Molecular Adsorbent Recirculating System Research Articles

165 Molecular Adsorbent Recirculating System as Therapy for Hepatic Encephalopathy

165 Molecular Adsorbent Recirculating System as Therapy for Hepatic Encephalopathy

Actual vs Expected Survival With the Use of the Molecular Adsorbent Recirculating System for Acute Liver Failure

Actual vs Expected Survival With the Use of the Molecular Adsorbent Recirculating System for Acute Liver Failure

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.

Liver Injury after Selective Androgen Receptor Modulator Intake: A Case Report and Review of the Literature.

Liver injury associated with selective androgen receptor modulators (SARMs) is an issue that has not been reported often. We report a case of a previously healthy 24-year-old male, who was referred to our hospital for severe jaundice with intense pruritus. He had previously taken the SARM Enobosarm (also known as Ostarine) for muscle-building purposes. Blood serum levels of total bilirubin exceeded 30 mg/dL with only a slight elevation of liver enzymes. Liver biopsy revealed isolated hepatocellular cholestasis (bland cholestasis) with limited inflammation or necrosis. Supportive treatment was begun in our hospital with molecular adsorbent recirculation system (MARS) albumin dialysis, as well as cholestyramine for pruritus relief. During therapy, bilirubin levels and symptoms regressed, and after five sessions of dialysis, the patient could be released from our clinic in a markedly improved clinical and laboratory condition. However, bilirubin parameters regressed slowly after this, reaching normal levels as late as six months after first intake of the compound. Exome-based genetic testing brought about no pathogenic variants for cholestatic liver disease in our patient. Nevertheless, three common heterozygous polymorphisms associated with an increased risk for intrahepatic cholestasis could be identified. Our case demonstrates that SARMs can cause severe liver injuries not prominently mentioned in safety data sheets. Therefore, these compounds constitute a potential danger to the user's health. This holds especially true when taking SARMs without supervision by a medical professional, which should consist of a thorough monitoring of liver enzyme and bilirubin levels.

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

Extracorporeal albumin dialysis in critically ill patients with liver failure: Comparison of four different devices-A retrospective analysis.

Besides standard medical therapy and critical care monitoring, extracorporeal liver support may provide a therapeutic option in patients with liver failure. However, little is known about detoxification capabilities, efficacy, and efficiency among different devices. Retrospective single-center analysis of patients treated with extracorporeal albumin dialysis. Generalized Estimating Equations with robust variance estimator were used to account for repeated measurements of several cycles and devices per patient. Between 2015 and 2021 n = 341 cycles in n = 96 patients were eligible for evaluation, thereof n = 54 (15.8%) treatments with Molecular Adsorbent Recirculating System, n = 64 (18.7%) with OpenAlbumin, n = 167 (48.8%) Advanced Organ Support treatments, and n = 56 (16.4%) using Single Pass Albumin Dialysis. Albumin dialysis resulted in significant bilirubin reduction without differences between the devices. However, ammonia levels only declined significantly in ADVOS and OPAL. First ECAD cycle was associated with highest percentage reduction in serum bilirubin. With the exception of SPAD all devices were able to remove the water-soluble substances creatinine and urea and stabilized metabolic dysfunction by increasing pH and negative base excess values. Platelets and fibrinogen levels frequently declined during treatment. Periprocedural bleeding and transfusion of red blood cells were common findings in these patients. From this clinical perspective ADVOS and OPAL may provide higher reduction capabilities of liver solutes (i.e. bilirubin and ammonia) in comparison to MARS and SPAD. However, further prospective studies comparing the effectiveness of the devices to support liver impairment (i.e. bile acid clearance or albumin binding capacity) as well as markers of renal recovery are warranted.

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.

Efficacy of Prostacyclin Anticoagulation in Critically Ill Patients Requiring Extracorporeal Support: A Systematic Review and Meta-Analysis.

