Molecular Adsorbent Recycling System Treatment Research Articles

A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System

IntroductionThe Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens.MethodsWe performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis.ResultsOf a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events.ConclusionsRegional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure.

Preoperative risk factor analysis in orthotopic liver transplant-ation with pretransplant artificial liver support therapy

To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT). Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d) after OLT. In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30 d observation was: 28 kept alive and 6 patients died. Pre-operative SOFA, level of creatinine, INR, TNF-alpha, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantation can relieve these factors significantly.

Catholic University Experience With Molecular Adsorbent Recycling System in Patients With Severe Liver Failure

Background and aim Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. Materials Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin ≥10 mg/dL and at least one of the following: hepatic encephalopathy (HE) ≥II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin ≥5 mg/dL and HE ≥I grade for acute patients. Results MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. Conclusions Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.

Preoperation risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

Orthotopic liver transplantation (OLT) is an accepted therapy for selected patients with advanced liver diseases. However, the early mortality rate after OLT remains relatively high due to the poor selection of candidates with various serious conditions. The aim of this study is to assess the value of pretransplantation artificial liver support treatment in reducing the pre-operation risk factors relating to early mortality after OLT. 50 adult patients in various stages of different etiologies who underwent OLT procedures had been treated with molecular adsorbent recycling system (MARS) preoperatively. The study was designed in two parts: the first one was to evaluate the effectiveness of a single MARS therapy by using some clinical and laboratory parameters which were supposed to be therapeutical pretransplantation risk factors. The second part was to study the patients undergoing OLT by using the regression analysis on preoperation risk factors relating to early (within 30 d after OLT) mortality rate. Among the 50 patients, a statistically significant improvement of the biochemical parameters was observed (pretreatment vs posttreatment). 8 patients cancelled their scheduled LTXs due to significant improvements in their clinical conditions or recovery of their failing liver functions. 8 patients died and 34 patients successfully underwent LTX. The immediate outcome (within 30 postoperative days) of these 34 patients was that 28 were kept alive and 6 died. Preoperation sequential organ failure assessment (SOFA), level of creatinine, INR, TNFalpha, and IL-10 are the main preoperative risk factors relating to early death after an operation. MARS treatment before a transplant operation can relieve these factors significantly, hence improve survival rate of liver transplantation or even make the transplantation unnecessary.

Hypoglycemia in nondiabetic patients undergoing albumin dialysis by molecular adsorbent recirculating system

It was observed that patients developed episodes of hypoglycemia during molecular adsorbent recycling system (MARS) treatment. The aim of this study is to assess the effect of MARS treatment on blood glucose concentration to formulate appropriate dextrose replacement guidelines during MARS dialysis. Five patients with liver failure each underwent a 6- to 8-hour MARS treatment. No patient had a history of diabetes or was administered insulin or oral antihyperglycemic agents throughout the period of albumin dialysis. There was no active intervention or restriction on glucose intake. Rather, a dextrose drip and boluses were allowed based on each patient's condition and the clinical judgment of the attending physician. Blood glucose concentration was monitored hourly during the period of MARS treatment. Glucose loss in dialysate fluid was quantified hourly by measuring the total volume of dialysate fluid and assaying the glucose concentration in dialysate fluid. Mean glucose removal during a 6-hour MARS session was 37.19 ± 5.58 g. Mean glucose removal rate was 6.20 ± 0.93 g/h. In addition to a maintenance drip supporting the caloric requirement of patients, a dextrose replacement drip that paralleled the rate of glucose removal would prevent patients from experiencing episodes of hypoglycemia during MARS treatment. Dextrose replacement at a mean rate of 6 g/h (range, 5 to 7 g/h) in patients without diabetes undergoing albumin dialysis by MARS is recommended. (Liver Transpl 2003;9:949-953.)

Successful MARS treatment in severe cholestatic patients with acute on chronic liver failure.

