Artificial liver support systems.

Artificial liver systems are used to bridge between transplantation or to allow a patient's liver to recover. They are used in patients with acute liver failure (ALF) and acute-on-chronic liver failure. There are five artificial systems currently in use: molecular adsorbent recirculating system (MARS), single-pass albumin dialysis (SPAD), Prometheus, selective plasma filtration therapy, and hemodiafiltration. The aim is to compare existing data on the efficiency of these devices. A literature search was conducted using online libraries. Inclusion criteria included randomized control trials or comparative human studies published after the year 2000. A systematic review was conducted for the five individual devices with a more detailed comparison of the biochemistry for the SPAD and MARS systems. Eighty-nine patients were involved in the review comparing SPAD and MARS. Results showed that there was an average reduction in bilirubin (-53 µmol/L in MARS and -50 µmol/L in SPAD), creatinine (-19.5 µmol/L in MARS and -7.5 µmol/L in SPAD), urea (-0.9 mmol/L in MARS and -0.75 mmol/L in SPAD), and gamma-glutamyl transferase (-0.215 µmol/L·s in MARS and -0.295 µmol/L·s in SPAD) in both SPAD and MARS. However, there was no significant difference between the changes in the two systems. This review demonstrated that both MARS and SPAD aid recovery of ALF. There is no difference between the efficiency of MARS and SPAD. Because of the limited data, there is a need for more randomized control trials. Evaluating cost and patient preference would aid in differentiating the systems.

Cytokine Blood Filtration Responses in COVID-19.

The real issue with the COVID-19 pandemic is that a rapidly increasing number of patients with life-threatening complications are admitted in hospitals and are not well-administered. Although a limited number of patients use the intensive care unit (ICU), they consume medical resources, safety equipment, and enormous equipment with little possibility of rapid recovery and ICU discharge. This work reviews effective methods of using filtration devices in treatment to reduce the level of various inflammatory mediators and discharge patients from the ICU faster. Extracorporeal technologies have been reviewed as a medical approach to absorb cytokines. Although these devices do not kill or remove the virus, they are a promising solution for treating patients and their faster removal from the ICU, thus relieving the bottleneck.

Application of the Molecular Adsorbent Recirculating System in Type 1 Hepatorenal Syndrome in the Course of Alcohol-Related Acute on Chronic Liver Failure.

BACKGROUND This study aimed to evaluate the Molecular Adsorbent Recirculating System (MARS) effectiveness in patients with alcohol-related acute-on-chronic liver failure (AoCLF) complicated with type 1 hepatorenal syndrome (HRS). So far, MARS efficacy and safety has been demonstrated in various acute liver failure scenarios. MATERIAL AND METHODS Data from 41 MARS procedures (10 patients with type 1 HRS, in the course of alcohol-related AoCLF were considered for this study. Biochemical tests of blood serum were performed before and after each procedure. The condition of patients was determined before and after the treatment with the use of the model for end-stage liver disease - sodium (MELD-Na) and the stage of encephalopathy severity based on the West Haven criteria. RESULTS During the observation period (20.5±13.9 days), 5 patients died, and the remaining 5 surviving patients were discharged from the hospital. In the group of 10, the 14-day survival, starting from the first MARS treatment, was 90%. The MARS procedure was associated with a 19% reduction in bilirubin (27.5±6.1 versus 22.3±4.0 mg/dL, P<0.001), 37% reduction in ammonia (44.1±22.5 versus 27.6±20.9 P<0.001), 27% reduction in creatinine (1.5±1.0 versus 1.1±0.6 mg/dL, P<0.001) and 14% reduction urea (83.8±36.1 versus 72.1±33.3, P<0.001) in blood serum samples, with stable hemodynamic parameters. In the group of patients discharged from the clinic (n=5), the MARS treatments resulted in an improvement in hepatic encephalopathy (West Haven; P=0.043), as well as a reduction in the MELD-Na score (P=0.015). CONCLUSIONS MARS is a hemodynamically safe method for supporting the function of the liver and the kidneys. Application of the MARS reduces the symptoms of encephalopathy in patients with alcohol-related type 1 HRS.

