Fractionated Plasma Separation And Adsorption Research Articles

Efficacy of albumin dialysis as a bridge to transplantation in children with end-stage liver disease

Liver transplantation is the only effective treatment modality for end-stage liver disease. However, donor organs are not always available. In some cases, the gravity of the patient’s condition makes transplantation impossible. In this regard, the use of artificial liver support systems helps in preparing a patient for transplant surgery. Objective: to conduct a retrospective study aimed at evaluating the efficiency of fractionated plasma separation and adsorption system. Materials and methods. From January 2019 to May 2020, 139 pediatric liver transplants were. We analyzed the data of 5 pediatric patients (2 girls and 3 boys, aged 12 to 17 years) who received fractionated plasma separation and adsorption (FPSA) sessions as a bridge to transplantation. The main clinical indication for FPSA was severe hepatic encephalopathy (grade 3 according to the West Haven Criteria), which was observed at 350–872 μmol/L (average 597 ± 98 μmol/L) serum bilirubin level. The FPSA sessions were conducted on a Prometheus device using AV-600 hemofilters as dialyzers (Fresenius Medical Care, Germany). Results. Depending on the extent of bilirubinemia in patients, it took from one (in one case) to three (in one case) daily FPSA sessions to restore clear consciousness, appetite and physical activity. Average bilirubin levels after treatment cycles decreased from 597 ± 98 to 236 ± 73 μmol/L. All patients successfully underwent liver transplant surgery within two to five days, two patients received a liver fragment from a living related donor. Conclusion. The FPSA system stabilizes the condition of potential recipients with acute liver failure. Further research is required to develop optimal regimens for albumin dialysis.

An Evaluation of the Usefulness of Extracorporeal Liver Support Techniques in Patients Hospitalized in the ICU for Severe Liver Dysfunction Secondary to Alcoholic Liver Disease.

BackgroundThe mortality rate in patients with severe liver dysfunction secondary to alcoholic liver disease (ALD) who do not respond to the standard treatment is exceptionally high.ObjectivesThe main aim of this study was to evaluate the usefulness of applying extracorporeal liver support techniques to treat this group of patients.Patients and MethodsThe data from 23 hospital admissions of 21 patients with ALD who were admitted to the department of anesthesiology and intensive therapy (A&IT) at the Dr Wł. Biegański Regional Specialist Hospital in Łódź between March 2013 and July 2015 were retrospectively analyzed.ResultsA total of 111 liver dialysis procedures were performed during the 23 hospitalizations, including 13 dialyses using fractionated plasma separation and adsorption (FPSA) with the Prometheus® system, and 98 procedures using the single pass albumin dialysis (SPAD) system. Upon admission to the intensive care unit (ICU), the median (interquartile range [IQR]) Glasgow coma scale (GCS), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II, and simplified acute physiology score (SAPS) II scores were 15 (14 - 15), 9 (7 - 13), 17 (14 - 24), and 32 (22 - 50), respectively. The ICU, 30-day, and three-month mortality rates were 43.48%, 39.13%, and 73.91%, respectively. As determined by the receiver operative characteristic (ROC) analysis for single-factor models, the significant predictors of death in the ICU included the patients’ SOFA, APACHE II, SAPS II, and model of end-stage liver disease modified by the united network for organ sharing (MELD UNOS Modification) scores; the duration of stay (in days) in the A&IT Department; and bile acid, creatinine and albumin levels upon ICU admission. The ROC analysis indicated the significant discriminating power of the SOFA, APACHE II, SAPS II, and MELD UNOS modification scores on the three-month mortality rate.ConclusionsThe application of extracorporeal liver support techniques in patients with severe liver dysfunction secondary to ALD appears justified in the subset of patients with MELD UNOS Modification scores of 18 - 30.

Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs

BackgroundCerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP.MethodsA surgical resection model of ALF was used in 21 pigs. We measured plasma ammonia concentration, brain concentrations of glucose, lactate, pyruvate, glutamate and glutamine, and ICP. Animals were randomized into three groups: in one group eight animals received 6 hours of FPSA treatment 2 hours after induction of ALF; in another group 10 animals received supportive treatment for ALF only; and in the final group three underwent sham surgery.ResultsThe ICP was significantly higher in the ALF group than in the FPSA group 9 hours after surgery. The lactate/pyruvate (L/P) ratio was significantly lower in the FPSA group than the ALF group 5 hours after surgery, before any significant difference in ICP was detected. Indeed, significant changes in the L/P ratio could be observed within 1 hour of treatment. Glutamine levels were significantly lower in the FPSA group than the ALF group between 6 hours and 10 hours after surgery.ConclusionsBrain lactate/pyruvate ratio and concentration of glutamine measured by cerebral microdialysis reflected the beneficial effects of FPSA treatment on cerebral metabolism more precisely and rapidly than ICP in pigs with fulminant ALF. The role of glutamine as a marker of the efficacy of FPSA treatment for ALF appears promising, but needs further evaluation.

The role of intracerebral glutamine levels as a marker of the therapeutic efficiency of FPSA (fractionated plasma separation and adsorption) in acute liver failure treatment - a controlled study in pigs

Prazak, J.; Laszikova, E.; Pantoflicek, T.; Ryska, O.; Koblihova, E.; Ryska, M. Author Information

The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure

Patients with acute liver failure have a disturbed amino acid metabolism and a compromised oxidative metabolism in the brain. A limited number of clinically neuroprotective interventions are available. This study aimed at assessing the effect of fractionated plasma separation and adsorption (FPSA), an extracorporeal liver support system, on cerebral amino acids and lactate to pyruvate ratio. Seven patients with acute liver failure and high risk of intracranial hypertension were included for cerebral microdialysis and intracranial pressure monitoring. Microdialysate, arterial blood, and venous blood from the jugular bulb were sampled, before and after an FPSA session, and the content of nineteen amino acids, lactate, and pyruvate was determined. The total amino acid concentration in arterial plasma was not significantly reduced by FPSA (11.2 mM (3.0-26.0 mM) vs. 9.7 mM (2.7-13.6 mM); median with range). The total amino acid content in the microdialysate was 5.6 mM both before and after FPSA and no change in glutamine content was observed in plasma or microdialysate. The content of aromatic amino acids in arterial plasma, but not in microdialysate, was marginally reduced (p<0.05). Arterial lactate concentration and lactate to pyruvate ratio in the microdialysate did not change following FPSA. One single treatment session with FPSA had a marginal effect on plasma amino acid composition. We found minimal changes in the amino acids content in the microdialysate, and the lactate to pyruvate ratio was unaffected.

Effects of Fractionated Plasma Separation and Adsorption on Survival in Patients With Acute-on-Chronic Liver Failure

Fractionated plasma separation and adsorption (FPSA) is an extracorporeal procedure that supports liver function by removing endogenous toxins that cause complications from acute-on-chronic liver failure (AOCLF). We performed a randomized trial to investigate survival of patients with AOCLF treated with FPSA. Patients with AOCLF were randomly assigned to groups given a combination of FPSA and standard medical therapy (SMT) (FPSA group, n = 77) or only SMT (SMT group, n = 68). The Prometheus liver support system was used to provide 8 to 11 rounds of FPSA (minimum of 4 hours each) for 3 weeks. Primary end points were survival probabilities at days 28 and 90, irrespective of liver transplantation. Baseline clinical parameters and number of transplant patients were similar between study arms. Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Baseline factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects. Among all patients with AOCLF, extracorporeal liver support with FPSA does not increase the probability of survival. Further studies are needed to assess whether therapy might be beneficial in specific subsets of patients.

