Safety and Efficacy of hiHep Bioartificial Liver Support System to Treat Acute Liver Failure

Study Overview
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Brief Summary
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This study tend to evaluate safety and efficacy of hiHep bioartificial liver support system in treating acute liver failure.

Detailed Description
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Liver damage remains a life-threatening syndrome. With the increasing number of patients awaiting transplantation, efforts have been made to develop extracorporeal methods to support or replace the function of the failing organ. A bioartificial liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. It may prolonger the expected survival time of acute liver failure patients. Direct reprogramming of fibroblasts to hepatic lineages could offer a new type of solution to bioartificial liver support system. The investigators have already generated human induced hepatocytes (hiHeps) from fibroblasts by lentiviral expression of FOXA3, HNF1A, and HNF4A. hiHeps express hepatic gene programs, can be expanded in vitro, and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity and biliary drug clearance. hiHeps can restore the liver function and prolong survival. This study tends to evaluate safety and efficacy of hiHep bioartificial liver support system in treating acute liver failure.

Official Title
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Safety and Efficacy of hiHep Bioartificial Liver Support System to Treat Acute Liver Failure

Conditions
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Liver Failure, Acute

Intervention / Treatment
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* Procedure: hiHep Bioartificial Liver Support System
* Procedure: Standard care for ALF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weight more than 45 kg; Age more than 18; Diagnosis of ALF; Subjects must not be listed for transplant at the time of Enrollment or, if listed, in the opinion of the Investigator are unlikely to be transplanted within 72 hours; Exclusion Criteria: Acute clinical symptoms that are likely to result in death within 48 hours; Presence of sepsis or septic shock; Concomitant disease including chronic congestive heart failure, severe vascular disease, emphysema, AIDS, cancer; Portal hypertension; Liver dysfunction due to trauma;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>Standard care for ALF | Procedure: Standard care for ALF<br>* A standard of care for subjects with acute liver failure.<br>|
| Experimental: Experimental group<br>Continuous treatment with the hiHep bioartificial liver support system. | Procedure: hiHep Bioartificial Liver Support System<br>* Continuous treatment with the hiHep bioartificial liver support system for a minimum of 3 days to a maximum of 14 days. The subject's ultrafiltrated blood is circulated through 4 cartridges. The parameter is set to Circuit 1：120-200ml/min；Circuit 2：30-50ml/min；Circuit 3：200 ml/min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival of ALF subjects | Overall survival in subjects with acute liver failure will be summarized and compared with control subjects through Study Day 28. | Study Day 1 through Study Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complication rate | Proportion of subjects who suffer complications caused by bioartificial liver support system | Study Day 1 through Study Day 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioartificial Liver, Acute Liver Failure