Clinical Effect of the Acrylonitrile-Co-Methallyl Sulfonate Surface-Treated Membrane as a Cytokine Adsorption Therapy for Sepsis due to Acute Panperitonitis: A Retrospective Cohort Study.

INTRODUCTION: Sepsis is a systemic inflammatory response syndrome caused by infectious diseases, with cytokines possibly having an important role in the disease mechanism. Acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane is expected to improve the outcomes of patients with sepsis through cytokine adsorption. OBJECTIVE: This study aimed to investigate the clinical effect of the AN69ST membrane in comparison to standard continuous renal replacement therapy (CRRT) membranes for panperitonitis due to lower gastrointestinal perforation. METHODS: Using the Diagnosis Procedure Combination database, we identified adult patients with sepsis due to panperitonitis receiving any CRRT. Propensity score matching was used to compare patients who received CRRT with the AN69ST membrane (AN69ST group) and those who received CRRT with other membranes (non-AN69ST group). The primary outcome measure was in-hospital mortality. RESULTS: A total of 528 and 1,445 patients were included in the AN69ST group and in the non-AN69ST group, respectively. Propensity score matching resulted in 521 pairs. There was no significant difference in in-hospital mortality (32.1 vs. 35.5%; p = 0.265) and 30-day mortality (41.3 vs. 42.8%, p = 0.074) between the AN69ST group and the non-AN69ST group. CONCLUSION: There is no significant difference in-hospital mortality between CRRT with the AN69ST membrane and CRRT with standard CRRT membranes for panperitonitis due to lower gastrointestinal perforation. These results indicate that the AN69ST membrane is not superior to the standard CRRT membrane.

AST-120, an Adsorbent of Uremic Toxins, Improves the Pathophysiology of Heart Failure in Conscious Dogs.

PURPOSE: Several lines of evidence suggest that renal dysfunction is associated with cardiovascular toxicity through the action of uremic toxins. The levels of those uremic toxins can be reportedly reduced by the spherical carbon adsorbent AST-120. Because heart failure (HF) causes renal dysfunction by low cardiac output and renal edema, the removal of uremic toxins could be cardioprotective. METHOD: To determine whether blood levels of the uremic toxin indoxyl sulfate (IS) increase in HF and whether AST-120 can reduce those levels and improve HF. We induced HF in 12 beagle dogs by 6 weeks of rapid right ventricular pacing at 230 beats per min. We treated six dogs with a 1-g/kg/day oral dosage of AST-120 for 14 days from week 4 after the start of rapid ventricular pacing. The other six dogs did not receive any treatment (control group). RESULTS: In the untreated dogs, IS levels increased as cardiac function deteriorated. In contrast, plasma IS levels in the treated dogs decreased to baseline levels, with both left ventricular fractional shortening and pulmonary capillary wedge pressure also improving when compared with untreated dogs. Finally, AST-120 treatment was shown to reduce both myocardial apoptosis and fibrosis along with decreases in extracellular signal-regulated kinase phosphorylation, the Bax/Bcl-2 ratio, and TGF-ß1 expression and increases in AKT phosphorylation. CONCLUSIONS: IS levels are increased in HF. AST-120 treatment reduces the levels of IS and improves the pathophysiology of HF in a canine model. AST-120 could be a novel candidate for the treatment of HF.

Removal of Bilirubin with a New Adsorbent System: In Vitro Kinetics.

BACKGROUND/AIMS: Many potentially toxic molecules accumulate in the blood during hepatic dysfunction. In clinical practice, it is very difficult to remove bilirubin, the most widely studied toxin, and particularly the unconjugated form, strongly albumin-bound. The aim of this in vitro study was to assess irreversible bilirubin adsorption as a protein-bound compound marker, using Cytosorb® (Cytosorbents Corp.), a new hemoadsorption device designed to remove cytokines. METHODS: We performed 4 in vitro experiments, dynamic and static, with different albumin-bilirubin solutions. RESULTS: All experiments showed the resin's ability to break the albumin-bilirubin complex (Experiment 1, 2), leading to efficient bilirubin removal for 24 h (Removal Rate: 90% Experiment 3) with minimal albumin loss. No sign of bilirubin release from the charged resin was detected (Experiment 4). CONCLUSION: Cytosorb® seems a promising artificial liver support, thanks to its ability to adsorb bilirubin and its proven ability to modulate the cytokines involved in hepatic dysfunction.

