Early Postoperative Extracorporal Liver Support Therapy (ELS) as a Tool to Manage Post Hepatectomy Liver Failure (PLF)

Study Overview
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Brief Summary
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Early postoperative extracorporal liver support therapy (ELS) as a tool to manage post hepatectomy liver failure (PLF). Post-operative liver failure (PLF) has been identified as a major risk factor leading to increased morbidity and mortality. The incidence of PLF varies largely between 0-30%, and may be accounted for the main reason of postoperative mortality related to liver surgery (reported figures ranging from 18 to 75 %). Currently, there are only a few treatment options for PLF, mainly restricted to the treatment of complications like bile leakage, infections as well as the prevention of further liver damage caused by e.g. thrombosis or haemorrhage as well as administration of liver toxic drugs. Recently the international study group on liver surgery (ISGLS) published criteria for a new definition of PLF which will greatly facilitate the comparison of results from future studies on a variety of aspects on liver failure. ELS by using the Molecular Adsorbent Recirculating System (MARS) is based on a modified haemodialysis that allows the removal of water-soluble and protein bound toxins over an albumin-coated high flux membrane against recycled exogenous albumin. Thus, MARS can support the compromised detoxification capacity of the liver as well as improve physiological parameters. This would offer the potential for temporary support for the harmed liver after liver resection allowing for a more uneventful recovery. For obvious reasons previous reports contain few patients, present heterogonous treatment groups and all suffer from lack of standardized treatment protocols. Few if any surviving patients, thus providing no evidence to encourage ELS as a possible treatment option for patients suffering of PLF. However, studies with defined patient populations and treatments according to a predefined standardised treatment protocol are warranted. Primary issues to be addressed: Can ELS be applied in an early phase of PLF? Is ELS safe and feasible for the treatment of PLF when practised according to a predefined protocol? Secondary issues to be addressed: The development of predictive laboratory-chemical markers of liver failure Indirect measures of portal flow and portal pressure Indocyanine green clearance (ICG) under ELS treatment Clearance of toxic products as assessed in aliquots taken from the dialysate

Detailed Description
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Primary issues to be addressed Can ELS be applied in an early phase of PLF? Is ELS safe and feasible for the treatment of PLF when practised according to a predefined protocol? Secondary issues to be addressed The development of predictive laboratory-chemical markers of liver failure Indirect measures of portal flow and portal pressure Indocyanine green clearance (ICG) under ELS treatment Clearance of toxic products as assessed in aliquots taken from the dialysate Design Prospective phase 1 safety and feasibility study Study Population 10 consecutive patients being subjected to extended liver surgery (at least right sided or extended right/left sided hemihepatectomy)

Official Title
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Early Postoperative Extracorporal Liver Support Therapy (ELS) as a Tool to Manage Post Hepatectomy Liver Failure (PLF)

Conditions
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Post Hepatectomy Liver Failure

Intervention / Treatment
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* Device: Extracorporeal liver support therapy (ELS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 70 years Patients subjected for major liver surgery (4 or more Couinaud segments, ca. 50 % or more of total liver volume) Pre-operative chemotherapy and/or biological agents are allowed Liver cirrhosis Child Pugh Score A is allowed Exclusion Criteria: Any contra indication for ELS such as uncontrolled active bleeding or platelet counts <20.000 /µl Macroscopic liver cirrhosis (Child Pugh Score B and C) Inability or unwilling to give informed consent

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Postoperative Extracorporal Liver Support Therapy (ELS)<br>Early Postoperative Extracorporal Liver Support Therapy (ELS) by using the Molecular Adsorbent Recirculating System (MARS) | Device: Extracorporeal liver support therapy (ELS)<br>* ELS by using the Molecular Adsorbent Recirculating System (MARS) is based on a modified haemodialysis that allows the removal of water-soluble and protein bound toxins over an albumin-coated high flux membrane against recycled exogenous albumin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of PLF patients who develop serious adverse events during ELS according to SOFA scores and Westhaven criteria | At least five sessions of Mars. SOFA (score 1-4). | First two weeks postoperatively after major hepatectomy | 
| Number of PLF patients who develop serious adverse events during ELS | At least five sessions of Mars. Westhaven (criteria 1-4) | First two weeks postoperatively after major hepatectomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The predictive value of liver enzymes and bilirubin changes as marker of liver failure | At least five sessions of Mars. Liver enzymes measured( liver transaminases microkat/L ), bilirubin (mmol/L) | First two weeks postoperatively after major hepatectomy | 
| Portal flow (ml/minute) before and during ELS | At least five sessions of Mars | First two weeks postoperatively after major hepatectomy | 
| To assess liver function by use of Indocyanine green clearance (ICG)(% clearance/unit time) under ELS treatment | At least five sessions of Mars | First two weeks postoperatively after major hepatectomy | 
| Portal pressure (cmH2O) before and during ELS | At least five sessions of Mars | First two weeks postoperatively after major hepatectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver resection, post hepatectomy liver failure, liver dialysis, encephalopathy, mortality