Serum Hepatitis B Surface Antigen Levels to Guide the Stopping of Entecavir in HBeAg-negative Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Observational

Summary: 
      This will be a multi-center study in Hong Kong. This is a retrospective-prospective study in
      HBeAg-negative chronic hepatitis B patients. HBeAg-negative patients on entecavir followed up
      in the liver clinics will be identified from the existing database. All patients had HBV DNA
      testing every 6 months as a clinic routine. Serum HBsAg levels will be tested in the residual
      serum samples at the pre-treatment and last follow-up visits. Eligible patients will be
      discussed on the plan of stopping entecavir therapy. All patients will have written informed
      consent before recruited into this study. All patients will be followed up for 12 months
      after stopping entecavir treatment. As entecavir is most commonly used antiviral drug in Hong
      Kong and in the Western countries, the investigators aim to investigate and validate the use
      of serum HBsAg quantification to guide the timing of stopping entecavir in HBeAg-negative
      patients. The results of this study will provide scientific evidence on the use of this new
      serum marker to predict sustained remission after stopping entecavir. In the long-run, it can
      improve patient compliance, reduce the need of long-term antiviral and reduce the drug cost
      in the management of HBeAg-negative chronic hepatitis B.

      All patients will stop entecavir according to the Asian Pacific guideline with written
      informed consent and close subsequent monitoring. In the protocol, there is a safety net for
      re-treatment. There will not be any invasive procedure. There is no major ethical issue.
    

Detailed description: 
      Chronic hepatitis B is the commonest cause of liver cirrhosis and hepatocellular carcinoma in
      Hong Kong. Approximately 50% of patients had negative hepatitis B e antigen (HBeAg), which
      indicates an escape of host immune clearance by the host. Oral antiviral drugs are very
      effective in suppressing viral replication and inducing biochemical remission [1]. However,
      the timing to stop oral antiviral agents is controversial. Hepatitis B surface antigen
      (HBsAg) seroclearance has been recommended as the best time for drug cessation for
      HBeAg-negative patients [2,3], but its occurrence is very uncommon especially among Asian
      patients. The Asian Pacific guideline recommended stopping treatment when serum HBV DNA
      became undetectable for three times within 12 months [4], but approximately 50% of patients
      will experience virologic relapse post-treatment [5,6].

      HBsAg quantification has been shown to correlate with the concentration of covalently closed
      circular DNA in the liver [7]. In a Hong Kong study among 53 HBeAg-negative patients who
      stopped lamivudine, HBsAg ≤ 100 IU/ml and/or reduction of > 1 log at the end of treatment
      could predict sustained response up to 5 years post-treatment [8]. In other words, it is
      probable that patients who have a lower serum HBsAg level, which may reflect a lower
      concentration of virus inside the liver, have a lower risk of viral relapse after stopping
      antiviral therapy.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        HBeAg-negative patients on entecavir followed up in the liver clinics will be identified
        from the existing database. All patients had HBV DNA testing every 6 months as a clinic
        routine. Serum HBsAg levels will be tested in the residual serum samples at the
        pre-treatment and last follow-up visits. Eligible patients will be discussed on the plan of
        stopping entecavir therapy. All patients will have written informed consent before
        recruited into this study. All patients will be followed up for 12 months after stopping
        entecavir treatment.