Fractionated plasma separation and adsorption: current practice and future options

Fractionated plasma separation and adsorption (FPSA) is a method of albumin dialysis that is integrated into an extracorporeal liver support device (Prometheus(®)). This concept allows the effective removal of both protein-bound and water-soluble substances without the need for external albumin. Several studies comparing the in vivo extraction capacities of FPSA and molecular adsorbent recirculating system (MARS) concluded that detoxification by FPSA seems to be more effective than by MARS. Overall, FPSA therapy has been shown to be safe. Over the last few years, the anticoagulation protocol for FPSA therapy was optimised by using regional anticoagulation with citrate to avoid clotting of system components. Recently, the results of a large randomised-controlled multicentre trial (HELIOS) have been presented. Survival after 1 and 3 months was evaluated in 145 patients with acute-on-chronic liver failure comparing FPSA therapy with standard medical treatment versus standard medical treatment alone. There was no statistically significant survival benefit for patients undergoing FPSA therapy. However, patients with hepatorenal syndrome type I or MELD score >30 showed a significant survival benefit under FPSA in a predefined subgroup analysis. Furthermore, there have been promising results with FPSA in the treatment of refractory cholestatic pruritus. Regarding acute liver failure, only few data are currently available.

The Effect of Prometheus Device on Laboratory Markers of Inflammation and Tissue Regeneration in Acute Liver Failure Management

Prometheus, based on modified fractionated plasma separation and adsorption (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver transplantation. As the therapeutic effect of Prometheus is caused not only by the elimination of terminal metabolites, the aim of the study was to identify the effect of FPSA on the levels of cytokines and markers of inflammation and liver regeneration. Previous studies assessing cytokine levels involved mostly acute-on-chronic liver failure patients. Data concerning markers of inflammation and liver regeneration are not published yet. Eleven patients (three males, eight females) with acute liver failure were investigated. These patients underwent 37 therapeutic sessions on Prometheus device. Before and after each treatment, the plasma levels of selected cytokines, tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), procalcitonin (PCT), hepatocyte growth factor (HGF), and α 1 fetoprotein, were measured, and the kinetics of their plasma concentrations was evaluated. Before the therapy, elevated levels of interleukin (IL)-6, IL-8, IL-10, TNFα, CRP, and PCT were detected. The level of TNFα, CRP, PCT, and α 1 fetoprotein decreased significantly during the therapy. In contrast, an increase of HGF was detected. The decline of IL-6, IL-8, and IL-10 concentrations was not significant. Our results show that Prometheus is highly effective in clearing inflammatory mediators responsible for systemic inflammatory response syndrome and affects the serum levels of inflammatory and regeneration markers important for management of acute liver failure.

Changes in Plasma Amino Acids During Extracorporeal Liver Support by Fractionated Plasma Separation and Adsorption

In patients with liver failure, amino acid dysbalance is common and associated with hepatic encephalopathy. Prometheus is a newly designed extracorporeal liver support system based upon fractionated plasma separation and adsorption (FPSA). We evaluated the influence of FPSA on plasma amino acid patterns in patients with liver failure and hepatic encephalopathy. We studied nine patients with acute-on-chronic liver failure, hepatic encephalopathy, and concomitant renal failure. A single session of FPSA therapy for 5 +/- 1 h was performed in all patients. Twenty-six different plasma amino acids were measured by high-performance liquid chromatography before and after FPSA treatment. Total amino acids as well as Fischer index were calculated. Additionally, a variety of clinical and biochemical parameters were assessed. Before FPSA was started, plasma levels of most amino acids were elevated. Plasma ammonia levels correlated with glutamine levels (P < 0.04). During FPSA, plasma levels of nearly all amino acids significantly decreased except for branched-chain amino acids. The Fischer index improved without reaching statistical significance. FPSA therapy tends to normalize plasma amino acids in patients with combined liver and renal failure. This may contribute to positive pathophysiologic effects, especially on hepatic encephalopathy. However, the clinical significance of these findings needs to be further evaluated.

The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications

Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute-on-chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post-treatment data were performed using paired t-test. The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 +/- 9.46 mg/dL vs. 9.76 +/- 7.05 mg/dL; P < 0.0001), ammonia (167.6 +/- 75 mg/dL vs. 120 +/- 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 +/- 13.03 mg/dL vs. 8.18 +/- 8.15 mg/dL; P < 0.0001), creatinine (0.54 +/- 0.47 mg/dL vs. 0.46 +/- 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 +/- 0.05 vs. 7.44 +/- 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment.

