Effect of Entecavir Treatment on Regression and Disease Outcome in HBV-induced Liver Fibrosis and Cirrhosis Patients

Study Overview
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Brief Summary
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Patients who have completed 2 years follow-up of the past National 12th Five-Year Major Project on Infectious Diseases will receive another 8 years treatment with entecavir (10 years in total). Collect serology, imaging, and other clinical data to evaluate the incidence and mortality of decompensated cirrhosis and hepatocellular carcinoma. Understand the effects of long-term antiviral therapy on HBV-induced liver fibrosis/cirrhosis.

Detailed Description
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Patients who have completed 2-years entecavir-based treatment in Regress Study will receive another 8 years of entecavir extension therapy. Patients will be assessed at baseline and every six months for blood cell count, liver function test, HBV-DNA, AFP, prothrombin time, liver ultrasonography, and Fibroscan; A third liver biopsy will be performed at the 5th year of treatment in patients who have significant fibrosis at second biopsy. CT /MRI and endoscopy will be performed at baseline and the 5th and 10th year of treatment.

Official Title
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Effect of Entecavir Treatment on Regression and Long-term Disease Outcome in Patients With HBV-induced Liver Fibrosis and Cirrhosis (Regress Extension Study)

Conditions
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Hepatitis B, Liver Cirrhosis

Intervention / Treatment
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* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Subjects who completed the 2 years of entecavir-based therapy in Regress study; Subjects who are willing to participate the extension study. Exclusion Criteria: - Any complication of severe heart, lung, kidney, brain, blood diseases or other important systematic diseases; Pregnant women; Subjects who could not compliance with the protocol judged by investigators; Subjects who are not suitable for the study judged by investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>entecavir oral，0.5mg daily for 8 years | Drug: Entecavir<br>* oral entecavir 0.5mg daily for 8 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibrosis regression rate | Ishak fibrosis score decrease after long-term treatment | year 3 | 
| Cumulative incidence of liver decompensation | Cumulative incidence of liver decompensation (including ascites, hepatic encephalopathy, esophageal varices bleeding and Hepatocellular Carcinoma) and death after long-term treatment | year 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological response | Percentage of patients achieving hepatitis B virus (HBV) DNA < 20IU/mL at year 3, 5, 7 and 10 | year 3, 5, 7 and 10 | 
| Aminotransferase response | The percentage of patients with alanine aminotransferase (ALT) normalization at year 3, 5, 7 and 10 | year 3, 5, 7 and 10 | 
| HBeAg loss or HBeAg seroconversion | Percentage of patients with HBeAg loss or HBeAg seroconversion at year 2, 5, 7 and 10 | year 2, 5, 7 and 10 | 
| HBsAg loss or HBsAg seroconversion rate | Percentage of patients with HBsAg loss or HBsAg seroconversion at year 2, 5, 7 and 10 | year 2, 5, 7 and 10 | 
| Dynamic changes of Child-Pugh score | Dynamic changes of Child-Pugh score after 3, 5, 7 and 10 years of treatment | year 3, 5, 7 and 10 | 
| Dynamic changes of MELD score | Dynamic changes of MELD score after 3, 5, 7 and 10 years of treatment | year 3, 5, 7 and 10 | 
| Dynamic changes of liver stiffness values measured by Transient Elastography | Dynamic changes of liver stiffness values after 3, 5, 7 and 10 years of treatment | year 3, 5, 7 and 10 | 
| Improvement of life quality (SF36 and EQ-5D) | Improvement of life quality after 3, 5, 7 and 10 years of treatment | year 3, 5, 7 and 10 |