SCCM Resource Library-Molecular Adsorbent Recirculating System Therapy for Acute Liver Failure: Institutional Indications

Video Transcription

Hello, my name is Guinevere Johnson, and I am a research assistant at the R. Adams Callie  Shock Trauma Center at the University of Maryland Medical Center, or Shock Trauma for short.  This presentation is called Molecular Adsorbent Recirculating System Therapy for Acute Liver Failure Institutional Indications.  Molecular adsorbent recirculating system, also known as MARS, is a liver support system that could potentially help a range of people, but has not yet been widely implemented.  This study examines observed outcomes from patients who underwent MARS at our institution. Liver disease is responsible for approximately 2 million deaths a year.  Acute liver failure, or ALF, is defined as severe liver injury for less than 26 weeks, encephalopathy, and INR over 1.5 in patients without pre-existing liver disease.  The mortality rate of ALF is 50%. There are not enough livers available for every person who needs a transplant, so there is an obvious need for therapeutic alternatives.  One such alternative is the use of extracorporeal liver support devices, which can be used to remove toxins which, in turn, can improve hepatic function and serve as a bridge to  liver transplant or to recovery. MARS is a form of albumin dialysis. Blood is dialyzed against a human serum albumin, HSA, dialysate solution that allows blood  detoxification of both water-soluble and protein-bound toxins. The albumin dialysate is then regenerated in a closed loop in the MARS circuit by passing  through the fibers of a low-flux dialysis filter to clear water-soluble toxins and provide electrolyte-acid-based balance.  Next, the albumin dialysate passes through two different absorption columns. Protein-bound substances are removed by the charcoal filter, and anionic substances are  removed by the cholecysteiramine filter and anion exchange resin. The albumin solution is then ready to initiate another detoxifying cycle of the patient's  blood that can be sustained until both absorption columns are saturated, eliminating the need to continuously infuse albumin into the system during treatment.  Our hypothesis is that the application of institutional criteria at a center that offers MARS for acute liver failure is associated with higher than predicted survival rates.  Institutional indications for MARS includes acetaminophen intoxication, pre-transplant candidates, patients who are anatomically antipathic and awaiting liver transplant,  post-transplant patients with primary graft non-function, and patients with reversible forms of multiple organ failure.  Data were analyzed with parametric and non-parametric statistics as indicated. Standardized mortality ratios were calculated for each indication.  The MARS program at shock trauma was initiated in 2015. We looked at data from all 61 adults that underwent treatment from that time up until February 2021.  The youngest patient was 18, and the oldest was 73, while the median age of all patients was 43.6.  55.7% of the patients were female, and the average body mass index was 29.9. 55% of the patients were Caucasian, approximately 40% were African-American, about 2% were Asian,  and 3% were identified as other. 31% of patients were reported as actively abusing alcohol, 3% were reported as having  prior alcohol abuse, 53% had no alcohol abuse, and 13%'s alcohol abuse status was unknown or unclear.  Patients could be marked as having more than one etiology of their acute liver failure, with the majority of etiologies being either alcohol-related or drug toxicity.  Similarly, patients could have more than one institutional indication for MARS. By far, the most common indication was acute liver failure and transplant candidates.  Patients had a medium of two MARS sessions, each lasting eight hours, with the exception of antiepatic patients, who were on MARS continuously.  The median model for end-stage liver disease sodium, aka MELD sodium, score was 33, and  the mean sequential organ failure assessment, aka SOFA, score was 13.4, indicating an expected mortality of over 50% for the entire cohort.  Actual survival rate at 30 days after the last MARS session was 60.7%. 18 patients required a liver transplant, and 78% of these transplant recipients survived  to discharge from the hospital. 13 patients did not survive more than 24 hours after their final MARS session.  Patients who died within 24 hours of their last MARS session or received a liver transplant  within that same timeframe were not included in the data analyses for the following figures. The following figures represent data before the first MARS session in red, after the  first MARS session in teal, after the second MARS session in purple, and within 24 hours of completion of all sessions in yellow.  Shown here are the differences among the sessions for AST and ALT levels. The decrease in levels of both AST and ALT after the final MARS session, when compared  to before the first MARS session, were statistically significant. These are the results of the ammonia and INR levels before and after MARS.  There was no statistically significant change in the ammonia levels. However, even though MARS doesn't provide support for the liver in terms of synthetic  function, INR levels had a statistically significant decrease post-MARS, which indicates the ability of MARS to help the liver recover and resume synthetic function.  Norepinephrine doses also had a statistically significant decrease pre- and post-MARS, which indicates reversal of shock.  The number of observed deaths within each subgroup is shown here, in addition to the number of expected deaths within each subgroup, which was calculated from indirect adjustment.  From this, the standardized mortality ratio, abbreviated SMR, was calculated. The SMR is the number of observed deaths in the study population, divided by the number  of expected deaths, multiplied by 100. We found statistically significant lower-than-expected mortality in both the acute fulminant liver  failure and transplant candidates and primary non-function post-transplant groups. In the acetaminophen intoxication and anatomically adhepatic groups, the lower-than-expected  mortality that was observed was not statistically significant. In conclusion, we report one of the largest single-center North American series of acute  liver failure patients treated with molecular adsorbent recirculating system. Using institutional criteria and a multidisciplinary approach, a higher-than-expected survival  rate in certain subgroups was observed. SMRs can improve laboratory parameters, allow time for hepatic recovery, and avert liver transplantation.  This data adds to a growing body of literature in support of SMRs therapy. Thank you for your time.

