Clinical Course Study in Chronic Hepatitis B After Nucleos(t)Ide Analogue Therapy

Background:

Taiwan is one of the area with the highest prevalence of chronic hepatitis B (CHB), and many patients die of hepatitis B virus (HBV)-related cirrhosis or liver cancer that have been the leading causes of death in Taiwan for many years. For effectively treating CHB, antiviral therapy for CHB has been reimbursed by the National Health Insurance in Taiwan since 1998, and nucleos(t)ide analogues (NAs) can be used for patients with active hepatitis B and high viral load in a maximum duration of three years. However, there is a significant proportion of patients suffering from hepatitis B recurrence after discontinuation of NA therapy, and hepatitis B recurrence may result in liver cirrhosis and liver cancer. To the best of current knowledge, in what conditions that the NA therapy can be successfully discontinued without hepatitis recurrence remain largely unclear. Therefore, this study is designed to evaluate the clinical and virological changes of CHB patients after stopping NA therapy, and finding the prognostic indicators may be an important basis for stopping NA therapy in CHB patients in the future.

Objectives:

1. To access the clinical and virological changes after stopping NA therapy
2. To determine important prognostic indicators for stopping NA therapy

Methods:

In this prospective cohort study, the investigators plan to recruit CHB patients who are indicated for stopping NA therapy in the outpatient clinics according to the inclusion and exclusion criteria of this study, and clinical and virological data will be collected during routine clinic visits after stopping NA therapy. Prognostic factors will be analyzed according the following data:

1. Patient characteristics: including age, sex, height, weight, waist circumference, history of alcohol drinking, antiviral therapy history, hepatitis history, and drug history.
2. Blood tests: During routine clinic visits and blood tests every 12 weeks or at hepatitis flare in the first 2 years after stopping NA therapy, liver function and virological status tests will be conducted for analysis.

Study Overview

• Status: Completed
• Conditions: Prognosis; Virological Breakthrough
• Intervention / Treatment: Other: Observation for clinical and virological changes

Detailed Description

Background:

Taiwan is one of the area with the highest prevalence of chronic hepatitis B (CHB), and many patients die of hepatitis B virus (HBV)-related cirrhosis or liver cancer that have been the leading causes of death in Taiwan for many years. For effectively treating CHB, antiviral therapy for CHB has been reimbursed by the National Health Insurance in Taiwan since 1998, and nucleos(t)ide analogues (NAs) can be used for patients with active hepatitis B and high viral load in a maximum duration of three years. However, there is a significant proportion of patients suffering from hepatitis B recurrence after discontinuation of NA therapy, and hepatitis B recurrence may result in liver cirrhosis and liver cancer. To the best of current knowledge, in what conditions that the NA therapy can be successfully discontinued without hepatitis recurrence remain largely unclear. Therefore, this study is designed to evaluate the clinical and virological changes of CHB patients after stopping NA therapy, and finding the prognostic indicators may be an important basis for stopping NA therapy in CHB patients in the future.

Objectives:

1. To access the clinical and virological changes after stopping NA therapy
2. To determine important prognostic indicators for stopping NA therapy

Methods:

In this prospective cohort study, the investigators plan to recruit CHB patients who are indicated for stopping NA therapy in the outpatient clinics according to the inclusion and exclusion criteria of this study, and clinical and virological data will be collected during routine clinic visits after stopping NA therapy. Prognostic factors will be analyzed according the following data:

1. Patient characteristics: including age, sex, height, weight, waist circumference, history of alcohol drinking, antiviral therapy history, hepatitis history, and drug history.
2. Blood tests: During routine clinic visits and blood tests every 12 weeks or at hepatitis flare in the first 2 years after stopping NA therapy, liver function and virological status tests will be conducted for analysis.

Importance:

To clinicians in treating chronic hepatitis B, this study will provide important data regarding the clinical courses after stopping NA therapy, and important prognostic indicators may be determined. These findings could help clinicians in decision making for discontinuation of NA therapy and booking follow-up schedules. To basic scientists, this study will provide the virological changes after stopping NA therapy, and these findings may help developing further virological researches.

• Study Type: Observational
• Enrollment (Actual): 347

Contacts and Locations

Study Locations

• Taiwan
  • Changhua, Taiwan
    • Show Chwan Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 40705
    • Chung Shan Medical University Hospital
  • Taichung, Taiwan, 40705
    • Cheng Ching General Hospital-Chung Kang Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Chronic hepatitis B patients who are indicated for stopping nucleos(t)ide analogue therapy in the outpatient clinics according to the inclusion and exclusion criteria of this study

Description

Inclusion Criteria:

1. Age > or = 20 years old
2. Chronic hepatitis B patients who received tenofovir or entecavir as their first anti-HBV therapy
3. Patients who have received nucleos(t)ide analogue therapy for > 3 years or reached the stopping criteria of APASL ( HBeAg+ patients: HBeAg seroconversion > 12 months; HBeAg - patients: HBV DNA undetectable > 12 months)

Exclusion Criteria:

1. History of liver cirrhosis or hepatocellular carcinoma
2. Recipients of liver transplantation
3. Concurrent malignancies (except curable skin cancers)
4. Concomitant use of immunosuppressants
5. Coinfection with HCV, HDV, HIV

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tenofovir; Chronic hepatitis B patients who receive tenofovir as their first anti-HBV therapy and are indicated for stopping tenofovir therapy	Other: Observation for clinical and virological changes; Only observation after stopping nucleos(t)ide analogue
Entecavir; Chronic hepatitis B patients who receive entecavir as their first anti-HBV therapy and are indicated for stopping entecavir therapy	Other: Observation for clinical and virological changes; Only observation after stopping nucleos(t)ide analogue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBsAg seroconversion	HBsAg negative, anti-HBs positive	2 years after stopping nucleos(t)ide analogue

Collaborators and Investigators

• Sponsor: Taichung Veterans General Hospital
• Investigators: Study Chair: Teng-Yu Lee, MD, PhD, Taichung Veterans General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): October 1, 2020
• Study Completion (Actual): March 13, 2021

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: October 20, 2015
• First Posted (Estimate): October 21, 2015

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: March 14, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Hepatitis B; Hepatitis B, Chronic
• Other Study ID Numbers: CF15240B