Extracorporeal Albumin Dialysis Research Articles

#3067 Comparison of the removal of bile acids between hemoperfusion and new extracorporeal albumin detoxification device (Albunique) in critical care

Abstract Background and Aims In subjects with multiorgan failure and in need for CRRT, new onset of jaundice is associated with a significant mortality. Recent research suggests that elevated serum bile acids contribute to severe immune dysfunction, hepatocellular apoptosis, vasodilation, tubular necrosis and thereby are important drivers of multi-organ failure in new onset of liver dysfunction. Extracorporeal Albumin Detoxification and Dialysis (ECAD) and Hemoperfusion have been used to sustain or recover organ function. Recently, Cytosorb, a hemoperfusion device developed for the removal of proinflammatory molecules in cytokine storm showed a reduction of bilirubin and bile acids in vitro. The aim of this study was to compare the reduction of small albumin bound bile acids with the current standard (ECAD), which was developed not to affect the plasma proteome but effectively remove toxins. Method After obtaining consent, plasma samples were obtained from the extracorporeal circuit of subjects on CRRT due to acute on chronic liver failure (ACLF) and bile acids above 50 µmol/l before and after a day of treatment from the venous and arterial ports and the total removed bile acids were calculated by Area under the curve calculation. The measurements were done during Cytosorb treatments versus during ECAD using a new Albunique Device based on a new recycling technology. Results Despite a high initial reduction rate the capacity of Cytosorb decreased and the total amount of extracorporeal removal was 1720+1189 µmol whereas Albunique removed 7111+2556 µmol, more than 4 times as much and was not saturated after 24 hours. Conclusion Although Cytosorb may prove a role in ACLF with hyperinflammation in the future, hemoperfusion appears to loose efficacy for toxic, albumin bound small molecules and therapies based on diffusion appear to be more cost effective and less additional effects with an unclear impact on the course of ACLF.

Extracorporeal albumin dialysis in critically ill patients with liver failure: Comparison of four different devices-A retrospective analysis.

Besides standard medical therapy and critical care monitoring, extracorporeal liver support may provide a therapeutic option in patients with liver failure. However, little is known about detoxification capabilities, efficacy, and efficiency among different devices. Retrospective single-center analysis of patients treated with extracorporeal albumin dialysis. Generalized Estimating Equations with robust variance estimator were used to account for repeated measurements of several cycles and devices per patient. Between 2015 and 2021 n = 341 cycles in n = 96 patients were eligible for evaluation, thereof n = 54 (15.8%) treatments with Molecular Adsorbent Recirculating System, n = 64 (18.7%) with OpenAlbumin, n = 167 (48.8%) Advanced Organ Support treatments, and n = 56 (16.4%) using Single Pass Albumin Dialysis. Albumin dialysis resulted in significant bilirubin reduction without differences between the devices. However, ammonia levels only declined significantly in ADVOS and OPAL. First ECAD cycle was associated with highest percentage reduction in serum bilirubin. With the exception of SPAD all devices were able to remove the water-soluble substances creatinine and urea and stabilized metabolic dysfunction by increasing pH and negative base excess values. Platelets and fibrinogen levels frequently declined during treatment. Periprocedural bleeding and transfusion of red blood cells were common findings in these patients. From this clinical perspective ADVOS and OPAL may provide higher reduction capabilities of liver solutes (i.e. bilirubin and ammonia) in comparison to MARS and SPAD. However, further prospective studies comparing the effectiveness of the devices to support liver impairment (i.e. bile acid clearance or albumin binding capacity) as well as markers of renal recovery are warranted.

Artificial liver support in patients with liver failure: a modified DELPHI consensus of international experts.

The present narrative review on albumin dialysis provides evidence-based and expert opinion guidelines for clinicians caring for adult patients with different types of liver failure. The review was prepared by an expert panel of 13 members with liver and ntensive care expertise in extracorporeal liver support therapies for the management of patients with liver failure. The coordinating committee developed the questions according to their importance in the management of patients with liver failure. For each indication, experts conducted a comprehensive review of the literature aiming to identify the best available evidence and assessed the quality of evidence based on the literature and their experience. Summary statements and expert's recommendations covered all indications of albumin dialysis therapy in patients with liver failure, timing and intensity of treatment, efficacy, technical issues related to the device and safety. The panel supports the data from the literature that albumin dialysis showed a beneficial effect on hepatic encephalopathy, refractory pruritus, renal function, reduction of cholestasis and jaundice. However, the trials lacked to show a clear beneficial effect on overall survival. A short-term survival benefit at 15 and 21 days respectively in acute and acute-on-chronic liver failure has been reported in recent studies. The technique should be limited to patients with a transplant project, to centers experienced in the management of advanced liver disease. The use of extracorporeal albumin dialysis could be beneficial in selected patients with advanced liver diseases listed for transplant or with a transplant project. Waiting future large randomized controlled trials, this panel experts' statements may help careful patient selection and better treatment modalities.

