Early Liver Support With MARS in Post-hepatectomy Liver Failure

Early Liver Support With MARS in Post-hepatectomy Liver Failure: a Randomized, Multicentre Trial

Status

UNKNOWN

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03761238

Acronym

ELISH

Enrollment

Registered

2018-12-03

Start date

2019-03-15

Completion date

2022-09-15

Last updated

2018-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Liver Failure as A Complication of Care

Keywords

Molecular Adsorbent Recirculating System, post-hepatectomy liver failure, liver dialysis, post-hepatectomy liver dysfunction

Brief summary

This is a prospective, randomized, open-label, multicentre study involving European centers with experience in the management of PHLF to assess the impact of early liver support with MARS on survival in patients with post-hepatectomy liver failure (PHLF).

Detailed description

PHLF is a major risk factor for mortality in patients who underwent major hepatectomy. A specific treatment is yet not available. In a primary proof-of-concept study, it was shown that it is safe and feasible to use MARS in patients with PHLF early after hepatectomy. Survival was superior to a historical control group. This study will include patients with early, primary PHLF (based on the 50:50 criteria) after major liver surgery. Patients will be randomized 1:1 to receive standard treatment alone or standard treatment + liver dialysis using the Molecular Adsorbent Recirculating System (MARS). Relevant outcome along with several physiological parameters will be assessed.

Interventions

DEVICEMolecular Adsorbent Recirculating System

MARS therapy will start within 24-48 h after randomization and be given on 3 consecutive days in sessions of 8-12 h. The patients are observed for 2 days following the last session, with focus on bilirubin INR and signs of encephalopathy, and can thereafter receive 3 additional sessions in case of no or partial response to treatment.

OTHERStandard medical treatment (SMT)

Patient management and standard medical treatment (SMT) as specified in the study protocol.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Patients subjected for major liver surgery (4 or more Couinaud segments) or patients undergoing a 2nd, 3rd or 4th hepatic resection. Pre-operative chemotherapy and/or biological agents are allowed. * Primary PHLF occurring early after surgery defined by the 50:50 criteria (from PO day 5 to day 14) or by the presence of hepatic encephalopathy grade 2 or more and the 50:50 criteria (from PO day 3 to 4). * Written informed consent.

Exclusion criteria

* ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) procedure. * In patients with chronic liver disease presence of significant portal hypertension (hepatic venous pressure gradient ≥ 10 mmHg and/or Fibroscan ≥ 21kPa) prior to surgical intervention. * Any contraindication for MARS therapy such as uncontrolled active bleeding, platelet counts \<20.000 /µl or uncontrolled infection (presence of fever or adequate antibiotic therapy for less than 48h), septic shock, haemodynamic instability requiring inotropic support (noradrenaline \> 1mg/h). * PHLF occurring after post operative day 14. * Secondary PHLF: post-operative liver failure secondary to vascular (outflow or inflow thrombosis) or septic problems. * Persistant biliary complications (infected biloma, main biliary tree damage). * Inability or unwilling of the patient or family to give informed consent.

Design outcomes

Primary

Measure	Time frame	Description
60 day survival	From randomization to death from any cause, assessed up to 60 days postop	Overall survival rate from time of randomization to death from any cause

Secondary

Contacts

Primary ContactStefan Gilg, MD PhD

stefan.gilg@ki.se0702677722

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Measure	Time frame	Description
90 day survival	From randomization to death from any cause, assessed up to 90 days postop	Overall survival rate from time of randomization to death from any cause.
6 month survival	From randomization to death from any cause, assessed up to 6 months postop	Overall survival rate from time of randomization to death from any cause.
1 year survival	From randomization to death from any cause, assessed up to 1 year.	Overall survival rate from time of randomization to death from any cause.
Impact of MARS therapy on liver function	From randomization up to 1 year.	Impact of MARS therapy on liver function according to Child Pugh score (grade A, B and C)
Impact of MARS therapy on extra-hepatic function (APACHE-II scoring)	From randomization up to 1 year.	Impact of MARS therapy on extra-hepatic function assessed by the Acute Physiology And Chronic Health Evaluation II (APACHE II) scoring system (range 0-71 points, lower points indicate less severe disease).
Impact of MARS therapy on extra-hepatic function (SOFA scoring)	From randomization up to 1 year.	Impact of MARS therapy on extra-hepatic function assessed by the Sequential Organ Failure Assessment (SOFA) scoring system (0-24 points, higher points indicate more severe disease).
Impact of MARS therapy on extra-hepatic function (CLIF-SOFA scoring)	From randomization up to 1 year.	Impact of MARS therapy on extra-hepatic function assessed by the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) scoring system (0-24 points, higher points indicate more severe disease).
Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow.	At randomization (day 0) and on day 10.	Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow (ml/min).
Impact of MARS therapy on splanchnic hemodynamics assessed by indirect estimation of portal blood flow using ultrasonography.	At randomization (day 0) and on day 10.	Impact of MARS therapy on splanchnic hemodynamics assessed by indirect estimation of portal blood flow using ultrasonography (ml/min).
28 day survival	From randomization to death from any cause, assessed up to 28 days post-op	Overall survival rate from time of randomization to death from any cause.
Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).	At randomization (day 0) and on days 5, 10 and 30 .	Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).
Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.	At randomization (day 0) and on days 5 and 10.	Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.
Impact of MARS therapy on liver regeneration assessed by serum levels of alphafetoprotein.	At randomization (day 0) and on days 5 and 10.	Impact of MARS therapy on liver regeneration assessed by serum levels of alphafetoprotein.
Impact of MARS therapy on liver regeneration assessed by serum levels of hepatocyte growth factor.	At randomization (day 0) and on days 5 and 10.	Impact of MARS therapy on liver regeneration assessed by serum levels of hepatocyte growth factor.
Impact of MARS therapy on liver performance status.	At randomization (day 0) and on days 5 and 10.	Impact of MARS therapy on liver performance status estimated using indocyanine green (ICG) clearance.
Impact of MARS therapy on liver toxins (bile acids) in serum and dialysate.	At randomization (day 0) and on days 5 and 10.	impact of MARS therapy on liver toxins (ammonia, bile acids and cytokines (IL-6 and TNF-alpha)). Determinations in serum and in the dialysate.
Impact of MARS therapy on liver toxins (ammonia) in serum and dialysate.	At randomization (day 0) and on days 5 and 10.	impact of MARS therapy on liver toxins (ammonia). Determinations in serum and in the dialysate.
Impact of MARS therapy on liver toxins (IL-6) in serum and dialysate.	At randomization (day 0) and on days 5 and 10.	impact of MARS therapy on liver toxins (IL-6). Determinations in serum and in the dialysate.
Impact of MARS therapy on liver toxins (TNF-alpha) in serum and dialysate.	At randomization (day 0) and on days 5 and 10.	impact of MARS therapy on liver toxins (TNF-alpha). Determinations in serum and in the dialysate.
Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.	At randomization (day 0) and on day 10.	Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.