Similarities, Differences, and Potential Synergies in the Mechanism of Action of Albumin Dialysis Using the MARS Albumin Dialysis Device and the CytoSorb Hemoperfusion Device in the Treatment of Liver Failure

Introduction: Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). Methods: We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 μmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. Results: Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (−83 ± 67 μmol/L after MARS; −122 ± 118 μmol/L after SPAD session), conjugated bilirubin (−82 ± 61 μmol/L after MARS; −105 ± 96 μmol/L after SPAD session), and bile acid levels (−64 ± 75 μmol/L after MARS; −56 ± 56 μmol/L after SPAD session), all nondifferent comparing MARS to SPAD. Conclusion: A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.

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Vasoactive mediators in patients with acute liver failure treated with albumin dialysis

Liver International ◽

10.1111/j.1478-3231.2009.02129.x ◽

2010 ◽

Vol 30 (4) ◽

pp. 634-636 ◽

Cited By ~ 4

Author(s):

Andreas Kortgen ◽

Hubert Hetz ◽

Nils G. Morgenthaler ◽

Gudrun Paxian ◽

Philip Hitzler ◽

...

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Albumin Dialysis ◽

Vasoactive Mediators

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Reduction of Elevated Cytokine Levels in Acute/Acute-on-Chronic Liver Failure Using Super-Large Pore Albumin Dialysis Treatment: An In Vitro Study

Therapeutic Apheresis and Dialysis ◽

10.1111/1744-9987.12146 ◽

2013 ◽

Vol 18 (4) ◽

pp. 347-352 ◽

Cited By ~ 11

Author(s):

Adrian Dominik ◽

Jan Stange ◽

Claudia Pfensig ◽

Luise Borufka ◽

Helga Weiss-Reining ◽

...

Keyword(s):

Liver Failure ◽

In Vitro Study ◽

Chronic Liver ◽

Vitro Study ◽

Chronic Liver Failure ◽

Albumin Dialysis ◽

Dialysis Treatment ◽

Large Pore ◽

Cytokine Levels

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Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819879565 ◽

2019 ◽

Vol 12 ◽

pp. 175628481987956 ◽

Cited By ~ 9

Author(s):

Rafael Bañares ◽

Luis Ibáñez-Samaniego ◽

Josep María Torner ◽

Marco Pavesi ◽

Carmen Olmedo ◽

...

Keyword(s):

Liver Failure ◽

Individual Patient Data ◽

Meta Analysis ◽

Patient Data ◽

Chronic Liver ◽

Treatment Intensity ◽

Chronic Liver Failure ◽

Albumin Dialysis ◽

Liver Support ◽

Molecular Adsorbent Recirculating System

Background: Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues. Methods: We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus ⩽ 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality. Results: Three RCTs suitable for the meta-analysis ( n = 285, ACLF patients = 165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p = 0.001; 30-day survival: 73.9% versus 64.3%, p = 0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p = 0.001; 30-day survival: 73.3% versus 58.5%, p = 0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy. Conclusion: HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials.

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Review of Methods to Remove Protein-Bound Substances in Liver Failure

The International Journal of Artificial Organs ◽

10.1177/039139880202501003 ◽

2002 ◽

Vol 25 (10) ◽

pp. 911-917 ◽

Cited By ~ 30

Author(s):

R.D. Hughes

Keyword(s):

Liver Failure ◽

Plasma Proteins ◽

High Volume ◽

Toxic Substances ◽

Albumin Dialysis ◽

Liver Support ◽

Excretory Function ◽

Bioartificial Liver Support ◽

Wide Range

A wide range of toxic substances accumulates in the circulation of patients with liver failure, including more lipid-soluble substances, which bind to plasma proteins. Serum albumin is the most important binding protein for ligands such as bilirubin and bile acids, which are potentially toxic and can cause apoptosis in astrocytes and hepatocytes respectively in vitro. Resin haemoperfusion was originally investigated to remove these compounds, as well as inflammatory cytokines. Current effective methods for removal of protein-bound compounds in patients with liver failure include high volume plasmapheresis and different forms of albumin dialysis. Bioartificial liver support systems need adsorbent and/or dialysis modules to replace the lack of excretory function.

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Albumin dialysis with molecular adsorbent recirculating system (MARS) for the treatment of hepatic encephalopathy in liver failure

Annals of Hepatology ◽

10.1016/s1665-2681(19)31611-4 ◽

2011 ◽

Vol 10 ◽

pp. S70-S76 ◽

Cited By ~ 12

Author(s):

Ramón A. Kobashi-Margáin ◽

Juan G. Gavilanes-Espinar ◽

Ylse Gutiérrez-Grabe ◽

Ángel A. Gutiérrez-Jiménez ◽

Norberto Chávez-Tapia ◽

...

Keyword(s):

Hepatic Encephalopathy ◽

Liver Failure ◽

Albumin Dialysis ◽

Molecular Adsorbent Recirculating System ◽

Molecular Adsorbent

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Single-Pass Albumin Dialysis in the Treatment of Children with Liver Failure

Blood Purification ◽

10.1159/000502938 ◽

2019 ◽

Vol 49 (1-2) ◽

pp. 55-62

Author(s):

Johannes Holle ◽

Alexander Gratopp ◽

Sophie Balmer ◽

Verena Varnholt ◽

Stephan Henning ◽

...

Keyword(s):

Liver Failure ◽

Pediatric Patients ◽

Serum Levels ◽

Albumin Dialysis ◽

Liver Support ◽

Single Pass ◽

Medical Chart Review ◽

Extracorporeal Liver Support ◽

Life Threatening ◽

Catecholamine Therapy

Background and Aims: Acute and acute on chronic liver failure are life-threatening conditions, and bridging to transplantation is complicated by a paucity of suitable organs for children. While different modalities of extracorporeal liver support exist, their use in children is complicated by a large extracorporeal volume, and data on their use in children is limited. The aim of this analysis was to investigate the efficacy and safety of single-pass albumin dialysis (SPAD) in children with liver failure. Methods: Retrospective medical chart review of pediatric patients with liver failure treated with SPAD. The decrease in hepatic encephalopathy (HE) and the serum levels of bilirubin and ammonia were measured to determine efficacy. Adverse events were documented to assess safety. Results: Nineteen pediatric patients with a median age of 25.5 months and a median body weight of 11.9 kg were treated with SPAD between January 2011 and March 2018. Total bilirubin (p < 0.001) and ammonia (p = 0.02) significantly decreased after treatment with SPAD. As clinical outcome parameter, HE significantly improved (p = 0.001). Twelve patients were bridged successfully to liver transplantation. In all patients, 71 SPAD sessions were run. Clotting in the dialysis circuit was observed in 49% of all sessions. Heparin and citrate were used for anticoagulation and were significantly superior to dialysis without any anticoagulation (p= 0.03). Transfusion of packed blood cells (57%) and catecholamine therapy (49%) were frequently necessary. Conclusions: Treatment with SPAD was effective in detoxification, as measured by significant improvement of HE and clearance from surrogate laboratory parameters.

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