Molecular Adsorbent Recirculating System Therapy Research Articles

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

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

The Effect of Molecular Adsorbent Recirculating System in Patients With Liver Failure: A Case Series of 44 Patients

Liver failure is associated with a high mortality rate, with many patients requiring transplant for definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a nonbiologic system that provides extracorporeal support.Literature on MARS therapy is mixed: outcomes support MARS therapy for patients with isolated acute liver failure, but data on patients with chronic disease is varied. Several case studies report success using MARS as a bridging treatment for patients awaiting transplant. The purpose of this case series is to present the outcomes of 44 patients who underwent MARS therapy forliver failure, 19 of whom used MARS therapy as a bridging therapy to transplant. This study retrospectively identified 44 patients who underwent MARS therapy for liver failure at Mayo Clinic, Jacksonville, between January 2014 and April 2021. Variables of interest included changes in laboratory markers of hepatic functioning, number and length of MARS therapy sessions, transplantation status, and mortality. Following MARS therapy, there were improvements in mean serum bilirubin, ammonia, urea, creatinine, International Normalized Ratio, alanine aminotransferase, and aspartate aminotransferase levels. Twenty-seven patients (61.36%) survived the hospital stay; 17 (38.63%) died in the hospital. The majority of surviving patients (n = 19; 73.07%) receivedliver transplant. Six did not require transplant (22.22%). All but 1 patient who received MARS as a bridging treatment to transplant survived the follow-up period (n = 18; 94.74%). Outcomes of these 44 cases suggest that MARS improves liver failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant.

S3598 Autoimmune Hepatitis and Primary Biliary Cholangitis Overlap Syndrome Presenting as Refractory Pruritus Requiring Molecular Adsorbent Recirculating System Therapy

S3598 Autoimmune Hepatitis and Primary Biliary Cholangitis Overlap Syndrome Presenting as Refractory Pruritus Requiring Molecular Adsorbent Recirculating System Therapy

Kidney Outcomes Following Utilization of Molecular Adsorbent Recirculating System

Molecular adsorbent recirculating system (MARS) is an extracorporeal system combining conventional veno-venous hemodiafiltration and adsorption to provide rescue support in fulminant hepatic failure. Acute kidney injury (AKI) is common in patients with hepatic failure warranting continuous kidney replacement therapy (CKRT). Our primary aim was to characterize a cohort of patients who received MARS therapy and examine kidney events given the current paucity of available data. Patients initiating MARS in a tertiary care setting from January 2014 through December 2020 were assessed for treatment indications, transplantation, CKRT, kidney recovery, and death. Data was collected using the REDCAP software. A total of 49 patients (67% female; 75% White) received MARS therapy with 29 patients (59%) requiring concomitant CKRT. Hepatic encephalopathy (HE) was the most common indication for MARS initiation (55%). In-hospital mortality was 41% (12/29) among patients who received CKRT versus 10% (2/20) among those not requiring CKRT (relative risk [RR] 4.15, 95% confidence interval [CI] 1.04 to 16.52, P=0.044); this persisted following adjustment for prespecified patient characteristics (all RR≥ 3.76, all P≤0.060). One-year mortality post-MARS initiation was high overall but highest among the CKRT group (59% [17/29] vs. 25% [5/20] unadjusted RR 2.92, 95% CI 1.08 to 7.94, P= 0.035). Liver transplant after MARS occurred in 41% of patients (20/49). After CKRT, 39% of patients (9/29) recovered kidney function prior to hospital discharge. Patients requiring MARS frequently have AKI warranting the use of concomitant CKRT, which is associated with a high rate of in-hospital and 1-year mortality.

Liver-Support Therapies in Critical Illness-A Comparative Analysis of Procedural Characteristics and Safety.

