Stopping Antiviral Treatment in Chronic Hepatitis B

NCT ID: NCT04431245

Last Updated: 2023-05-10

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 54 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2024-12-31

Brief 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.

Detailed 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.

Conditions

Chronic Hepatitis b

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Stop antiviral

HBeAg-negative non-cirrhotic CHB patients on long-term NA ≥3 years will be identified. Only those who have undetectable serum HBV DNA by the conventional assay (Cobas Taqman, Roche Diagnostics, Branchburg, NJ) which has a lower limit of detection (LLOD) of 10 IU/mL will be recruited. CHB patients were treated with potent oral NA (i.e. tenofovir or entecavir). All recruited patients will have written informed consent for participation of study. Patients with HCC, cirrhosis, history of liver transplantation, or on immunosuppressants, will be excluded.

Entecavir

Intervention Type: DRUG

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

Interventions

Entecavir

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

Intervention Type: DRUG

Other Intervention Names

oral nucleoside analogue

Eligibility Criteria

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,

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Professor Yuen Man Fung

Chair Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Man-Fung Yuen, DSc, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

Man Fung Yuen

Hong Kong, Please Select One ..., Hong Kong

Countries

Hong Kong

Other Identifiers

HKUUW20-425

Identifier Type: -

Identifier Source: org_study_id