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For more than 10 years, children at our national center for pediatric liver transplantation (LT) have been treated with Molecular Adsorbent Recirculating System (MARS) liver dialysis as a bridging therapy to high-urgency LT. Treatment was reserved for 20 patients with the highest degrees of hepatic encephalopathy (HE; median grade?=?3.5). Death from neurological sequelae was considered imminent for these patients, and this was further reflected in significantly higher international normalized ratios and ammonia levels and worse prognostic liver indices (Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores and liver injury units) in comparison with 32 wait-listed patients who did not receive MARS dialysis. MARS therapy was generally well tolerated, with a reduction in thrombocytes and hemorrhaging as the most common side effects. HE improvement was documented in 30% of the treated patients, but progression to grade IV encephalopathy occurred in 45% of the patients despite the treatment. Serum ammonia, bilirubin, bile acid, and creatinine levels significantly decreased during treatment. Eighty percent of MARS-treated patients survived to undergo LT, and their survival was equivalent to that of non-MARS-treated patients with severe liver failure (69%, P?=?0.52). The heterogeneity between MARS-treated patients and non-MARS-treated patients in our cohort precluded a statistical evaluation of a benefit from MARS for patient survival. Our data demonstrate the safety of MARS even in the most severely ill patients awaiting LT, but strategies that promote the more rapid and widespread availability of high-quality donor organs remain of critical importance for improving patient survival in cases of severe acute liver failure.? 2015 American Association for the Study of Liver Diseases.

Background Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of “liver dialysis”. During a 72-h extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (hRBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the hRBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of hRBCs seen during extracorporeal porcine liver xenoperfusion. Methods Ex vivo studies were performed using wild type pig livers perfused with isolated hRBCs for 72-h in the presence of an anti-porcine sialoadhesin antibody or isotype control. Results The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of hRBC over a 72-h period. Sustained liver function was demonstrated throughout the perfusion. Conclusions This study illustrates the role of sialoadhesin in mediating the destruction of hRBCs in an extracorporeal porcine liver xenoperfusion model.

Obesity is a worldwide epidemic leading to severe comorbidity that damages end-organ function. Overall transplant outcomes in this population are inferior to those in nonobese patients. Large population studies show decreased patient and graft survival in obese kidney transplant patients. Despite the poorer outcomes, kidney transplantation is considered because of the survival benefit as compared with the wait-listed dialysis patients. In liver transplantation, the benefit to transplantation as compared with remaining on the list is obvious, as there is no viable liver dialysis at this time. Obesity in potential organ donors impacts both medical and surgical issues. Obesity-related kidney disease affects both the remaining and transplanted kidney. Pancreas donor organs are associated with decreased early graft survival. Liver donor organs with significant steatosis lead to an increased risk for delayed or nonfunction of the organ. Immunosuppressive drugs with variable lipophilicity and altered volume of distribution can greatly affect the therapeutic usefulness of these drugs. Transplant candidates benefit from a multidisciplinary team approach to their care. As the epidemic progresses and less-invasive treatments for metabolic surgery evolve, we are likely to require more patients to lose weight prior to transplantation as we continue to strive for improved outcomes.

Mounting evidence suggests beneficial effects of albumin dialysis-based liver support in patients suffering from acute-on-chronic liver failure. Molecular adsorbent recirculating system (MARS) is a nonbiological liver support device, based on the exchange of albumin-bound toxins between the patient's blood and a 20% human serum albumin solution in a secondary circuit. Bound toxins are continuously removed from the circulating albumin by exposure to activated charcoal and an ion-exchange resin. The aim of the present in vitro study was to determine the impact of exposure to charcoal and resin on the ligand binding properties of albumins, containing various levels of stabilizers and obtained from different suppliers (Baxter, CAF-DCF [Red Cross], and Sigma-Aldrich). Albumin binding properties were assessed by measuring equilibrium binding properties of warfarin, diazepam, and salicylate before and after incubation (for up to 7 h) with adsorbing materials; albumin-associated esterase-like activities were also determined. Notable changes in albumin binding upon incubation with adsorbing materials were only observed when using warfarin as a ligand. Affinity of warfarin for the Baxter and Sigma albumins showed a pronounced decrease (higher K(d) ) after the 1-7-h exposure to charcoal or resin. In the absence of adsorbing materials, similar effects were found, indicating that incubation time per se affects albumin binding properties. Following exposure to resin, Baxter albumin binding capacity (B(max)) increased about twofold. For albumin obtained from CAF-DCF, binding affinity and capacity for warfarin were constant under all conditions tested. Esterase-like activities associated with these albumins were either maintained or enhanced (up to 2.5-fold in case of Sigma albumin) following 7-h incubations with adsorbing materials. Our data suggest limited direct influence of the presence of stabilizers in therapeutic albumin solutions on baseline binding properties of human albumin. However, in vitro incubations of these albumins for several hours resulted in supplier-specific changes in warfarin binding, suggesting an influence of stabilizers on the stability of binding properties. Further preclinical and clinical studies are required to elucidate the clinical relevance of these in vitro results, that is, to what extent these changes in albumin binding properties result in altered performance of albumins in the secondary circuit during the MARS procedure.

Patients with liver failure still present a high mortality. It can only be significantly improved by the rare resource of liver transplantation. Extracorporeal liver support devices have been developed to temporarily support liver detoxification. Artificial devices without hepatocytes ("liver dialysis" or "albumin dialysis") are already widely used in Europe. The two best-known systems, MARS and Prometheus, use a different technical approach to remove water-soluble as well as albumin-bound toxins from the blood. In MARS, toxins diffuse along a concentration gradient through an albumin-impermeable membrane into a secondary circuit that is pre-filled with an albumin solution. The albumin is continuously "recycled" inside the secondary circuit by different adsorber and low flux dialysis. In contrast, Prometheus includes an albumin-permeable filter allowing separation of the albumin fraction into the secondary circuit where the albumin-bound toxins are directly removed by two adsorbers. Thereafter, high flux dialysis is performed inside the primary circuit. For both extracorporeal systems, an improvement of hepatic encephalopathy and biochemical markers such as bilirubin is consistently reported. In-vivo comparisons of both systems showed significantly higher extraction capacities for protein-bound and water-soluble substances under Prometheus than under MARS treatment. Possible pathophysiological mechanisms could be a reduction of portal pressure or a removal of vasoactive cytokines. However, only few randomised controlled trials with low patient numbers and conflictive results regarding patient survival exist. Nevertheless, a Cochrane meta-analysis revealed a significant survival benefit for extracorporeal liver support devices in patients with acute-on-chronic liver failure. Other promising indications are severe refractory cholestatic pruritus, intoxication with protein-bound substances and graft dysfunction after liver transplantation. As large randomised controlled multi-center trials are currently underway, better evidence will be available soon to define the clinical role of extracorporeal liver support devices.

Albumin liver dialysis using the Molecular Adsorbent Recirculating System (MARS) (Teraklin AG, Rostock, Germany) is used in severe acute liver failure (ALF). We hypothesized that intradialytic heparin worsens preexisting hemostatic defects without enhancing system longevity or therapeutic efficacy. This was a retrospective, single center study of 10 critically ill patients (M : F = 8:2; mean age 58.5 +/- 16.5 years old; Acute Physiology and Chronic Health Evaluation II 25.0 +/- 3.5) treated with 31 MARS sessions (intradialytically heparinized : nonheparinized = 18:13). Mortality in this cohort was 80%. All MARS circuits were primed with dilute heparinized saline before commencement. However, intradialytic, intermittent, bolus heparin was administered on an ad hoc basis with circuit saline flush where indicated. Acute renal replacement therapy was instituted where indicated. Average total intradialytic heparin used was 757 +/- 389 IU. Circuit pressures were stable with or without intradialytic heparin. Significant reductions in serum urea, creatinine, ammonia, and total bilirubin were achieved using intradialytically heparinized and nonheparinized MARS. Thrombocytopenia and elevated activated partial thromboplastin time (aPTT) were further deranged post-MARS for both circuit types, but significantly so in intradialytically heparinized MARS: pre- versus post-MARS aPTT (s) 57.8 +/- 17.6 versus 88.7 +/- 48.0, P = 0.011, and platelet count (x 10(3)/L) 102.9 +/- 61.1 versus 84.4 +/- 50.5; P = 0.009. The use of low dose, intradialytic heparin during MARS exacerbates preexisting severe coagulopathy and thrombocytopenia in patients with severe ALF without enhancing circuit function and longevity. However, the role and safety of heparinized saline prime need further investigation.

Background: The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin-bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong. Methods: From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients. The cause of liver failure included acute liver failure (n=2), acute on chronic liver failure (n=12), posthepatectomy liver failure (n=4), and posttransplantation allograft failure (n=4). Results: MARS treatment showed significant reduction in total bilirubin level, serum ammonia level and blood urea, and nitrogen (P

Rationale: Fulminant liver failure from drug ingestion is associated with a high mortality, and the introduction of liver transplantation has improved the mortality significantly if done in a timely fashion. Recently, molecular adsorbent recycling system (MARS™) liver dialysis has been introduced as a support for liver failure with varying results. We review our experience with drug-induced liver failure and the impact of MARS™ liver dialysis on the outcome, in a setting where cadaveric liver transplantation is rarely available. Results: A total of 13 patients were treated, and 40 sessions of MARS™ liver dialysis were conducted in the intensive care unit. The majority of cases were because of herbal medicine toxicity. Total bilirubin, conjugated bilirubin, and delta bilirubin were significantly reduced, with no change in unconjugated bilirubin. All patients satisfied the criteria for urgent liver transplantation with an average Model End Stage Liver Disease (MELD) score of 35. Only one patient received a liver transplantation from a live donor (right lobe). Overall mortality was 85%. Median time-to-death from the start of MARS™ was 8 days. Conclusions: MARS™ liver dialysis in a setting without timely liver transplantation is associated with a poor outcome. It does, however, provide a window of time for consideration of living donors in the setting of limited cadaveric donors.

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.

Objectives: The short-term medical benefit of the liver dialysis system MARS in patients with severe acute liver disease has clearly been demonstrated. An economic analysis of MARS has not been presented previously. Objective of the study is to calculate the costs per life saved and life year gained and to measure health related quality of life in patients who survived acute liver failure. First results on survival and HRQL are presented here. Study design: Cost effectiveness and cost utility analysis of MARS are performed. All patients since 1993 with chronic liver failure (Bilirubin > 300 µmol/l) of the university hospital Rostock are included in the original sample (n = 141). Survival data are calculated. Surviving patients were contacted personally, thus quality of life data (EQ 5D and SF12) determined. Patients were compared in case control study design. In a later stage inpatient hospital costs, direct and indirect outpatients costs are included in the analysis. Preliminary results: MARS-Patients show a higher survival: Kaplan-Meier cumulative survival after 100 days: 0.59 after MARS, 0.39 without (P

Acute liver failure after hepatic surgery is still plaqued with high mortality rate. Recently, a liver dialysis system (MARS®) that allows detoxification of albumin-bound substances and may hereby support liver regeneration and patient's recovery has been developed. In the present study, we report our experiences with MARS® dialysis in patients with liver failure after hepatic resection or transplantation. Between September 1999 and January 2001, five patients were treated with MARS® (2–5 courses). Though beneficial effects such as improvement of encephalopathy and renal function as well as reduced bilirubin levels were recorded during MARS® therapy, only one patient survived. Neither significant technical problems nor adverse effects occurred by using MARS® dialysis. We conclude that in surgical patients, acute liver failure is usually part of a complicated clinical course affecting multipleorgan systems. Thus, it is difficult to determine the specific influence of MARS® on patient's outcome. However, beneficial effects observed in our patients justify its continuous use and may stimulate further evaluation in controlled studies with surgical patients.