Optimized Treatment and Regression of HBV-induced Compensated Liver Cirrhosis

Study Overview
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Brief Summary
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Six hundreds patients with chronic hepatitis B clinically diagnosed as compensated liver cirrhosis are randomly assigned in a 1:1 ratio. One arm is entecavir alone for 2 years; the other is entecavir alone for the first 0.5 year, entecavir plus thymosin-α for 1 year, entecavir for another additional 0.5 year.Patients will be assessed at baseline, at every six months for blood cell count, liver function test, HBVDNA, AFP, prothrombin time, liver ultrasonography, and Fibroscan;

Official Title
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Optimized Treatment and Regression of HBV-induced Compensated Liver 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 ; Male or female; Treatment-naive patients of clinically diagnosed as HBV-induced compensated cirrhosis(meet one of the following two criterions); endoscopy: esophageal varices , exclusion of noncirrhotic portal hypertension if no endoscopy,should meet two of the four Criterias: Imaging (US, CT or MRI, et al) showing Surface nodularity: Echogenecity Platelet (PLT) < 100×10 < 9 >/L , no other interpretation Albumin (ALB) < 35.0 g/L, or International Standard Value (INR) > 1.3 (Prothrombin Time (PT) prolonged > 3s), or Cholinesterase (CHE) decrease Liver stiffness measurement value > 12.4 kpa (ALT<5×ULN) HBeAg-positive, HBVDNA > 2×10<3> IU/ml or with HBeAg-negative patients, HBVDNA > 2×10<2> IU/ml; Agree to be followed up regularly; Signature of written inform 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 medicine 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 100ng/ml and possible malignant lesion on image, or AFP level higher than 100ng/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 system 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, 0.5mg, qd, oral, for 2 years | Drug: Entecavir<br>* anti-viral therapy<br>* Other names: Entecavir dispersible tablets;|
| Experimental: Entecavir plus thymosin therapy<br>Entecavir plus thymosin-α 1.6μg, Twice a week, ih, in the middle one year | Drug: Entecavir<br>* anti-viral therapy<br>* Other names: Entecavir dispersible tablets;Drug: Thymosin-α<br>* anti-viral and antitherapy<br>* Other names: Zadaxin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decompensated rate of Liver Cirrhosis after 2 years treatment | Decompensated rate of Liver Cirrhosis (ascites, hepatic encephalopathy, esophageal varices bleeding and Hepatocellular Carcinoma) after 2 years treatment. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child-Pugh and MELD scores | The progress of Child-Pugh and MELD scores after 1 and 2-year treatment | 1 and 2-year | 
| The HBV DNA undetectable rate | The HBV DNA undetectable rate after 1 and 2-year treatment | 1 and 2-year | 
| Liver stiffness measurement | Liver stiffness measurement change after 1 and 2-year treatment. | 1 and 2-year | 
| Quality of Life | Quality of life after 1 and 2-year treatment by SF-36 and EQ-5D questionares | 1 and 2-year | 

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