A comparison among three different apheretic techniques for treatment of hyperbilirubinemia.

Liver failure is associated to high mortality due to the accumulation of protein-bound metabolites, such as bilirubin, not removed by conventional hemodialysis. Different methods can efficiently remove them, such as the molecular adsorbent recirculating system (MARS), plasma exchange (PEX), and bilirubin or plasma adsorption perfusion (PAP). No direct comparison exists between MARS, PEX and PAP, and current guidelines do not specify which method (and when) to use. We have retrospectively evaluated MARS, PEX and PAP in their effectiveness in lowering plasma bilirubin concentration, and their effects on liver and kidney function. A total of 98 patients have been recruited, which comprised 68 patients treated with PAP (177 sessions), 16 patients with PEX (41 sessions) and 11 patients with MARS (21 sessions). Bilirubin, creatinine, liver enzymes were analyzed before and after the first treatment with each technique. The three methods did not differ for bilirubin lowering efficiency, with MARS showing only slightly less effective reductions. Finally, the three techniques did not differ in the amount of change of cholinesterase, but a lower reduction in AST was found using PAP. Our retrospective observation is one of the largest case series of hepatic failure treated with bilirubin absorption. The choice of the technique cannot be based on the desired reduction in bilirubin concentration. Based on costs and duration of treatment, we suggest that PAP could be considered as a first-line approach. In case of kidney involvement, MARS remains a valuable option.

Sorption technique as a tool for reduction of genotoxicity.

In the present study, the Allium cepa root chromosomal aberration assay was used to determine the genotoxic effects of copper and cadmium ions solutions before and after sorption processes. The sorption process was carried out using unmodified Dendrocalamus strictus charcoal powder, nitrilotriacetic acid (NTA)-modified D. strictus charcoal powder, and Saccharomyces cerevisiae. The frequency of total chromosomal aberrations was observed to be 24.30-45.13% for copper and 13.16-45.14% for cadmium at different concentrations (1-500 mg/l) before the sorption process. Both metal ions solutions resulted in significant reduction of chromosomal aberrations after all the modes of the sorption processes. However, the order of reduction of percentage chromosomal aberrations for copper and cadmium solutions was found to be 45.29-70.04% and 47.80-84.57%, respectively (NTA-modified D. strictus charcoal powder); >44.53-54.32% and 37.10-79.40%, respectively (unmodified D. strictus charcoal powder); >15.59-48.51% and 13.63-21.50%, respectively (S. cerevisiae).

Adjuvant treatment of severe/refractory bullous pemphigoid with protein A immunoadsorption.

BACKGROUND: While depletion of circulating autoantibodies using immunoadsorption (IA) is an established therapeutic approach in patients with pemphigus vulgaris, IA has only sporadically been used in other autoimmune bullous disorders. Although bullous pemphigoid (BP) usually responds well to topical and systemic corticosteroids, rapid depletion of serum autoantibodies may be an effective adjuvant treatment option in patients with severe and/or refractory disease. PATIENTS AND METHODS: Case series of 20 patients (13 women, 7 men; mean age 78.6 years; range 56-94 years) with severe or refractory BP. In addition to oral prednisolone (0.25-0.5 mg/kg/day), dapsone (1.0-1.5 mg/kg/day), and clobetasol propionate 0.05 % ointment (lesional application, twice daily), treatment consisted of protein A IA (three sessions on consecutive days). The mean follow-up period was 33.6 months (1-84 months). RESULTS: The majority of patients showed a rapid and sustained response. One month after treatment, eight patients (42 %; 19 patients were included in the follow-up) were in complete remission; at the last follow-up visit (after 1 to 84 months), that number was 13 (68 %). Not only was there an initial drop in anti-BP180 autoantibodies (by 92 %), the effect also continued after one and three months, with mean autoantibody levels at 26 % and 13 % of baseline, respectively (p < 0.001). Both previously treated and treatment-naive patients showed a significant reduction in anti-BP180NC16A antibody levels throughout the observation period. Adverse events occurred in 13 of the 20 patients (65 %). Three were severe of which two were likely or probably related to IA. CONCLUSION: Immunoadsorption is an effective adjuvant treatment option for (the usually elderly) patients with severe and/or refractory BP.

