In this study we will prospectively stop NA in both Caucasian and non-Caucasian patients matched for gender and age, to validate the observed host and viral parameters for future roll-out of this treatment strategy.

An estimated 290 million people worldwide are chronically infected with the Hepatitis B Virus (HBV). One fourth of untreated patients develop progressive liver damage and are at risk of liver-related death, which can be prevented by treatment with Nucleos(t)ide Analogues (NA). These drugs efficiently suppress viral replication, but seroclearance of the virus, defined as loss of Hepatitis B surface Antigen (HBsAg), is predicted to require an average of 36 to 52 years of treatment. Cessation of NA after long-term viral suppression in patients without HBV seroclearance might reduce costs and may even increase the chance of subsequent HBsAg loss. We have recently shown in a retrospective multicentric international study, that Caucasian ethnicity and off-treatment viral control are associated with HBsAg loss after NA cessation. In this study we will prospectively stop NA in both Caucasian and non-Caucasian patients matched for gender and age, to validate the observed host and viral parameters for future roll-out of this treatment strategy.

Inclusion Criteria:

• Chronic hepatitis B
• Under continuous NA treatment
• >= 18 years old and <= 75 years
• HBeAg negative at start of treatment
• HBV DNA undetectable >36 months or <100 IU/mL >48 months
• ALT <= 80 U/L

Exclusion Criteria:

• Fibrosis >F2
• Active coinfection with HCV, HDV or HIV
• Pregnancy or lactation
• Immunocompromised patients
• Ever HCC or family history of HCC
• Ever participated in HBV siRNA therapeutic trials

Upon reasonable request and after publication of the results