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Steffen Mitzner - One of the best experts on this subject based on the ideXlab platform.

  • extracorporeal liver support Albumin Dialysis with the molecular adsorbent recirculating system mars
    Annals of Hepatology, 2011
    Co-Authors: Steffen Mitzner
    Abstract:

    Extracorporeal liver support has been a much studied topic throughout the last 50 years. Albumin Dialysis as a therapeutic option for patients with acute liver failure or acute decompensation of chronic liver disease was introduced in the mid-nineties. The Molecular Adsorbent Recirculating System (MARS) is based on the concept of Albumin Dialysis and allows for the removal of protein-bound as well as water-soluble toxins. Besides its role as a sufficient volume expander human serum Albumin is an important scavenger for molecules with pathophysiological relevance in liver failure. Albumin Dialysis enables the selective regene

  • extracorporeal liver support Albumin Dialysis with the molecular adsorbent recirculating system mars
    Annals of Hepatology, 2011
    Co-Authors: Steffen Mitzner
    Abstract:

    Extracorporeal liver support has been a much studied topic throughout the last 50 years. Albumin Dialysis as a therapeutic option for patients with acute liver failure or acute decompensation of chronic liver disease was introduced in the mid-nineties. The Molecular Adsorbent Recirculating System (MARS) is based on the concept of Albumin Dialysis and allows for the removal of protein-bound as well as water-soluble toxins. Besides its role as a sufficient volume expander human serum Albumin is an important scavenger for molecules with pathophysiological relevance in liver failure. Albumin Dialysis enables the selective regeneration of patient's Albumin resulting in an increase of Albumin binding capacity. Clinically, an improvement of central and local hemodynamics as well as liver-, brain-, and kidney-functions were observed. Thus, the treatment can contribute to liver regeneration and stabilization of vital organ functions and thus help to bridge patients to liver transplantation or to recovery of native liver function. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive pre-requisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Today, Albumin Dialysis MARS is among the best studied liver support methods. It appears as a valuable therapeutic tool for the treatment of various complications of of liver failure, especially hemodynamic instability and hepatic encephalopathy. Further studies will need to help defining the optimal patient selection and technical process parameters such as session length and frequency of treatment.

  • treatment of thyrotoxic crisis with plasmapheresis and single pass Albumin Dialysis a case report
    Artificial Organs, 2010
    Co-Authors: Sebastian Koball, Jan Stange, Heiko Hickstein, Michael Hinz, Martin Gloger, Jorg Henschel, Steffen Mitzner
    Abstract:

    Thyrotoxic crisis (thyroid storm) is a life-threatening condition. Standard therapy is based on thiamazole, prednisolone, and nonselective beta-blockers. Extracorporeal plasmapheresis is an additional tool for removing circulating thyroxine in patients who do not respond quickly to conventional standard therapy. As thyroxine can be bound by Albumin, the aims of the present therapy report were to investigate the potential of extracorporeal single-pass Albumin Dialysis (SPAD) to remove thyroid hormones and to compare it with plasmapheresis. A 68-year-old female with thyrotoxic crisis refractory to conventional therapy underwent two sessions of plasmapheresis without clinical response. For the treatment dose to be increased, the patient was then treated with a modified continuous veno-venous hemoDialysis with a dialysate containing 4% of human serum Albumin (SPAD) intended to bind and remove thyroxines continuously. In total, the patient received three sessions of plasmapheresis and four SPAD treatments. Thyroxine levels were detected in the patient and in exchanged plasma or Albumin dialysate, respectively, to calculate the amount removed. The main finding was that SPAD treatments were tolerated well by the patient. Due to continuous approach, SPAD sessions removed more thyroid hormone than plasmapheresis did, resulting in the improvement of the clinical status of the patient (reduction of heart rate and catecholamine dosage), which enabled bridging the patient to thyroidectomy as the ultimate surgical treatment. This is the first clinical report of the use of Albumin Dialysis in thyroid storm. SPAD represents a safe and efficient alternative to plasmapheresis as it can be performed continuously in this critical condition.

