Cohort Study of Clinical Outcomes in Chronic HBV Infection Patients With Low HBsAg Under Unplanned Intervention

Study Overview
=================
Brief Summary
-----------------
All chronic hepatitis B (CHB) patients were diagnosed and treated in the liver disease department of the Hepatology Center of Beijing Ditan Hospital affiliated to Capital Medical University and those who received antiviral therapy (interferon and nucleoside analogues) reached HBsAg<100 IU/ml. The enrolled subjects were divided into the following six observation cohorts: 1) CHB patients in the immunological control period, without any clinical treatment intervention; 2) After interferon therapy, HBsAg<100 IU/ml, continued interferon therapy; 3) After interferon therapy, HBsAg<100 IU/ml, stopped interferon treatment; 4) After interferon therapy, HBsAg<100 IU/ml, sequential nucleoside analog treatment; 5) After nucleoside analogue treatment, HBsAg<100 IU/ml, sequential interferon treatment; 6) After treated with nucleoside analogues, HBsAg<100 IU/ml, continuing the nucleoside analog treatment. The follow-up observation period was 96 weeks under non-planned intervention. During the observation period, HBV indicators and biochemical indicators, serum AFP and liver imaging (liver ultrasound) were examined regularly. The main evaluation index was the incidence of HBsAg disappearance during the observation period. Secondary evaluation indicators: the rate of HBV DNA turning positive, the rate of HBeAg turning positive and hepatitis incidence. To observe the inactive carrier status of low HBsAg content and the incidence of HBsAg disappearance, clinical outcomes and influencing factors in patients with CHB under different antiviral interventions.

Detailed Description
-----------------
This study is a clinical observational cohort study. All chronic hepatitis B patients were diagnosed and treated in the liver disease department of the Hepatology Center of Beijing Ditan Hospital affiliated to Capital Medical University and those who received antiviral therapy (interferon and nucleoside analogues) reached HBsAg<100 IU/ml. The enrolled subjects were divided into the following six observation cohorts: 1) chronic Hepatitis B patients in the immunological control period, without any clinical treatment intervention in this cohort; 2) After interferon therapy, HBsAg<100 IU/ml, continued interferon therapy in this cohort; 3) After interferon therapy, HBsAg<100 IU/ml, stopped interferon treatment in this cohort; 4) After interferon therapy, HBsAg<100 IU/ml, sequential nucleoside analog treatment in this cohort; 5) After nucleoside analogue treatment, HBsAg<100 IU/ml, sequential interferon treatment in this cohort; 6) After treated with nucleoside analogues, HBsAg<100 IU/ml, continuing the nucleoside analog treatment in this cohort. The follow-up observation period was 96 weeks under non-planned intervention. During the observation period, HBV DNA loads, HBsAg/anti-HBs, HBeAg/anti-HBe and biochemical indicators, serum AFP and liver imaging (liver ultrasound) were examined regularly. The main evaluation index was the incidence of HBsAg disappearance during the observation period. Secondary evaluation indicators: the rate of HBV DNA turning positive, the rate of HBeAg turning positive and hepatitis incidence. To observe the inactive carrier status of low HBsAg content and the incidence of HBsAg disappearance, clinical outcomes and influencing factors in patients with CHB under different antiviral interventions.

Official Title
-----------------
Cohort Study of Clinical Outcomes in Chronic HBV Infection Patients With Low HBsAg Loads Under Unplanned Intervention

Conditions
-----------------
Chronic Hepatitis B Infection

Intervention / Treatment
-----------------
* Drug: Interferon
* Drug: nucleoside analogues


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inactive carrier status and chronic hepatitis B (CHB) patients with anti-viral therapy (interferon and nucleoside analogues) reaching HBsAg < 100 IU/ml. Exclusion Criteria: coinfection with other viruses including HCV, HDV, and HIV; syphilis antibody positive; co-exist other liver diseases including alcoholic liver disease, metabolic liver disease, fatty liver, drug induce liver injury, and autoimmune liver disease; complication of cirrhosis or liver cancer.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| chronic hepatitis B patients during the immune control period<br>Patients with chronic HBV infection during the immune control period do not have any clinical treatment intervention cohort | |
| Therapy group A<br>After chronic hepatitis B patients were treated with interferon, HBsAg level of these patients < 100 IU / ml, and they continued to be treated with interferon | Drug: Interferon<br>* chronic hepatitis B patients with interferon therapy<br>|
| Therapy group B<br>After chronic hepatitis B patients were treated with interferon, HBsAg level of these patients < 100 IU / ml, and they stopped to be treated with interferon | Drug: Interferon<br>* chronic hepatitis B patients with interferon therapy<br>|
| Therapy group C<br>After chronic hepatitis B patients were treated with interferon, HBsAg level of these patients < 100 IU / ml, and they continued to be treated with sequential nucleoside analogues | Drug: Interferon<br>* chronic hepatitis B patients with interferon therapy<br>Drug: nucleoside analogues<br>* chronic hepatitis B patients with interferon therapy<br>|
| Therapy group D<br>After chronic hepatitis B patients were treated with nucleoside analogues, HBsAg level of these patients < 100 IU / ml, and they continued to be treated with sequential interferon | Drug: Interferon<br>* chronic hepatitis B patients with interferon therapy<br>Drug: nucleoside analogues<br>* chronic hepatitis B patients with interferon therapy<br>|
| Therapy group E<br>After chronic hepatitis B patients were treated with nucleoside analogues, HBsAg level of these patients < 100 IU / ml, and they continued to be treated with the nucleoside analogues | Drug: nucleoside analogues<br>* chronic hepatitis B patients with interferon therapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of HBsAg disappearance during the 96-week study in different observation cohorts | The incidence of HBsAg disappearance during the 96-week study in different observation cohorts | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV DNA re-yang rate during the 96-week study period in different observation cohorts | HBV DNA re-yang rate and HBeAg re-yang rate during the 96-week study period in different observation cohorts | 96 weeks | 
| HBeAg re-yang rate during the 96-week study | HBeAg re-yang rate during the 96-week study | 96 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic hepatitis B, interferon, nucleotide, HBV, HBsAg, HBV DNA