Molecular Adsorbent Recirculating System Group Research Articles

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.

Treatment of patients with chronic liver failure according to disease etiology

Aim. Improving the efficiency of treatment of patients with chronic liver failure by optimizing the application of extracorporeal detoxification methods.Methods. The study included 292 patients with chronic liver failure (188 males and 104 females). The main causes of chronic liver failure were nutritional factor (alcohol abuse), viral liver diseases, and the combination of alcoholic and viral factors. All patients regardless of the disease etiology were divided into groups. Patients in group 1 received standard conservative therapy, aimed at relieving the symptoms of chronic liver failure. Patients in group 2 were additionally administered plasma exchange, in group 3 - PE and high-volume venovenous hemofiltration, and in group 4 - sessions of molecular adsorbent recirculating system (MARS).Results. Mortality of patients with chronic liver failure on conservative treatment accounted for 84.0% and was 1.5-2.1 times higher than in other groups (53% in plasma exchange group, 52% when using plasma exchange and high-volume venovenous hemofiltration and 40.6% in MARS group), these differences being statistically significant when compared with group 1 (χ2 from of 18.3 to 23.4, p 0.05). Indicators, reflecting the time of 50% mortality of patients with chronic liver failure of different etiology, suggest that in chronic liver failure of alcoholic origin plasma exchange and a combination of plasma exchange and high-volume venovenous hemofiltration are the most effective, and in chronic liver failure of viral and mixed etiology the best results are obtained when using MARS.Conclusion. The effectiveness of treatment of patients with chronic liver failure depends on the etiology of the disease: in alcoholic chronic liver failure plasma exchange and a combination of plasma exchange and high-volume venovenous hemofiltration are most rational, and in chronic liver failure of viral and mixed etiology MARS sessions are rational.

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.

Comparison of Plasmapheresis and Molecular Adsorbent Recirculating System Efficacy in Graft Failure After Living Donor Liver Transplantation

IntroductionLiver transplantation may result in graft failure, requiring time and supportive treatment for regeneration of the graft. The aim of this study was to compare the laboratory parameter changes after single-session molecular adsorbent recirculating system (MARS) and plasmapheresis procedures among living donor liver transplantation patients experiencing graft failure. Patients and MethodWe analyzed retrospectively the results in 45 liver transplantation patients treated with plasmapheresis and/or MARS between June 2011 and July 2012: (plasmapheresis, n = 17; MARS, n = 15; MARS + plasmapheresis, n = 13). When cadaveric donor cases (n = 11) were excluded, the remaining 34 included patients, underwent. MARS (n = 18) or plasmapheresis (n = 16) at the first session. FindingsBoth groups were similar in age, sex, and body mass index features. The MARS group displayed significantly higher levels of international normalized ratio, blood urea nitrogen, and Model for End-stage Liver Disease score. The plasmapheresis cohort, displayed significantly higher levels of initial direct bilirubin and gamma glutamyl transferase (P < .05). The plasmapheresis group showed a significant decrease in GGT after treatment (P < .05). ResultsAn initial MARS session provided significantly greater decrease in renal function associated with graft failure after living donor liver transplantation.

Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: The RELIEF trial

Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189 patients with ACLF were randomized either to MARS (n=95) or to standard therapy (SMT) (n=94). Ten patients (five per group) were excluded due to protocol violations. In addition, 23 patients (MARS: 19; SMT: 4) were excluded from per-protocol (PP) analysis (PP population n=156). Up to 10 6-8-hour MARS sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event was almost significantly greater in the MARS group. The 28-day survival was similar in the two groups in the ITT and PP populations (60.7% versus 58.9%; 60% versus 59.2% respectively). After adjusting for confounders, a significant beneficial effect of MARS on survival was not observed (odds ratio [OR]: 0.87, 95% confidence interval [CI] 0.44-1.72). MELD score and HE at admission and the increase in serum bilirubin at day 4 were independent predictors of death. At day 4, a greater decrease in serum creatinine (P=0.02) and bilirubin (P=0.001) and a more frequent improvement in HE (from grade II-IV to grade 0-I; 62.5% versus 38.2%; P=0.07) was observed in the MARS group. Severe adverse events were similar. At scheduled doses, a beneficial effect on survival of MARS therapy in patients with ACLF could not be demonstrated. However, MARS has an acceptable safety profile, has significant dialysis effect, and nonsignificantly improves severe HE.