Liver support systems today

Liver failure carries a high mortality, both the acute type with no pre-existing liver disease (acute liver failure) and the acute decompensation superimposed on a chronic liver disorder (acute on chronic liver failure). Today, liver transplantation still represents the only curative treatment for liver failure due to end-stage liver diseases. Donor organ shortage is still the major limitation and many patients die while awaiting transplantation. Due to the scarcity of donor organs, liver support technologies are being developed to support patients with severe liver failure until either an organ becomes available for transplantation or their livers recover from injury. Early devices including hemodialysis, hemoperfusion, exchange transfusion, cross-hemodialysis, cross-circulation and plasmapheresis appeared inefficient. In the present day, liver support systems' designs fall into two main categories: cell-based, so-called bioartificial and non-cell-based, also known as artificial systems. Bioartificial liver support systems use either porcine hepatocytes or human hepatoma cell lines housed within a hollow-fiber bioreactor. The system perfuses the patient's whole blood or separated plasma through the luminal space in the bioreactor. Theoretically, these methods should optimally resemble normal hepatic tissue structure and function. However, the existing bioartificial systems are far from ideal solution in terms of immunological, infectological, oncological and financial problems and must still be thought of as experimental. The artificial systems are already available for the clinicians in limited quantities. These non-cell-based devices are intended to remove protein-bound and water-soluble toxins without providing synthetic function, which can be partially replaced with substitution of the failing substances (plasma proteins, coagulation factors). These systems include the hemodiabsorption (Liver Dialysis Unit) which is commercially available in the United States, the albumin dialysis which is available in Europe and the newly developed fractionated plasma separation and adsorption (FPSA) system. The simple method of albumin dialysis is "single pass albumin dialysis" (SPAD), which evolved into the so-called "molecular adsorbent recirculating system"(MARS). Prometheus system combines the FPSA method with high-flux hemodialysis. Although the results of many experimental and clinical trials prove the efficacy of the above mentioned methods, large randomized controlled trials are mandatory to establish the impact on survival benefit of artificial and bioartificial support systems versus standard therapy.

Extracorporeal Liver Support Therapy With Prometheus in Patients With Liver Failure in the Intensive Care Unit

Acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF) are associated with a high mortality. In these patients an accumulation of both water-soluble and water-insoluble, protein-bound, metabolic waste products occurs. Conventional extracorporeal blood purification techniques based on diffusion and/or convection such as hemodialysis or hemofiltration may only eliminate small molecular weight, water-soluble compounds. In recent years, fractionated plasma separation and adsorption (FPSA) with the Prometheus system has been introduced for extracorporeal liver support therapy. To date, however, only limited data is available regarding the effect of this treatment on mortality and outcome of patients with advanced liver disease. Here we report on our experience with 23 patients with severe liver failure who were treated with Prometheus in our medical intensive care unit. Fourteen patients had AoCLF, and nine patients experienced ALF. The median bilirubin level at the start of Prometheus therapy was 30.5 mg/dL and the median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 26. During 40 individual treatment sessions lasting 5-6 h, Prometheus therapy reduced serum bilirubin levels from 23.7 mg/dL to 15.0 mg/dL (median values) (P < 0.001), and the overall survival was 26%. ALF patients had a better survival compared to AoCLF patients (44% vs. 22%; P = 0.022). Apart from one patient who developed hemodynamic instability during a treatment session, Prometheus therapy was well tolerated without relevant side-effects. In conclusion, extracorporeal liver support therapy with Prometheus is a novel and safe treatment option in patients with severe liver failure. In this series, patients with ALF showed a significantly better outcome with Prometheus therapy compared to AoCLF patients.

Coagulation and Fractionated Plasma Separation and Adsorption

To the Editor,We are pleased that Rifai et al. share our concerns oncoagulation abnormalities induced by the extracorporealliversupportdevicePrometheus(Fresenius,BadHomburg,Germany) (1). We previously reported on repeated occlu-sive thrombosis of the arterio-venous conduit, during frac-tionated plasma separation and adsorption (FPSA) usingPrometheus in hemodialysis patients (2). Similar to theirfindings, we failed to detect overt thrombotic events inliver failure patients treated with the Prometheus

Therapeutic Efficacy of the Latest Extracorporeal Elimination Procedure (Prometheus® Treatment) in Acute Hepatic Failure due to Intoxication

