Stopping Antiviral Treatment in Chronic Hepatitis B

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: Entecavir

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.

• Study Type: Observational
• Enrollment (Anticipated): 54

Contacts and Locations

Study Locations

• Hong Kong
  • Please Select One ...
    • Hong Kong, Please Select One ..., Hong Kong
      • Man Fung Yuen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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,

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.

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.; Other Names: oral nucleoside analogue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The immunological profile in CHB patients who stopped antiviral therapy	The investigators will perform analysis for the immunological aspects for these patients	24 months
The virological profile in CHB patients who stopped antiviral therapy	The investigators will perform analysis for the virological aspects for these patients	24 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Man-Fung Yuen, DSc, MD, PhD, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: May 31, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: antiviral therapy; functional cure; nucleoside analogue
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: HKUUW20-425

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant's personal identification data will be only accessed by the PI and study team.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No