Chronic hepatitis B (CHB) affects more than 350 million people worldwide. The most common form in Europe is CHB HBeAg-negative. Antiviral treatment of CHB HBeAg-negative patients includes chronic administration of nucleos(t)ide analogues (NUC) or pegylated interferon (PegIFN) during 12 months. Typically, PegIFN allows immune control of CHB and antigen "s" (HBsAg) loss in around 4% of patients compared to less than 0,1% using NUC. Recently, it has been described that HBsAg quantification (HBsAg-q) is useful to identify patients with high probability to lose HBsAg during follow-up. In addition, a proof-of-concept study with nine HBeAg-negative patients receiving NUC showed that adding PegIFN (16 weeks) achieved HBsAg loss in one patient (11%). The aim of our study is to evaluate the efficacy and safety adding PegIFN (48 weeks) in treated HBeAg-negative patients with NUC.

Inclusion Criteria:

• Chronic hepatitis B (HBeAg-negative)
• Signed inform consent
• Aged > 18

Exclusion Criteria:

• Contraindications for Pegylated interferon (cirrhosis, pregnancy, others)
• Previous treatment with interferon or Pegylated interferon
• Previous HBsAg loss
• Treatment duration with Nucleos(t)ide analogues less than 2 years
• Poor adherence to Nucleos(t)ide analogues