Single Pass Albumin Dialysis-A Dose-Finding Study to Define Optimal Albumin Concentration and Dialysate Flow.

Several artificial liver support concepts have been evaluated both in vitro and clinically. Single pass albumin dialysis (SPAD) has shown to be one of the most simple approaches for removing albumin-bound toxins and water-soluble substances. Being faced with acute liver failure (ALF) in everyday practice encouraged our attempt to define the optimal conditions for SPAD more precisely in a standardized experimental setup. Albumin concentration was adjusted to either 1%, 2%, 3%, or 4%, while the flow rate of the dialysate was kept constant at a speed of 700 mL/h. The flow rate of the dialysate was altered between 350, 500, 700, and 1000 mL/h, whereas the albumin concentration was continuously kept at 3%. This study revealed that the detoxification of albumin-bound substances could be improved by increasing the concentration of albumin in the dialysate with an optimum at 3%. A further increase of the albumin concentration to 4% did not lead to a significant increase in detoxification. Furthermore, we observed a gradual increase of the detoxification efficiency for albumin-bound substances, from 350 mL/h to 700 mL/h (for bilirubin) or 1000 mL/h (for bile acids) of dialysate flow. Water-soluble toxins (ammonia, creatinine, urea, uric acid) were removed almost completely, regardless of albumin concentration or flow rate. In conclusion, this study confirmed that SPAD is effective in eliminating albumin-bound as well as water-soluble toxins using a simulation of ALF. Furthermore, this project was successful in evaluating the most effective combination of albumin concentration (3%) and dialysate flow (700 mL/h-1000 mL/h) in SPAD for the first time.

[COMPARATIVE ESTIMATION OF THE APPLICATION EFFICACY FOR THE COMPOSITION, BASING ON NANODISPERSE SILICA, OWING ANTIMICROBIAL PROPERTIES FOR LOCAL TREATMENT OF PURULENT-INFLAMMATORY PROCESSES].

Comparative estimation of the local treatment results for purulent-inflammatory diseases of soft tissues, using standard methods and composition, owing sorption and antimicrobial properties and basing on a nanodispersedsilica, was conducted. The composition application in complex of treatment have promoted more rapid clearance from necrotized tissues and microorganisms, rapid appearance of granulations, the intoxication severity reduction, the phase I of the wound process duration shortening, what have permitted to put secondary sutures on the wound on the 6 ­ 7th postoperative day, and total duration of the patients' stationary treatment have reduced by 3.7 days.

Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation.

Synthetic polymers incorporating the cationic charge and hydrophobicity to mimic the function of antimicrobial peptides (AMPs) have been developed. These cationic-amphiphilic polymers bind to bacterial membranes that generally contain negatively charged phospholipids and cause membrane disintegration resulting in cell death; however, cationic-amphiphilic antibacterial polymers with endotoxin neutralization properties, to the best of our knowledge, have not been reported. Bacterial endotoxins such as lipopolysaccharide (LPS) cause sepsis that is responsible for a great amount of mortality worldwide. These cationic-amphiphilic polymers can also bind to negatively charged and hydrophobic LPS and cause detoxification. Hence, we envisaged that cationic-amphiphilic polymers can have both antibacterial as well as LPS binding properties. Here we report synthetic amphiphilic polymers with both antibacterial as well as endotoxin neutralizing properties. Levels of proinflammatory cytokines in human monocytes caused by LPS stimulation were inhibited by >80% when coincubated with these polymers. These reductions were found to be dependent on concentration and, more importantly, on the side-chain chemical structure due to variations in the hydrophobicity profiles of these polymers. These cationic-amphiphilic polymers bind and cause LPS neutralization and detoxification. Investigations of polymer interaction with LPS using fluorescence spectroscopy and dynamic light scattering (DLS) showed that these polymers bind but neither dissociate nor promote LPS aggregation. We show that polymer binding to LPS leads to sort of a pseudoaggregate formation resulting in LPS neutralization/detoxification. These findings provide an unusual mechanism of LPS neutralization using novel synthetic cationic-amphiphilic polymers.

