Optimized Treatment and Regression of HBV-induced Early Cirrhosis

Study Overview
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Brief Summary
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Patients with chronic hepatitis B histologically confirmed of early cirrhosis S4 (similar to metavir F4, Ishak 5/6) are randomly assigned in a 1:1 ratio. One arm is entecavir alone for 2 years; the other is entecavir for the first 0.5 year, entecavir plus thymosin for 1 year, entecavir for another additional 0.5 year. Patients will be assessed at baseline, at every six months for blood count, liver function test, HBVDNA, AFP, prothrombin time, liver ultrasonography, and Fibroscan. The second liver biopsy will be performed to evaluate regression rate of liver fibrosis 1.5 years after initial therapy.

Official Title
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Optimized Treatment and Regression of HBV-induced Early Cirrhosis

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: entecavir
* Drug: Thymosin-α


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients from age 18 to 65 years old; Male or female; Treatment-naive patients with chronic hepatitis B histologically confirmed of early cirrhosis S4 (similar to metavir F4, Ishak 5/6) who consent to undergo liver biopsy before and after treatment; Patients with HBeAg-positive, HBVDNA>2×10<3>IU/ml or patients with HBeAg-negative, HBVDNA>2×10<2> IU/ml； Agree to be followed up regularly; Signature of written informed consent. Exclusion Criteria: Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or hepatocelluar carcinoma; Patients who are allergic to entecavir, thymosin or their components, and those considered not suitable for drugs used in this study; Patients with HCV or HIV infection, alcoholic liver disease, autoimmune liver disease, genetic liver disease, drug-induced liver injury, severe non-alcoholic fatty liver disease or other chronic liver diseases; Patients with baseline AFP level higher than 100 ng/ml and possible malignant lesion on image, or AFP level higher than 100 ng/ml for more than three months; Creatinine >1.5×ULN; Patients with other uncured malignant tumors; Patients with severe diseases of heart, lung, kidney, brain, blood or other organs; Patients with any other reasons not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Entecavir Therapy<br>Entecavir monotherapy: entecavir, 0.5mg, qd, oral, for 2 years. | Drug: entecavir<br>* anti-viral therapy<br>* Other names: entecavir dispersible tablets;|
| Experimental: Entecavir plus Thymosin-α<br>entecavir plus Thymosin-α 1.6μg, Twice a week, ih, in the middle of 1 year. | Drug: entecavir<br>* anti-viral therapy<br>* Other names: entecavir dispersible tablets;Drug: Thymosin-α<br>* antiviral and antifibrosis therapy<br>* Other names: Zadaxin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regression of HBV-induced liver cirrhosis | Liver cirrhosis regression of 1 point by Ishak scoring system | 1.5 to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child-Pugh score | Child-Pugh score change after 1 and 2-year treatment | 1 year and 2 years | 
| HBVDNA undetectable rate | The HBVDNA undetectable rate after 1 and 2-year treatment. | 1 year and 2 years | 
| Fibroscan value | Fibroscan value change after 1 and 2-year treatment | 1 year and 2 years | 
| Life Quality | Life quality change after 1 and 2-year treatment by SF-36 and EQ-5D questionaire | 1 year and 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, Liver Cirrhosis, Regression, Efficacy