Influence of Advanced Organ Support (ADVOS) on Cytokine Levels in Patients with Acute-on-Chronic Liver Failure (ACLF).

Background: ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis that supports multiorgan function in patients with acute-on-chronic liver failure (ACLF). No data exist on whether ADVOS affects inflammatory cytokine levels, which play a relevant role in ACLF. Aim: Our aim was to quantify cytokine levels both before and after a single ADVOS treatment in patients with ACLF at a regular dialysis ward. Methods and results: In this prospective study, 15 patients (60% men) with ACLF and an indication for renal replacement therapy were included. Patient liver function was severely compromised, reflected by a median CLIF-consortium ACLF score of 38 (IQR 35; 40). Blood samples were directly taken before and after ADVOS dialysis. The concentration of cytokines for IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 were quantified via a cytometric bead array. We found no significant (p > 0.05) change in cytokine levels, even when patients were stratified for dialysis time (<480 min versus ≥480 min). The relevance of the assessed cytokines in contributing to systemic inflammation in ACLF was demonstrated by Ingenuity pathway analysis®. Conclusion: Concentrations of pathomechanistically relevant cytokines remained unchanged both before and after ADVOS treatment in patients with ACLF.

Extracorporeal Albumin Dialysis in Liver Failure with MARS and SPAD: A Randomized Crossover Trial

Introduction: Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). Methods: We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 μmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. Results: Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (−83 ± 67 μmol/L after MARS; −122 ± 118 μmol/L after SPAD session), conjugated bilirubin (−82 ± 61 μmol/L after MARS; −105 ± 96 μmol/L after SPAD session), and bile acid levels (−64 ± 75 μmol/L after MARS; −56 ± 56 μmol/L after SPAD session), all nondifferent comparing MARS to SPAD. Conclusion: A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.

Applicability and safety of discontinuous ADVanced Organ Support (ADVOS) in the treatment of patients with acute-on-chronic liver failure (ACLF) outside of intensive care

ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis and holds promise to sustain liver function and recovery of patients with acute-on-chronic liver failure (ACLF). Previously, ADVOS was tested as continuous treatment for intensive care patients with liver failure. Data related to the applicability and safety as discontinuous treatment outside of ICU is not available. Evaluation of ADVOS as discontinuous treatment for patients with ACLF outside intensive care unit and comparison with a matched historic cohort. In this retrospective study, 26 patients with ACLF and the indication for renal replacement therapy related to HRS-AKI were included. Majority of patients were male (65%) with alcoholic cirrhosis in 88% and infections as a trigger of ACLF in 96%. Liver function was severely compromised reflected by high median MELD and CLIF-C ACLF scores of 37 (IQR 32;40) and 56.5 (IQR 51;60), respectively. Patients were treated discontinuously with ADVOS over a median time of 12 days (IQR 8.25;17) and received 8 (IQR 4.25;9.75) treatment cycles on average. No treatment related adverse events were recorded, and safety laboratory parameters remained constant during the observation time. After 16 h cumulative dialysis therapy, ADVOS significantly reduced protein-bound bilirubin (14%), creatinine (11.8%) and blood urea nitrogen (BUN, 33%). Using a matched cohort with ACLF treated with hemodialysis, ADVOS achieved a stronger decrease in bilirubin (p = 0.01), while detoxification of water-soluble catabolites' including creatinine and BUN was comparable. The 28-days mortality in the ADVOS group was 56% (14/26) and was not inferior to predicted survival (predicted median 28-days mortality was 44%, IQR 30; 59). Discontinuous ADVOS treatment was safe and effective in patients with ACLF outside intensive care and outperformed hemodialysis in reducing protein-bound metabolites.