Despite intensive therapy, the mortality of acute hepatic failure is 60 to 90% without liver transplantation. Due to the limited number of transplantable organs, however, a significant percentage of patients die while on the waiting list. In order to reduce mortality, several attempts have been made to remove the albumin-bound and water-soluble toxic substances accumulated in hepatic failure, aimed at supporting spontaneous regeneration of the liver and maintaining patients alive until liver transplantation. Prometheus® treatment is a relatively new technique combining Fractionated Plasma Separation and Adsorption (FPSA) with high-flux dialysis. During the procedure the patient’s own separated albumin-rich plasma flows through special adsorbers, allowing elimination of toxins bound to albumin, while the water-soluble toxins are removed by haemodialysis. Objective: The authors’ intention was to demonstrate the efficacy of Prometheus® treatment in patients with acute hepatic failure due to intoxication. Pat...

Removal of the Uremic Retention Solute p‐Cresol Using Fractionated Plasma Separation and Adsorption

Removal of protein-bound uremic retention solutes, including p-cresol, by peritoneal dialysis and hemodialysis (HD) is limited. p-Cresol, mainly circulating as sulfate conjugate (p-cresyl sulfate [PCS]), is independently associated with mortality. Fractionated plasma separation and adsorption (FPSA) is a nonbiologic detoxification system for the treatment of liver failure. The FPSA clearance of uremic retention solutes is unknown. We studied PCS clearance by FPSA, using the Prometheus system. The neutral resin adsorbent and the anion exchange adsorbent bind PCS in vitro (reduction ratios [RRs] 37 and 70%). Ex vivo, the adsorbent mass removal (MR) (median 47.5 mg) contributes more than half to total MR (median 89.6 mg). In vivo, PCS RR during FPSA (50%) exceeded the RR during high flux HD (30%). We halted the study after four inclusions due to repeated thrombosis of the arterio-venous conduit. In conclusion, FPSA is a promising technique to improve clearance of protein-bound uremic retention solutes.

The therapeutical efficiency of the newest extracorporal elimination procedure (Prometheus® treatment) in acute liver failure caused by intoxication

Despite intensive therapy the mortality of acute liver failure without organ transplantation is 60-90%. Because of organ shortage in liver transplantation, a significant number of patients dies while being on the waiting list. In order to diminish the mortality, various trials were introduced to remove the albumin-bound and water-soluble toxins in liver failure with the aim to support the spontaneous regeneration of the liver and maintaining the patients alive until liver transplantation. Prometheus treatment is a relatively new technique combining Fractionated Plasma Separation and Adsorption (FPSA) with a high-flux dialysis. During the procedure the patient's own separated albumin-rich plasma passes through special adsorbents making possible the elimination of albumin-bound toxins, while hemodialysis gets rid of water-soluble toxins. The authors' intention was to demonstrate the efficiency of Prometheus treatment in acute liver failure caused by intoxication. Prometheus treatment was indicated in three patients who suffered from severe intoxication with paracetamol, potassium permanganate and Amanita phalloides, which resulted in a hepatic failure incurable with conservative therapy. Ten treatments were performed in the three female patients. No serious complication was observed. Due to the treatment the albumin-bound (indirect bilirubin p = 0.048; bile acid p = 0.001) and water-soluble (direct bilirubin p = 0.002; creatinine p = 0.007) toxins were significantly decreased. The level of ammonia, urea nitrogen, fibrinogen and antithrombin III did not change significantly. All the three patients were cured without liver transplantation. Prometheus treatment removes efficiently the accumulating toxins in acute liver failure. It is a safe elimination technique. In cases untreatable with conservative therapy it makes possible maintaining the patients alive until the liver regenerates spontaneously, or liver transplantation is feasible.