Randomized Controlled Study of Plasma Exchange Combined With Molecular Adsorbent Re-Circulating System for the Treatment of Liver Failure Complicated with Hepatic Encephalopathy

To evaluate the use of plasma exchange (PE) combined with the molecular adsorbent re-circulating system (MARS) for the treatment of liver failure complicated with hepatic encephalopathy. A prospective randomized controlled study was conducted to compare the therapeutic effect of MARS treatment (MARS group, n=60) with that of PE combined with MARS treatment (PE+MARS group, n=60) in patients with liver failure complicated with hepatic encephalopathy. The serum total bilirubin and blood ammonia levels were significantly decreased compared with pretreatment levels after 3 days of both the MARS treatment (p=0.0001, p<0.001) and PE+MARS treatment (both p<0.0001) and the Glasgow coma scale score was significantly increased (both p<0.0001). The 30-day mortality rate was 10.0% (6/60) in the MARS group and 11.7% (7/60) in the PE + MARS group. The per capita cost of treatment was significantly lower in the PE + MARS group than in the MARS group (p=0.0003). Both MARS and PE + MARS therapy can safely and effectively be used to treat liver failure complicated with hepatic encephalopathy, but PE + MARS therapy reduces serum total bilirubin level more effectively and is more cost-effective.

Predictive Parameters After Molecular Absorbent Recirculating System Treatment Integrated With Model for End Stage Liver Disease Model in Patients With Acute-on-Chronic Liver Failure

Aim The aim of study was to highlight parameters that in association with Model for End-stage Liver Disease (MELD) provide predictive criteria for long-term survival after treatment with the Molecular Adsorbent Recirculating System (MARS). Two homogenous groups were studied: one treated with standard medical therapy (SMT) and the other, with MARS. Materials and methods Twenty acute-on-chronic liver failure patients on the waiting list for liver transplantation and affected by alcoholic cirrhosis with similar MELD scores (20–29) were evaluated for 7 days from inclusion and for 6-month survival. Ten patients (seven males and three females) were treated with MARS. Their mean age was 48.5 years (range = 35–61). The number of MARS applications was six for 6 consecutive days, and the length of the applications was 8 hours. Ten other patients (seven males and three females) were treated with SMT, including prophylaxis against bacterial infections and judicious use of diuretics. The precipitating factors were also treated appropriately. The mean age of the patients was 51 years (range = 37–64). All the variables that were significant upon univariate analysis were enrolled in a receiver operating characteristic analysis, with the intention to detect predictive parameters for patient death at 6 months. We considered a significant area under curve (AUC) value to be greater than 0.5. Results Among 11 patients who died within 6 months there were in the MARS group and eight in the SMT group: the 3- and 6-month patient survival rates were 90% and 70% versus 30% and 20% in the two groups, respectively. Nine measures resulted in an AUC > 0.5: DeltaMELD; interleukin (IL)-8; IL-6; tumor necrosis factor- alpha, MELD score; creatinine, bilirubin international normalized ratio (INR) and cardiac index. DeltaMELD and postoperative IL-8 concentrations showed better results (AUC = 0.899), followed by postoperative creatinine (AUC = 0.879), postoperative cardiac index (AUC = 0.833), and postoperative INR (AUC = 0.818). Postoperative creatinine showed the best sensitivity (100%), while IL-8, the best specificity (88.9%). Conclusion A combination of biochemical and clinical variables probably represent the best way to predict the survival of patients, allowing physicians to select the best therapies for each patient.