Extracorporeal liver-support therapies remain controversial in critically ill patients, as most studies have failed to show an improvement in outcomes. However, heterogeneous timing and inclusion criteria, an insufficient number of treatments, and the lack of a situation-dependent selection of available liver-support modalities may have contributed to negative study results. We retrospectively investigated the procedural characteristics and safety of the three liver-support therapies CytoSorb, Molecular Adsorbent Recirculating System (MARS) and therapeutic plasma exchange (TPE). Whereas TPE had its strengths in a shorter treatment duration, in clearing larger molecules, affecting platelet numbers less, and improving systemic coagulation and hemodynamics, CytoSorb and MARS were associated with a superior reduction in particularly small protein-bound and water-soluble substances. The clearance magnitude was concentration-dependent for all three therapies, but additionally related to the molecular weight for CytoSorb and MARS therapy. Severe complications did not appear. In conclusion, a better characterization of disease-driving as well as beneficial molecules in critically ill patients with acute liver dysfunction is crucial to improve the use of liver-support therapy in critically ill patients. TPE may be beneficial in patients at high risk for bleeding complications and impaired liver synthesis and hemodynamics, while CytoSorb and MARS may be considered for patients in whom the elimination of smaller toxic compounds is a primary objective.

1277: USE OF MOLECULAR ADSORBENT RECIRCULATING SYSTEM LEADING TO IMPROVED TRANSPLANT-FREE SURVIVAL

Introduction: Acute liver failure (ALF) has many different etiologies and carries significant morbidity and mortality. Hepatic encephalopathy (HE) is a main cause of mortality in these patients and is associated with cerebral edema and risk for progression to brainstem herniation. Albumin dialysis, mainly utilizing the Molecular Adsorbent Recirculating System (MARS) has been demonstrated in the past to improve HE, although data on mortality benefit has been inconsistent. The Children’s Hospital at Montefiore is a children’s hospital within a larger adult healthcare system. We report our single center experience utilizing extracorporeal liver support via the MARS device on pediatric and adult patients over our inaugural year. Methods: This is a retrospective report of all patients who underwent MARS therapy during the first year of our program. As per our institutional guidelines, all patients were eligible for MARS due to having grade 3+ HE or grade 2 HE with an additional failing organ system. All patients, despite their age, were treated by the pediatric MARS team. Results: Four pediatric and two adult patients underwent MARS therapy. The underlying etiologies of the acute liver failure were: acetaminophen overdose in one, indeterminate in three, disseminated varicella in one, and acute fatty liver of pregnancy with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and atypical hemolytic uremic syndrome in one. Survival was 100%. Of the two adults, one had severe Grade 4 HE with loss of multiple brainstem reflexes upon initiation of MARS support. Her neurologic exam demonstrated improvement during her first MARS treatment cycle, and she was successfully transplanted later that night. The second adult, as well as all four pediatric patients were able to achieve full recovery of their native liver function without need for transplantation. Conclusions: The use of MARS therapy appears in this cohort to allow for liver recovery and improved transplant free survival.

S3257 A Fatal Case of Herpes Simplex Hepatitis in Pregnancy

Introduction: Herpes Simplex Virus (HSV) hepatitis is a rare but potentially fatal presentation of HSV that can affect immunocompromised individuals such as pregnant women, particularly in the 3rd trimester. It can lead to liver failure with mortality up to 75%. Early recognition with the initiation of antivirals and supportive therapy has been shown to reduce mortality, however, insult to the liver can lead to liver failure complicated with encephalopathy and ascites. We present a case of HSV hepatitis in pregnancy which despite supportive therapy and acyclovir, resulted in demise. Case Description/Methods: A 24 year old pregnant female at 23 weeks gestation presented to a facility with complaints of fevers and fatigue. She was discharged and treated symptomatically. 2 weeks later she developed encephalopathy, profound liver failure, and thrombocytopenia, with induction of labor and loss of the infant. She was intubated and developed shock requiring pressors. She was placed on Molecular Adsorbent Recirculating System (MARS) dialysis for support. Cultures were collected, including HSV panel, which was positive for HSV-1. Acyclovir was immediately started, and patient continued to be on supportive therapy. She improved on MARS and acyclovir, with improvement of her liver enzymes and viral load, and later extubated. Patient appeared to return to baseline, however days later, patient developed jaundice, ascites significant for spontaneous bacterial peritonitis, and encephalopathy refractory to lactulose and rifaximin. Despite acyclovir, broad-spectrum antibiotics, and prior MARS therapy, her liver enzymes increased and patient had to be reintubated, where she had multiorgan failure and expired to disseminated HSV. Discussion: This case demonstrates a rare occurrence of HSV hepatitis in a pregnant woman. Recognition of HSV occurred once patient developed acute liver failure and encephalopathy, however, based on her history patient likely presented with HSV symptoms, such as fevers, and fatigue that remained untreated. Despite supportive therapy such as MARs and Acyclovir, patient expired of liver failure from HSV. This case shows the importance of considering HSV in the pregnant population, for if it were recognized and treated earlier, patient may not have reached fulminant liver failure resulting in death. In conclusion, HSV hepatitis and initiation of early antiviral therapy should be considered in all pregnant patients with concern for evolving hepatic failure.