Comparison of two different modes of molecular adsorbent recycling systems for liver dialysis.

BACKGROUND: In children acute liver failure is a rare but life-threatening condition from which two-thirds do not recover with supportive therapy. Treatment is limited by the availability of liver transplants. Molecular adsorbent recirculating system (MARS) dialysis is a bridge to transplantation that enhances the chances of survival during the waiting period for a transplant, although it cannot improve survival. Open albumin dialysis (OPAL) is a new mode of albumin dialysis developed to further improve dialysis efficiency. CASE DIAGNOSIS/TREATMENT: We report a paediatric case of acute-on-chronic liver failure and compare the two modes of albumin dialysis, namely, the MARS and OPAL, used to treat this patient's cholestatic pruritus. Removal of total and direct bilirubin, ammonia and bile acids were measured by serial blood tests. There was an increased removal of bile acids with the OPAL mode, whereas the removal of total and direct bilirubin and ammonia was similar in both modes. The patient reported better improvement in pruritus following OPAL compared to dialysis with the MARS. CONCLUSION: OPAL may offer a better solution than the MARS in the treatment of refractory pruritus in liver failure.

Adsorption of Selected Antibiotics to Resins in Extracorporeal Blood Purification.

BACKGROUND/AIMS: Extracorporeal blood purification systems (EBS) use specific adsorbents for the elimination of toxins and cytokines. The aim of this study was to test different adsorbents for their ability to reduce antibiotics in parallel to extracorporeal blood purification therapy. METHODS: The in vitro adsorption experiments were carried out in human plasma with a newly established hydrophobic resin (Amberchrom CG161c) and adsorbents commercially available and approved in the clinics. The concentration of antibiotic was chosen equivalent to the recommended therapeutic dosage applied intravenously and was measured in plasma using ELISA test kits and high-performance liquid chromatography methods. RESULTS: The adsorbent that reduced all tested antibiotics in plasma close to the detection limit was the dia MARS AC250, which is an activated charcoal involved in the Molecular Adsorbents Recirculation System. CONCLUSION: For better antibiotic monitoring in sepsis treatment, further investigations have to be performed to determine the clearance rate of antibiotics by different EBS devices.

Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis.

 Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. MATERIAL AND METHODS: We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed. RESULTS: After MARS® procedure, patients' symptoms improved, as well as liver function tests, thus avoiding liver transplantation. CONCLUSION: Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.

Early initiation of MARS® dialysis in Amanita phalloides-induced acute liver injury prevents liver transplantation.

 Amanita phalloides is the most relevant mushroom intoxication leading to acute liver failure. The two principal groups of toxins, the amatoxins and the phallotoxins, are small oligopeptides highly resistant to chemical and physical influences. The amatoxins inhibit eukaryotic RNA polymerase II causing transcription arrest affecting mainly metabolically highly active cells like hepatocytes and renal cells. The clinically most characteristic symptom is a 6-40 h lag phase before onset of gastrointestinal symptoms and the rapid progression of acute liver failure leading to multi-organ failure and death within a week if left untreated. Extracorporeal albumin dialysis (ECAD) was reported to improve patient's outcome or facilitate bridging to transplantation. In our tertiary center, out of nine intoxicated individuals from five non-related families six patients presented with acute liver injury; all of them were treated with ECAD using the MARS® system. Four of them were listed on admission for high urgency liver transplantation. In addition to standard medical treatment for Amanita intoxication we initiated ECAD once patients were admitted to our center. Overall 16 dialysis sessions were performed. All patients survived with full native liver recovery without the need for transplantation. ECAD was well tolerated; no severe adverse events were reported during treatment. Coagulopathy resolved within days in all patients, and acute kidney injury in all but one individual. In conclusion, ECAD is highly effective in treating intoxication with Amanita phalloides. Based on these experiences we suggest early initiation and repeated sessions depending on response to ECAD with the chance of avoiding liver transplantation.