Cost-utility of molecular adsorbent recirculating system treatment in acute liver failure

To determine the short-term cost-utility of molecular adsorbent recirculating system (MARS) treatment in acute liver failure (ALF). A controlled retrospective study was conducted with 90 ALF patients treated with MARS from 2001 to 2005. Comparisons were made with a historical control group of 17 ALF patients treated from 2000 to 2001 in the same intensive care unit (ICU) specializing in liver diseases. The 3-year outcomes and number of liver transplantations were recorded. All direct liver disease-related medical expenses from 6 mo before to 3 years after ICU treatment were determined for 31 MARS patients and 16 control patients. The health-related quality of life (HRQoL) before MARS treatment was estimated by a panel of ICU doctors and after MARS using a mailed 15D (15-dimensional generic health-related quality of life instrument) questionnaire. The HRQoL, cost, and survival data were combined and the incremental cost/quality-adjusted life years (QALYs) was calculated. In surviving ALF patients, the health-related quality of life after treatment was generally high and comparable to the age- and gender-matched general Finnish population. Compared to the controls, the average cost per QALY was considerably lower in the MARS group (64,732 euros vs 133,858 euros) within a timeframe of 3.5 years. The incremental cost of standard medical treatment alone compared to MARS was 10,928 euros, and the incremental number of QALYs gained by MARS was 0.66. MARS treatment combined with standard medical treatment for ALF in an ICU setting is more cost-effective than standard medical treatment alone.

Cytokine Level Modifications: Molecular Adsorbent Recirculating System Versus Standard Medical Therapy

Introduction Acute-on-chronic liver failure (ACLF) is a systemic inflammatory reaction, which is characterized by a predominantly proinflammatory cytokine profile, causing the transition from stable cirrhosis to ACLF. The aim of the present study was to evaluate the changes in several cytokines associated with inflammatory liver disease and liver regeneration among 15 ACLF patients treated with the Molecular Adsorbent Recirculating System (MARS) compared with 15 patients treated with standard medical therapy (SMT). The subjects showed various disease etiologies but similar values for Model End-stage Liver Disease scores. Methods In the MARS group, 15 (10 male and 5 female) patients were treated with MARS (Gambro). The number of MARS applications was nine; the length of applications was 8 hours. In the SMT group; 15 (10 male and 5 female) patients were treated with SMT. The patients were monitored for 30 days from inclusion with a survival follow-up at 3 months. Statistical results were calculated with SPSS14.0 (SPSS Inc, Chicago, Ill). A P < .07 was considered significant. Results In the MARS group, we observed significant changes in the levels of Interleukin (IL)-6, IL-1, IL-10, and tumor necrosis factor (TNF)-α in association with improved hepatocyte growth factor. Patient survival at 3 months was 60%. The SMT group showed only a significant change in TNF-α ( P = .03). Patient survival at 3 months was 30%. Conclusion The MARS liver support device corrected pathophysiologies of ALF and may be used to enhance spontaneous recovery or as a bridge to transplantation.

The effect of molecular adsorbent recirculating system treatment on survival, native liver recovery, and need for liver transplantation in acute liver failure patients*

Acute liver failure (ALF) is a medical emergency. Molecular adsorbent recirculating system (MARS), an artificial liver support system, can partly compensate for the detoxifying function of the liver by removing toxins from blood. To analyze the efficacy of MARS treatment, the outcomes of 113 ALF patients, treated with MARS between 2001 and 2007, were compared with a historical control group of 46 ALF patients treated without MARS between 1995 and 2001. Overall survival of transplanted patients was 94% in the MARS group and 77% in the control group (P=0.06). Without transplantation, survival was 66% and 40% (P=0.03), respectively. However, the etiological distribution of ALF differed significantly between the groups. In ALF patients with unknown etiology, groups were comparable at baseline; 91% and 69% of transplanted patients survived the MARS and control groups and the native liver recovered in 20% and 8% of the patients, respectively. Of the originally nonencephalopathic patients of unknown etiology, 36% underwent liver transplantation in the MARS group compared to 100% in the control group. Interpretation of the results was difficult in toxic etiology patients on account of differing baseline statuses. MARS treatment might partly explain the trend toward increased survival of ALF patients with unknown etiology.