EUS-Guided Micro-Forceps Biopsy for the Diagnosis of Lymphoma: A Case Series

Extracorporeal Albumin Dialysis (ECAD) is a therapy option for pruritus in cholestatic liver disease. The aim was to evaluate the feasibility for ECAD using two different devices. A subgroup with intractable pruritus of a prospective randomized crossover study in liver patients was analyzed. Randomly subjects received either MARSTM first and new HepalbinTMCluster12 albumin dialysis (OPALTM) second or vice versa. Visual Analogue Score, total bile acids as well as albumin binding function were measured before and after each treatment. 8 subjects suffering from cholestatic liver disease and pruritus were enrolled. Subjects in both arms were comparable. Albumin dialysis could reduce albumin bound toxins, the binding function of patient’s albumin improved in OPAL, but not in MARS. Which one of the biomarker changes are responsible for the improvement of pruritus remains unknown and requires more research. The procedure was safe in all subjects.

HEPATORENAL SYNDROME WITH ACUTE RENAL FAILURE IN PATIENTS WITH CHRONIC LIVER DISEASE: MODERN ASPECTS OF CLINICAL PRESENTATION AND INTENSIVE CARE

Introduction.Acute renal failure is considered a functional, progressive, oliguric, but reversible kidney disease that occurs due to severe liver disease with hepatic insufficiency. In the development of the syndrome, the leading role is played by the “classical hypothesis of peripheral vasodilation”. Important differentiation in verification of diagnosis is primarily with pseudo hepatorenal syndrome. In the type I (of hepatorenal syndrome) mortality in the first 10 days without an adequate management in intensive care unit is extremely high. The chronic, type II, is a slow process, but requires adequate therapy for up to six months. In general, all clinical manifestations of hepatorenal syndrome are combined into three groups: cardiac insufficiency, systemic vasodilation, and vasoconstriction of renal vessels. The goals of the therapy include restoration of blood flow through the vessels, management of inflammatory processes, prevention of further hepatic tissue destruction, and stabilization of arterial blood pressure in kidney vessels. The core in medical management is adequate albumin infusion and minimal crystalloid support of blood volume, vasopressors, adequate antidote and antibacterial therapy. Additional methods include extracorporeal albumin dialysis to bridge patient to liver transplantation. The orthotopic liver transplantation is the established surgical treatment, as well as transjugular intrahepatic portosystemic shunt (TIPS) or peritoneovenous shunt. Survival rate of patients with hepatorenal syndrome type I on terlipressin in patients with hypoalbuminemia correction is close to 60–75%; survival of with hepatorenal syndrome type II is more favorable in most cases.Methods. The literature review examines diagnostics possibilities of hepatorenal syndrome, importance of timely relevant differential diagnoses and adequate intensive care management.Conclusion. The differential diagnosis between hepatorenal syndrome and pseudo hepatorenal syndrome remains a challenge in routine diagnostic examinations. Intensive care management of such patients requires immediate treatment, which may not be always the most appropriate option. The refore new strategies are needed to improve management of this medical condition.

Hyperthyroidism with Severe Liver Dysfunction Can Be Managed by RAI and Extracorporeal Albumin Dialysis and Hemodialysis

Clinical ThyroidologyVol. 29, No. 4 SummariesHyperthyroidism with Severe Liver Dysfunction Can Be Managed by RAI and Extracorporeal Albumin Dialysis and HemodialysisJacques OrgiazziJacques OrgiazziSearch for more papers by this authorPublished Online:1 Apr 2017https://doi.org/10.1089/ct.2017;29.153-156AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 29Issue 4Apr 2017 InformationCopyright 2017 American Thyroid Association, Inc.To cite this article:Jacques Orgiazzi.Hyperthyroidism with Severe Liver Dysfunction Can Be Managed by RAI and Extracorporeal Albumin Dialysis and Hemodialysis.Clinical Thyroidology.Apr 2017.153-156.http://doi.org/10.1089/ct.2017;29.153-156Published in Volume: 29 Issue 4: April 1, 2017PDF download

Molecular adsorbent recirculating system and single-pass albumin dialysis in liver failure--a prospective, randomised crossover study.

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.

No sustained impact of intermittent extracorporeal liver support on thrombocyte time course in a randomized controlled albumin dialysis trial.

