Traditional Chinese Medicine Combined With Entecavir to Treat Refractory Liver Fibrosis in Liver Cirrhosis Due to HBV

Study Overview
=================
Brief Summary
-----------------
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 regress or reverse liver fibrosis in patients with chronic Hepatitis and liver cirrhosis due to HBV, however some patients keep existence or development although HBV DNA is under-detectable after anti-virals. Theses refractory liver fibrosis is required the anti-fibrotic treatment focusing on the regulation of hepatic extracellular matrix, 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 refractory liver fibrosis in liver cirrhosis due to HBV. The primary objective of this study is to establish the safety and efficacy of the combination of Entecavir and Traditional Chinese Medicine in refractory liver fibrosis in liver cirrhosis due to HBV.

Official Title
-----------------
A Multi-Center Study to Assess the Efficacy and Safety of Traditional Chinese Medicine Combined With Entecavir for Patients With Refractory Liver Fibrosis in Liver Cirrhosis Due to HBV

Conditions
-----------------
Hepatitis B Virus Related Cirrhosis

Intervention / Treatment
-----------------
* Drug: Entecavir+Fuzheng Huayu+TCM Granule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hepatitis B history or more than 6 months history of positive HBsAg Within 2 years of Entecavir treatment, HBV-DNA is negative but has not reach the clinical endpoint (HBeAg seroconversion or HBsAg loss in HBeAg-positive patients; HBsAg loss or anti-HBs seroconversion in HBeAg-negative patients) Age 18-60 Ishak fibrosis score of the biopsy within 6 months ≥5, no anti-fibrosis drug was taken within 6 months. Child-Pugh<7 (Stage A) The patient or the patient's guardian agrees to participate the random controlled trial and sign the Informed Consent Form. Exclusion Criteria: 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 other anti-viral drug within 6 months. Patients who are participating other trials. Other situation where PI thinks the patient should be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entecavir+Fuzheng Huayu+TCM Granule<br>Tablet with Entecavir+ Tablet with Fuzheng Huayu+ Granule with TCM | Drug: Entecavir+Fuzheng Huayu+TCM Granule<br>* The subjects will be taking 1 Entecavir tablet per day, 4 Fuzheng Huayu tablets three times a day and specific Traditional Chinese Medicine granule for 48 weeks.<br>* Other names: FZHY;|

What is the study measuring?
-----------------
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 |