Extracorporeal support modalities are highly prothrombotic. Anticoagulation is frequently used for patients receiving Continuous Renal Replacement Therapy (CRRT), Molecular Adsorbent Recirculating System (MARS), and Extracorporeal Membrane Oxygenation (ECMO). The objective of this systematic review and meta-analysis is to determine if prostacyclin-based anticoagulation strategies are effective compared to other anticoagulation strategies, in critically ill children and adults who needs extracorporeal support, such as continuous renal replacement therapy. We conducted a systematic review and meta-analysis using multiple electronic databases and included studies from inception to June 1, 2022. Circuit lifespan, proportion of bleeding, thrombotic, and hypotensive events, and mortality were evaluated. Out of 2,078 studies that were screened, 17 studies (1,333 patients) were included. The mean circuit lifespan was 29.7 hours in the patients in the prostacyclin-based anticoagulation series and 27.3 hours in the patients in the heparin- or citrate-based anticoagulation series, with a mean difference of 2.5 hours (95%CI -12.0;16.9, p=0.74, I2=0.99, n=4,003 circuits). Bleeding occurred in 9.5% of the patients in the prostacyclin-based anticoagulation series and in 17.1%of the patients in the control series, which was a statistically significant decrease (LogOR -1.14 (95%CI -1.91;-0.37), p<0.001, I2=0.19, n=470). Thrombotic events occurred in 3.6% of the patients in the prostacyclin-based anticoagulation series and in 2.2% of the patients in the control series, which was not statistically different (LogOR 0.97 (95%CI -1.09;3.04), p=0.35, I2=0.0, n=115). Hypotensive events occurred in 13.4% of the patients in the prostacyclin-based anticoagulation series and in 11.0% of the patients in the control series, which was not statistically different (LogOR -0.56 (95%CI -1.87;0.74), p=0.40, I2=0.35, n=299). The mortality rate was 26.3% in the prostacyclin-based anticoagulation series, and 32.7% in the control series, which was not statistically different (LogOR -0.40 (95%CI -0.87;0.08), p=0.10, I2=0.00, n=390). The overall risk of bias was low to moderate. In this systematic review and meta-analysis of 17 studies, prostacyclin-based anticoagulation was associated with fewer bleeding events, but with similar circuit lifespans, thrombotic events, hypotensive events, and mortality rates. The potential benefits of prostacyclin-based anticoagulation should be explored in large randomized controlled trials.

Artificial Liver Support with CytoSorb and MARS in Liver Failure: A Retrospective Propensity Matched Analysis.

Liver failure represents a life-threatening organ dysfunction with liver transplantation as the only proven curable therapy to date. Liver assist devices have been extensively researched to either bridge such patients to transplantation or promote spontaneous recovery. The aim of our study was to compare two such devices, the Molecular Adsorbent Recirculating System (MARS) and CytoSorb, in patients with liver failure. We retrospectively included 15 patients who underwent MARS during their intensive care unit stay and matched them to 15 patients who underwent hemoadsorption using CytoSorb. Clinical and paraclinical data obtained after each individual session, after the course of treatment, as well as at the end of the intensive care unit stay were compared between the two groups. Single sessions of CytoSorb and MARS were both associated with a significant decrease in bilirubin (p = 0.04 and p = 0.04, respectively) and ammonia levels (p = 0.04 and p = 0.04, respectively), but only CytoSorb therapy was associated with a decrease in lactate dehydrogenase levels (p = 0.04) and in platelet count (p = 0.04). After the course of treatment, only CytoSorb was associated with a significant decrease in lactate (p = 0.01), bilirubin (p = 0.01), ammonia (p = 0.02), and lactate dehydrogenase levels (p = 0.01), while patients treated with MARS did not show any improvement in paraclinical liver tests. In addition, only CytoSorb treatment was associated with a significant improvement in the Model for End-Stage Liver Disease Score (p = 0.04). In conclusion, our results show a potential benefit of CytoSorb in rebalancing liver functional tests in patients with liver failure compared to MARS but the exact effects on patient outcome, including hospital length of stay and survival, should be further investigated in randomized control trials.

Holestatski virusni hepatitis A praćen upornim svrabom koji je uspešno lečen kombinacijom sistema za recirkulaciju molekularnih adsorbenata i kortikosteroida - prikaz slučaja

Introduction. Hepatitis A virus is a major cause of acute viral hepatitis worldwide, with approximately 1.5 million cases annually. Clinical manifestations of the hepatitis A virus infection range from asymptomatic to acute liver failure. Cholestatic viral hepatitis A is a rare clinical manifestation characterized by a prolonged course, refractory pruritus, imminent acute liver failure and generally good prognosis. The treatment of pruritus in cholestatic viral hepatitis A can be challenging because a response to conventional therapy is limited. Case report. We present the effects of a combination of pulse doses of prednisolone and two cycles of MARS (Molecular Adsorbent Recirculating System) in the treatment of a young female patient with cholestatic viral hepatitis A. This treatment option significantly reduced the duration of the disease and the intensity of pruritus and led to full recovery of the patient and normalization of laboratory parameters of cholestasis. Conclusion. This treatment combination has proven to have significant and lasting effects with no relapse of pruritus. Low doses of corticosteroids administered for a short time reduce the risk of side effects. The importance of vaccination of international travellers should be also pointed out here.