MARS and Prometheus: Our Clinical Experience in Acute Chronic Liver Failure

Introduction In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. Materials and methods The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. Results The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. Conclusion Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.

Albumindialyse bei Patienten mit sekundärem Leberversagen nach kardiogenem Schock

Die MARS-Lebertherapie (Molecular Adsorbent Recirculating System) konnte zeigen, dass das Uberleben von Patienten mit einer akuten Dekompensation einer chronischen Lebererkrankung durch den Einsatz der Therapie verlangert wird. MARS ist eine extrakorporale Behandlung, bei der als Dialysat Humanalbumin verwendet wird und die so albumingebundene Substanzen aus dem Blut entfernen kann. Das Albumin wird uber in einem geschlossenen Kreislauf uber Aktivkohle- und Anionenadsorber geleitet und so fur eine kontinuierliche Behandlung gereinigt. Trotz der Fortschritte der Technologie und der modernen Intensivtherapie, ist die Uberlebensprognose von Patienten mit kardiogenem Schock schlecht. Die Mortalitatsrate betragt bis zu 80%, haufig bedingt durch anhaltendes Multiorganversagen. Um herauszufinden, ob diese Patienten mit hypoxischem Leberversagen nach Herzoperationen von MARS profitieren, wurde eine prospektive, kontrollierte, randomisierte Studie durchgefuhrt. Als primares Zielkriterium galt das Uberleben auf der Intensivstation. Im Zeitraum von 8/00 bis 6/02 wurden 40 Patienten in die Studie eingeschlossen; 20 in die MARSGruppe (M) und 20 in die Gruppe mit Standardtherapie (ST). Alle wiesen Bilirubinspiegel >8 mg/dl auf. Zwischen den beiden Gruppen zeigten sich bei Einschluss keine wesentlichen Unterschiede. Die M-Gruppe wurde an 3 aufeinander folgenden Tagen mit MARS behandelt. Wenn danach die Bilirubinspiegel >6 mg/dl waren, wurde MARS fortgesetzt. Die STGruppe erhielt intensivmedizinische Standardtherapie. ST-Patienten mit weiter ansteigendem Bilirubin >15 mg/dl erhielten aus ethischen Grunden spater MARS (SM Gruppe; n=13). In der M-Gruppe (n=20) gab es 8 Uberlebende (40%) auf der Intensivstation, in der Gruppe der Patienten, die niemals mit MARS (KM) behandelt wurden (n=7) nur einen Uberlebenden (14,3%) (p=0,438). Trotz der geringen Anzahl von Patienten in dieser Analyse, kann MARS empfohlen werden fur die Therapie von akutem hypoxischen Leberversagen, da die Therapie lebensverlangernd sein kann. Weitere Studien sind notig um diese Ergebnisse zu verifizieren.

Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure

IntroductionPatients with acute-on-chronic liver failure show an aggravated hyperdynamic circulation. We evaluated, in a controlled manner, potential changes in systemic haemodynamics induced by the molecular adsorbent recirculating system (MARS) and the Prometheus system liver detoxification devices in a group of patients with acute-on-chronic liver failure.MethodsEighteen patients (51.2 ± 2.3 years old; Child–Pugh score, 12.5 ± 0.2; Maddrey score, 63.1 ± 5.0; hepatic venous pressure gradient, 17.6 ± 0.9 mmHg) with biopsy-proven alcoholic cirrhosis and superimposed alcoholic hepatitis were either treated with standard medical therapy (SMT) combined with MARS (n = 6) or Prometheus (n = 6) or were treated with SMT alone (n = 6) on three consecutive days (6 hours/session). Liver tests, systemic haemodynamics and vasoactive substances were determined before and after each session.ResultsGroups were comparable for baseline haemodynamics and levels of vasoactive substances. Both MARS and Prometheus decreased serum bilirubin levels (P < 0.005 versus SMT), the Prometheus device being more effective than MARS (P = 0.002). Only MARS showed significant improvement in the mean arterial pressure (Δchange, +9 ± 2.4 mmHg versus -0.3 ± 2.4 mmHg with Prometheus and -5.2 ± 2.1 mmHg with SMT, P < 0.05) and in the systemic vascular resistance index (Δchange, +131.5 ± 46.2 dyne.s/cm5/m2 versus -92.8 ± 85.2 dyne.s/cm5/m2with Prometheus and -30.7 ± 32.5 dyne.s/cm5/m2 with SMT; P < 0.05), while the cardiac index and central filling remained constant. This circulatory improvement in the MARS group was paralleled by a decrease in plasma renin activity (P < 0.05), aldosterone (P < 0.03), norepinephrine (P < 0.05), vasopressin (P = 0.005) and nitrate/nitrite levels (P < 0.02).ConclusionThe MARS device, and not the Prometheus device, significantly attenuates the hyperdynamic circulation in acute-on-chronic liver failure, presumably by a difference in removal rate of certain vasoactive substances. These findings suggest conspicuous conceptual differences among the albumin dialysis devices.