  • Albumin Dialysis mars knowledge from 10 years of clinical investigation
    Asaio Journal, 2009
    Co-Authors: Steffen Mitzner, S Klammt, Jan Stange, Sebastian Koball, Heiko Hickstein, Emil C Reisinger
    Abstract:

    A decade ago, Albumin Dialysis was introduced as a new extracorporeal detoxification method for patients with liver failure. Today, the molecular adsorbent recirculating system is the most frequently used type of Albumin Dialysis and most studied liver-support technique. Numerous preclinical and clinical studies demonstrated the importance of Albumin as a scavenger for molecules with pathophysiological relevance in liver failure. Albumin Dialysis enables the selective regeneration of Albumin. The resulting increase of Albumin binding capacity is paralleled by improvement of central and local hemodynamics and liver, brain, and kidney functions. The treatment can contribute to liver regeneration and prolongation of patient survival in the context of acute liver failure, decompensated chronic liver disease, and bridging of patients to liver transplantation. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive prerequisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Taken together, Albumin Dialysis represents a valuable therapeutic tool for the treatment of various types of liver failure. Ongoing and future studies will help define the optimal patient selection and technical process parameters such as session length and frequency of treatment.

  • improvement of impaired Albumin binding capacity in acute on chronic liver failure by Albumin Dialysis
    Liver Transplantation, 2008
    Co-Authors: S Klammt, Uwe Heemann, J Loock, Steffen Mitzner, Jan Stange, Emil C Reisinger, Jorg Emmrich, Reinhard Schmidt
    Abstract:

    Extracorporeal Albumin Dialysis (ECAD) enables the elimination of Albumin bound substances and is used as artificial liver support system. Albumin binding function for the benzodiazepine binding site specific marker Dansylsarcosine was estimated in plasma samples of 22 patients with cirrhosis and hyperbilirubinaemia (ECAD: n = 12; control: n = 10) during a period of 30 days in a randomized controlled clinical ECAD trial. Albumin Binding Capacity (ABiC) at baseline was reduced to 31.8% (median; range 24%-74%) and correlated to the severity of liver disease. Within two weeks a significant improvement of ABiC and a reduction of the Albumin bound markers bilirubin and bile acids were observed in the ECAD group. During single treatments a significant decrease of Albumin bound substances (bilirubin and bile acids) as well as an increase in ABiC was observed. In the control group, baseline ABiC was significantly lower in patients who died during study period (34.2% vs. 41.7%; P < 0.028), whereas no significant differences were observed for CHILD, coagulation factors, Albumin, bile acids nor bilirubin. At baseline 13 patients had a severely impaired ABiC (<40%), improvement of ABiC was more frequent in the ECAD group (5/6) than in the SMT group (2/7). Reduced Albumin binding function is present in decompensated liver failure and is related to severity and 30 day survival. ABiC can be improved by ECAD. The beneficial effect of this treatment may be related to the improvement of Albumin binding function more than to the elimination of specific substances. Characterization of Albumin function by the ABiC test may help to evaluate different liver support systems and other therapeutic measures.

Jan Stange - One of the best experts on this subject based on the ideXlab platform.

  • similarities differences and potential synergies in the mechanism of action of Albumin Dialysis using the mars Albumin Dialysis device and the cytosorb hemoperfusion device in the treatment of liver failure
    Blood Purification, 2021
    Co-Authors: Adrian Dominik, Jan Stange
    Abstract:

    Introduction Liver failure is characterized by compromised hepatic detoxification, protein synthesis, and metabolic derangements leading to an accumulation of a broad spectrum of water-soluble and lipophilic toxins as well as immune system mediators. Exploring complex detoxification mechanisms to therapeutically target those components, this article will focus on similarities, differences, and potential synergies in the mechanism of Albumin Dialysis and hemoperfusion. Methods An in vitro two-compartment model for the comparison of liver support techniques was used to compare MARS Albumin Dialysis modified with novel charcoal adsorbents to CytoSorb hemoperfusion with added hemoDialysis for effects on marker molecule removal. Results MARS and CytoSorb performed similar in the removal of water-soluble toxins. Ammonia removal was increased using CytoSorb. CytoSorb lead to a statistically significant reduction of Albumin-bound toxins, total bilirubin and subfractions. Bile acid removal was comparable. MARS demonstrated no removal of cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), whereas CytoSorb allowed for near complete removal. Notably, CytoSorb displayed 50% of lipophilic substance and cytokine removal during the first hour of treatment. Conclusion Compared to MARS, CytoSorb hemoperfusion leads to an initially fast removal of cytokines, TNF-α and IL-6, as well as reduction of Albumin-bound toxins such as indirect bilirubin and bile acids in our model. The initial removal is also associated with removal of Albumin.