Use of the Molecular Adsorbent Recirculating System in Acute Liver Failure: Results of a Multicenter Propensity Score-Matched Study.

The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy. Propensity score-matched retrospective cohort analysis. Tertiary North American liver transplant centers. Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009-2019) and controls from the U.S. Acute Liver Failure Study Group registry. Molecular adsorbent recirculating system treatment versus standard medical therapy (control). One-hundred four molecular adsorbent recirculating system patients were propensity score-matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King's College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07-3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone ("model 2"; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05-3.31; p = 0.033), and further adjustment of the "main model" for mechanical ventilation, and grade 3/4 hepatic encephalopathy ("model 3"; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07-3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 µmol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 µmol/L; p ≤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 µmol/L), creatinine (83.1 vs 133.5 µmol/L), and ammonia (111.5 vs 140.0 µmol/L; p ≤ 0.022 for all). Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure.

Transplant Hepatectomy With Portacaval Shunt and MARS Therapy for Perioperative Catastrophe: A Series of Four Liver Transplant Cases.

Background.Increased worldwide focus on maximal donor utilization and transplantation of patients once considered too ill to survive liver transplantation may increase the otherwise rare frequency of catastrophic graft failure. Although the deleterious effects of an acutely failing allograft have been established for decades, the optimal strategy in this patient population in the perioperative period remains ill-defined.Methods.A retrospective review of all liver transplant recipients with perioperative failure leading to transplant hepatectomy between January 1, 2014 and June 30, 2017 was performed. All patients were supported with MARS therapy while awaiting retransplantation.Results.Four patients experienced catastrophic graft failure from massive exsanguination and liver fracture (1), portal vein and hepatic artery thrombosis (1), idiopathic necrosis (1), and necrosis from inadequate donor flushing/primary nonfunction (1). All patients improved following transplant hepatectomy with portacaval shunting. Patients were supported with intubation, vasopressors, renal replacement therapy, and Molecular Adsorbent Recirculating System therapy. All patients underwent retransplantation after a mean anhepatic phase of 48.8 (± 5.13) h. Survival to discharge was 75%.Conclusions.Although catastrophic liver failure is highly challenging, acceptable outcomes can be achieved with timely hepatectomy with portacaval shunt and retransplantation, particularly in patients supported with the Molecular Adsorbent Recirculating System device.

Efficacy and safety of liver support devices in acute and hyperacute liver failure: a systematic review and network meta-analysis

Acute liver failure (ALF) is a potentially life-threatening condition. Liver support therapies can be applied as a bridging-to-transplantation or bridging-to-recovery; however, results of clinical trials are controversial. Our aim was to compare liver support systems in acute and hyperacute liver failure with network meta-analysis. After systematic search, randomized controlled trials (RCT) comparing liver support therapies in adults with acute or hyperacute liver failure were included. In-hospital mortality was the primary outcome, the secondary outcomes were hepatic encephalopathy and mortality-by-aetiology. A Bayesian-method was used to perform network meta-analysis and calculate surface under the cumulative ranking curve (SUCRA) values to rank interventions. Eleven RCTs were included. BioLogic-DT and molecular adsorbent recirculating system (MARS) resulted in the lowest mortality (SUCRAs: 76% and 73%, respectively). In non-paracetamol-poisoned patients, BioLogic-DT, charcoal hemoperfusion and MARS may be equally efficient regarding mortality (SUCRAs: 53%, 52% and 52%, respectively). Considering hepatic encephalopathy, extracorporeal liver assist device (ELAD) may be the most effective option (SUCRA: 78%). However, in pairwise meta-analysis, there were no statistically significant differences between the interventions in the outcomes. In conclusion, MARS therapy seems to be the best available option in reducing mortality. Further research is needed on currently available and new therapeutic modalities. (CRD42020160133).

