HBeAg Positive Chronic Hepatitis B
Conditions
Keywords
hepatitis B,chronic; Interferon ; Nucleosides;child
Brief summary
The purpose of this study is to provide theoretical and real world evidence for the optimization of antiviral treatment by IFN combined with Nucleosides analog in HBeAg positive chronic hepatitis B patients aged 1-16 years，so that the functional cure could be achieved in the greatest extent in pediatric patients
Detailed description
This research is a national multicenter, randomized, prospective study. The planned sample size is 200 subjects in 1-16 years pediatric patients with HBeAg positive Chronic Hepatitis B (CHB). These subjects will be randomized (1:1) to group A(treated with NAs + IFN for 96 weeks) and group B(treated with NAs for 48 weeks, then NAs combined with IFN for 96 weeks).Meanwhile, 1-6 years and 7-16 years patients should be distributed by 1:1 ratio by random method in both groups. Regularly Blood cell count, biochemical test, hepatitis B viral markers test, and lymphocyte subsets test were exerted. To compare the curative effect of group A and group B, The primary monitoring indicator is HBsAg clearance rate, and the secondary monitoring indicator is hepatitis B virus (HBV) DNA clearance，HBeAg seroconversion in these patients,. So that we can make the optimal antiviral treatment strategy for 1-16-year-old children with CHB，and try to find out the possible influencing factors of function cure
Interventions
DRUGNAs+IFN-α
NAs+IFN-α:(NAs +IFN)/96 weeks：NAs（when the CHB patients\<2years old, the drug is LAM）combined with IFN-α（when the CHB patients\<3years old, the drug is IFN-α）for 96 weeks。 NAs+(NAs+IFN-α) :NAs/48weeks+(NAs+ IFN)/96 weeks：NAs（when the CHB patients\<2years old, the drug is LAM）for 48 weeks ，then combined with IFN-α（when the CHB patients\<3years old, the drug is IFN-α）for 96weeks。 Response guided treatment（RGT） by HBsAg quantification： The course of interferon alpha was 24 weeks after HBsAg and HBeAg turned negative up to 96 weeks, and NAs was discontinued 12 months after HBsAg serological conversion.
Sponsors
Beijing 302 Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
These subjects will be randomized (1:1) to group A(treated with NAs + IFN for 96 weeks) and group B(treated with NAs for 48 weeks, then NAs combined with IFN for 96 weeks).Meanwhile, 1-6 years and 7-16 years patients should be distributed by 1:1 ratio by random method in both groups.
Eligibility
Sex/Gender
ALL
Age
1 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 1 to 16 years old. 2. Chronic Hepatitis B (CHB) patients or HBsAg positive \> 6 months patients who are line with the diagnostic criteria for chronic hepatitis B infection. 3. ALT:40～400 U/L. 4. HBeAg positive. 5. HBV DNA\>2×104IU/L. 6. Liver histology: G\<3. 7. Agree to sign the Informed Consent Form (Children aged 1-6 years may be signed by the guardian; children between the ages of 7 and 11 are in principle signed by the child and the guardian; those over the age of 12 must be signed by the child and the guardian)
Exclusion criteria
1. white blood cell (WBC)\< 3.5×109/L，PLT\< 80×1012/L，Pt A\<60%，total bilirubin (TBIL)\>34umol/L，ALB\<35g/L，Cr\>133umol/L. 2. Combined with HAV、HCV、HDV、HEV or HIV-infected persons. 3. Patients combined with other causes of liver disease：alcoholic or non-alcoholic liver disease，thyroid disease，autoimmune liver disease，genetic metabolic liver disease，bile duct diseases，or Parasitic infection of hepatobiliary tract. 4. Patients with decompensated cirrhosis，including ascites. 5. Received the following medications（Immunosuppressant and Systemic cytotoxic drugs）in six months. 6. Patients who are allergy to IFNs and NAs; 7. Patients with other severe or active psychosomatic diseases （kidney, heart, lungs, vascular, neurological, digestive including history of pancreatitis, metabolic diseases including diabetes, thyroid and Adrenal disease, adrenal disease or tumor), Researchers believe which affect the treatment, evaluation or compliance of patients with the study plan. 8. Patients who unable to comply with the study arrangement judged by researcher.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The rates of HBsAg serological disappearance / conversion in CHB patients at 48 weeks | 48 weeks | The rates of HBsAg serological disappearance / conversion in CHB patients at 48 weeks |
| The rates of HBsAg serological disappearance / conversion in CHB patients at 168 weeks | 168 weeks | The rates of HBsAg serological disappearance / conversion in CHB patients at 168 weeks |
| The rates of HBsAg serological disappearance / conversion in CHB patients at 144 weeks | 144 weeks | The rates of HBsAg serological disappearance / conversion in CHB patients at 144 weeks |
| The rates of HBsAg serological disappearance / conversion in CHB patients at 96 weeks | 96 weeks | The rates of HBsAg serological disappearance / conversion in CHB patients at 96 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HBV DNA negative conversion rate | 168 weeks | HBV DNA negative conversion rate in patients with CHB |
| The rate of HBeAg clearance / seroconversion | 168 weeks | The rate of HBeAg clearance / seroconversion in patients with CHB |
| ALT(Alanine aminotransferase) recovery rate | 168 weeks | ALT recovery rate in patients with CHB |
Other
| Measure | Time frame | Description |
|---|---|---|
| Average duration of HBeAg seroconversion | 168 weeks | Average duration of HBeAg seroconversion during treatment |
| Rate of relapse in patients after stop of antiviral therapy of NAs | 168 weeks | Rate of relapse in patients after stop of antiviral therapy of NAs |
| Assessed the changes of liver stiffness measure by FibroScan after antiviral therapy | 168 weeks | Comparison the changes of liver stiffness before and after antiviral treatment (evaluated by FibroScan) |
| Average duration of disappearance of HBsAg | 168 weeks | Average duration of disappearance of HBsAg during treatment |
| Number of participants with treatment-related side effect and safety events as assessed by GSI | 168 weeks | Side effect and safety events include adverse events, adverse drug reactions etc. during the treatment |
Countries
China
Contacts
Primary ContactMin Zhang, Doctor
Outcome results
None listed