[Role of correction of the syndrome of intestinal failure and abdominal hypertension in the prevention of infection of pancreatic necrosis]. / Rol' korrektsii sindromov kishechnoi nedostatochnosti i vnutribryushnoi gipertenzii v profilaktike infitsirovaniya pankreonekroza.

UNLABELLED: The number of patients with acute pancreatitis and pancreatic necrosis has been steadily increasing. Mortality in infected pancreatic necrosis remains high. AIM: To develop measures to prevent infection of pancreatic necrosis by timely correction of intra-abdominal hypertension and the syndrome of intestinal failure. MATERIAL AND METHODS: Developed a package of measures, consisting of early intestinal lavage and enterosorption, intravenous highdoses of octreotide, epidural blockade, adequate detox and the start of effective antimicrobial therapy. Comparative evaluation of clinical, laboratory and instrumental data in the primary (n=50) and control (n=50) groups. RESULTS: In the main group pancreatogenic sepsis occurred in 10%, control 18%. Mortality, respectively, was 8 and 16%.

[VARICOSE DISEASE OF THE LOWER EXTREMITIES: CAUSES, COMPLICATIONS, CHOICE OF METHODS FOR TREATMENT AND PROPHYLAXIS].

Abstract The results of 1142 patients treatment for varicose disease of the lower extremities in 2006-2014 yrs were adduced. The patients were divided on 3 groups, depending on the clinical signs severity and method of treatment. There were operated 59 patients, in 65--the proposed scheme of treatment was applied.

Effective Sequestration of Clostridium difficile Protein Toxins by Calcium Aluminosilicate.

Clostridium difficile is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for C. difficile infection. Toxin A (TcdA) and toxin B (TcdB) are nearly indispensable virulence factors for Clostridium difficile pathogenesis. Given the toxin-centric mechanism by which C. difficile pathogenesis occurs, the selective sequestration with neutralization of TcdA and TcdB by nonantibiotic agents represents a novel mode of action to prevent or treat C. difficile-associated disease. In this preclinical study, we used quantitative enzyme immunoassays to determine the extent by which a novel drug, calcium aluminosilicate uniform particle size nonswelling M-1 (CAS UPSN M-1), is capable of sequestering TcdA and TcdB in vitro. The following major findings were derived from the present study. First, we show that CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Second, we show that CAS UPSN M-1's affinity for TcdA is greater than its affinity for TcdB. Last, we show that CAS UPSN M-1 exhibited limited binding affinity for nontarget proteins. Taken together, these results suggest that ingestion of calcium aluminosilicate might protect gastrointestinal tissues from antibiotic- or chemotherapy-induced C. difficile infection by neutralizing the cytotoxic and proinflammatory effects of luminal TcdA and TcdB.

Experience with molecular adsorbent recirculating system treatment in 20 children listed for high-urgency liver transplantation.

For more than 10 years, children at our national center for pediatric liver transplantation (LT) have been treated with Molecular Adsorbent Recirculating System (MARS) liver dialysis as a bridging therapy to high-urgency LT. Treatment was reserved for 20 patients with the highest degrees of hepatic encephalopathy (HE; median grade = 3.5). Death from neurological sequelae was considered imminent for these patients, and this was further reflected in significantly higher international normalized ratios and ammonia levels and worse prognostic liver indices (Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores and liver injury units) in comparison with 32 wait-listed patients who did not receive MARS dialysis. MARS therapy was generally well tolerated, with a reduction in thrombocytes and hemorrhaging as the most common side effects. HE improvement was documented in 30% of the treated patients, but progression to grade IV encephalopathy occurred in 45% of the patients despite the treatment. Serum ammonia, bilirubin, bile acid, and creatinine levels significantly decreased during treatment. Eighty percent of MARS-treated patients survived to undergo LT, and their survival was equivalent to that of non-MARS-treated patients with severe liver failure (69%, P = 0.52). The heterogeneity between MARS-treated patients and non-MARS-treated patients in our cohort precluded a statistical evaluation of a benefit from MARS for patient survival. Our data demonstrate the safety of MARS even in the most severely ill patients awaiting LT, but strategies that promote the more rapid and widespread availability of high-quality donor organs remain of critical importance for improving patient survival in cases of severe acute liver failure.