  • targeting Albumin binding function as a therapy goal in liver failure development of a novel adsorbent for Albumin Dialysis
    Therapeutic Apheresis and Dialysis, 2018
    Co-Authors: Adrian Dominik, Jan Stange, Claudia Pfensig, Anja K Baumann, Matthias Suraj, Badr Ibrahim, Martin Eggert
    Abstract:

    Liver failure results in impaired hepatic detoxification combined with diminished Albumin synthesis and is associated with secondary organ failure. The accumulation of liver toxins has shown to saturate Albumin binding sites. This was previously demonstrated by an in vitro test for Albumin binding capacity (ABiC) that has shown to inversely correlate with the established MELD (Model for End-Stage Liver Disease) score. In this study, we introduced a new adsorbent material for Albumin Dialysis treatments that improves Albumin binding capacity. The new charcoal adsorbent was developed by an evolutionary test schedule. Batch testing of charcoals was performed as steady-state experiments. The charcoal reflecting the highest increase in Albumin binding capacity was then introduced to kinetic models: Perfusion tests were designed to evaluate adsorption capacity and kinetics for liver failure marker toxins. A dynamic recirculation model for liver failure was used for upscaling and comparison against conventional MARS adsorbents as the gold standard in an Albumin Dialysis setting. Batch tests revealed that powdered activated Hepalbin charcoal displayed the highest ABiC score. Hepalbin charcoal also demonstrated higher adsorptive capacity and kinetics for liver failure marker toxins as determined by perfusion tests. These findings translated to tests of upscaled adsorbents in a dynamic model for liver failure: upscaled Hepalbin adsorbent removes bile acids, direct bilirubin and indirect bilirubin significantly better than MARS adsorbents and significantly increases ABiC. The novel adsorbent Hepalbin offers a significant improvement over both MARS adsorbents concerning liver failure marker toxin removal and ABiC improvement.

  • a new application for Albumin Dialysis in extracorporeal organ support characterization of a putative interaction between human Albumin and proinflammatory cytokines il 6 and tnfα
    Artificial Organs, 2016
    Co-Authors: Claudia Pfensig, Jan Stange, Adrian Dominik, Luise Borufka, Michael Hinz, Martin Eggert
    Abstract:

    Albumin Dialysis in extracorporeal organ support is often performed in the treatment of liver failure as it facilitates the removal of toxic components from the blood. Here, we describe a possible effect of Albumin Dialysis on proinflammatory cytokine levels in vitro. Initially, Albumin samples were incubated with different amounts of cytokines and analyzed by enzyme-linked immunosorbent assay (ELISA). Analysis of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) levels indicated that increased concentrations of Albumin reduce the measureable amount of the respective cytokines. This led to the hypothesis that the used proinflammatory cytokines may interact with Albumin. Size exclusion chromatography of Albumin spiked with cytokines was carried out using high-performance liquid chromatography analysis. The corresponding fractions were evaluated by immunoblotting. We detected Albumin and cytokines in the same fractions indicating an interaction of the small-sized cytokines IL-6 and TNFα with the larger-sized Albumin. Finally, a two-compartment Albumin Dialysis in vitro model was used to analyze the effect of Albumin on proinflammatory cytokines in the recirculation circuit during 6-h treatment. These in vitro Albumin Dialysis experiments indicated a significant decrease of IL-6, but not of TNFα, when Albumin was added to the dialysate solution. Taken together, we were able to show a putative in vitro interaction of human Albumin with the proinflammatory cytokine IL-6, but with less evidence for TNFα, and demonstrated an additional application for Albumin Dialysis in liver support therapy where IL-6 removal might be indicated.

  • reduction of elevated cytokine levels in acute acute on chronic liver failure using super large pore Albumin Dialysis treatment an in vitro study
    Therapeutic Apheresis and Dialysis, 2014
    Co-Authors: Adrian Dominik, Jan Stange, Claudia Pfensig, Luise Borufka, Helga Weissreining, Martin Eggert
    Abstract:

    The removal of small water soluble toxins and Albumin-bound toxins in acute liver failure patients (ALF) or acute-on-chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut-offs should be considered in extracorporeal liver support devices based on Albumin Dialysis in order to address these problems, as the introduction of super-large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment Albumin Dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin-bound toxins were removed more efficiently using novel large (Emic2) to super-large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL-6 and tumor necrosis factor-α was drastically improved using super-large pore membranes. The Emic2 membrane predominantly removed IL-6. In vitro data suggest that the usage of larger pore sized membranes in Albumin Dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super-large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified.