Major Coagulation Disturbances During Fractionated Plasma Separation and Adsorption

Fractionated Plasma Separation and Adsorption (FPSA) is a novel nonbiologic detoxification system for the removal of protein-bound solutes. FPSA is used to bridge patients during fulminant liver failure, either to functional recovery or to liver transplantation. Besides liver failure associated protein bound solutes, several important uremic retention solutes share important protein binding. We observed repeated occlusive thrombosis of the arterio-venous conduit during FPSA in hemodialysis (HD) patients, resulting in acute loss of function. A major reduction of several coagulation factors was demonstrated, exceeding 50% for factor II, factor X and protein C. Broad disturbances of the coagulation system were confirmed in FPSA treated liver failure patients. An ex vivo recirculation model demonstrated nonspecific adsorption of coagulation factors protein S and protein C on the anion exchange cartridge. Direct contact between fractionated plasma and the Prometh02 anion exchanger causes significant adsorption of procoagulant and anti-coagulant factors, associated with clinically relevant adverse events.

Review Article: Clinical Experience With Prometheus

Prometheus is a new extracorporeal liver support device which facilitates the combined removal of both albumin-bound and water-soluble toxins based upon the method of fractionated plasma separation and adsorption (FPSA). The pilot trial included 11 patients with acute-on-chronic liver failure and concomitant renal failure. Prometheus therapy was found to be safe except for a reversible decrease of blood pressure. In three patients, clotting of the secondary system occurred. Prometheus treatment significantly improved blood levels of protein-bound (conjugated bilirubin, bile acids, ammonia) and water-soluble (creatinine, urea) substances. Thus, Prometheus might be a new therapeutic option in patients with severe hepatorenal syndrome. Furthermore, there is some preliminary experience with Prometheus in the treatment of refractory cholestatic pruritus and in successful bridging to liver transplantation. In order to compare extraction capacities of Prometheus and the molecular adsorbent recirculating system (MARS), five patients were crossover-treated with both systems. Prometheus resulted in significantly higher reduction ratios of bilirubin, ammonia and urea. Another study closely monitored whether the device causes an unselective removal. Neither important cytokines nor coagulation factors were found to be removed. In conclusion, Prometheus seems to be a new therapeutic option in artificial liver support. A significant improvement of the biochemical milieu was already observed after two treatments. The potential to remove protein-bound and water-soluble substances has been shown without signs of a significant unselective removal.

Orthotopic Liver Transplantation for Fulminant Hepatic Failure

This paper presents the results of liver transplantation for fulminant hepatic failure in 31 patients qualified as UNOS-1 class (extra-urgent indication for transplantation), operated from January 1989 to April 2005. Twenty-one patients (61.8%) survived the 3-month postoperative period. Three-year survival rate with good liver graft function was 52.9% (18 patients). Before the transplantation, eight patients (23.5%) underwent hepatic dialysis using Fractionated Plasma Separation and Adsorption (FPSA) with the use of a Prometheus 4008H System. Liver transplantation remains the only life-saving procedure for the treatment of fulminant liver failure, regardless of its cause.

A NOVEL DETOXIFICATION DEVICE FOR THE TREATMENT OF HEPATIC FAILURE (HF)

Blood purification in patients with HF remains still difficult as many toxins are strongly hound to albumin. Hence, current systems exhibit low removal efficacy or poor biocompatibility. In this paper we present a novel device, Prometheus, for the removal of toxins derived from HF. Prometheus represents a fractionated plasma separation and adsorption (FPSA) technology. Blood flows through a hollow-fiber filter, Albu-Flow, which enables albumin to enter a closed-loop circuit containing two adsorbent cartridges, prometh 01 and prometh 02. Exposure to adsorbents depletes albumin from toxic substances by direct adsorption. Purified albumin finally re-enters the blood stream, which passes through a downstream high-flux dialyzer for HD. Laboratory investigations revealed effective elimination of HF markers such als unconjugated bilirubin (clearance at 200 ml blood flow: 23 ml/min), cholic acid (48 ml/min), tryptophan (93 ml/min), and phenol (177 ml/min). Removal was selective as albumin, ATIII, fibrinogen, immunoglobulins and other plasma components were not affected. Cellular and humoral indices (e.g., PLT, complement, cytokine induction) proved biocompatibility of the treatment. Fractionated plasma separation with direct adsorption translates into effective, selective and biocompatible blood purification for patients with HF. Preliminary multicenter experience with Prometheus confirms excellent performance and showed easy handling in the clinical setting.