The Effects of Double Plasma Molecular Adsorption System in Acute on Chronic Liver Failure Patients

Study Overview
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Brief Summary
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Acute liver failure patients posed high mortality rate despite receiving standard therapy. The severity and mortality even higher in patients with underlying liver disease. Acute liver failure cause hyperinflammatory response in early stage and immunoparalysis in later stage. The surge of proinflammatory cytokines leads to multiorgan failure and more liver injury. Subsequent immunoparalysis may lead to lethal secondary infections. Liver support system had been used in acute and acute ontop chronic liver disease for last several decades. Double plasma molecular adsorption system (DPMAS) is one of the promising non-biological liver support system that have been extensively investigated in acute ontop chronic liver failure from hepatits B viral. DPMAS circuit consist of BS330 (bilirubin adsorber) and HA330 (Cytokines adsorber). Thus, DPMAS can also remove various cytokines. The effect of DPMAS on immune function in these patients has not been explored. Recent randomized controlled trial by Srisawat et al. demonstrated improvement of mHLA-DR in septic shock patients who received polymyxin B extracorporeal therapy compare to control arm. Since liver failure show change of immunological profile resemble to sepsis. Investigators proposed that removal of toxic liver toxins and lethal cytokines by DPMAS will improve immunological profiles in acute ontop chronic liver failure patients. Investigators plan to conduct a randomized controlled trial in acute ontop chronic liver failure patients who admitted to intensive care unit. Investigators plan to compare the immunomodulatory effects of DPMAS with standard treatments.

Official Title
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The Effects of Double Plasma Molecular Adsorption System in Acute on Chronic Liver Failure Patients

Conditions
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Acute-On-Chronic Liver Failure, Acute on Chronic Hepatic Failure

Intervention / Treatment
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* Device: DPMAS
* Other: standard treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or more Diagnosis of Acute ontop chronic liver failure by Asian Pacific association for the study of the liver (APASL) criteria Admitted to intensive care unit Exclusion Criteria: Pregnancy Received steroid treatment Expected dead within 24 hour WBC < 500/mm3 Allergy to DPMAS History of organ transplant Terminal illness with do not resuscitation order

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intervention group will receive DPMAS extracorporeal treatment one session per day for 3 consecutive days plus standard therapy. We plan to use blood flow rate of 100-120 ml/hour with filtration fraction for plasma separation of 25-30%. DPMAS circuit consist of Plasmaflo OP cartridge (Asahi Medical, Tokyo, Japan), Ion exchange resin hemoperfusion cartridge (BS330; Jafron, Zhuhai City, China), and Neutral adsorption resin hemoperfusion cartridge (HA330-II; Jafron, Zhuhai City, China) We do not use any anticoagulant. | Device: DPMAS<br>* DPMAS circuit consist of Plasmaflo OP cartridge (Asahi Medical, Tokyo, Japan), Ion exchange resin hemoperfusion cartridge (BS330; Jafron, Zhuhai City, China), and Neutral adsorption resin hemoperfusion cartridge (HA330-II; Jafron, Zhuhai City, China)<br>Other: standard treatment<br>* standard treatment according to EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure 2017.<br>|
| Active Comparator: Standard care<br>Standard treatment according to EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure 2017 | Other: standard treatment<br>* standard treatment according to EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure 2017.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mHLA-DR expression | mHLA-DR expression | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival rate | survival rate | 28 days | 
| Reduction of total bilirubin | Reduction of total bilirubin | 7 days | 
| hepatic encephalopathy grading | hepatic encephalopathy grading | 28 days | 
| subsequent bacterial infection | subsequent bacterial infection | 28 days | 
| CD11b expression | CD11b expression | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemoperfusion, Acute-On-Chronic Liver Failure, Cytokine adsorbant therapy, HA-330