Reduction of platelets is a common finding in patients with liver disease and can be aggravated by extracorporeal therapies, e.g. artificial liver support. The impact of extracorporeal albumin dialysis on the time count and time course of platelets in liver failure patients was evaluated in a randomized controlled clinical trial. Mean thrombocyte reduction during a single extracorporeal liver support therapy was -15.1% [95%CI: -17.7; -12.5]. No differences were found between treatments of patients with a more reduced platelet count (<100 GPT/L: -15.6% [-19.5; -11.7%]; n = 43) compared to patients with normal or slightly decreased thrombocytes (-14.6% [-18.3%; -11.0%]; n = 43; P = 0.719). The variation of platelet count within 24 h after onset of extracorporeal therapy treatment was less, albeit significant (-3.5% [-6.3%; -0.7%], P < 0.016). Absolute thrombocyte variability was comparable between both groups (with extracorporeal therapy -5.6 GPT/L [-9.7; -1.4], without extracorporeal therapy -1.3 GPT/L [-7.3; 4.7]; P = 0.243), whereas relative decrease of thrombocytes within a 24-h period of extracorporeal therapy was greater than the changes in patients without extracorporeal therapy (-3.5% [-6.3%; -0.7%] vs. 2.0% [-2.0%; 5.9%]; P = 0.026]. Within a period of two weeks after enrollment, no significant differences of platelet count were observed either between the two groups or in the time course (P(group) = 0.337, P(time) = 0.277). Reduction of platelets during intermittent extracorporeal liver support was less pronounced within a 24-h period as before and after a single treatment and was comparable to variations in the control group without extracorporeal therapy.

Fulminant hepatitis E in a pregnant woman

Hepatitis E is an inflammatory liver disease caused by hepatitis E virus (HEV) infection, which is endemic in China, India, Nepal, and in several Asian and African countries, where the prevalence can be as high as 50%. In non-endemic countries, an increasing number of non-travel associated HEV has been reported in recent years, particularly in Europe.The authors describe the clinical case of a puerperal 24-year-old woman from Pakistan admitted to our Tertiary Care Medical Center with acute hepatic failure developed during the third trimester of her pregnancy. She was icteric with grade III encephalopathy and hypothermia. Laboratory values showed significant AST, ALT and LDH elevations of twelve times the upper normal limit, and total bilirubin was significantly elevated (41.20mg/dL). Prothrombin time was prolonged (4s) and factor V activity was diminished (15.1%). Extracorporeal albumin dialysis was initiated, but clinical deterioration occurred within 48h, so she underwent OLT at day 4 post-admission.Severe forms of HEV are known to be more pronounced in pregnant women. Even though most of the described cases of acute hepatic failure associated to HEV during pregnancy had a favorable clinical course, some cases of fulminant liver failure and death are described. It is unknown whether liver transplant outcomes in this setting are different from other causes of acute liver failure. To our knowledge, this is the first case report in Portugal from a pregnant woman who developed hepatic failure due to fulminant hepatitis E that underwent successful liver transplantation.

24‐Hour Performance of Albumin Dialysis Assessed by a New Two‐Compartment In Vitro Model

Extracorporeal albumin dialysis as a measure to remove water soluble and protein bound toxins simultaneously has been shown to improve complications of liver failure. However, recent research suggests that only treatments associated with a measurable improvement of patient's albumin binding function by effective removal of albumin bound toxins leads to better survival. The aim of the present work was to develop a test platform for upcoming devices to evaluate long term effectiveness on toxin removal and improvement of patients' albumin binding capacity. The classical one compartment model consisting of a closed pool of toxin spiked plasma was combined with continuous infusion of water soluble and protein bound toxins mimicking physiological rebound rates reflected in the literature. The model was used to demonstrate the effect of stabilizer contamination of dialysate albumin on toxin clearance and albumin binding function. In comparison to the classical one compartment model, the two compartment model allows for long term effectiveness tests of liver assist devices not only for strongly albumin-bound, but also water-soluble molecules. The limitations of commercial albumin overloaded with caprylate ligands (5:1 molar ratio) were demonstrated by presenting a significant improvement of albumin binding function using 80 g deligandized albumin compared to no significant improvement using the standard 120 g albumin as dialysate. The new two compartment model allows for pre-clinical evaluation of new upcoming devices aiming for improvement of patients' albumin binding function as a measure for clinically meaningful extracorporeal detoxification of albumin-bound toxins.

