Chronic Hepatitis B
Conditions
Brief summary
This study evaluates whether Peg-IFN alfa-2a can reduce the recurrence rate of hepatitis B in 96 weeks after nucleoside analogue (NUC) withdrawal. The HBV HBeAg-Negative patients who received NUC anti-virus treatment for 2.5 years and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010) were randomly assigned into three groups: One group discontinue the NUC treatment and follow up for 96 weeks,One discontinue the NUC treatment ,receive Peg-IFN alfa-2a 180 μg by week for 24 weeks and follow up for 72 weeks,The other discontinue the NUC treatment ,receive Peg-IFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks.
Detailed description
NUC is a potent inhibitor of hepatitis B viral(HBV) replication, but long-term therapy may be required. Therefore, NUC resistance is an important clinical risk resulting from long-term therapy in chronic hepatitis B (CHB) management. Discontinuation of NUC is a feasible strategy to reduce resistance. However, the high rate of relapse after cessation of NUC treatment in CHB patients remains a big problem. NUC treatment of how to safely stop drug needs to be solved. Peg-IFN can clear HBV by direct anti-viral and immune regulation mechanisms including enhancing natural killer cell response, increased cluster of differentiation 8(CD8 +) T lymphocytes and other mechanisms to restore and enhance the immune response in patients with CHB. Response to PEG-IFN is frequently sustained after a finite treatment course due to its immune modulating capacity.
Interventions
DRUGPegIFN alfa-2a
180 μg/ 0.5 ml ,hypodermic injection once a week
Sponsors
Huashan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. HBeAg-Negative Chronic Hepatitis B Patients：HBsAg-Positive,HBsAb-Negative,HBeAg-Negative,HBeAb-Positive during screening period and before NA treatment 2. NUC monotherapy (including adefovir and entecavir) for more than 2.5 years,and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010):the patients who achieved undetectable HBV DNA (\<300 copies/mL) with normal alanine aminotransferase (ALT) and the consolidation therapy reached 1.5 years ,total course of the treatment reached 2.5 years can stop NUC therapy 3. Willing to stop the drug, and signed a written informed consent
Exclusion criteria
1. HBsAb positive in screening period 2. Compensated or Decompensated liver cirrhosis:with history of cirrhosis before NUC treatment or Child-Pugh score ≥ 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding 3. Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN 4. A history of immunoregulation drug therapy within one year before entry including IFN and so on. 5. Coinfection with HAV、HCV、HDV、HEV 、HIV or with Other chronic liver diseases such as Alcoholic Liver Disease,Inherited Metabolic Liver Disease,Drug induced Liver Disease and nonalcoholic fatty liver 6. Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on. 7. Hepatocellular carcinoma(HCC) or alpha feto protein(AFP) levels more than 100 ng/ml and Hepatic malignant potential of Imaging examination or AFP levels more than 100 ng/ml for 3 months 8. A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter 9. A serum creatinine level that was more than 1.5 times the upper limit of the normal range 10. With other malignant tumors(exclude the cured ones) 11. Severe organ dysfunction 12. With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on 13. Uncontrolled diabetes, hypertension or thyroid disease 14. Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period 15. Participate in other clinical studies at the same time 16. Patients unsuitable for the research
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who relapse | 96 weeks | The total number of relapse (HBV DNA\>2000 IU/ml on 2 separate occasions 1 months apart) during the research period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who relapse | 48 weeks | The total number of relapse (HBV DNA\>2000 IU/ml on 2 separate occasions 1 months apart) during the research period. |
| Number of participants who achieve HBsAg seroconversion | At the point of discontinuation of PegIFN therapy | To investigate whether Peg-IFN alfa-2a can improve the HBsAg seroconversion in CHB patients at the point of discontinuation of PegIFN therapy compared to the control group ,which will be measured by the number of participants who achieve HBsAg seroconversion. Pegasys 24 weeks Group:24 weeks and Pegasys 48 weeks Group:48 weeks |
| HBsAg changes from Baseline | 12,24 and 48 weeks | Pegasys 24 weeks Group:12,24 weeks and Pegasys 48 weeks Group:12,24,48 weeks |
| Predictive value of other markers for recurrence after NUC withdrawal | 48 weeks and 96 weeks | To investigate whether the other markers including HBcAb quantification and so on can predict the recurrence of hepatitis B. |
Countries
China
Outcome results
None listed