Extracorporeal liver devices have gained great attention as a complementary approach to liver transplantation in patients with acute on chronic liver failure. Among others, Molecular Adsorbent Recycling System (MARS) is a hemodiafiltration against albumin able to remove low molecular weight toxins. We aimed to validate the use of MARS in patients presenting with acute on chronic liver failure with severe cholestasis. We enrolled 7 patients with acute on chronic liver failure, presenting with bilirubin >25 mg/dl and hepatorenal syndrome and/or hepatic encephalopathy grade >II. Liver biochemistry, coagulation, blood cell count, electrolytes, ammonia, lactate, blood urea nitrogen, creatinine, bile acids, Fischer ratio, and encephalopathy grade were assessed before and after each MARS treatment. MARS can represent a safe therapeutic choice to achieve a quick improvement of neurological status, a hemodynamic stability, and a better clinical outcome. In particular, our encouraging results suggest that also, patients with severe cholestasis may represent in the future a good indication for MARS treatment.

Detoxifying Capacity and Kinetics of the Molecular Adsorbent Recycling System: Contribution of the Different Filters Inbuilt

Extracorporeal liver support therapies have been used for several decades as a bridging therapy prior to liver transplantation or as an addendum to standard medical therapy. The molecular adsorbent recycling system (MARS) represents a cell-free, extracorporeal, liver assistance method for the removal of both albumin-bound and water-soluble endogenous toxins. The aim of the present study was to evaluate the short-and long-term removal capacity and selectivity of the different inbuilt dialysers and adsorption columns (uncoated charcoal, anion exchanger resin). Levels of endogenous toxins and parameters of hepatic synthesis and necrosis were therefore monitored before, during, and after the MARS treatment phase in 10 patients. Moreover, blood and dialysate clearances of urea nitrogen, creatinine, bilirubin and bile acids were determined during a single treatment. The significant increasing time course of total bilirubin blood levels before the start of the treatment could be stopped and reversed in a significant decreasing time course (Linear Mixed Models, P < 0.05). The removal rate of urea nitrogen, bilirubin, and bile acids during a single treatment amounted to 55.5 ± 4.0%, 28.3 ± 3.9%, and 55.4 ± 4.0%(mean ± SEM), respectively. Bile acids and bilirubin were mainly removed by the activated charcoal and anion exchanger column, respectively. The efficacy of removal of albumin-bound toxins sharply declined early after initiation of the treatment to become negligible after 6 h. In conclusion, both albumin-bound and water-soluble toxins are adequately removed by the MARS. Our data suggest that the rate and efficacy of removal of albumin-bound toxins is related to both the strength of the albumin binding and the saturation of the adsorption columns.

Detoxifying Capacity and Kinetics of the Molecular Adsorbent Recycling System

The molecular adsorbent recycling system (MARS) represents a cell-free, extracorporeal, liver assistance method for the removal of both albumin-bound and water-soluble endogenous toxins. The aim of the present study was to evaluate the short- and long-term removal capacity and selectivity of the different inbuilt dialysers and adsorption columns (uncoated charcoal, anion exchanger resin). Levels of endogenous toxins and parameters of hepatic synthesis and necrosis were therefore monitored before, during and after the MARS treatment phase in 10 patients. Moreover, blood and dialysate clearances of urea, creatinine, bilirubin and bile acids were determined during a single treatment. The significant increasing time course of total bilirubin blood levels before the start of the treatment could be stopped and reversed in a significant decreasing time course. The removal rates of urea nitrogen, bilirubin and bile acids during a single treatment amounted to 55.5 ± 4.0, 28.3 ± 3.9, and 55.4 ± 4.0% (mean ± SEM), respectively. The efficacy of removal of albumin-bound toxins sharply declined early after initiation of the treatment to become negligible after 6 h. In conclusion, both albumin-bound and water-soluble toxins are adequately removed by the MARS. Our data suggest that the rate and efficacy of removal of albumin-bound toxins are related to both the strength of the albumin binding and the saturation of the adsorption columns.