Dataset Information

Molecular Adsorbent Recirculating System for Acute Liver Failure in a New Pediatric-Based Extracorporeal Liver Support Program.

ABSTRACT:

Importance

Acute liver failure (ALF) carries significant morbidity and mortality, for both pediatric and adult patients. Albumin dialysis via the molecular adsorbent recirculating system (MARS) is a form of extracorporeal liver support (ELS) that can reduce hepatic encephalopathy (HE), a main driver of mortality in ALF. However, data on MARS and its benefit on mortality have been inconsistent.

Objectives

We sought to report our experiences and patient outcomes from the first 2 years of operation of a new ELS program, within an established pediatric liver transplantation center.

Design setting and participants

Retrospective review of outcomes in pediatric and adult patients treated with MARS therapy for ALF, from 2021 to 2022.

Main outcomes and measures

Outcomes included reduction in HE and biochemical markers of ALF after MARS therapy, survival, and transplant-free survival. Comparisons were made via Wilcoxon signed-rank test.

Results

Five pediatric and two adult patients underwent MARS for ALF. Ages ranged from 2 to 29 years. Overall, 21 MARS runs were performed (median 3 runs per patient, 12.4 hr per run [interquartile range, IQR 10.1-17]). Overall survival was 85.7%, and transplant-free survival was 71.4%. There was a statistically significant reduction in HE score with MARS therapy (median 3 [IQR 3-4] to 1 [IQR 0-1], p = 0.03), and in ALF biomarkers including ammonia (256 µL/dL [195-265] to 75 µL/dL [58-101], p = 0.02), aspartate aminotransferase (6,362 U/L [920-8,305] to 212 U/L [72-431], p = 0.02), alanine aminotransferase (8,362 U/L [3,866-9,189] to 953 U/L [437-1,351], p = 0.02), and international normalized ratio (4.5 [3.3-6.7] to 1.3 [1.2-1.4], p = 0.02).

Conclusions and relevance

MARS therapy for ALF was well tolerated by both pediatric and adult patients, and resulted in significant improvement in clinical and biochemical parameters. We demonstrated encouraging overall and transplant-free survival, suggesting that early initiation of MARS with relatively long and frequent cycle times may be of significant benefit to ALF patients, and is worthy of additional study in larger cohorts.

SUBMITTER: Baker DR

PROVIDER: S-EPMC10635609 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Molecular Adsorbent Recirculating System for Acute Liver Failure in a New Pediatric-Based Extracorporeal Liver Support Program.

Baker David R DR Mac Helen H Steinman Benjamin B Soshnick Sara H SH Frager Shalom Z SZ Goilav Beatrice B Kogan-Liberman Debora D Ovchinsky Nadia N Shlomovich Mark M

Critical care explorations 20231108 11

<h4>Importance</h4>Acute liver failure (ALF) carries significant morbidity and mortality, for both pediatric and adult patients. Albumin dialysis via the molecular adsorbent recirculating system (MARS) is a form of extracorporeal liver support (ELS) that can reduce hepatic encephalopathy (HE), a main driver of mortality in ALF. However, data on MARS and its benefit on mortality have been inconsistent.<h4>Objectives</h4>We sought to report our experiences and patient outcomes from the first 2 yea ...[more]

PMID: 37954902

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Project description:To describe outcomes of a cohort of patients with paediatric acute liver failure (PALF) treated with either one of two extracorporeal therapies (ECT) - continuous renal replacement therapy (CRRT) and molecular adsorbent recirculatory system (MARS®). Retrospective, observational, cohort study at two European paediatric intensive care units (PICUs) - UK (2006-2017, CRRT) and the Netherlands (2003-2017, MARS® and CRRT). Patients were children (0-18 years) admitted to the PICU with PALF who required CRRT or MARS®. Between each group, we compared baseline characteristics, biochemical parameters at 0 and 24 h after commencing MARS®/CRRT, and clinical outcomes. In total, 95 patients (23 MARS®, 72 CRRT) were included. The median age at admission for the whole cohort was 4.3 years (interquartile range (IQR) 1.0-12.1), and 47/95 (49.5%) of patients had an indeterminate aetiology. A lower proportion of patients in the MARS® group were on inotropes or were ventilated at admission, and they had a lower Pediatric Index of Mortality 3 risk % than the CRRT group (14.5% (7.5-22) vs 20.4% (16.8-26.4), p = 0.002). After treatment, there were no significant differences detected between groups in survival with native liver, or overall survival (15/23 (65.2%) for MARS® and 49/72 (68.1%) for CRRT, p = 0.998).ConclusionWe did not detect a significant difference in clinical outcomes between PALF patients treated with CRRT or MARS®, despite a relatively sicker cohort in the CRRT group. Further high-quality evidence is necessary regarding the role of extracorporeal therapies in PALF, with consideration of clinical outcomes, feasibility, and cost.What is known• Outcomes for children with paediatric acute liver failure (PALF) have improved in recent years secondary to improved supportive care aimed at avoiding liver transplantation. • Extracorporeal therapies, in particular continuous renal replacement therapy (CRRT), are increasingly applied in the management of these children; however few studies have compared outcomes between different extracorporeal therapies.What is new• In this retrospective study across two centres, outcomes between patients with PALF treated with CRRT were compared to patients treated with MARS®. • There was no significant difference in key clinical outcomes between groups, including survival with native liver and overall survival.

