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Hepatitis B surface antigen (HBsAg) clearance marks the prime event of HBV elimination in chronic hepatitis B and is associated with better overall outcome. Despite reliable viral suppression under standard treatment with nucleos(t)ide analogues (NUCs) the goal of HBsAg clearance is rarely achieved. Also synchronous combination of NUCs with pegylated interferon-α-2a (peg-IFNα) has not been superior compared to peg-IFNα monotherapy in prospective randomized trials. However, sequential addition of peg-IFNα to an ongoing NUC regimen has provided higher HBsAg clearance rates in uncontrolled pilot studies. In this protocol we investigate the sequential addition of open-label peg-IFNα for 48 weeks to an ongoing NUC regimen following patients written informed consent. Included are patients with HBeAg negative chronic hepatitis B and a suppressed HBV DNA (<20 IU/mL) for a minimum of 12 months under NUCs prior to trial enrollment. Patients are randomized (2:1 ratio) to peg-IFNα add-on/ NUC treatment or a control group receiving continuous NUCs only
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