Reply to Letter from Drs. O’Beirne and Auzinger regarding article, “First Use of the Molecular Adsorbent Recirculating System Technique on Patients with Hypoxic Liver Failure after Cardiogenic Shock”, ASAIO J 50; 332–337, 2004.

Thank you for your comments concerning our article. In this first interim analysis of our study, we did not claim that the survival benefit of the Molecular Adsorbent Recirculating System (MARS) group was statistically significant. Nonetheless, an improvement in survival was shown in this patient cohort of the most critically ill patients that one may find in cardiothoracic surgery. Despite the use of mechanical circulatory support, these patients have mortality rates of usually up to 80% after persistent cardiogenic shock.1 To improve survival in these patients is an extremely difficult task. The better survival rate in the MARS group is raising hope and certainly has clinical significance. The study end-point was survival to hospital discharge, which usually was beyond 30 days. As clearly expressed in the Study Methods section, sepsis was an exclusion criteria for our study. Why MARS, though, should not be used, or even the role of it assessed for this patient cohort remains unclear from the reasoning of Drs. O’Beirne and Auzinger. The cardiac performance was comparable at the time of enrollment in both groups and afterwards treated according to necessity. Whether and to which extent continuous veno-venous hemofiltration (CVVH) can clear cytokines is, to our knowledge, disputable. The in vivo study by Kellum et al. cited by our critical readers could only demonstrate a reduction in tumor necrosis factor (TNF)-α and not of any other cytokines; moreover, the study was performed upon septic patients in whom the levels of cytokines might be different from our patients. It is, on the other hand, an accepted fact that MARS therapy does eliminate cytokines. Within the interim analysis, six of the non-MARS group patients were cross-over patients. The total study included 20 patients in each group, with a total of 9 cross-over patients. The overall MARS frequency was 10.5 times per patient and, thus, indeed similar in both groups (8.6 times for the non-MARS group compared with 8.2 times for the MARS group). The untreated patients in the non-MARS group died during the first 48 hours after study inclusion (because of multiple organ failure). The complete study analysis showed, within the surviving group, an average MARS frequency of 4.8 times. Patients requiring more than 14 settings of MARS therapy all died. This supports our initial results that MARS should be used early, and as this became obvious fairly soon in our study, it was the reason for allowing a cross-over group. The increase in bleeding episodes that might be related with MARS therapy and were described by other investigators are more or less observational findings in studies including a very small number of patients, and again their patient cohorts were essentially different from ours. Doria et al.2 performed a study on 10 patients with cirrhosis and described several observations from which they assume that MARS caused a coagulopathy. We did not perform thromboelastogram (TEG) examinations on all of our patients included in the MARS study, but we regularly apply this method now for our mechanical circulatory support patients. Up to now, in case these patients undergo MARS therapy again, we have not observed a relationship between MARS and a worsening of the TEG, but we are certainly keen to verify this in a further MARS study. Hartl et al. applied MARS to five postsurgical patients, of whom two had primary liver disease, two others had pancreatic carcinoma, and the last one had persistent biliary leak and cholangitis. All patients were only included in the study if they presented septic multiple organ dysfunction. Again, we would not apply MARS in septic patients, and we do not think that the patient cohorts are comparable. In our patients, no bleeding complications occurred and no coagulopathy developed. Maybe our primarily cardiac patients do react differently than those with primary liver or abdominal disease. Nevertheless, we still think that there is a chance for selected patients to benefit from MARS therapy. All nonevidence based therapies need to be applied with caution and respect but should be given a chance to become evidence based. Aly El-Banayosy Dagmar Cobaugh Department of Cardiothoracic Surgery, Heart Center NRW, Ruhr University Bochum, Georgstrasse, Oeynhausen, Germany.