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.

S3085 Molecular Adsorbent Recirculating System in Acute Liver Injury

Introduction: Acetaminophen (APAP) toxicity is common and has been known as a cause of acute liver failure (ALF). ALF has high mortality rate, and in many cases, liver transplantation (LT) is the only lifesaving treatment. Unfortunately, many ALF patients are not candidates for transplant due to many factors. In addition, Hemodialysis have minimal to no effect on liver detoxification. Alternative approach could be albumin dialysis using Molecular Adsorbent Recirculation System (MARS). The evidence of effectiveness of MARS is limited with very few clinical studies. Here we report a case of ALF in an adult due to APAP toxicity who was not a candidate for LT, and treatment therefore included the use of MARS. Case Description/Methods: A 44 y/o M with hx of heavy alcohol use presented with altered mental status. It was reported that he may have taken 40 APAP tablets over the last 1-2 days. Physical exam was significant for confusion, tachycardia and scleral icterus. CMP: total bilirubin of 10.6 mg/dL, alkaline phosphatase 195 U/L, AST 5605 U/L, ALT 7000 U/L, albumin of 2.6 g/L and INR of 3.9. Ammonia was 215 umol/L and Tylenol of 75 ug/ml. Autoimmune workup, viral hepatitis panel and a broad infectious workup were negative. Alpha 1 antitrypsin and ceruloplasmin were normal. US of the liver was normal. Etiology of ALF believed to be due to APAP toxicity. He was admitted to the ICU and started on N-acetylcysteine infusion. He was evaluated for LT and deemed to be not a candidate given psychosocial concerns. After multidisciplinary discussion, MARS was initiated and planned for 5 days. The patient was monitored with serial CMP and coagulation studies. Mental status, INR, bilirubin and hepatic transaminases rapidly improved while on MARS. Patient ultimately became clinically stable to be transferred to a regular medical floor and continued to show improvement in his liver functions. (Figure) Discussion: In USA, ALF due to APAP toxicity is very common. LT is the only intervention with known survival benefits in ALF, but many factors can play a rule in LT evaluation and can lead to delay or might exclude patients from being candidates for LT, as seen in our patient. MARS, works on the concept of removal of albumin-bound substances accumulating in ALF, may be an ideal bridge to spontaneous recovery during liver regeneration. MARS could be a promising treatment with improvement of clinical response, laboratory parameters and liver function. Further studies are needed to better understand the efficacy of MARS on ALF outcomes.Figure 1.: Total Bilirubin and INR levels before, during and after MARS treatment in a patient with Acute Liver Failure. The arrows indicate the first treatment session.

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.

S1271 Clinical Characteristics and Outcomes of Patients With Liver Failure Treated With Molecular Adsorbent Recirculating System (MARS): A Single Center Experience

S1271 Clinical Characteristics and Outcomes of Patients With Liver Failure Treated With Molecular Adsorbent Recirculating System (MARS): A Single Center Experience

Hyperammonemia Refractory to Continuous Renal Replacement Therapy, a Fatal Complication Post-Lung Transplant