Liver transplantation in patients with sickle cell disease: possible but challenging-a cohort study.

The liver is frequently affected in patients with sickle cell disease (SCD), but few reports have described liver transplantation (LT) in patients with SCD. We present a thorough analysis of the largest single-center series of LT in patients with SCD and the first systematic review. There were 21 patients with a median age of 37.6years. LT was performed for acute liver failure related to the sickling process (57%) or electively for end-stage liver disease (43%). Prior to LT, 13 patients (62%) were in the intensive care unit and required mechanical ventilation (33%), vasopressor therapy (24%), renal replacement therapy (10%), or molecular adsorbent recirculating system therapy (19%). Post-LT morbidity and mortality were 95% and 33%, respectively. Patient survival at 1 and 5years were 58.3% and 41.7%, respectively, in the urgent group and 88.9% and 77.8%, respectively, in the elective group. A total of 22 transplant patients with SCD are described in 20 articles in the literature. The 1- and 5-year patient survival rates for the 18 evaluable patients were 75% and 65%, respectively. LT improves survival in patients with SCD and acute liver failure or end-stage liver disease but is associated with high morbidity during the early postoperative course.

Outcomes of Acute Liver Injury in Adults Due to Wilson's Disease: Is Survival Without Transplant Possible?

Wilson's disease (WD) is a rare cause of acute liver failure (ALF) that is thought to have a uniformly fatal outcome without liver transplantation (LT). Previous studies proposed diagnostic and prognostic criteria for WD-ALF. It is not known whether these apply to WD patients presenting as severe acute liver injury (ALI) without encephalopathy. From 2008 to 2018, 822 patients with ALI in the US Acute Liver Failure Study Group (ALFSG) registry were enrolled and prospectively followed. The diagnosis of WD-ALI was confirmed in 8 patients. Serum biochemical diagnostic ratios predicting WD-ALF (alkaline phosphatase [ALP]:total bilirubin(TB) and aspartate aminotransferase [AST]:alanine aminotransferase [ALT]) were determined in these patients, and predictors of prognosis for WD-ALI were evaluated. Of these 8 ALI-WD patients, 5 received an LT. Ratios of both ALP:TB of <4 and AST:ALT of >2.2 on study admission were met in 4 LT patients. All LT patients were female. The Model for End-Stage Liver Disease scores on admission were generally higher in LT patients. All transplanted patients had an initial revised WD score of >11 (>10 predicting poor outcome without LT in WD-ALF), whereas in non-LT patients, 2 had scores of 9, and 1 a score of 13. Also, 3 LT patients were started on chelation therapy, 2 were started on plasmapheresis, and 1 was started on Molecular Adsorbent Recirculating System therapy. All non-LT patients were treated with chelation. At 21days, all patients were alive and discharged from the hospital. In conclusion, some patients with ALI due to WD may survive without LT. Revised Wilson index scores >10 predict poor outcome in most patients with WD-ALI, as they do for WD-ALF, and they correlate positively with the ALI model in this cohort. Biochemical ratios for WD diagnosis appear more applicable to ALF compared with WD-ALI.

Use of the Molecular Adsorbent Recirculating System in Acute Fatty Liver of Pregnancy: a Case Report

Acute fatty liver of pregnancy (AFLP) can cause liver failure in the third trimester and lead to fatal complications of mother and fetus. Prompt delivery has been known as the best treatment but the importance of the maternal care is also considered an option for accomplishing maternal recovery. We report a case of 28 year-old nullipara with 36+1 weeks who was clinically diagnosed AFLP. Although the patient had an uneventful delivery, she was suffered from acute hepatic failure, coagulopathy, hepatic encephalopathy, postpartum hemorrhage, and renal failure. We decided to assist the patient’s liver function by using artificial liver support therapy such as molecular adsorbent recirculating system (MARS). After the intensive care with MARS and continuous renal replacement therapy, she was discharged with good condition in general. In conclusion, MARS can be a treatment option for AFLP as well as for prompt delivery. However, more studies need to be done to better understand the role of MARS in assisting liver function for AFLP.

