DAAs Treatment for Chronic HCV/HBV Co-infection Patients(DASCO)

Study Overview
=================
Brief Summary
-----------------
This is a prospective study to determine the incidence, morbidity, mortality and predisposing factors for the reactivation of hepatitis B virus replication during direct anti-HCV treatment of HCV/HBV co-infection patients.

Detailed Description
-----------------
Patients who receive direct-acting anti-HCV treatment will be prospectively studied during 2-year period. All patients have HCV/HBV co-infection. The inclusion/exclusion criteria and the follow up plan will be listed in following part.

Official Title
-----------------
Direct Antiviral Agents for the Treatment of Chronic HCV/HBV Co-infection Patients

Conditions
-----------------
Chronic Hepatitis C Infection, HBV Coinfection, Hepatitis B Reactivation

Intervention / Treatment
-----------------
* Drug: Ledipasvir/Sofosbuvir
* Drug: Sofosbuvir and Daclatasvir
* Drug: Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir
* Drug: Entecavir
* Drug: Tenofovir disoproxil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HCV RNA positive, HBsAg positive with detectable or undetectable HBV DNA, Receiving pan oral direct-acting anti-HCV regimen Exclusion Criteria: Pregnant or nursing female or male with pregnant female partner; HIV infection; Hematologic or biochemical parameters at Screening outside the protocol- specified requirements; Active or recent history (≤ 1 year) of drug or alcohol abuse; History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prophylactic/Early anti-HBV treatment<br>HCV/HBV co-infection patients in this arm will receive nucleos(t)ides analog (Entecavir or Tenofovir disoproxil fumarate) for the treatment of hepatitis B infection before or at the commencement of direct anti-HCV treatment using DAAs (Ledipasvir/Sofosbuvir; or Sofosbuvir and Daclatasvir, or Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir; or Sofosbuvir+Ribavirin). . | Drug: Ledipasvir/Sofosbuvir<br>* Oral direct anti-HCV agent. Ledipasvir/Sofosbuvir(LDV/SOF) 400mg/90mg fixed-dose combination(FDC) tablet, administered orally once daily.<br>* Other names: GS-5885;Drug: Sofosbuvir and Daclatasvir<br>* TWO oral direct anti-HCV agent: Sofosbuvir(SOF), 400mg tablet administered orally once daily. Daclatavir(DCV), 60mg tablet administered orally once daily.<br>* Other names: Daklinza®,BMS-790052;Drug: Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir<br>* VIEKIRA PAK includes ombitasvir, a hepatitis C virus NS5A inhibitor, paritaprevir, a hepatitis C virus NS3/4A protease inhibitor, ritonavir, a CYP3A inhibitor and dasabuvir, a hepatitis C virus non-nucleoside NS5B palm polymerase inhibitor.<br>* Other names: VIEKIRA PAK™;Drug: Entecavir<br>* Nucleoside-inhibitor-treatment-naïve with compensated liver disease (greater than or equal to 16 years old): 0.5 mg once daily.<br>* Other names: BARACLUDE®;Drug: Tenofovir disoproxil<br>* VIREAD is indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.<br>* Other names: VIREAD®;|
| Experimental: Deferred anti-HBV treatment<br>HCV/HBV co-infection patients in this arm will receive nucleos(t)ides analog (Entecavir or Tenofovir disoproxil fumarate) for the treatment of hepatitis B infection when HBV viral breakthrough occurred during anti-HCV treatment using DAAs (Ledipasvir/Sofosbuvir; or Sofosbuvir and Daclatasvir, or Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir; or Sofosbuvir+Ribavirin). | Drug: Ledipasvir/Sofosbuvir<br>* Oral direct anti-HCV agent. Ledipasvir/Sofosbuvir(LDV/SOF) 400mg/90mg fixed-dose combination(FDC) tablet, administered orally once daily.<br>* Other names: GS-5885;Drug: Sofosbuvir and Daclatasvir<br>* TWO oral direct anti-HCV agent: Sofosbuvir(SOF), 400mg tablet administered orally once daily. Daclatavir(DCV), 60mg tablet administered orally once daily.<br>* Other names: Daklinza®,BMS-790052;Drug: Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir<br>* VIEKIRA PAK includes ombitasvir, a hepatitis C virus NS5A inhibitor, paritaprevir, a hepatitis C virus NS3/4A protease inhibitor, ritonavir, a CYP3A inhibitor and dasabuvir, a hepatitis C virus non-nucleoside NS5B palm polymerase inhibitor.<br>* Other names: VIEKIRA PAK™;Drug: Entecavir<br>* Nucleoside-inhibitor-treatment-naïve with compensated liver disease (greater than or equal to 16 years old): 0.5 mg once daily.<br>* Other names: BARACLUDE®;Drug: Tenofovir disoproxil<br>* VIREAD is indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.<br>* Other names: VIREAD®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who experience virological breakthrough | Virological breakthrough is defined as 1 logIU/ml increase during and/or post DAAs treatment for the baseline or nadir. | From the commencement of DAAs treatment to 12 weeks post DAAs treatment | 
| Proportion of participants who experience virological rebound | Virological rebound is defined as 2 logIU/ml increase during and/or post DAAs treatment for the baseline or nadir. | From the commencement of DAAs treatment to 12 weeks post DAAs treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participant who experience biochemical rebound | Biochemical rebound is defined as | From the commencement of DAAs treatment to 12 weeks post DAAs treatment |