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NCT Number: NCT02069678

Serum Hepatitis B Surface Antigen Levels to Guide the Stopping of Entecavir in HBeAg-negative Chronic Hepatitis B

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.

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Key information

Conditions

Chronic Hepatitis B Blood-Borne Infections Chronic Disease Communicable Diseases DNA Virus Infections Digestive System Diseases Disease Attributes Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis B, Chronic Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Virus Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • HBeAg-negative patients on entecavir monotherapy for at least 24 months
  • Undetectable HBV DNA by PCR-based assay on 3 separate occasions 6 months apart (as per Asian Pacific guideline in 2008).
  • Normal ALT levels according to the local laboratory reference value on 2 separate occasions 6 months apart

Exclusion criteria

  • Patients previously or currently on interferon therapy
  • Patients who have experienced another antiviral agent besides entecavir
  • Patients with hepatitis C virus infection as indicated by a positive anti-HCV serology test
  • Patients with Child's B liver cirrhosis, cirrhotic complications or hepatocellular carcinoma
  • Patients with organ transplantation
  • Serious medical illnesses or malignancy
  • Age < 18 years or > 65 years
  • No patient consent

Treatment and study plan

Primary outcomes

  1. sustained response, defined as HBV DNA persistently ≤ 200 IU/ml

    Time frame: 12 months after stopping Entecavir

Secondary outcomes

  1. HBsAg < 1000 IU/ml and 100 IU/ml

    Time frame: 12 months post-treatment

  2. HBV DNA < 200 IU/ml and 20 IU/ml

    Time frame: 12 months post-treatment

  3. virological relapse

    Time frame: 5 years post-treastment

  4. HBsAg clearance

    Time frame: 5 years post-treatment

Sponsors and collaborators

Lead sponsor

Chinese University of Hong Kong

Other

Registry information

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Feb 24, 2014
Registry last updated
Feb 24, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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