1085 The Use of the Molecular Adsorbent Recirculating System (MARS) in Treatment of Cholestatic Drug Induced Liver Injury

INTRODUCTION: Cholestatic drug induced liver injury (DILI) is a subtype of DILI defined by elevated alkaline phosphatase (ALP) or bilirubin levels from exposure to a drug causing cholestasis. It is a challenging diagnosis with limited treatment options. The molecular adsorbent recirculating system (MARS) allows for hemofiltration of albumin-bound substances that can improve cholestatic hepatitis, pruritus, and hepatic encephalopathy (HE). Here we report six cases of acute cholestatic DILI treated with MARS. METHODS: Patients with cholestatic DILI who underwent MARS were identified at a single institution. Pre-MARS, post-MARS and post hospitalization data on ALP, bilirubin, INR and HE were collected. Completion of MARS therapy was defined as continuous therapy for three to five days. RESULTS: Six cases were identified, one of which progressed to acute liver failure (ALF). Hepatotoxic medications included acetaminophen, phentermine, methimazole, OxyElite and two cases of the anabolic steroid Methyl-1-etiocholenololepietiocholanolone. Mean total bilirubin prior to MARS was 34.5 mg/dl. Over the course of therapy, patients had significant improvement with an average bilirubin of 13.4 mg/dl at completion of MARS and 2.4 mg/dl at follow up. Coagulopathy was seen in the case of ALF from acetaminophen with pre-MARS INR of 1.9 and post-MARS INR of 1.7. This patient also had grade 4 HE prior to MARS with improvement to grade 0 post-MARS. ALP levels were not abnormal and did not change. Clinical improvement in pruritis and jaundice was seen in all cases. CONCLUSION: This case series highlights six patients with cholestatic DILI who had significant improvement in bilirubin, pruritis and jaundice with MARS. This improvement in cholestasis was thought to be due to filtration of bilirubin. Removal of bilirubin also improved jaundice. In conjunction with medical therapy and withdrawal of the offending agent, there was sustained improvement in bilirubin that continued even on outpatient follow up. There was also improvement in pruritis that was refractory to maximal medical therapy. It is unclear which substance is the principal pruritogen associated with cholestasis. However, MARS provided significant symptomatic relief that persisted. In the one case of cholestatic DILI causing acute liver failure, MARS resulted in resolution of HE and served as a bridge to spontaneous hepatic recovery. Our case series shows that MARS is a viable option in treating acute cholestatic liver injury refractory to medical therapy.

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

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.

Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis.

Acute-on-chronic liver failure is associated with numerous consecutive organ failures and a high short-term mortality rate. Molecular adsorbent recirculating system therapy has demonstrated beneficial effects on the distinct symptoms, but the associated mortality data remain controversial. Retrospective analysis of acute-on-chronic liver failure patients receiving either standard medical treatment or standard medical treatment and molecular adsorbent recirculating system. Secondary analysis of data from the prospective randomized Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial by applying the recently introduced Chronic Liver Failure-criteria. Medical Departments of University Hospital Muenster (Germany). This analysis was conducted in two parts. First, 101 patients with acute-on-chronic liver failure grades 1-3 and Chronic Liver Failure-C-Organ Failure liver subscore equals to 3 but stable pulmonary function were identified and received either standard medical treatment (standard medical treatment, n = 54) or standard medical treatment and molecular adsorbent recirculating system (n = 47) at the University Hospital Muenster. Second, the results of this retrospective analysis were tested against the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial. Standard medical treatment and molecular adsorbent recirculating system. Additionally to improved laboratory variables (bilirubin and creatinine), the short-term mortality (up to day 14) of the molecular adsorbent recirculating system group was significantly reduced compared with standard medical treatment. A reduced 14-day mortality rate was observed in the molecular adsorbent recirculating system group (9.5% vs 50.0% with standard medical treatment; p = 0.004), especially in patients with multiple organ failure (acute-on-chronic liver failure grade 2-3). Concerning the affected organ system, this effect of molecular adsorbent recirculating system on mortality was particularly evident among patients with increased kidney, brain, or coagulation Chronic Liver Failure-C-Organ Failure subscores. Subsequent reanalysis of the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure dataset with adoption of the Chronic Liver Failure-classification resulted in similar findings. Molecular adsorbent recirculating system treatment was associated with an improved short-term survival of patients with acute-on-chronic liver failure and multiple organ failure. Among these high-risk patients, molecular adsorbent recirculating system treatment might bridge to liver recovery or liver transplantation.

