Combination Treatment of NAs and Peg IFN α-2b for Hepatitis B Related, Compensatory Cirrhosis Patients

Study Overview
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Brief Summary
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The study aims to demonstrate that whether treatment of nucleoside （acid）analogues (NAs) plus pegylated interferon (Peg IFN) α-2b for those NAs treated, low level of HBsAg, hepatitis B related compensatory cirrhosis patients will result in higher HBsAg clearance rate and reduce the risk of liver cancer. The investigators plan to enroll about 84 hepatitis B related compensatory cirrhosis patients, who have received NAs treatment more than 1 year with the level of HBsAg <1000IU/ml. These participants will be devided into 2 groups. Group A will receive the treatment of NAs plus Peg IFNα-2b. Group B will be treated with NAs as before enrollment. The participants in both groups will be followed up for 96 weeks. The primary endpoint is to compare the clearance rate of HBsAg between two groups. The secondary endpoint includes: (1) comparing the incidence of liver cancer during the 96 weeks follow-up, (2) comparing adverse side effects between the 2 groups. (3) comparing the virological and biochemical responses between the 2 groups.

Detailed Description
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Clearance of hepatitis B virus surface antigen (HBsAg) is considered to be the ultimate therapeutic goal for hepatitis B patients, for it is related with low incidence of fibrosis and liver cancer. The investigators' previous study show that nucleoside （acid）analogues (NAs) treated, non-cirrhosis hepatitis B patients switched to /or combined with pegylated interferon (Peg IFN)α-2b could obtain a higher HBsAg clearance rate. Hence, the investigators' hypothesis is that treatment of NAs plus Peg IFNα-2b for those NAs treated, low level of HBsAg, hepatitis B related compensatory cirrhosis patients result in higher HBsAg clearance rate and reduce the risk of liver cancer. The investigators plan to enroll about 84 hepatitis B related compensatory cirrhosis patients, who have received NAs treatment more than 1 year with the level of HBsAg <1000IU/ml. These participants will be devided into 2 groups according to their wishes. Group A will receive the treatment of NAs (patients previously treated with telbivudine will be changed to entecavir) plus Peg IFNα-2b （180ug per week, the dose will be changed to 135ug or 90ug per week during the treatment if patients could not tolerate the side effects of Peg IFNα-2b）. Peg IFNα-2b treatment will be performed until HBsAg <0.05IU/ml, with a maximum duration of 48 weeks. Group B will be treated with NAs as before enrollment. The participants in both groups will be followed up for 96 weeks. The primary endpoint is to compare the clearance rate of HBsAg between two groups. The secondary endpoint includes: (1) comparing the incidence of liver cancer during the 96 weeks follow-up, (2) comparing adverse side effects, such as ascites, gastrointestinal bleeding, encephalopathy, hepatorenal syndrome between the 2 groups. (3) comparing the virological and biochemical responses between the 2 groups.

Official Title
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Combination Treatment of Nucleoside （Acid）Analogue (NAs) and Pegylated Interferon α-2b for NAs Treated, Hepatitis B Related, Compensatory Cirrhosis Patients With Low Level Hepatitis b Virus Surface Antigen (HBsAg)

Conditions
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Cirrhosis of Liver Due to Hepatitis B (Disorder)

Intervention / Treatment
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* Drug: pegylated interferon (Peg IFN)α-2b
* Drug: Nucleoside （acid）analogue (NAs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 16-65 years old; Clinical diagnosis of compensatory cirrhosis; Child-Pugh grade A; Positive serum hepatitis B surface antigen (HBsAg); HBsAg titer < 1000IU/ml; Treated by nucleoside （acid）analogues (NAs) more than 1 year; HBV DNA <20 IU/ml; Negative serum hepatitis B e antigen (HBeAg); 15 minutes retention rate of indocyanine green <10%; The blood routine examination: 4×10e9/L<WBC<10×10e9/L、100×10e9/L<PLT<300×10e9/L. Exclusion Criteria: Treated by interferon within half a year; Drug induce liver diseases; Autoimmune liver diseases; Liver diseases caused by metabolic factors; Superinfection with hepatitis A, C, D, E viruses; Infected by HIV virus; Severe respiratory diseases; Severe circulatory diseases, ; Severe digestive diseases; Severe neurological diseases; Need for immunosuppressive therapy for other diseases; Need for radiotherapy/chemotherapy for other diseases; Thyroid diseases; Rheumatic diseases; Malignant tumors; Severe varicose esophageal and gastric fundus veins; Mental or psychological disorders; Alcohol or drug abusers (average alcohol consumption >40g/d for men, >20g/d for women); With contraindications to interferon therapy; Pregnancy or having pregnancy plan in 3 years; Lactation; Can not comply with the study protocol; Fail to sign the informed consent; Other conditions that are not suitable for enrollment determined by researchers.

Ages Eligible for Study
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Minimum Age: 16 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAs+Peg IFN Group<br>NAs+Peg IFN Group will receive the treatment of NAs (patients previously treated with telbivudine will be changed to entecavir) plus pegylated interferon (Peg IFN)α-2b. | Drug: pegylated interferon (Peg IFN)α-2b<br>* Participants in NAs+Peg IFN Group will be treated by Peg IFNα-2b （180ug per week, the dose will be changed to 135ug or 90ug per week during the treatment if patients could not tolerate the side effects of Peg IFNα-2b). Peg IFNα-2b treatment will be performed until HBsAg <0.05IU/ml, with a maximum duration of 48 weeks.<br>* Other names: Pi Gebin;Drug: Nucleoside （acid）analogue (NAs)<br>* Both of NAs Group and NAs+Peg IFN Group will be treated with NAs as before enrollment.<br>* Other names: Boludine;|
| Other: NAs Group<br>NAs Group will be treated with NAs as before enrollment. | Drug: Nucleoside （acid）analogue (NAs)<br>* Both of NAs Group and NAs+Peg IFN Group will be treated with NAs as before enrollment.<br>* Other names: Boludine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The clearance rate of HBsAg for both groups during 96 weeks. | The clearance rate of HBsAg will be compared between 2 groups. | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of liver cancer for both groups during 96 weeks | The incidence of liver cancer will be compared between 2 groups. | 96 weeks | 
| Occurance rate of adverse side effects in both groups | Adverse side effects, such as ascites, gastrointestinal bleeding, encephalopathy, hepatorenal syndrome will be compared between 2 groups | 96 weeks | 
| The change of liver functions in both groups | The levels of alanine transaminase, glutamic-oxalacetic transaminase, albumin, total bilirubin, INR will be compared between the 2 groups. | 96 weeks | 
| The change of blood routine test indexes in both groups | The levels of WBC, Hb, PLT will be compared between the 2 groups. | 96 weeks |