Three Types of Nucleotide/Nucleoside Analogues Treatment in HBV Related ACLF

Study Overview
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Brief Summary
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This study is to investigate the clinical efficacy of three types of nucleotide/nucleoside analogues in treatment of HBV-related acute-on-chronic liver failure.

Detailed Description
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Hepatitis b virus (HBV) related acute-on-chronic liver failure (ACLF) is a serious condition with high mortality rate in China. Nucleotide/nucleoside analogues are used for anti-virus treatment in these patients. Entecavir, Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide are first line drug in China. But there still lacks of data of Tenofovir Alafenamide in treatment of HBV related ACLF. This study is to investigate the clinical efficacy of three types of nucleotide/nucleoside analogues in treatment of HBV related ACLF.

Official Title
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Study on Three Types of Nucleotide/Nucleoside Analogues Treatment in Patients With Hepatitis b Virus Related Acute-on-chronic Liver Failure

Conditions
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Hepatitis B, Acute-On-Chronic Liver Failure

Intervention / Treatment
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* Drug: Entecavir
* Drug: Tenofovir Disoproxil Fumarate
* Drug: Tenofovir Alafenamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive hepatitis b surface antigen or hepatitis b virus DNA > 0.5 year; Age from 18 to 55 years old; Serum total bilirubin level > 10 times upper limit of normal; Prothrombin time activity < 40% or prothrombin time international ratio > 1.5； Do not receive nucleotide/nucleoside analogues treatment in the past half year. Exclusion Criteria: Other active liver diseases; Hepatocellular carcinoma or other malignancy; Pregnancy or lactation; Human immunodeficiency virus infection or congenital immune deficiency diseases; Severe diabetes, autoimmune diseases; Other important organ dysfunctions; Using glucocorticoid; Patients can not follow-up; Investigator considering inappropriate.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ETV group<br>50 patients would receive treatment of oral entecavir (ETV) 0.5 mg once per day from baseline to life-long. | Drug: Entecavir<br>* Patients would receive treatment of oral entecavir (ETV) 0.5 mg once per day.<br>* Other names: Baraclude;|
| Active Comparator: TDF group<br>50 patients would receive treatment of oral tenofovir disoproxil fumarate (TDF) 300 mg once per day from baseline to life-long. | Drug: Tenofovir Disoproxil Fumarate<br>* Patients would receive treatment of oral tenofovir disoproxil fumarate (TDF) 300 mg once per day.<br>* Other names: Viread;|
| Experimental: TAF group<br>50 patients would receive treatment of oral tenofovir alafenamide (TAF) 25 mg once per day from baseline to life-long. | Drug: Tenofovir Alafenamide<br>* Patients would receive treatment of oral tenofovir alafenamide (TAF) 25 mg once per day.<br>* Other names: Vemlidy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate in the follow-up | Whether patients will survive after treatment is observed in the follow-up. | 144 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Model for end-stage liver disease (MELD) score is recorded after treatment | The calculation of model for end-stage liver disease (MELD) score is: R=0.378ln[serum total bilirubin (mg/dl)]+1.12ln(prothrombin time international normalized ratio)+0.95ln[serum creatinin(mg/dl)]+0.64. The higher the MELD score, the higher the mortality rate. MELD score is recorded after treatment. | 0 week, 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 
| Ratio of patients with undetectable hepatitis b virus DNA after treatment | Hepatitis b virus DNA would be tested to know the ratio of patients with undetectable hepatitis b virus DNA at 7 time points after treatment. | 4 week, 8 week, 12 week, 24 week, 48 week, 72 week,144 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis b virus, acute-on-chronic liver failure, nucleotide, nucleoside