarkers studied.

In summary , combination strategies and biomarker monitoring may be used to optimize current treatment options in a selected group of patients. However when biomarkers are used in treatment monitoring, one should we aware of patient-related and virus-related factors that affect serum levels, such as HBV genotype.