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

Not Applicable

Completed

• Conditions: Post Hepatectomy Liver Failure
• Interventions: Device: Extracorporeal liver support therapy (ELS)

• Registration Number: NCT03011424
• Lead Sponsor: Karolinska University Hospital

Brief Summary

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:

1. Can ELS be applied in an early phase of PLF?

2. Is ELS safe and feasible for the treatment of PLF when practised according to a predefined protocol?

Secondary issues to be addressed:

1. The development of predictive laboratory-chemical markers of liver failure

2. Indirect measures of portal flow and portal pressure

3. Indocyanine green clearance (ICG) under ELS treatment

4. Clearance of toxic products as assessed in aliquots taken from the dialysate

Detailed Description

Primary issues to be addressed

1. Can ELS be applied in an early phase of PLF?

2. Is ELS safe and feasible for the treatment of PLF when practised according to a predefined protocol?

Secondary issues to be addressed

1. The development of predictive laboratory-chemical markers of liver failure

2. Indirect measures of portal flow and portal pressure

3. Indocyanine green clearance (ICG) under ELS treatment

4. 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)

Study Timeline

• Study Start: 2013-10
• Primary Completion: 2015-05
• Study Completion: 2015-11
• Study First Submitted: 2016-10-24
• Study First Submitted QC: 2017-01-04
• Study First Posted: 2017-01-05
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-02
• Last Update Posted: 2019-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Early Postoperative Extracorporal Liver Support Therapy (ELS)	Extracorporeal liver support therapy (ELS)	Early Postoperative Extracorporal Liver Support Therapy (ELS) by using the Molecular Adsorbent Recirculating System (MARS)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Surgery Gastrocentrum Karolinska Univeristy Hospital; 🇸🇪 Stockholm, Sweden