HBsAg Seroclearance in Adults With HBV Related Liver Fibrosis After Receiving Combined Therapy of Peg-IFN and Tenofovir.

Study Overview
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Brief Summary
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Liver fibrosis caused by hepatitis B virus (HBV) infection is easy to progress to liver cirrhosis and liver cancer, with great harm and poor therapeutic effect. Nucleos(t)ide analogues (NAs) are the most commonly anti-HBV drugs currently . Long-term use of NAs can inhibit HBV DNA and achieve the purpose of reducing poor prognosis. However, adverse prognosis, such as liver cirrhosis and liver cancer, cannot be completely eliminated even under the status of virologic inhibition under THE action of NAs. Current studies have shown that the lower the HBV surface antigen (HBsAg) is, the better the long-term prognosis is. As another anti-HBV drug, pegylated-interferon-α (peg-IFN-α) has the immune regulation effect that NAs do not have, which can bring irreplaceable effects in HBsAg reduction and liver fibrosis reversal. Therefore, the combined therapy of NAs and peg-IFN-α is a hot issue in the field of liver diseases over the world, but the research and application of the combined therapy in patients with liver fibrosis are very few. The preliminary results of our previous research showed that the combined therapy of peg-IFN-α and NAs in patients with HBV related fibrosis were safe, and had a significant effect on HBsAg decline. On this basis, this study intends to carry out a multicentre, randomized controlled study, comparing the safety and efficacy between combined therapy (peg-IFN-α plus tenofovir) and tenofovir monotherapy in patients with liver fibrosis, especially focusing on HBsAg's decline and clearance, and the improvement of liver fibrosis degree, in order to find a better therapy, and to guide the clinical decision making.

Official Title
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A Multicentre, Randomized Controlled Trial in HBsAg Seroclearance After Receiving Combined Therapy of Peginterferon and Tenofovir in Nucleos(t)Ide Analogue-treated Patients With HBV Related Liver Fibrosis.

Conditions
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Liver Fibrosis

Intervention / Treatment
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* Drug: PEG-Interferon Alfa, Tenofovir Disoproxil Fumarate
* Drug: Tenofovir Disoproxil Fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Positive hepatitis b surface antigen; 2.Infection of hepatitis b virus DNA > 0.5 year before anti-HBV treatment; 3.Receiving treatment of nucleoside/nucleotide analogues at least one year before recruited; 4.Age from 18 to 55 years old; 5.Normal liver function(ALT<ULN,AST<ULN and TBil<ULN); 6.Undetectable hepatitis b virus DNA or less than 100IU/ml; 7.Liver biopsy suggested fibrosis of liver into F1 F3(Metavir score system) or LSM between 6 and 12 kpa measured by fibroscan; 8.Liver ultrasound: normal or echo thickening, and portal vein diameter ≤ 12mm. Exclusion Criteria: 1.Decompensated cirrhosis, hepatocellular carcinoma or other malignancy; 2.Pregnancy, lactation or female has plan of pregnancy within 18 months; 3.Accompanied with other active liver diseases(HAV, HCV, HDV, HEV, autoimmune liver disease, drug-induced liver injury, alcoholic liver disease, genetic metabolic liver disease, etc.)； 4.Accompanied with human immunodeficiency virus infection or congenital immune deficiency diseases; 5.Accompanied with severe diabetes, autoimmune diseases etc. and other important organ dysfunctions; 6.Patients who fail to comply with this research arrangement and sign an informed consent form; 7.Patients can not follow-up; 8.Investigator considering inappropriate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: TDF group<br>tenofovir 300mg taken orally per day. | Drug: Tenofovir Disoproxil Fumarate<br>* TDF monotherapy<br>|
| Experimental: peg-IFN-α plus TDF group<br>peg-IFN-α 180ug given subcutaneous injection per week combined with tenofovir 300mg taken orally per day . | Drug: PEG-Interferon Alfa, Tenofovir Disoproxil Fumarate<br>* Combination therapy group was treated with PEG-interferon Alfa in addition to TDF monotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of HBsAg seroclearance/seroconversion | proportion of seroclearance or seroconversion of HBV surface antigen compared with baseline | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of HBsAg seroclearance/seroconversion | Proportion of seroclearance or seroconversion of HBV surface antigen compared with baseline | 96 weeks | 
| proportion of fibrosis improvement | Proportion of patients with improved fibrosis compared with baseline | 96 weeks |