Economic evaluation and 1-year survival analysis of MARS in patients with alcoholic liver disease.

Objective of this study was to determine 1-year survival, costs and cost-effectiveness of the artificial liver support system Molecular Adsorbent Recirculating System (MARS) in patients with acute-on-chronic liver failure (ACLF) and an underlying alcoholic liver disease. In a case-control study, 13 patients treated with MARS were compared to 23 controls of similar age, sex and severity of disease. Inpatient hospital costs data were extracted from patients' files and hospital's internal costing. Patients and treating GPs were contacted, thus determining resource use and survival 1-year after treatment. Mean 1-year survival time in MARS group was 261 days and 148 days in controls. Kaplan-Meier analysis shows advantages of MARS patients (Logrank: P=0.057). Direct medical costs per patient for initial hospital stay and 1-year follow-up from a payer's perspective were Euro 18,792 for MARS patients and Euro 9638 for controls. The costs per life-year gained are Euro 29,719 (time horizon 1 year). From a societal perspective, the numbers are higher (costs per life-year gained: Euro 79,075), mainly because of the fact that there is no regular reimbursement of MARS and therefore intervention costs were not calculated from payer's perspective. A trade-off between medical benefit and higher costs has to be made, but 1-year results suggest an acceptable cost-effectiveness of MARS. Prolonging the time horizon and including indirect costs, which will be done in future research, would probably improve cost-effectiveness.

The role of MARS in patients suffering from hypoxic liver failure secondary to cardiogenic shock

For patients with hepatorenal syndrome improvement of survival and of multiple organ functions was proven by the use of MARS (Molecular Adsorbent Recirculating System). MARS is a modified dialysis using an albumin-containing dialysate, that is recirculated and on-line perfused through charcoal and anion exchanger columns. It allows the selective removal of albumin-bound substances. Despite advances in medical therapy and technology, the prognosis of patients with cardiogenic shock remains poor. Mortality rates as high as 80%, often caused by persistent multiple organ failure are unacceptable. Therefore we conducted a prospective, randomized, and controlled study with patients suffering from hypoxic liver failure following cardiogenic shock after cardiac surgery. Main aim was to prove that MARS improves survival. We report a interim analysis of the 17 patients, who were included between 8/00 and 8/01 in our study. Eight patients formed the MARS group (MG) and 9 were in the non-MARS group (NMG). All patients had bilirubin levels >8 mg/ mL. The risk profile of both groups was almost identical. The MG received MARS for 3 consecutive days — if bilirubin was still >6 mg/ dl afterwards MARS was continued. The NMG received conventional therapy. Results: There were 6 survivors in the MG, compared to 1 survivor in the NMG ( P=0.015). Moreover Bilirubin levels declined faster to lower levels in the MG. Conclusion: Despite the limited number of patients included in this interim analysis, MARS can be recommended for patients with acute, hypoxic liver failure as it might significantly improve survival.

Improvement of hepatorenal syndrome with extracorporeal albumin dialysis mars: Results of a prospective, randomized, controlled clinical trial

In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level,15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 ± 1.0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 ± 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 ± 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels ( P < .01) and increase in serum sodium level and prothrombin activity ( P < .01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively ( P < .01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.