Stopping Antiviral Treatment in Chronic Hepatitis B

Chronic Hepatitis b Clinical Trial

Official title:

Stopping Antiviral Treatment and Subsequent Flare in Chronic Hepatitis B Infection: Immunological and Virological Profiling

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04431245
• Other study ID #: HKUUW20-425
• Status: Active, not recruiting
• Start date: June 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2023
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Chronic hepatitis B (CHB) infection affected 292 million individuals in the world, translating to about 3.9% of global prevalence. Up to 40% of patients with CHB will develop liver-related complications. Many patients require long-term oral antiviral therapy since off-treatment sustained virological control can only be achieved in a minority of patients. It is uncommon for patients taking long-term antivirals to be able to stop the treatment if favorable factors are not present. Those include low viral load, long enough duration of treatment, and absence of cirrhosis. Some studies have found that inducing a mild flare is beneficial for achieving functional cure in chronic hepatitis B infection. There is lack of data in the immunological and virological profile in patients who stop their long-term antiviral therapy, and in those who developed flare after treatment cessation.

Description:

Chronic hepatitis B infection (CHB) affected 292 million individuals in the world in 2016 according to the Polaris Observatory estimation, translating to about 3.9% global prevalence. Up to 40% of patients with CHB will develop liver-related complications and there were 890,000 deaths from these complications in 2015. Current antiviral therapy is aimed to achieve effective viral suppression, biochemical remission, histological improvement, and risk reductions in liver-related complications including cirrhosis and liver cancer. Many patients require long-term oral nucleos(t)ide analogues (NA) since off-treatment sustained virological control can only be achieved in a minority of patients. For HBeAg-negative CHB patients, variable rates of durable virological response were observed after cessation of NA. Only a small proportion of HBeAg-negative Asian patients (<10%) can successfully stop NA without virological breakthrough, compared to more than 60% of Caucasian patients maintaining a durable virologic response and even HBsAg seroclearance in up to 30%. Therefore, current guidelines in general recommend indefinite duration of NA therapy in HBeAg-negative patients, unless guaranteed close monitoring could be provided after cessation of NA in suitable subjects. Favourable factors predictive of partial cure include lower baseline HBV DNA, lower HBsAg titre or hepatitis B core-related antigen at NA cessation and longer duration of consolidation therapy in HBeAg-negative patients. There is lack of data in the immunological and virological profile in patients who stop their long-term NA, and in those who developed post-NA cessation flare.

The investigators aim to study the virological and immunological profile in patients who stopped long-term NA therapy, with or without post-NA cessation flare. In addition, the investigators would like to investigate the effect of mild flare after monitored NA-cessation on subsequent virological activity and HBsAg seroclearance.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 54
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HBeAg-negative

• non-cirrhotic

• on long-term NA =3 years (entecavir or tenofovir)

• undetectable serum HBV DNA

Exclusion Criteria:

• HCC, cirrhosis, history of liver transplantation, or on immunosuppressants,

Related Conditions & MeSH terms

• Chronic Hepatitis b
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Entecavir
Study subjects will stop the antiviral therapy. Patients will be closely monitored every 6-8 weeks for virological flare and/or biochemical flare.

Locations

Country	Name	City	State
Hong Kong	Man Fung Yuen	Hong Kong	Please Select One ...

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The immunological profile in CHB patients who stopped antiviral therapy	The investigators will perform analysis for the immunological aspects for these patients	24 months
Primary	The virological profile in CHB patients who stopped antiviral therapy	The investigators will perform analysis for the virological aspects for these patients	24 months