Treatment of Liver Cirrhosis Due to Hepatitis B Virus With Fuzheng Huayu and Entecavir

Study Overview
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Brief Summary
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Liver Cirrhosis is a common pathological consequence of chronic liver disease. Hepatitis B Virus (HBV) is one of most etiologies of liver cirrhosis in China. The effective inhibition of HBV can partially stop or reverse liver fibrosis in patients with chronic Hepatitis and liver cirrhosis due to HBV, and the anti-fibrotic strategy focusing on the regulation of hepatic extracellular matrix is still required and hopefully improve the efficacy of anti-virals for liver fibrotic patients with HBV, especially is necessary for in the patients with advance fibrosis stage ie. liver cirrhosis. Fuzheng Huayu has been found to enhance the degradation of collagens in fibrotic liver and have a good action against liver fibrosis in patients with chronic hepatitis B. However, there are no high quality clinical evidences which can demonstrate if the combination of anti-viral and anti-fibrotic therapy can improve the reversion of liver cirrhosis due to HBV. The primary objective of this study is to establish the safety and efficacy of the combination of Entecavir and Fuzheng Huayu for the reversion of liver fibrosis in patients with liver cirrhosis due to HBV.

Official Title
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A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study to Assess the Efficacy and Safety of Fuzheng Huayu Combined With Entecavir in Liver Cirrhosis Patients Due to Hepatitis B Virus

Conditions
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Liver Cirrhosis Due to Hepatitis B Virus

Intervention / Treatment
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* Drug: Entecavir + Placebo
* Drug: Entecavir + Fuzheng Huayu Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: More than 6 months history of serum positive HBsAg Positive HBV-DNA Age 18-60 Ishak fibrosis score of the biopsy within 6 months ≥5, no anti-virus or anti-fibrosis drug was taken within 6 months. Child-Pugh<7 (Stage A) The patient or the patient's guardian agrees to participate the trial and sign the informed Consent Form. Exclusion Criteria: Primary Lamivudine, Adefovir dipivoxil and Entecavir resistance Decompensated liver cirrhosis HCC Liver histology conforming to other chronic liver diseases, such as moderate or severe non-alcoholic fatty liver disease(more than 1/3 steatosis in liver ), chronic hepatitis C, chronic hepatitis D, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, inherited metabolic liver disease, drug or toxic induced liver injury, parasitic infections, alcoholic liver disease. Have psychiatric history or uncontrollable epilepsy patient. Uncontrollable diabetic patient History of hemoglobin disease (such as alpha- or beta-thalassemia, sickle cell disease, spherocytosis) or patients with toxic or autoimmune hemolytic anemia. Severe background disease like chronic respiratory failure, circulatory failure, kidney failure etc. In situ organ transplantation (such as liver, kidney, lung and heart) or bone marrow transplantation and stem cell transplantation. Immunocompromised patients: such as HIV infection or take immunosuppressor or glucocorticoid (such as cyclosporin, azathioprine, adrenocortical hormone) within 3 months or chemotherapy drugs (such as cyclophosphamide, ammonia and cancer chemotherapy) and radioactive therapy. Gestation or lactation period women and women who plan to get pregnant during the study period. Patient who are allergy to the experimental drug. Using history of anti-viral or anti-fibrosis drug within 6 months. Patients who are participating other trials. Other situation where PI thinks the patient should be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Entecavir + Placebo<br>Tablet with Entrcavir+ Tablet with starch | Drug: Entecavir + Placebo<br>* The subjects will be taking 1 Entecavir tablet per day and 4 Placebo tablets three times a day for 48 weeks.<br>|
| Experimental: Entecavir + Fuzheng Huayu Tablet<br>Tablet with Entrcavir+ Tablet with Fuzheng Huayu | Drug: Entecavir + Fuzheng Huayu Tablet<br>* The subjects will be taking 1 Entecavir tablet per day and 4 Fuzheng Huayu tablets three times a day for 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of liver fibrosis | The collagen of liver tissue from 48 week post-treatment patients was stained. 3 pathologists read the slides independently and score the slides with Ishak system. If the Ishak score decrease 1 or more than 1 score, then it is recorded as regression. | 48 weeks |