Project description:The aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure.Patients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4% albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model.Sixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median -68 μmol/L, interquartile range [IQR] -107.5 to -33.5, p = 0.001; SPAD: -59 μmol/L, -84.5 to +36.5, p = 0.001). However, bile acids (MARS: -39 μmol/L, -105.6 to -8.3, p < 0.001; SPAD: -9 μmol/L, -36.9 to +11.4, p = 0.131), creatinine (MARS: -24 μmol/L, -46.5 to -8.0, p < 0.001; SPAD: -2 μmol/L, -9.0 to +7.0/L, p = 0.314) and urea (MARS: -0.9 mmol/L, -1.93 to -0.10, p = 0.024; SPAD: -0.1 mmol/L, -1.0 to +0.68, p = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10%, -0.8 to +20.9%, p < 0.001; SPAD: +7%, -7.5 to +15.5%, p = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD.Both procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation.German Clinical Trials Register ( www.drks.de) DRKS00000371. Registered 8 April 2010.

Project description:BackgroundThe primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated.AimWe studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD).MethodsWe report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10).ResultsThe entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3-5 sessions). Independent of the underlying etiology, MARS improved the patients' bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0-15.3); SMT 3.3% (95% CI: 0-9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0-44.7), SMT 11.1% (95% CI: 0-31.7), p = 0.478).ConclusionsAlthough it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of MARS therapy resulted in the sustained stabilization of liver function and improved liver regeneration. A short-term response to MARS may predict the future course of the disease.

Project description:INTRODUCTION: Patients with acute-on-chronic liver failure show an aggravated hyperdynamic circulation. We evaluated, in a controlled manner, potential changes in systemic haemodynamics induced by the molecular adsorbent recirculating system (MARS) and the Prometheus system liver detoxification devices in a group of patients with acute-on-chronic liver failure. METHODS: Eighteen patients (51.2 +/- 2.3 years old; Child-Pugh score, 12.5 +/- 0.2; Maddrey score, 63.1 +/- 5.0; hepatic venous pressure gradient, 17.6 +/- 0.9 mmHg) with biopsy-proven alcoholic cirrhosis and superimposed alcoholic hepatitis were either treated with standard medical therapy (SMT) combined with MARS (n = 6) or Prometheus (n = 6) or were treated with SMT alone (n = 6) on three consecutive days (6 hours/session). Liver tests, systemic haemodynamics and vasoactive substances were determined before and after each session. RESULTS: Groups were comparable for baseline haemodynamics and levels of vasoactive substances. Both MARS and Prometheus decreased serum bilirubin levels (P < 0.005 versus SMT), the Prometheus device being more effective than MARS (P = 0.002). Only MARS showed significant improvement in the mean arterial pressure (Deltachange, +9 +/- 2.4 mmHg versus -0.3 +/- 2.4 mmHg with Prometheus and -5.2 +/- 2.1 mmHg with SMT, P < 0.05) and in the systemic vascular resistance index (Deltachange, +131.5 +/- 46.2 dyne x s/cm5/m2 versus -92.8 +/- 85.2 dyne x s/cm5/m2 with Prometheus and -30.7 +/- 32.5 dyne x s/cm5/m2 with SMT; P < 0.05), while the cardiac index and central filling remained constant. This circulatory improvement in the MARS group was paralleled by a decrease in plasma renin activity (P < 0.05), aldosterone (P < 0.03), norepinephrine (P < 0.05), vasopressin (P = 0.005) and nitrate/nitrite levels (P < 0.02). CONCLUSION: The MARS device, and not the Prometheus device, significantly attenuates the hyperdynamic circulation in acute-on-chronic liver failure, presumably by a difference in removal rate of certain vasoactive substances. These findings suggest conspicuous conceptual differences among the albumin dialysis devices.

Dataset Information

Molecular Adsorbent Recirculating System for Acute Liver Failure in a New Pediatric-Based Extracorporeal Liver Support Program.

Importance

Objectives

Design setting and participants

Main outcomes and measures

Results

Conclusions and relevance

Publications

Molecular Adsorbent Recirculating System for Acute Liver Failure in a New Pediatric-Based Extracorporeal Liver Support Program.

Similar Datasets

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