  • treatment of thyrotoxic crisis with plasmapheresis and single pass Albumin Dialysis a case report
    Artificial Organs, 2010
    Co-Authors: Sebastian Koball, Jan Stange, Heiko Hickstein, Michael Hinz, Martin Gloger, Jorg Henschel, Steffen Mitzner
    Abstract:

    Thyrotoxic crisis (thyroid storm) is a life-threatening condition. Standard therapy is based on thiamazole, prednisolone, and nonselective beta-blockers. Extracorporeal plasmapheresis is an additional tool for removing circulating thyroxine in patients who do not respond quickly to conventional standard therapy. As thyroxine can be bound by Albumin, the aims of the present therapy report were to investigate the potential of extracorporeal single-pass Albumin Dialysis (SPAD) to remove thyroid hormones and to compare it with plasmapheresis. A 68-year-old female with thyrotoxic crisis refractory to conventional therapy underwent two sessions of plasmapheresis without clinical response. For the treatment dose to be increased, the patient was then treated with a modified continuous veno-venous hemoDialysis with a dialysate containing 4% of human serum Albumin (SPAD) intended to bind and remove thyroxines continuously. In total, the patient received three sessions of plasmapheresis and four SPAD treatments. Thyroxine levels were detected in the patient and in exchanged plasma or Albumin dialysate, respectively, to calculate the amount removed. The main finding was that SPAD treatments were tolerated well by the patient. Due to continuous approach, SPAD sessions removed more thyroid hormone than plasmapheresis did, resulting in the improvement of the clinical status of the patient (reduction of heart rate and catecholamine dosage), which enabled bridging the patient to thyroidectomy as the ultimate surgical treatment. This is the first clinical report of the use of Albumin Dialysis in thyroid storm. SPAD represents a safe and efficient alternative to plasmapheresis as it can be performed continuously in this critical condition.

S Klammt - One of the best experts on this subject based on the ideXlab platform.

  • molecular adsorbent recirculating system and single pass Albumin Dialysis in liver failure a prospective randomised crossover study
    Critical Care, 2015
    Co-Authors: Christoph Sponholz, S Klammt, U Settmacher, Katja Matthes, Dina Rupp, Wolf Backaus, Diana Karailieva, A Bauschke, Matthias Kohl, Mark G Clemens
    Abstract:

    The 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. Patients 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. Sixty-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. Both 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. German Clinical Trials Register ( www.drks.de ) DRKS00000371 . Registered 8 April 2010.

  • Albumin Dialysis mars knowledge from 10 years of clinical investigation
    Asaio Journal, 2009
    Co-Authors: Steffen Mitzner, S Klammt, Jan Stange, Sebastian Koball, Heiko Hickstein, Emil C Reisinger
    Abstract:

    A decade ago, Albumin Dialysis was introduced as a new extracorporeal detoxification method for patients with liver failure. Today, the molecular adsorbent recirculating system is the most frequently used type of Albumin Dialysis and most studied liver-support technique. Numerous preclinical and clinical studies demonstrated the importance of Albumin as a scavenger for molecules with pathophysiological relevance in liver failure. Albumin Dialysis enables the selective regeneration of Albumin. The resulting increase of Albumin binding capacity is paralleled by improvement of central and local hemodynamics and liver, brain, and kidney functions. The treatment can contribute to liver regeneration and prolongation of patient survival in the context of acute liver failure, decompensated chronic liver disease, and bridging of patients to liver transplantation. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive prerequisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Taken together, Albumin Dialysis represents a valuable therapeutic tool for the treatment of various types of liver failure. Ongoing and future studies will help define the optimal patient selection and technical process parameters such as session length and frequency of treatment.