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

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

Cholestatischer Pruritus

Pruritus is a common symptom of hepatobiliary disorders and may considerably diminish quality of life. Cholestatic pruritus exerts a circadian rhythm and is typically most severe in the evening hours and early at night. Itching is reported often to be most intense at the palms and the soles, but may also be generalized. The pathophysiological mechanisms of cholestatic pruritus have not been completely clarified. In the past, bile salts, histamine, progesterone metabolites and opioids have been discussed as potential causal substances; a correlation with itch intensity could never be proven. The enzyme autotaxin, which releases lysophosphatidic acid, has recently been identified as potential cholestatic pruritogen. Treatment aims to bind pruritogens in the gut lumen by resins such as cholestyramine, to modulate pruritogen metabolism by rifampicin and to influence central itch signaling by µ-opioid antagonists and selective serotonin re-uptake inhibitors. In cases of refractory pruritus experimental treatment options such as UV-therapy, extracorporeal albumin dialysis and nasobiliary drainage may be considered.

Proteomic Analysis of Polypeptides Captured from Blood during Extracorporeal Albumin Dialysis in Patients with Cholestasis and Resistant Pruritus

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.

Effects of Intraperitoneal Albumin on Systemic and Cerebral Hemodynamics in a Swine Model of Acute Liver Failure

ABSTRACTBackground: Currently, albumin dialysis is the most widely used nonbiological liver support system. We hypothesized that direct peritoneal albumin exposure in the peritoneal cavity would stabilize blood flow and prevent liver and brain injury, in the same way that had previously been seen with extracorporeal albumin dialysis systems. Materials and Methods: Fourteen Landrace pigs (weight 25–30 kg) underwent 70% right hepatectomy and were randomly assigned into a control (C, n = 7) and an intraperitoneal albumin treated group (A, n = 7). The systemic, cerebral, and pulmonary hemodynamic parameters of the animals were recorded at 0, 6, 9, and 12 hr following reperfusion of the liver remnant. Results: Mean arterial blood pressure, cardiac output, and stroke volume were significantly higher in group A at the end of the experiment. Significantly higher mean intracranial pressure (ICP) values were observed in group C compared to group A, both at 9 hr (21.3 ± 5.2 versus 14.1 ± 3.5 mmHg, p < .0005) and 12 hr (23 ± 4.3 versus 11 ± 3.5 mmHg, p < .0005). On the contrary, cerebral perfusion pressure (CPP) remained stable in albumin-treated groups after the sixth postreperfusion hour. Mean pulmonary artery pressure and pulmonary vascular resistance (PVR) were significantly lower in group A compared to group C at 12 hr, while pulmonary capillary wedge pressure (PCWP) stabilized in albumin-treated animals. Conclusions: This study provides the first evidence that intraperitoneal albumin may be able to attenuate systemic, pulmonary, and cerebral hemodynamic disturbances associated with acute liver failure.

Treatment of Thyrotoxic Crisis With Plasmapheresis and Single Pass Albumin Dialysis: A Case Report

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.

Liver Transplantation Avoided in Patients With Fulminant Hepatic Failure Who Received Albumin Dialysis With the Molecular Adsorbent Recirculating System While on the Waiting List: Impact of the Duration of Therapy

Eighteen patients with fulminant hepatic failure due to various medical causes were listed for emergency liver transplantation and treated with extracorporeal albumin dialysis sessions using the molecular adsorbent recirculating system (MARS) at our center over a 74-month period. Due to improvement of liver function, transplantation could be avoided in 9 patients (50%, 95% confidence interval 29% to 71%) who fully recovered afterwards. This improvement rate was higher than the rate of improvement in the French cohort of fulminant hepatic failure patients with similar etiologies (19.3%, 95% confidence interval 14.9% to 24.6%, P = 0.002). In our 18 patients, there were no statistically significant differences in any baseline characteristics or in the time with liver failure meeting transplant criteria between the patients who improved while waiting and those who did not. However, the patients who improved received a greater number of sessions and a longer total duration of MARS therapy (all P < 0.001). In the whole study population, a MARS therapy duration > or =15 h was significantly associated with improvement of liver function without transplantation (adjusted adds ratio [OR] 65.76, 2.48-1743.11, P = 0.01). Tolerance of therapy was acceptable. These results suggest that MARS therapy could contribute to native liver recovery and is safe in patients on the waiting list for fulminant hepatic failure. A minimum duration of therapy (> or =15 h) could be necessary to expect significant liver function improvement.

Increase of Octanoate Concentrations During Extracorporeal Albumin Dialysis Treatments

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.