A Study in Reversing Hepatic Fibrosis or Cirrhosis Related to Hepatitis B Virus and Finding Biomarkers

Not Applicable

• Conditions: Liver Fibrosis; Hepatitis B
• Interventions: Drug: Entecavir 0.5 mg; Drug: Anluohuaxian Pill 12g

• Registration Number: NCT03568578
• Lead Sponsor: Peking University First Hospital

Brief Summary

The aim of our study is to validate the non-invasive model which was constructed by our previous study for evaluating liver fibrosis or cirrhosis caused by hepatitis B virus in mainland China and to find a therapeutic regimen to reverse liver fibrosis and cirrhosis.

Detailed Description

450 patients who are infected with hepatitis B virus for at least 6 months will be included in the study. They will be divided into two groups. One group will be treated with Entecavir while another treated with Entecavir and Anluohuaxian Pill. Liver biopsy samples and blood samples from the patients will be used to validate the non-invasive model. Furthermore, the samples will be used to evaluate if Anluohuaxian Pill could reverse liver fibrosis and cirrhosis.

Study Timeline

• Study Start: 2018-01-28
• Study First Submitted: 2018-05-30
• Status Verified: 2018-06
• Study First Submitted QC: 2018-06-13
• Last Update Submitted: 2018-06-25
• Study First Posted: 2018-06-26
• Last Update Posted: 2018-06-27
• Primary Completion: 2020-12-31
• Study Completion: 2021-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

1. HBsAg positive for at least 6 months
2. Agree to have liver biopsy
3. Male or female aged 18 to 70 years old -

Exclusion Criteria

1. Patients with alcoholic liver disease, autoimmune liver disease, heretic liver disease, drug induced liver disease, nonalcoholic liver disease or other chronic liver disease
2. Platelet count < 80 × 10^9/L
3. Prothrombin activity ≤ 60%
4. Decompensated liver cirrhosis
5. Patients with any disease or condition which the investigator or treating physician feels would interfere with the trial or the safety of the subject -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Entecavir Group	Entecavir 0.5 mg	Patients in this arm will be given Entecavir 0.5 mg a day for 2 years.
Entecavir and Anluohuaxian Group	Entecavir 0.5 mg	Patients in this arm will be given Entecavir 0.5 mg and Anluohuaxian Pill 12 g a day for 2 years.
Entecavir and Anluohuaxian Group	Anluohuaxian Pill 12g	Patients in this arm will be given Entecavir 0.5 mg and Anluohuaxian Pill 12 g a day for 2 years.

Primary Outcome Measures

Name	Time	Method
Construct a non-invasive model based on laboratory tests	26 weeks after liver biopsy	We will measure the following biomarkers: TIMP1，CXCL10，CD25，YKL-40，collagen IV，von Willebrand Factor，TGF-β1，ANGPTL2，MMP-9，IL-2R，PDGF-AA，PDGF-BB，TGF-a，LN，MMP-1, soluble CD163 and CXCL9. To formulate the predictive models for detecting significant fibrosis (Ishak fibrosis score ≥3)， univariate analysis was performed on variables between patients with and without significant fibrosis. The significant variables (p\<0.05) were then subjected to multivariate stepwise logistic regression, using backward approaches, and were combined using the logistic regression function. The diagnostic value of each regression model was assessed using receiver operating characteristics curves.

Secondary Outcome Measures

Name	Time	Method
Compare the difference of fibrosis reverse rates between the two groups	26 weeks after liver biopsy	Liver biopsy samples will be evaluated by Ishak fibrosis score. Then we compare the difference of fibrosis reverse rates between the two groups by Ishak fibrosis score.

Trial Locations

Locations (16)

Guiqiang Wang; 🇨🇳 Beijing, Beijing, China

Shanghai Ruijin Hospital; 🇨🇳 Shanghai, Shanghai, China

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China

The People's Hospital of Guangxi Zhuang Autonomous Region; 🇨🇳 Nanning, Guangxi, China

Nanfang Hospital; 🇨🇳 Guangzhou, Guangdong, China

Shanghai Public Health Clinical Center; 🇨🇳 Shanghai, Shanghai, China

Beijing Youan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Zhejiang First Hospital; 🇨🇳 Hangzhou, Zhejiang, China

The Second Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

The First Affiliated Hospital with Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China

Henan Provincial People's Hospital; 🇨🇳 Zhengzhou, Henan, China

Wuxi the Fifth People's Hospital; 🇨🇳 Wuxi, Jiangsu, China

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China

Peking University First hospital; 🇨🇳 Beijing, Beijing, China