  • improvement of impaired Albumin binding capacity in acute on chronic liver failure by Albumin Dialysis
    Liver Transplantation, 2008
    Co-Authors: S Klammt, Uwe Heemann, J Loock, Steffen Mitzner, Jan Stange, Emil C Reisinger, Jorg Emmrich, Reinhard Schmidt
    Abstract:

    Extracorporeal Albumin Dialysis (ECAD) enables the elimination of Albumin bound substances and is used as artificial liver support system. Albumin binding function for the benzodiazepine binding site specific marker Dansylsarcosine was estimated in plasma samples of 22 patients with cirrhosis and hyperbilirubinaemia (ECAD: n = 12; control: n = 10) during a period of 30 days in a randomized controlled clinical ECAD trial. Albumin Binding Capacity (ABiC) at baseline was reduced to 31.8% (median; range 24%-74%) and correlated to the severity of liver disease. Within two weeks a significant improvement of ABiC and a reduction of the Albumin bound markers bilirubin and bile acids were observed in the ECAD group. During single treatments a significant decrease of Albumin bound substances (bilirubin and bile acids) as well as an increase in ABiC was observed. In the control group, baseline ABiC was significantly lower in patients who died during study period (34.2% vs. 41.7%; P < 0.028), whereas no significant differences were observed for CHILD, coagulation factors, Albumin, bile acids nor bilirubin. At baseline 13 patients had a severely impaired ABiC (<40%), improvement of ABiC was more frequent in the ECAD group (5/6) than in the SMT group (2/7). Reduced Albumin binding function is present in decompensated liver failure and is related to severity and 30 day survival. ABiC can be improved by ECAD. The beneficial effect of this treatment may be related to the improvement of Albumin binding function more than to the elimination of specific substances. Characterization of Albumin function by the ABiC test may help to evaluate different liver support systems and other therapeutic measures.

  • Albumin regeneration in liver support comparison of different methods
    Therapeutic Apheresis and Dialysis, 2006
    Co-Authors: Steffen Mitzner, S Klammt, Jan Stange, Reinhart Schmidt
    Abstract:

    Abstract:  Albumin is the most abundant human plasma protein. Among many other functions it is an important transporter of hydrophobic internal and external substances such as intermediate and end products of metabolism and drugs. In liver failure the Albumin binding capacity is decreased because of a disproportion between available Albumin molecules caused by decreased hepatic synthesis and hydrophobic toxins because of decreased hepatic clearance. The resulting increase in plasma and tissue concentrations of these substances is associated with multiple organ dysfunctions frequently seen in severe liver failure. The scope of the present article is to compare different liver support strategies with regard to their ability to regenerate the patients Albumin pool by removing Albumin-bound toxins. Most prominent technique in this group is the molecular adsorbent recirculating system (MARS). It will be compared with single pass Albumin Dialysis (SPAD), fractionated plasma separation and adsorption system (FPSA, Prometheus), and plasma perfusion/bilirubin adsorption with special regard to efficacy and selectivity.

  • Albumin Dialysis in cirrhosis with superimposed acute liver injury a prospective controlled study
    Hepatology, 2002
    Co-Authors: Uwe Heemann, U Treichel, J Loock, Thomas Philipp, Guido Gerken, Massimo Malago, S Klammt, Matthias Loehr, S Liebe, Steffen Mitzner
    Abstract:

    Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal Albumin Dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% Albumin. Albumin-bound molecules transfer to dialysate Albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P < .05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.

Rajiv Jalan - One of the best experts on this subject based on the ideXlab platform.

  • extracorporeal Albumin Dialysis with the molecular adsorbent recirculating system in acute on chronic liver failure the relief trial
    Hepatology, 2013
    Co-Authors: Frederik Nevens, Fin Stolze Larsen, Faouzi Saliba, Rajiv Jalan, Rafael Banares, Agustin Albillos, M M Dollinger, T Sauerbruch
    Abstract:

    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. Conclusion: 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. (HEPATOLOGY 2013)

  • out patient Albumin Dialysis for cholestatic patients with intractable pruritus
    Alimentary Pharmacology & Therapeutics, 2012
    Co-Authors: P Leckie, Giovanni Tritto, Rajeshwar P Mookerjee, Nathan Davies, David Jones, Rajiv Jalan
    Abstract:

    Summary Background Intractable pruritus is a major problem for some patients with cholestasis. Albumin Dialysis has been shown to ameliorate pruritus, but long-term outcome data are limited. Aim To evaluate the safety and efficacy of ‘out-patient’ Albumin Dialysis using the molecular adsorbent recirculating system (MARS) in the treatment of intractable pruritus in cholestatic patients referred for liver transplantation for symptomatic relief. Methods Fifteen patients who failed to respond to standard medical therapy to control pruritus were included. Three MARS (6 h) sessions were performed per admission, and were repeated, if necessary. The intensity and severity of itch was quantified using itch severity and visual analogue scales (ISS and VAS). Results Molecular adsorbent recirculating system treatment was safe and associated with immediate and complete response in 11 patients; two patients had a partial response and two patients had no response. Thirty-four treatments were performed during a follow-up period of 15.7 months (3–46) with patients requiring a mean of two admissions (1–6). The mean VAS and ISS improved significantly (both P < 0.001) with improvement in the patient's perception of their quality of life. The duration of acceptable relief in responders was 3.3 months (range 2–5). No serious adverse events were recorded, but the platelet count and haemoglobin were reduced significantly. Conclusion Molecular adsorbent recirculating system therapy delivered in an ‘out-patient’ setting is safe and effective with a high degree of patient acceptability. Albumin Dialysis can be considered a viable therapeutic option for patients with severe intractable pruritus, in whom, the only other effective treatment option is liver transplantation.

  • Albumin Dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis
    Journal of Hepatology, 2005
    Co-Authors: Sambit Sen, Rajeshwar P Mookerjee, Nathan Davies, Roger Williams, L Cheshire, Rajiv Jalan
    Abstract:

    Background/Aims In patients with alcoholic hepatitis (AH), inflammation contributes to the severity of portal hypertension. This study evaluates the acute effects of Albumin Dialysis, using the Molecular Adsorbents Recirculating System (MARS), on portal pressure in AH. Methods Eleven patients with AH and portal hypertension were treated with MARS (n=8) or haemofiltration (n=3). All patients had associated organ failure manifested by hepatic encephalopathy (Grade 2 or more) or renal failure. Hepatic venous pressure gradient (HVPG) was measured before, during and after the treatment session. Results A rapid significant reduction of HVPG was observed by 6 h (falling by ≥20% in 7/8 patients, reaching 12 mmHg in 6/8), which was sustained up to 18 h after stopping Dialysis. Similar rapid sustained improvements of systemic haemodynamics were also observed. No changes occurred in three patients receiving haemofiltration alone. Conclusions Albumin Dialysis produces clinically significant, acute reduction in portal pressure but the mechanism by which this effect is achieved is not clear. Our results suggest that MARS may be a useful adjunct in management of portal hypertension, particularly in patients with severe AH with associated organ failure.

  • binding of bilirubin and bromosulphthalein to Albumin implications for understanding the pathophysiology of liver failure and its management
    Liver Transplantation, 2004
    Co-Authors: Christian Steiner, Jan Stange, Sambit Sen, Roger Williams, Rajiv Jalan
    Abstract:

    The binding/transporting functions of Albumin provide the rationale for using Albumin Dialysis (e.g., molecular adsorbents recirculating system [MARS]) in liver failure. This study investigates these properties in vitro, validating the findings in vivo. In vitro bromosulphthalein (BSP) and bilirubin-spiked plasma were dialyzed against Albumin and sampled. In vivo serum biochemistry was analyzed in: 7 MARS-treated liver failure patients; 98 MARS-treated patients from the MARS Registry; and 8 patients receiving Albumin infusion. In vitro BSP concentrations did not equilibrate, but the molar ratio of BSP to Albumin (CBSP/Calb) did, with no subsequent transmembrane transport, suggesting that the CBSP/Calb gradient (rather than simple diffusion) drives BSP transport. Bilirubin was transported similarly. In vivo serum bilirubin reduction during MARS sessions (n = 26) correlated with pre-treatment bilirubin (r = 0.42), but better (r = 0.85) with pre-treatment molar ratio of bilirubin to Albumin (Cbilirubin/Calb). The strongest correlation was between Cbilirubin/Calb reduction and pre-treatment Cbilirubin/Calb (r = 0.9). A similar pattern was observed in the MARS Registry patients. After Albumin infusion (n = 8), both serum Albumin and bilirubin increased, while Cbilirubin/Calb remained unchanged. Cbilirubin/Calb appears to be important in Albumin Dialysis, and generally in liver disease patients, reinforcing the importance of the toxin-binding functions of Albumin in liver disease. (Liver Transpl 2004;10:1531–1538.)