Video Summary

The video presentation discusses the use of Molecular Adsorbent Recirculating System (MARS) therapy for Acute Liver Failure at the R. Adams Callie Shock Trauma Center. MARS is a liver support system that removes toxins from the blood, improving liver function and potentially serving as a bridge to transplant or recovery. The study analyzed outcomes from patients who underwent MARS therapy, focusing on institutional indications such as acetaminophen intoxication, pre-transplant candidates, and post-transplant patients with primary graft non-function. The data showed higher-than-expected survival rates in certain subgroups. MARS therapy can improve laboratory parameters, allow for hepatic recovery, and potentially avoid the need for liver transplantation.

Asset Subtitle

GI and Nutrition, Research, 2022

Asset Caption

INTRODUCTION: Molecular Adsorbent Recirculating System (MARS) is an extracorporeal liver support system that removes water-soluble and albumin-bound toxins. We report our experience as one of the few North American centers that offers MARS for precise indications of acute liver failure (ALF) hypothesizing that the application of institutional criteria would be associated with higher-than predicted survival.
METHODS: Adults receiving MARS from 2015-2021 were analyzed. Institutional indications for MARS included acetaminophen intoxication (IT), pre-transplant candidates (PT), patients who were anatomically anhepatic and awaiting liver transplant (AH), post-transplant patients with primary graft non-function (GNF), and patients with reversible forms of multiple organ failure (MOF). Data were analyzed with parametric and non-parametric statistics as indicated. Standardized mortality ratios (SMR) were calculated for each indication.
RESULTS: Sixty one patients underwent MARS; 19.6% for IT, 70.5% PT, 8.2% AH, 16.4% GNF, and 16.8% MOF. Patients had a median of 2 sessions (IQR, 2-3), each lasting 8 hours. The median Model for End-stage Liver Disease-Sodium (MELD-Na) score was 33 (IQR, 25-40), and the mean SOFA score was 13.4 (±4.1) indicating an expected mortality of over 50% for the entire cohort. Actual survival at 30 days was 60.7%. MARS was associated with significant median decreases in INR (3.2 vs 1.5), creatinine (2.0 vs. 1.05 mg/dL), ALT (1681 vs. 347 U/L), AST (3334 vs. 344 U/L), ammonia (58 vs. 39 unmold/L), lactate (7.8 vs. 2.4 mmol/L) and norepinephrine dose (0.21 vs. 0.06 mcg/kg/min). Eighteen patients (29.5%) required a liver transplant with 78% surviving to hospital discharge. Significantly higher than expected survival was observed for PT (SMR 0.78; 95% CI, 0.63-0.93) and GNF (SMR 0.58; 95% CI, 0.32-0.84).
CONCLUSION: We report one of the largest single-center north American series of ALF patients treated with MARS. Using institutional criteria and a multidisciplinary approach, a higher than expected survival rate was observed. MARS can improve laboratory parameters, allow time for hepatic recovery, and avert liver transplantation. These data add to a growing body of literature in support of MARS therapy and motivateadditional clinical trials to determine greatest benefit.

Meta Tag

Content Type Presentation

Knowledge Area Research

Knowledge Area GI and Nutrition

Knowledge Area Pharmacology

Knowledge Level Advanced

Membership Level Select

Tag Liver

Tag Outcomes Research

Tag Toxicology

Year 2022

Keywords

Molecular Adsorbent Recirculating System

MARS therapy

Acute Liver Failure

toxin removal

hepatic recovery

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