Molecular adsorbent recirculating system (MARS) in acute liver injury and graft dysfunction: Results from a case-control study.

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.

Extracorporeal membrane oxygenation with multiple-organ failure: Can molecular adsorbent recirculating system therapy improve survival?

Liver dialysis, molecular adsorbent recirculating system (MARS) particularly, has been used in liver failure to bridge to transplantation. We expanded the indication for MARS to patients with acute shock liver failure and cardiopulmonary failure on extracorporeal membrane oxygenation (ECMO), aiming to improve survival to wean from ECMO. Retrospective chart analysis of patients on ECMO between 2010 and 2015 found 28 patients who met the criteria for acute liver failure, diagnosed by hyperbilirubinemia (total bilirubin ≥10 mg/dl) or by elevated transaminase (alanine transaminase >1,000 IU/liter). Of these patients, 14 underwent MARS treatment (Group M), and 14 were supported with optimal medical treatment without MARS (Group C). Patient characteristics, liver function, and survival were compared between groups. Demographics, clinical risk factors, and pre-ECMO laboratory data were identical between the groups. MARS was used continuously for 8 days ± 9 in Group M. Total bilirubin, alanine transaminase, and international normalized ratio were improved significantly in Group M. There were no MARS-related complications. Survival to wean from ECMO for Group M was 64% (9/14) vs 21% (3/14) for Group C (p = 0.02). Mortality related to worsening liver dysfunction during ECMO was 40% (2/5 deaths) in Group M and 100% (11/11 deaths) in Group C (p = 0.004). The 30-day survival after ECMO was 43% (6/14) in Group M and 14% (2/14) in Group C (p = 0.09). MARS therapy in patients on ECMO safely accelerated recovery of liver function and improved survival to wean from ECMO, without increasing complications.

Continuous molecular adsorbent recirculating system treatment in 69 patients listed for liver transplantation

Objective. The molecular adsorbent recirculating system (MARS) is used to purify blood from albumin-bound toxins in patients with liver failure. However, the application of MARS has not demonstrated improved survival in randomized clinical trials and the clinical utility has not been finally established. In our department, the use of MARS is now restricted to the most critically ill patients with acute or acute on chronic liver failure. Material and methods. Since 2005, we have treated 69 patients (30 males/39 females with median age of 49 years ranging from 1 months to 70 years) listed for liver transplantation (LT) with MARS. Median model of end-stage liver disease score in patients older than 12 years of age (n = 56) was 33 (interquartile range 26–39). The flow rate was 35–40 mL/kg/h and treatment kits were changed every 8–12 h. The patients were treated for a median of 27 h (range 1–144 h). Results. Fifty-six patients (81%) were transplanted. Nine died before they could be transplanted, and four patients recovered without transplantation. Forty-six (82%) of the transplanted patients were alive 30 days after transplantation. Ammonium decreased modestly from a median of 148 to 124 µM (p = 0.03) during MARS treatment. We detected worsening of coagulopathy with significant decreases in platelet count and fibrinogen concentrations, and increase in International Normalized Ratio. Phosphate and magnesium decreased significantly during MARS treatment. Conclusion. Continuous MARS therapy may bridge liver failure patients to LT under close observation and treatment of coagulopathy and electrolyte disturbances.

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.