Real World Study About Anti-viral Regimen Adjustment on Achieving Complete Response in CHB Patients

Study Overview
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Brief Summary
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In the treatment of chronic hepatitis B (CHB), viral suppression is closely related to disease progression, and the lower the viral load, the lower the risk of progression to cirrhosis and hepatocellular carcinoma (HCC). In addition, a considerable number of patients in China are still using non-first-line antiviral therapy, such as adefovir dipivoxil, lamivudine, and telbivudine (ADV/LAM/LdT). About 25% of patients who received entecavir(ETV) treatment for more than half a year and confirmed that their DNA had turned negative by non-high-precision detection methods still had low viremia (LLV,DNA>20 IU/ml,IU=international unit), and LLV patients were twice as likely to develop HCC as patients with complete viral response.Patients who have received ETV or second-line NA(LAM/ADV/LdT) treatment for more than half a year to 1 year and confirmed HBV-DNA>10IU/ml by high-precision detection method are recommended to adjust the treatment plan in order to reduce the DNA load below 10IU/ml as soon as possible. It is up to the doctor, in consultation with the patient, to decide whether or not to make the adjustment.

Detailed Description
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In our hospital, about 150 patients are screened for HBV-DNA every day. Therefore, 54 million patients will be tested for HBV-DNA within one year, of which 30% are estimated to be HBV-DNA ≥10 IU. These patients will be informed to the Department of Infectious Diseases of the Second Affiliated Hospital of Chongqing Medical University for follow-up, and will be randomly divided into three groups according to 1:1. Patients in all three groups will be educated about hepatitis B virus infection and antiviral treatment, and the treatment regimen will be adjusted according to whether their HBV DNA is ≥10 IU/ml or not. Patients in group 1: patients with persistant low level HBV DNA (<10 IU/ml). Patients in group 2: HBV-DNA≥10 IU/ml, receiving HBV-related education and being advised by the doctor to change or to add another NA. Patients in group 2: patients with persistant HBV DNA (>10 IU/ml) but refuse to change the regimen. Patients in group 3: patients with persistant HBV DNA (>10 IU/ml) and agree to change the regimen. Educational methods include videos, including an introduction to hepatitis B virus (disease profile, infection, outcome, HBV infection, vertical transmission and other risk factors) for 5 minutes, brochures with relevant information and consultations with physicians and nurses. All patients with chronic hepatitis B(CHB) receiving ETV or second-line NA(LAM/ADV/LdT) treatment for more than six months to one year will receive HBV-DNA detection, and patients with HBV-DNA≥10 IU/ml will be informed and recommended to adjust the treatment regimen so that the actual prevalence of HBV-DNA load < 10 IU/ml in Chongqing HBV cohort could be obtained . The investigators estimated that 30% of the patients had HBV-DNA≥ 10 IU/ml, so there were about 16,200 patients had HBV-DNA≥ 10 IU/ml among 54,000 patients a year. These patients will be diagnosed with LLV and will undergo a treatment regimen adjustment, with a recommendation to switch to or use a different type of nucleos(t)ide analogue (NA) for anti-viral treatment.

Official Title
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Real World Study on the Effect of HBV-DNA High-precision Detection Based Anti-viral Regimen Adjustment on Achieving Complete Virologic Response in Patients With Chronic Hepatitis B.(REACH)

Conditions
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Sustained Virologic Response, Hepatitis B, Chronic

Intervention / Treatment
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* Other: only monitoring
* Other: monitoring and regimen change if necessary
* Drug: regimen change


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: any patients treated with ETV\LAM\ADF\LDT\TDF\TAF.【ADV=adefovir dipivoxil, LAM=lamivudine, and LdT=telbivudine , TAF =Tenofovir alafenamide Fumarate, ETV=Entecavir and TDF=Tenofovir disoproxil fumarate 】 Exclusion Criteria: with a expected life span <48 weeks

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with persistant low level HBV DNA (<10 IU/ml)<br>No further intervention(s) to be administered except for monitoring of HBV DNA viraemia | Other: only monitoring<br>* monitoring the viraemia only<br>|
| patients with persistant HBV DNA (>10 IU/ml) but refuse to change the regimen<br>All patients with CHB receiving ETV or second-line NA(LAM/ADV/LdT) treatment for more than six months to one year will receive HBV-DNA detection, and patients with HBV-DNA≥10 IU/ml will be informed and recommended to adjust the treatment regimen. If those patients refuse to change the regimen which they are using , No further intervention(s) to be administered except for monitoring of HBV DNA viraemia until those patients change their idea | Other: monitoring and regimen change if necessary<br>* if those patients agree, the regimen will be changed.<br>|
| patients with persistant HBV DNA (>10 IU/ml) and agree to change the regimen<br>All patients with CHB receiving ETV or second-line NA(LAM/ADV/LdT) treatment for more than six months to one year will receive HBV-DNA detection, and patients with HBV-DNA≥10 IU/ml will be informed and recommended to adjust the treatment regimen.They will change their regimen according one which they are using. | Drug: regimen change<br>* Based on ongoing one, regimen will be changed . The principle for adjusting anti-viral regimen is as follows: 1. The patients were treated with second-line drugs: changing ADV to ETV/TAF/TDF , changing LAM to TAF/TDF and changing LdT to TAF/TDF; 2. The patients were treated with ETV: adding or switching to TAF/TDF;3. TAF or ETV is recommended for patients with one or more TDF risk factors, such as > 40 years old, patients with abnormal bone/kidney related indicators or patients with high risk of bone/kidney injuries.【ADV=adefovir dipivoxil, LAM=lamivudine, and LdT=telbivudine , TAF =Tenofovir alafenamide Fumarate, ETV=Entecavir and TDF=Tenofovir disoproxil fumarate 】<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who received a complete virologic response (HBV DNA<10IU/ml) at 24 weeks after therapy adjustment. | The proportion of patients who received a complete virologic response (HBV DNA<10IU/ml) at 24 weeks after therapy adjustment. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with complete virologic response (HBV DNA<10IU/ml) at 12 weeks, 48 weeks and 96 weeks after therapy adjustment. | The proportion of patients with complete virologic response (HBV DNA<10IU/ml) at 12 weeks, 48 weeks and 96 weeks after therapy adjustment. | 12 weeks, 48 weeks ,96 weeks | 
| he proportion of patients with normal Alanine transaminase（ALT） at baseline and at each follow-up time point | he proportion of patients with normal Alanine transaminase（ALT ）at baseline and at each follow-up time point | baseline,12 weeks,48 weeks,96 weeks | 
| Changes of estimated glomerularfiltrationratee(GFR) compared with baseline at each follow-up time point. | Changes of estimated glomerularfiltrationratee(GFR) compared with baseline at each follow-up time point. | baseline,12 weeks,48 weeks,96 weeks | 
| Changes of serum creatinine(SCr）compared with baseline at each follow-up time point. | Changes of serum creatinine(SCr) compared with baseline at each follow-up time point. | baseline,12 weeks,48 weeks,96 weeks | 
| Changes of bone mass density（BMD) compared with baseline at each follow-up time point. | Changes of bone mass density (BMD) compared with baseline at each follow-up time point. | baseline,12 weeks,48 weeks,96 weeks |