  • pathophysiological effects of Albumin Dialysis in acute on chronic liver failure a randomized controlled study
    Liver Transplantation, 2004
    Co-Authors: Sambit Sen, Rajeshwar P Mookerjee, Nathan Davies, Roger Williams, L Cheshire, Stephen J Hodges, Rajiv Jalan
    Abstract:

    The pathophysiological basis of acute-on-chronic liver failure (ACLF) is unclear but systemic inflammatory response is thought to be important. In patients with ACLF, the molecular adsorbents recirculating system (MARS) improves individual organ function, but the effect of MARS on the proposed mediators of systemic inflammatory response is unclear. The present study was designed to determine the effect of MARS on the cytokine profile, oxidative stress, nitric oxide, and ammonia. A total of 18 patients with alcohol-related ACLF due to inflammation-related precipitants were randomized to receive standard medical therapy (SMT) alone, or with MARS therapy over 7 days. Plasma cytokines, malondialdehyde (MDA), free radical production, nitrate / nitrite (NOx), and ammonia were measured. Encephalopathy improved significantly with MARS (P < .01), but not with SMT. Mean arterial pressure and renal function remained unchanged. No significant change of plasma cytokines and ammonia levels were observed in either group. Plasma MDA levels did not change either. There was a fall in NOx (P < .05) with MARS, but not with SMT. In conclusion, in inflammation-related ACLF patients, Albumin Dialysis using MARS results in improvement of encephalopathy, independent of changes of ammonia or cytokines, without improving blood pressure or renal function. These results should temper the liberal use of MARS until further data is available. (Liver Transpl 2004;10:1109–1119.)

Constantine J Karvellas - One of the best experts on this subject based on the ideXlab platform.

  • a case control study of single pass Albumin Dialysis for acetaminophen induced acute liver failure
    Blood Purification, 2009
    Co-Authors: Constantine J Karvellas, Vincent G Bain, Sean M Bagshaw, Robert C Mcdermid, Daniel E Stollery, R Noel T Gibney
    Abstract:

    Background: Extracorporeal support with single-pass Albumin Dialysis (SPAD) may remove protein-bound toxins in acute liver failure. We evaluated the clinical, physiological and labo

  • acetaminophen induced acute liver failure treated with single pass Albumin Dialysis report of a case
    International Journal of Artificial Organs, 2008
    Co-Authors: Constantine J Karvellas, Sean M Bagshaw, Robert C Mcdermid, Daniel E Stollery, R T N Gibney
    Abstract:

    Background: Acetaminophen (paracetamol) overdose is a leading cause of acute liver failure (ALF). When patients fulfill the King's College criteria for acetaminophen-induced ALF (AALF), they have a poor prognosis for survival without liver transplantation. Recent advances in artificial liver support have used Albumin as a binding and scavenging molecule in ALF. One method, single-pass Albumin Dialysis (SPAD), involves dialyzing blood against an Albumin-containing solution across a high-flux membrane to remove Albumin-bound toxins. Herein, we describe our protocol for SPAD and report its use in a case of AALF as a bridge to native liver recovery. Case: A 41-year-old female with no documented history of liver disease presented with acute aceta- minophen toxicity and developed hepatic encephalopathy, coagulopathy and lactic acidosis. The pa- tient met King's College criteria for liver transplantation, based on pH and INR, but was deemed not suitable as aa candidate due to psychosocial comorbidities. On day 3 of her ICU admission, she re- ceived the first of five consecutive daily runs (total ~77 hours) of SPAD. The patient's course was complicated by cerebral edema requiring mannitol. She was extubated on day 11 and transferred to the ward by day 13. At ICU discharge, her liver function (INR 1.9, bilirubin 435 mmol/L) and kidney function were recovering. She did not have any long-term neurological sequelae. By hospital dis- charge (day 46) her native liver function had recovered with a bilirubin <100mmol/L. Conclusion: We describe a case of a patient with acetaminophen-induced acute liver failure who was successfully bridged to spontaneous native liver recovery as a result of SPAD treatment. In pa- tients with ALF, SPAD may be an additional intervention for temporary extracorporeal support. Fur- ther investigation in larger prospective studies is warranted.

  • bench to bedside review current evidence for extracorporeal Albumin Dialysis systems in liver failure
    Critical Care, 2007
    Co-Authors: Constantine J Karvellas, Noel Gibney, Demetrios J Kutsogiannis, Julia Wendon, Vincent G Bain
    Abstract:

    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.