<h3>Introduction</h3> Post-lung transplant hyperammonemia is a rare complication associated with high mortality. Incidence is about 1-4% usually presenting within 2 weeks post-lung transplant. We describe a rare case of delayed-onset hyperammonemia post-lung transplant refractory to Continuous Renal Replacement Therapy (CRRT). <h3>Case Report</h3> A 30-year-old female underwent re-do bilateral lung transplantation for bronchiolitis obliterans syndrome. Her initial lung transplant was done for interstitial lung disease secondary to radiation-induced lung injury following treatment for childhood acute lymphocytic leukemia. Her first-week Bronchoalveolar lavage was positive for MRSA, <i>Pseudomonas</i> & <i>Ureaplasma</i> which were treated with antibiotics. Her postoperative course was complicated by prolonged hospitalization and need for ventilator support. She required Veno-venous Extra Corporeal Membrane Oxygenation support and CRRT. On POD 140, she was found to have decreased responsiveness. Workup revealed ammonia levels 353mmol/l. Her liver function was normal and repeat BAL cultures were negative for Ureaplasma & Mycoplasma. She was treated with lactulose, polyethylene glycol, levocarnitine, rifaximin, acarbose & sodium benzoate. Despite being on CRRT & this regimen, her ammonia levels continued to rise and peaked at 493 mmol/l. On continuous EEG, seizure-like activity was seen with features suggestive of metabolic encephalopathy. MRI revealed cerebral edema and findings consistent with hyperammonemic encephalopathy. MARS therapy (Molecular Adsorbent Recirculating System) was started, which resulted in a rapid decline in ammonia levels and some improvement in her mental status. In spite of improved ammonia levels, given her poor overall prognosis, the patient & family chose to transition to comfort measures and she subsequently passed away. <h3>Summary</h3> Post-lung transplant hyperammonemia is a poorly understood relatively uncommon condition associated with poor outcomes. Ammonia is a small molecule that does not bind to proteins & is amenable to removal by dialysis. Therefore, significantly elevated ammonia levels despite being on CRRT & medical management, so late following the lung transplant in the absence of any definitive etiology makes this rare. MARS has been proven to successfully treat refractory hyperammonemia post lung transplantation.

Bleeding complications associated with the molecular adsorbent recirculating system: a retrospective study.

BackgroundThe molecular adsorbent recirculating system (MARS) is a hepatic replacement system that supports excretory liver function in patients with liver failure. However, since MARS has been employed in our hospital, bleeding complications have occurred in many patients during or after MARS. The objective of this study was to determine how MARS affects coagulopathy and identify specific factors associated with bleeding complications.MethodsWe retrospectively analyzed data from 17 patients undergoing a total of 41 MARS sessions. Complete blood count, coagulation profiles, and blood chemistry values were compared before and after MARS. To identify pre-MARS factors associated with increased bleeding after MARS, we divided patients into bleeder and non-bleeder groups and compared their pre-MARS laboratory values.ResultsMARS significantly reduced bilirubin and creatinine levels. MARS also increased prothrombin time and reduced platelet and fibrinogen, thus negatively impacting coagulation. Pre-MARS hemoglobin was significantly lower in the bleeder group than in the non-bleeder group (P=0.015). When comparing the upper and lower 33% of MARS sessions based on the hemoglobin reduction rate, hemoglobin reduction was significantly greater in MARS sessions involving patients with low pre-MARS international normalized ratio of prothrombin time (PT-INR) and factor V (P=0.038 and P=0.023, respectively).ConclusionsMARS could appears to alter coagulation-related factors such as factor V and increase the risk of bleeding complications particularly in patient with low hemoglobin. However, individual differences among patients were large, and various factors, such as low hemoglobin, PT-INR, and factor V levels, appear to be involved.

589 Role of Liver Support Systems in The Management of Post Hepatectomy Liver Failure: A Meta-Analysis and Systematic Review of Literature

Abstract Aim Post hepatectomy liver failure (PHLF) is a rare but serious complication following liver resection. PHLF is associated with high mortality of up to 50% in severe cases. With limited treatment options available, there is a need to evaluate the role of systems that support the function of the liver as treatment modalities following PHLF development. Method The aim of this study was to review the literature and summarise the role of liver support systems (LSS) in the management of PHLF. Publications of interest were identified using systematically designed searches. Following screening, data from the relevant publications were extracted, pooled where possible, and analysed. Results Systematic review identified ten studies, which used either Plasma Exchange (PE) or Molecular Adsorbent Recirculating System (MARS) as LSS after PHLF development. The sample sizes of included studies were small, ranging from N = 2 to N = 13. Across all studies, the pooled 90-day mortality rate was 40% (95% CI: 15% - 68%). However, there was substantial heterogeneity (I2=64%), likely since the studies used a variety of definitions for PHLF and had different selection criteria for patient eligibility for LSS treatment. Conclusions Despite potential benefits, the current evidence is insufficient to recommend LSS for the routine management of severe PHLF, with the current literature consisting of only a limited number of studies. There is a definite need for larger, multicentre, prospective studies evaluating the conventional and newer modalities of support systems with a view to improve the outcomes in this group of patients.

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.