A Study in Reversing Hepatic Fibrosis or Cirrhosis Related to Hepatitis B Virus and Finding Biomarkers

Study Overview
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Brief Summary
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The aim of our study is to validate the non-invasive model which was constructed by our previous study for evaluating liver fibrosis or cirrhosis caused by hepatitis B virus in mainland China and to find a therapeutic regimen to reverse liver fibrosis and cirrhosis.

Detailed Description
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450 patients who are infected with hepatitis B virus for at least 6 months will be included in the study. They will be divided into two groups. One group will be treated with Entecavir while another treated with Entecavir and Anluohuaxian Pill. Liver biopsy samples and blood samples from the patients will be used to validate the non-invasive model. Furthermore, the samples will be used to evaluate if Anluohuaxian Pill could reverse liver fibrosis and cirrhosis.

Official Title
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A Study in Reversing Hepatic Fibrosis or Cirrhosis Related to Hepatitis B Virus and Finding Biomarkers

Conditions
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Hepatitis B, Liver Fibrosis

Intervention / Treatment
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* Drug: Entecavir 0.5 mg
* Drug: Anluohuaxian Pill 12g


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HBsAg positive for at least 6 months Agree to have liver biopsy Male or female aged 18 to 70 years old - Exclusion Criteria: Patients with alcoholic liver disease, autoimmune liver disease, heretic liver disease, drug induced liver disease, nonalcoholic liver disease or other chronic liver disease Platelet count < 80 × 10^9/L Prothrombin activity ≤ 60% Decompensated liver cirrhosis Patients with any disease or condition which the investigator or treating physician feels would interfere with the trial or the safety of the subject -

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Entecavir Group<br>Patients in this arm will be given Entecavir 0.5 mg a day for 2 years. | Drug: Entecavir 0.5 mg<br>* Patients in this group will be given Entecavir 0.5 mg a day for 2 years.<br>* Other names: ETV;|
| Experimental: Entecavir and Anluohuaxian Group<br>Patients in this arm will be given Entecavir 0.5 mg and Anluohuaxian Pill 12 g a day for 2 years. | Drug: Entecavir 0.5 mg<br>* Patients in this group will be given Entecavir 0.5 mg a day for 2 years.<br>* Other names: ETV;Drug: Anluohuaxian Pill 12g<br>* Patients in this group will be given Entecavir 0.5 mg and Anluohuaxian Pill 12g a day for 2 years<br>* Other names: ALHX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Construct a non-invasive model based on laboratory tests | We will measure the following biomarkers: TIMP1，CXCL10，CD25，YKL-40，collagen IV，von Willebrand Factor，TGF-β1，ANGPTL2，MMP-9，IL-2R，PDGF-AA，PDGF-BB，TGF-a，LN，MMP-1, soluble CD163 and CXCL9. To formulate the predictive models for detecting significant fibrosis (Ishak fibrosis score ≥3)， univariate analysis was performed on variables between patients with and without significant fibrosis. The significant variables (p<0.05) were then subjected to multivariate stepwise logistic regression, using backward approaches, and were combined using the logistic regression function. The diagnostic value of each regression model was assessed using receiver operating characteristics curves. | 26 weeks after liver biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the difference of fibrosis reverse rates between the two groups | Liver biopsy samples will be evaluated by Ishak fibrosis score. Then we compare the difference of fibrosis reverse rates between the two groups by Ishak fibrosis score. | 26 weeks after liver biopsy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibrosis, Liver Cirrhosis, non-invasive biopsy, hepatitis B virus