Long-term Outcomes of Anti-viral Therapies in Patients With Chronic Viral Hepatitis B

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, prospective, real-world study, recruiting patients with chronic hepatitis B under anti-viral treatment. The recruited participants will receive peginterferon alpha based regimen or nucleos(t)ide alone. The primary objective of this study is to compare the long-term outcomes (including hepatocellular carcinoma, decompensated cirrhosis, etc）of different anti-viral therapies. The secondary objective of this study is to compare the serological response rates of different anti-viral therapies, evaluate the predictive value of HBV-related laboratory testings and describe the kinetics of them results during antiviral treatment. The follow-up time course of this study will be 5 years.

Detailed Description
-----------------
The patients will be allocated into two cohorts based on the anti-viral treatment decided by their doctors. If they are going to take peginterferon alpha based regimen, they will be allocated in interferon cohort. If they are going to take nucleos(t)ide alone, they will be allocated in nucleos(t)ide cohort. The follow-up plan will be made by their doctors according to their conditions. No extra intervention or examination will be given in this study. The primary outcome is end-stage liver diseases including hepatocellular carcinoma and decompensated cirrhosis, and the rate of hepatocellular carcinoma and decompensated cirrhosis will be measure at 1 year，2 years，3 years, 4 years and 5 years from baseline. Secondary events including HBsAg loss, HBeAg conversion, fibrosis progression and fibrosis, which will be measured at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively. Results of laboratory testings will be recorded at each follow-up visit. The primary objective of this study is to compare the long-term outcomes (including hepatocellular carcinoma, decompensated cirrhosis, etc）of different anti-viral therapies. The secondary objective of this study is to compare the serological response rates of different anti-viral therapies, evaluate the predictive value of HBV-related laboratory testings and describe the kinetics of them results during antiviral treatment.

Official Title
-----------------
Long-term Outcomes of Anti-viral Therapies in Patients With Chronic Viral Hepatitis B: A Prospective, Multicenter, Real-world Study

Conditions
-----------------
Chronic Hepatitis b

Intervention / Treatment
-----------------
* Drug: peginterferon alpha based regimen
* Drug: nucleos(t)ide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients with age ≥18; subjects who are over 70 years of age must be in generally stable health conditions. There should be evidences that HBsAg has been positive for more than 6 months or HBV-related histological changes. Planned to receive or already receiving anti-viral treatment with nucleos(t)ide including Entecavir, Tenofovir, and Tenofoviralafenamide. Or planned to receive peginterferon alpha 2b, either treated or treatment-naive. Agree to participate in the study and sign the patient informed consent form. Exclusion Criteria: Currently treatment-related participating clinical trials.

Ages Eligible for Study
-----------------
Minimum Age: 18 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 |
| --- | --- |
| interferon cohort<br>Patients who are going to take peginterferon alpha based regimen | Drug: peginterferon alpha based regimen<br>* peginterferon alpha based regimen or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study<br>|
| nucleos(t)ide cohort<br>Patients who are going to take nucleos(t)ide alone | Drug: nucleos(t)ide<br>* peginterferon alpha based regimen or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of hepatocellular carcinoma at 1 year from baseline | Rate of hepatocellular carcinoma will be evaluated as an end-stage liver disease event at 1 year，2 years，3 years, 4 years and 5 years from baseline | 1 year from baseline | 
| rate of hepatocellular carcinoma at 3 years from baseline | Rate of hepatocellular carcinoma will be evaluated as an end-stage liver disease event at 1 year，2 years，3 years, 4 years and 5 years from baseline | 3 years from baseline | 
| rate of hepatocellular carcinoma at 3 years from baseline | Rate of hepatocellular carcinoma will be evaluated as an end-stage liver disease event at 1 year，2 years，3 years, 4 years and 5 years from baseline | 5 years from baseline | 
| rate of decompensated cirrhosis at 1 year from baseline | Rate of decompensated cirrhosis will be evaluated as an end-stage liver disease event at 1 year，2 years，3 years, 4 years and 5 years from baseline | 1 year from baseline | 
| rate of decompensated cirrhosis at 3 years from baseline | Rate of decompensated cirrhosis will be evaluated as an end-stage liver disease | 3 years from baseline | 
| rate of decompensated cirrhosis at 5 years from baseline | Rate of decompensated cirrhosis will be evaluated as an end-stage liver disease | 5 years from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of HBsAg loss | rate of HBsAg loss will be measured as a serological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively. | 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline | 
| rate of HBeAg loss | rate of HBeAg loss will be measured as a serological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively. | 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline | 
| rate of HBeAg conversion | rate of HBeAg conversion will be measured as a serological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively. | 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline | 
| rate of fibrosis progression | rate of fibrosis progression will be measured as a histological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively. | 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline | 
| rate of fibrosis regression | rate of fibrosis regression will be measured as a histological response event at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively. | 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline | 
| HBsAg level | HBsAg level will be measured at 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline, respectively, and kinetics will be described based on the results. | 24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline |