Artificial liver support systems.

Systematic review of artificial liver support systems: Current clinical challenges

See “Effect of Molecular Adsorbents Recirculating System Treatment in Children With Acute Liver Failure Caused by Wilson Diseas” by Rustom et al on page 162. Molecular adsorbents recirculating system (MARS) is a form of dialysis using albumin-enriched dialysate to remove albumin-bound toxins via a specialised membrane. The dialysate is then regenerated through activated charcoal and anion exchange resin columns. Haemofiltration is required simultaneously to control the blood and dialysate circuits. Single-pass albumin dialysis is another form of albumin dialysis, without a perfusion pump. The accumulation of albumin-bound toxins (eg, bilirubin, bile salts) in liver failure has led to the curiosity behind the potential use of MARS in improving the overall clinical condition for successful bridging to transplantation, or even avoiding transplantation, in cases of acute liver failure (ALF) or acute-on-chronic liver failure (AoCLF). In this study, Rustom et al (1) have set out to show that MARS therapy may be useful as a bridge to transplantation in acute Wilson disease (WD) in children. The concept of MARS as a method for removing liver failure–associated albumin-bound toxins, as well as the increased fraction of toxic albumin-bound copper in acute WD, is the basis for their hypothesis. Data were retrospectively analysed (2004–2009) for all of the children who presented with acute WD and had MARS treatment in a single centre. All of the patients (n = 4) had encephalopathy, renal failure, and a Wilson prognostic index >11. Hence, all of the patients were listed for transplantation. Biochemical data were available for 3 patients and showed reduction in bilirubin, ammonia, aspartate aminotransferase, creatinine, and serum copper levels after MARS sessions. Data available for 2 patients showed an improvement in the Fischer index. All 4 patients were reported to have stable or improved encephalopathy after MARS treatment. Platelet count was significantly reduced in all of the patients and 1 patient had an adverse incident secondary to vascular catheter insertion. There was no improvement in hepatic synthetic function. The median time for transplantation was 5.5 days. Rustom et al suggest that the observed improvement in biological and clinical parameters render MARS a promising treatment modality in acute WD in children; however, the group recognises the shortcomings of such a small sample size and the incomplete dataset. They also acknowledge that the treatment effect is difficult to determine in the absence of a control group and the presence of simultaneous haemofiltration. The exact methodology of encephalopathy measurement in the 2 ventilated cases was unclear. Furthermore, although there is a postulated association with a higher Fischer index and improved encephalopathy, this is, as yet, not a known validated tool in liver failure. Most crucially, this article is unable to shed further light on the following clinically relevant question: Do the observed improved biological and clinical parameters correlate to improved survival and/or morbidity outcomes? Small randomised controlled trials (2–4) in adult studies of AoCLF concur with Rustom et al, namely, biological and clinical improvement is demonstrated in the MARS treatment group compared with the standard medical treatment group. Similarly, some small uncontrolled adult studies of ALF (5) and MARS therapy have observed such improvement. With respect to acute WD, case reports (using MARS or single-pass albumin dialysis) (6–8) have documented enhanced biochemical parameters with or without improved encephalopathy while being successfully bridged to transplantation. One common feature among all of the studies was the acceptable safety profile of MARS, with only complications of thrombocytopaenia and vascular catheter insertion being noted. Two recent large multicentre randomised controlled trials have shown that the survival benefit of MARS remains uncertain. Bañares et al (9) have shown no beneficial effect on survival at 28 days in MARS compared with a standard medical treatment group for AoCLF, despite improved biochemistry and encephalopathy in this group. Saliba et al (10) did show a statistically nonsignificant improved 6-month posttransplant and nontransplant survival rate in patients with ALF in the MARS therapy group, but no improvement in biochemical or clinical parameters. In paediatrics, Dhawan et al (11) revealed a median time of 3.5 days for transplantation of acute WD. This brief period to transplantation raises the question of the need for MARS as a bridging technique. Paediatric data for MARS are limited. Auth et al (12) used MARS as a bridging technique to transplantation for 2 paediatric cases of acute WD. They demonstrated that the MARS circuit could extract toxic metabolites; however, this was not consistently reflected by reduced serum levels of certain metabolites (copper, ammonia, bilirubin), suggesting saturation of the albumin-binding capacity. Essential growth factors and precursors to glutathione synthesis were also noted to be extracted by the albumin circuit, which could negatively affect mortality and liver regeneration. MARS does not prevent transplantation, and survival outcome posttransplantation is unclear. There is no robust evidence to justify the financial implications of this intervention in a clinical setting. The present role of MARS remains within the research setting. Alas, the quest for “life on MARS” continues.

BackgroundThe aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure.MethodsPatients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4 % albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model.ResultsSixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median −68 μmol/L, interquartile range [IQR] −107.5 to −33.5, p = 0.001; SPAD: −59 μmol/L, −84.5 to +36.5, p = 0.001). However, bile acids (MARS: −39 μmol/L, −105.6 to −8.3, p < 0.001; SPAD: −9 μmol/L, −36.9 to +11.4, p = 0.131), creatinine (MARS: −24 μmol/L, −46.5 to −8.0, p < 0.001; SPAD: −2 μmol/L, −9.0 to +7.0/L, p = 0.314) and urea (MARS: −0.9 mmol/L, −1.93 to −0.10, p = 0.024; SPAD: −0.1 mmol/L, −1.0 to +0.68, p = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10 %, −0.8 to +20.9 %, p < 0.001; SPAD: +7 %, −7.5 to +15.5 %, p = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD.ConclusionsBoth procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation.Trial registrationGerman Clinical Trials Register (www.drks.de) DRKS00000371. Registered 8 April 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1159-3) contains supplementary material, which is available to authorized users.

Extracorporeal liver support procedures based on albumin dialysis require the use of pharmaceutical-grade human serum albumin (HSA). Those preparations contain octanoate, which is added as stabilizer during the production process. For octanoate, a direct involvement in the pathogenesis of liver failure complications as well as an indirect influence by competitive displacement effects at the albumin molecule have been described. During five Single Pass Albumin Dialysis (SPAD) and three Molecular Adsorbent Recirculating System (MARS) treatments the changes of octanoate concentrations in blood and dialysate were investigated. An octanoate increase in patient blood was observed during passage of the filter for both SPAD (585 micromol/L [338-1022 micromol/L]) (median [range]) and MARS (182 micromol/L [71-437 micromol/L]) during the first three hours of treatment. The molar ratio of octanoate/albumin at the blood outflow was significantly higher during SPAD treatments (1.73 [0.86-2.64] vs. 0.54 [0.31-1.1]; P = 0.001) during MARS. Changes of octanoate blood levels during SPAD were significantly higher than during MARS (P < 0.001). The shift of octanoate from the dialysate to the patient was persistent during SPAD (median 67.6 micromol/min), whereas during MARS a decrease over time was observed (from 25.5 to 7.5 micromol/min). During albumin dialysis procedures a transfer of octanoate into patient blood occurs. The time-course and extent are different between both albumin dialysis procedures. Given the positive clinical effects reported mainly for MARS, the clinical impact of albumin dialysis-associated transfer of octanoate during extracorporeal liver support needs to be evaluated further.

The single pass albumin dialysis (SPAD) was reported to be an alternative to the Molecular Adsorbent Recirculating System (MARS) for the effective removal of protein bound substances in liver failure. Three SPAD experiments using different albumin concentrations and dialysate flow rates were performed. In each experiment, 1000 ml human donor plasma, spiked with 250 mg unconjugated bilirubin, 200 mg sulfobromophthalein (BSP) and 115 mg glycocholic acid (N-[3alpha,7alpha,12alpha-trihydroxy-24-oxycholan-24-yl]glycine) - a conjugated bile acid (BA), circulated in a closed loop with 150 ml/min and was dialysed against albumin solution. These substances are bound to the different binding sites of albumin and have different association constants. For the comparison, the standard MARS experiment was performed using the same plasma flow rate of 150 ml/min. Moreover, the clearances of bilirubin for MARS and SPAD during clinical treatments were calculated using own data and those reported by Seige, Kreymann, Jeschke, et al. in Transplant Proc 1999; 31: 1371-5. The concentrations of bilirubin, BSP and BA were measured in plasma and dialysate and for these substances clearances (Cl) were calculated. It is known that the elimination rate of bilirubin is not very high during albumin dialysis in comparison to other substances, like bile acids, due to the high association constant. An increase of albumin concentration or the flow rate improved the efficacy but also raised the costs substantially. In this study, we have shown that MARS is the more effective kind of albumin dialysis for the important substances like bile acids. By SPAD an improvement of efficacy can be reached only by dramatic increase of the costs. Also, the earlier experiments showed that MARS is safer because of the removal of the stabilizers, which are normally included in the commercial albumin solutions.

Despite improvement in critical care, liver failure is still associated with high mortality. Therapeutic concepts are aimed at restoring endogenous liver function or to bridge the time to liver transplantation. In addition to standard medical treatment, extracorporeal liver support with albumin dialysis is used for this purpose. The aim of this study was to analyze the efficacy of single pass albumin dialysis (SPAD) in comparison to the molecular adsorbent recirculating system (MARS) in patients treated at our university hospital intensive care unit between July 2004 and August 2008. In this retrospective analysis we studied patients presenting with liver failure who were treated with albumin dialysis. Laboratory parameters, daily health scoring, the number of transfusions, and mortality were recorded. The (paired) t-test, Mann-Whitney U-test, and Wilcoxon test were used for statistical analysis. In all, 163 albumin dialysis treatments, 126 with MARS and 37 with SPAD, in 57 patients were performed. MARS resulted in a significant decrease in bilirubin (-38 +/- 66.5 micromol/L from a baseline of 301 +/- 154.6 micromol/L), gamma-glutamyltransferase (gamma-GT), alanine aminotransferase, creatinine, and urea. SPAD resulted in a significant decrease in bilirubin (-41 +/- 111.2 micromol/L from a baseline of 354 +/- 189.4 micromol/L) and gamma-GT, while lactate levels increased. No differences in the need for blood transfusion, health scoring, or mortality between the two treatment modalities were detected. This retrospective analysis suggests equal efficacy of MARS and SPAD; however, prospective assessment to further define the role of SPAD in the treatment of acute or acute-on-chronic liver failure is needed.

In their article in Critical Care, Sponholz et al. [1] compared two devices: the molecular adsorbent recirculating system (MARS) and single pass albumin dialysis (SPAD). As Sponholz et al. claim, SPAD is not an effective method for achieving a significant decrease in the concentration of bile acids, creatinine or urea, because a single SPAD procedure induces a 7.62 % (median) reduction in the level of bile acids and an increase in the concentrations of creatinine and urea by respectively 5.04 % (median) and 4.69 % (median), compared with pre-dialysis levels [1]. In contrast, our as yet unpublished study demonstrates that SPAD can effectively reduce not only the level of bile acids but also the concentration of ammonia. Based on our study, the application of the SPAD method with a dialysate flow rate of 1000 ml/h for a total of around 10 h reduces the level of bile acids by 21.9 % (median) and ammonia by 16.25 % (median). A question arises as to the possible causes of such discrepancies. Since continuous venovenous haemodialysis was performed in both studies, the divergence cannot be attributed to the technique. In our view, this divergence is associated with several factors. One of these factors is the difference in dialysate flow rate. An albumin dialysate flow rate of 700 ml/h is highly insufficient. Taking into consideration the results obtained by Sponholz et al., an increase in the albumin dialysate flow rate to at least 1000 ml/h appears to be a necessary precondition to ensure effective elimination of bile acids. Also, the methodology adopted for the study is questionable. In our opinion, comparing the effectiveness of urea and creatinine elimination at radically different dialysate flow rates (SPAD 700 ml/h vs MARS 2000 ml/h) is unjustified and may lead to erroneous conclusions, which in fact occurred [1]. Differences in efficacy between the MARS and SPAD procedures reported in the article in question may also be related to inappropriately selected haemofilters in the extracorporeal blood purification systems under comparison. Furthermore, Sponholz et al. [1] pointed out metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anticoagulation. In our view, increasing the dialysate flow rate would significantly contribute to preventing the irregularities noted in the study. On the other hand, we believe that the risk of citrate overdose during liver dialysis, but also during continuous venovenous haemodialysis, is very low [2–4]. In our medical centre, we have been successfully performing continuous venovenous haemodialysis procedures with regional citrate anticoagulation in patients with severe liver dysfunction, sometimes for up to several weeks. We have never noted any symptoms of overdose apart from end-stage liver failure.

We read with interest the article by Hassanein et al.1 and the editorial by Ferenci and Kramer2 and found the editorial too negative for a positive trial. A frequent problem in the assessment of artificial liver support systems (ALSSs) is that they are unconsciously compared to the artificial renal support systems (ARSSs). This has no justification. First, although we are in the golden era of ARSS, the molecular adsorbents recirculating system (MARS) had been introduced only a few years ago. We still do not know the best indication, time of application, and treatment schedule for this device. Second, whereas chronic liver failure (CLIF) is an extremely complex syndrome, chronic renal failure (CRF) is the result of a single defect, an intense reduction in glomerular filtration rate leading to retention of water-soluble substances that are easily removed with current technology. Finally, we have excellent markers of CRF that facilitate indication and dosing of ARSS. However, this is not the case for CLIF. CLIF involves not just impaired liver excretory function but also reduced hepatic synthetic function. Moreover, most problems associated with CLIF are related to a circulatory dysfunction due to splanchnic arterial vasodilation and reduction in cardiac function.3 There is marked stimulation of the renin-angiotensin and sympathetic nervous systems and vasopressin, which maintain arterial pressure by producing vasoconstriction in extrasplanchnic organs.4 Renal vasoconstriction causes hepatorenal syndrome. Cerebral vasoconstriction may contribute to cerebral dysfunction.5, 6 Relative adrenal insufficiency is also a common event in CLIF.7 Intrahepatic vasoconstriction leading to increase in portal pressure and decrease in hepatic blood flow has been reported in CLIF.3, 8 Finally, the increased sympathetic activity impairs intestinal motility and induces bacterial overgrowth, translocation of bacterial products, and chronic inflammatory reaction.9 The observation that parameters estimating systemic hemodynamics are better markers of CLIF severity than those estimating hepatic function is a clear indication of the complexity of the syndrome. Which parameters should then be used to evaluate ALSS? Survival is important. In fact, one of the arguments given by Ferenci and Kramer to suggest a lack of benefit of MARS was the similar mortality observed by Hassanein et al. in the MARS and standard medical therapy (SMT) groups. However, the design of the trial was to assess the effect of MARS on hepatic encephalopathy and not on survival. It would have been a miracle to get differences in survival after a mean of 2.7 dialysis sessions in the MARS group. A second approach is to assess the effect of MARS on complications associated with CLIF, and here we have evidence that we are dealing with a potentially effective device. Despite the methodological criticisms raised by Ferenci and Kramer, the study by Hassanein et al. supports a significant benefit of MARS on encephalopathy. There were more patients responding in the MARS group and they improved faster. Arguments given by Ferenci and Kramer to negate a benefit of MARS were weak and could be used in the opposite sense. For example, they consider that the longer period on SMT prior to randomization in the MARS group (5.6 versus 2.6 days) could partially account for the better response of encephalopathy in this group. However, because all patients had grade III-IV encephalopathy at randomization, an alternative possibility is that there were more patients with encephalopathy refractory to SMT in the MARS group. MARS treatment is also associated with clear improvement in cardiovascular function (increase in arterial pressure and vascular resistance and suppression of renin, noradrenaline, and vasopressin).10-12 Finally, MARS removes water-soluble substances and can replace renal function in severe hepatorenal syndrome. In summary, treatment of CLIF is more complex than treatment of CRF. In addition to extracorporeal devices to replace the hepatic excretory function, it is important to treat the impaired synthetic function and multiorgan failure associated with CLIF. We need more research on CLIF to identify potential targets for treatment. MARS, in addition to being a potentially useful device, could be an important tool to explore the pathogenesis of CLIF. Vicente Arroyo*, Javier Fernandez*, Antoni Mas*, Angels Escorsell*, * Liver Unit, Hospital Clinic, University of Barcelona, Spain.

In patients with liver failure, the accumulation of lipophilic, albumin-bound toxins occurs which cannot be eliminated by standard hemodialysis and hemofiltration techniques. For this purpose (artificial and bioartificial) liver support systems were developed. Extracorporeal systems for artificial liver support include: Molecular adsorbents recirculating system (MARS) Single-pass albumin dialysis (SPAD) Fractionated plasma separation and adsorption (Prometheus) Selective plasma exchange therapy (SEPET) Extracorporeal systems for bioartificial liver support include: Extracorporeal liver perfusion (ECLP) HepatAssist Extracorporeal liver-assist device (ELAD) Modular extracorporeal liver support system (MELS) Bioartificial liver of the Academisch Medisch Centrum (AMC-BAL) The MARS, SPAD, and Prometheus systems are available for clinical use and are mostly employed either for bridging the patient to transplant or else for bridging to recovery of liver function. Positive data exist regarding biochemical efficacy and clinical improvement of certain end points such as hepatic encephalopathy, but adequately powered clinical trials evaluating survival rates are at present lacking.

Acute liver failure (ALF) and acute on chronic liver failure (AoCLF) carry a high mortality. The rationale for extracorporeal systems is to provide an environment facilitating recovery or a window of opportunity for liver transplantation. Recent technologies have used albumin as a scavenging molecule. Two different albumin dialysis systems have been developed using this principle: MARS (Molecular Adsorbent Recirculation System) and SPAD (Single-Pass Albumin Dialysis). A third system, Prometheus (Fractionated Plasma Separation and Adsorption), differs from the others in that the patient's albumin is separated across a membrane and then is run over adsorptive columns. Although several trials have been published (particularly with MARS), currently there is a lack of controlled studies with homogenous patient populations. Many studies have combined patients with ALF and AoCLF. Others have included patients with different etiologies. Although MARS and Prometheus have shown biochemical improvements in AoCLF and ALF, additional studies are required to show conclusive benefit in short- and long-term survival. The appropriate comparator is standard medical therapy rather than head-to-head comparisons of different forms of albumin dialysis.

In recent years different artificial liver support systems are being developed for use in patients with acute decompensation of chronic liver disease or acute liver failure. The molecular adsorbents recirculating system (MARS), a device in which patient's blood is dialysed across an albumin-impregnated membrane against a recirculated albumin-containing solution, seems to be effective in removing albumin-bound toxins, such as fatty acids, bile acids and bilirubin. Although the clinical experience with MARS is scarce, some pilot studies have reported its effectiveness at improving liver function and hepatic encephalopathy in patients with acute decompensation of chronic liver disease, and renal function in patients with hepatorenal syndrome type I. Data regarding MARS experience in acute liver failure and in primary graft dysfunction are encouraging but limited. Its real usefulness in these settings is, at present, under evaluation in randomized controlled clinical trials.

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.

Acute liver failure (ALF) and acute on chronic liver failure (ACLF) represent severely compromised clinical conditions, characterised by high mortality and often candidates for liver transplantation. Recently, non-biological extracorporeal treatments (ECLSD) have gained an increasing role as temporary support through the removal of water-soluble and albumin-bound toxins. This paper provides an overview of the main available devices, including SPAD (single pass Albumin Dialysis), MARS (Molecular Adsorbent Recirculation System), Prometheus (Fractionated Plasma Separation and Adsorption), Cytosorb, CPFA (Coupled Plasma Filtration Adsorption) and DPMAS (Dual Plasma Molecular Adsorption System), illustrating their technical characteristics, efficacy and limitations. Cytosorb, although originally designed for the treatment of systemic inflammatory conditions, has shown surprising efficacy in reducing bilirubin and bile acids, surpassing the results of MARS in some retrospective studies. Special attention is given to our centre's experience with the RAED (Recirculated Albumin Extended Dialysis) and RHENOB (Reemplazo Hepático No Biológico) techniques, based on recirculated albumin circuits, with or without regeneration by DPMAS. In a series of seven patients with ALF or ACLF treated with RHENOB, a significant reduction in bilirubin (25-50%) was observed after only a few sessions, without haemodynamic adverse events. One patient subsequently received a successful liver transplant, completing the biochemical stabilisation course. The RAED and RHENOB techniques appear to be innovative, effective, cost-effective approaches that can be applied even in centres without advanced technology. However, controlled prospective studies are needed to consolidate their use in clinical practice.

Introduction: Molecular adsorbent recirculating system (MARS) for albumin liver dialysis has been used as a bridge to liver transplantation in patients with fulminant hepatic failure (FHF). This review examines the available data on its clinical use, its technical aspects and present gaps in knowledge. Methods: Peer-reviewed journals and monographs on the subject were covered. Results: FHF is associated with elevation in various substances including bilirubin, ammonia, lactate, free fatty acids and aromatic amino acids. Some of these toxic metabolites, such as ammonia and bilirubin, are believed to be central to the clinical manifestations of hepatic encephalopathy and acute renal failure. MARS ameliorates both biochemical and clinical manifestations of FHF by removing both water-soluble and protein-bound toxins. Among the benefits of MARS is the attenuation of severe cerebral oedema and raised intracranial pressure found in FHF, possibly through reduction in high concentrations of these toxins. Although MARS has been shown to be useful in FHF, its clinical efficacy in subfulminant hepatic failure and less severe forms of acute liver failure (ALF) remains uncertain. The current literature also suggests that it may be beneficial to treat cases of acute-on-chronic liver failure (AoCLF). Deranged systemic chemistries can be similarly ameliorated, but the impact of MARS on the natural history of AoCLF remains uncertain. The difficulty lies in being able to accurately quantify residual liver function and variability in the course of acute intercurrent events. The broader question is whether MARS can favourably change the natural history of ALF and FHF. For this, large multi-centre, randomised controlled trials are needed. Furthermore, it is also uncertain how hepatic excretory-assist devices, such as MARS, compare with bio-artificial liver-assist devices which have both synthetic and excretory hepatic functions in ALF treatment in intensive care unit patients. Nevertheless, MARS has proven to be a valuable homeostatic tool that may be useful in restoring the biochemical and clinical status quo in much the same way that continuous veno-venous haemofiltration and mechanical ventilation provide temporary artificial organ support while these organs are in distress. This is the evolving concept of multi-organ support therapy. Other major unresolved issues with MARS include the timing of initiation of albumin liver dialysis, the clinical and/or biochemical parameters to base this decision on, the intensity of MARS therapy (continuous versus intermittent) and the saturation capacity of the system for different metabolites in intermittent MARS. Conclusions: MARS is an effective and, thus far, safe homeostatic tool in treating FHF. More studies are needed to delineate its role as a homeostatic tool in less severe forms of ALF, including that which occurs in multi-organ failure and in AoCLF. Other studies need to focus on the optimal timing of initiation of and intensity of MARS albumin liver dialysis. The larger issue is to compare MARS with bio-assist liver devices in treating the whole spectrum of ALF.

Albumin dialysis is widely accepted as a liver-support technique for patients with liver failure. The Molecular Adsorbent Recirculating System, the widely accepted albumin dialysis technique, has limited use in developing countries because of its technical difficulties and high cost. Therefore, we assessed the efficacy of the more practical modality, the single-pass albumin dialysis (SPAD), in terms of bilirubin reduction, as a marker of albumin-bound toxins removal, as well as the patient outcomes. Twelve acute or acute-on-chronic patients with liver failure who had hyperbilirubinemia (total bilirubin > 20 mg/dL) were treated with SPAD by using 2% human serum albumin dialysate for 6 h. SPAD treatment significantly improved the levels of total bilirubin, conjugated bilirubin, urea, and creatinine (P < 0.001 for all parameters). The reduction ratios of these four parameters were 22.9 +/- 3.8%, 20.9 +/- 5%, 19.0 +/- 4.1%, and 27.7 +/- 3.2%, respectively. No significant difference was observed between serum ammonia before and after treatment. No significant changes in mean arterial pressures were noted during the maneuver, representing cardiovascular tolerability. No treatment-related complications were found. The 15-day in-hospital survival was 16.7%. However, a subgroup of the patients who had moderate severity showed 100% 15-day-survival rate (2 of 2 patients). In conclusion, SPAD is salutarily effective in reducing bilirubin in patients with liver failure. The procedure is safe and simply set up.