Clinical trial NCT02582333: Clinical Course Study in Chronic Hepatitis B After Nucleos(t)Ide Analogue Therapy
Official title: Clinical Course Study in Chronic Hepatitis B After Nucleos(t)Ide Analogue Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Virological Breakthrough
Prognosis
Lead sponsor: Taichung Veterans General Hospital
Sponsor class: OTHER
First posted: 2015-10-21
Enrollment: 347
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: HBsAg seroconversion
timeFrame: 2 years after stopping nucleos(t)ide analogue
Secondary outcomes:
Other outcomes:
Locations:
city: Changhua
country: Taiwan
facility: Show Chwan Memorial Hospital
city: Taichung
country: Taiwan
facility: Cheng Ching General Hospital-Chung Kang Branch
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
Study officials:
affiliation: Taichung Veterans General Hospital
name: Teng-Yu Lee, MD, PhD
role: STUDY_CHAIR
References: