The Effect of Molecular Adsorbent Recirculating System in Patients With Liver Failure: A Case Series of 44 Patients.

BACKGROUND: Liver failure is associated with a high mortality rate, with many patients requiring transplant for definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a nonbiologic system that provides extracorporeal support. Literature on MARS therapy is mixed: outcomes support MARS therapy for patients with isolated acute liver failure, but data on patients with chronic disease is varied. Several case studies report success using MARS as a bridging treatment for patients awaiting transplant. The purpose of this case series is to present the outcomes of 44 patients who underwent MARS therapy for liver failure, 19 of whom used MARS therapy as a bridging therapy to transplant. METHODS: This study retrospectively identified 44 patients who underwent MARS therapy for liver failure at Mayo Clinic, Jacksonville, between January 2014 and April 2021. Variables of interest included changes in laboratory markers of hepatic functioning, number and length of MARS therapy sessions, transplantation status, and mortality. RESULTS: Following MARS therapy, there were improvements in mean serum bilirubin, ammonia, urea, creatinine, International Normalized Ratio, alanine aminotransferase, and aspartate aminotransferase levels. Twenty-seven patients (61.36%) survived the hospital stay; 17 (38.63%) died in the hospital. The majority of surviving patients (n = 19; 73.07%) received liver transplant. Six did not require transplant (22.22%). All but 1 patient who received MARS as a bridging treatment to transplant survived the follow-up period (n = 18; 94.74%). CONCLUSIONS: Outcomes of these 44 cases suggest that MARS improves liver failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant.

Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center.

BACKGROUND: Molecular Adsorbent Recirculating System (MARS®) is a non-biological artificial liver device. The benefit risk ratio between uncertain clinical effects and potential adverse events remains difficult to assess. We sought to describe adverse events related to MARS® therapy as well as biological and clinical effects. METHODS: All intensive care unit (ICU) admissions to whom MARS® therapy was prescribed from March 2005 to August 2021 were consecutively and prospectively included. The main endpoint was the incidence of adverse events related to MARS® therapy. Secondary endpoints were the biological and clinical effects of MARS® therapy. RESULTS: We reported 180 admissions treated with MARS® therapy. Among the 180 admissions, 56 (31.1%) were for acute-on-chronic liver failure, 32 (17.8%) for acute liver failure, 28 (15.5%) for post-surgery liver failure, 52 (28.9%) for pruritus and 12 (6.7%) for drug intoxication. At least one adverse event occurred in 95 (52.8%) admissions. Thrombocytopenia was the most frequent adverse event which was recorded in 55 admissions (30.6%). Overall, platelets count was 131 (± 95) × 109/L before and 106 (± 72) × 109/L after MARS® therapy (p < .001). After MARS® therapy, total bilirubin was significantly decreased in all groups (p < 0.05). Hepatic encephalopathy significantly improved in both the acute-on-chronic and in the acute liver failure group (p = 0.01). In the pruritus group, pruritus intensity score was significantly decreased after MARS® therapy (p < 0.01). CONCLUSION: In this large cohort of patients treated with MARS® therapy we report frequent adverse events. Thrombocytopenia was the most frequent adverse event. In all applications significant clinical and biological improvements were shown with MARS® therapy.

Impact of anion exchange adsorbents on regional citrate anticoagulation.

INTRODUCTION: Heparin and citrate are commonly used anticoagulants in membrane/adsorption based extracorporeal liver support systems. However, anion exchange resins employed for the removal of negatively charged target molecules including bilirubin may also deplete these anticoagulants due to their negative charge. The aim of this study was to evaluate the adsorption of citrate by anion exchange resins and the impact on extracorporeal Ca2+ concentrations. METHODS: Liver support treatments were simulated in vitro. Citrate and Ca2+ concentrations were measured pre and post albumin filter as well as pre and post adsorbents. In addition, batch experiments were performed to quantify citrate adsorption. RESULTS: Pre albumin filter target Ca2+ concentrations were reached well with only minor deviations. Citrate was adsorbed by anion exchange resins, resulting in a higher Ca2+ concentration downstream of the adsorbent cartridges during the first hour of treatment. CONCLUSIONS: The anion exchange resin depletes citrate, leading to an increased Ca2+ concentration in the extracorporeal circuit, which may cause an increased risk of clotting during the first hour of treatment. An increase of citrate infusion during the first hour of treatment should therefore be considered to compensate for the adsorption of citrate.

Molecular Adsorbent Recirculating System Treatment Can Reduce Blood Levels of N-Acetylcysteine in Patients With Acetaminophen Overdose: Case Reports.

BACKGROUND: Acetaminophen poisoning continues to be a major cause of liver failure that can lead to liver transplantation. N-acetylcysteine (NAC) is the cornerstone of treatment. Some authors use a Molecular Adsorbent Recirculating System (MARS) system in acetaminophen poisoning. It is reported that the MARS system eliminates acetaminophen more efficiently than conventional dialysis. It is theoretically possible that treatment with MARS administered after NAC will increase the effectiveness of treatment. CASE REPORTS: The first patient, a woman of 14 years old, presented blood levels of 112 mg/dL 12 hours after ingestion of 15 g of acetaminophen. Treatment with NAC was initiated. At 17 and 23 hours after ingestion, blood levels were 23.5 µg/mL and 5.9 µg/mL, respectively. The second patient, a woman of 28 years old, presented blood levels of 115 mg/dL 4 hours after ingestion of 40 g of acetaminophen. Treatment with NAC was initiated. At 14 and 23 hours after ingestion, blood levels were 15.8 µg/mL and <2 µg/mL, respectively. In both patients, we performed MARS after completing treatment with NAC, and after the first session, blood levels were below the lower limit of detection (≤2 µg/mL). DISCUSSION: The correct timing of MARS to avoid interactions with the administered dose of NAC in acetaminophen overdose is essential so as to not impair the effectiveness of this treatment. These considerations in the management of this entity help in the resolution of liver failure, thus avoiding the need for a liver transplant.

A review on nanoparticle-based technologies for biodetoxification.

Nanotechnology has gained significant penetration to different fields of medicine including drug delivery, disease interrogation, targeting and bio-imaging. In recent years, efforts have been put forth to assess the use of this technology in biodetoxification. In this review, we will discuss the current status of nanostructured biomaterials/nanoparticle (NP)-based technologies as a candidate biodetoxifying agent. Patient hospitalization due to illicit drug consumption, suicidal attempts and accidental toxin exposure are major challenges in the medical field. Overdoses of drugs/toxic chemicals or exposure to bacterial toxins or poisons are conventionally treated by voiding the stomach, administering activated charcoal or by using specific antidotes, if the toxin is known. Because of the limitations of these methods for safe and effective detoxification, advancements in nanotechnology may offer novel ways in intoxication support by using nanostructured biomaterials, such as liposomes, micellar nanocarriers, liquid crystalline nanoassemblies and ligand-based NPs.

Comparison of two different modes of molecular adsorbent recycling systems for liver dialysis.

BACKGROUND: In children acute liver failure is a rare but life-threatening condition from which two-thirds do not recover with supportive therapy. Treatment is limited by the availability of liver transplants. Molecular adsorbent recirculating system (MARS) dialysis is a bridge to transplantation that enhances the chances of survival during the waiting period for a transplant, although it cannot improve survival. Open albumin dialysis (OPAL) is a new mode of albumin dialysis developed to further improve dialysis efficiency. CASE DIAGNOSIS/TREATMENT: We report a paediatric case of acute-on-chronic liver failure and compare the two modes of albumin dialysis, namely, the MARS and OPAL, used to treat this patient's cholestatic pruritus. Removal of total and direct bilirubin, ammonia and bile acids were measured by serial blood tests. There was an increased removal of bile acids with the OPAL mode, whereas the removal of total and direct bilirubin and ammonia was similar in both modes. The patient reported better improvement in pruritus following OPAL compared to dialysis with the MARS. CONCLUSION: OPAL may offer a better solution than the MARS in the treatment of refractory pruritus in liver failure.

RECCAS - REmoval of Cytokines during CArdiac Surgery: study protocol for a randomised controlled trial.

BACKGROUND: On-pump cardiac surgery triggers a significant postoperative systemic inflammatory response, sometimes resulting in multiple-organ dysfunction associated with poor clinical outcome. Extracorporeal cytokine elimination with a novel haemoadsorption (HA) device (CytoSorb®) promises to attenuate inflammatory response. This study primarily assesses the efficacy of intraoperative HA during cardiopulmonary bypass (CPB) to reduce the proinflammatory cytokine burden during and after on-pump cardiac surgery, and secondarily, we aim to evaluate effects on postoperative organ dysfunction and outcomes in patients at high risk. METHODS/DESIGN: This will be a single-centre randomised, two-arm, patient-blinded trial of intraoperative HA in patients undergoing on-pump cardiac surgery. Subjects will be allocated to receive either CPB with intraoperative HA or standard CPB without HA. The primary outcome is the difference in mean interleukin 6 (IL-6) serum levels between the two study groups on admission to the intensive care unit. A total number of 40 subjects was calculated as necessary to detect a clinically relevant 30 % reduction in postoperative IL-6 levels. Secondary objectives evaluate effects of HA on markers of inflammation up to 48 hours postoperatively, damage to the endothelial glycocalyx and effects on clinical scores and parameters of postoperative organ dysfunction and outcomes. DISCUSSION: In this pilot trial we try to assess whether intraoperative HA with CytoSorb® can relevantly reduce postoperative IL-6 levels in patients undergoing on-pump cardiac surgery. Differences in secondary outcome variables between the study groups may give rise to further studies and may lead to a better understanding of the mechanisms of haemoadsorption. TRIAL REGISTRATION: German Clinical Trials Register number DRKS00007928 (Date of registration 3 Aug 2015).

Lemon detox diet reduced body fat, insulin resistance, and serum hs-CRP level without hematological changes in overweight Korean women.

The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes.

Experience with molecular adsorbent recirculating system treatment in 20 children listed for high-urgency liver transplantation.

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

Molecular Absorbent Recirculating System therapy (MARS®) in pediatric acute liver failure: a single center experience.

BACKGROUND: Supportive care as a bridge to transplant or recovery remains challenging in children suffering from acute liver failure (ALF). We report our experience in children using the Molecular Absorbent Recirculating System (MARS(®)). METHODS: Retrospective data from children receiving therapy using MARS(®) from October 2009 to October 2012 were included in this single-center retrospective study. Patient characteristics, clinical presentation and complications of ALF, clinical and biological data before and after each MARS(®) session, technical modalities and adverse events were recorded. RESULTS: A total of six children underwent 17 MARS(®) sessions during the study period. Two adolescents were treated with the adult filter MARSFLUX(®) and four infants were treated with the MiniMARS(®) filter. The mean PEdiatric Logistic Dysfunction (PELOD) score at admission was 19 (range 11-33). All patients were mechanically ventilated, and four had acute kidney injury. The neurological course improved in one case, judged as stable in two cases and worsened in one case; data were unavailable in two cases. Mean serum ammonia levels decreased significantly following treatment with MARS(®) from an initial 89 ± 29 to 58 ± 35 mcmol/L (p = 0.02). No other significant biological improvement was observed. Hemodynamic status improved/remained unchanged in the adolescent group, but in the infants four of the seven sessions were poorly tolerated and two sessions were aborted. Three patients died, two were successfully transplanted and one recovered without transplantation. CONCLUSION: In our experience, treatment with MARS(®) is associated with encouraging results in adolescents, but it needs modification for very sick infants to improve tolerance.

Blood purification and mortality in sepsis: a meta-analysis of randomized trials.

OBJECTIVES: Although blood purification improves outcomes in animal studies of sepsis, results of clinical trials have been mixed. We conducted a systematic review and meta-analysis of randomized trials to determine the association between various blood purification techniques and all-cause mortality in humans with sepsis. DATA SOURCES: We searched for relevant studies in MEDLINE, EMBASE, and the Cochrane Library database from January 1966 to May 2012. STUDY SELECTION: Inclusion required a diagnosis of sepsis and comparison of blood purification techniques including hemofiltration, hemoperfusion, plasma exchange, or hemodialysis with no blood purification (control group). DATA EXTRACTION: Two authors independently selected studies and extracted data. Summary statistics, risk ratios, and CIs were calculated using random-effects modeling. Study quality was assessed using Jadad score, and publication bias was assessed using funnel plots and Egger's statistic. DATA SYNTHESIS: Overall, blood purification decreased mortality compared with no blood purification (35.7% vs 50.1%; risk ratio, 0.69 [95% CI, 0.56-0.84]; p<0.001; 16 trials, n=827). However, these results were driven mainly by hemoperfusion (risk ratio, 0.63 [95% CI, 0.50-0.80]; p<0.001; 10 trials, n=557) and plasma exchange (risk ratio, 0.63 [95% CI, 0.42-0.96]; p=0.03; two trials, n=128). Pooling of all trials of blood purification for treatment of sepsis was no longer associated with lower mortality (risk ratio, 0.89 [95% CI, 0.71-1.13]; p=0.36; eight trials, n=457) after excluding trials using polymyxin B hemoperfusion. CONCLUSIONS: Blood purification techniques including hemoperfusion, plasma exchange, and hemofiltration with hemoperfusion were associated with lower mortality in patients with sepsis. These results were mainly influenced by studies using polymyxin B hemoperfusion from Japan.

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

UNLABELLED: 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.

Randomized controlled study of plasma exchange combined with molecular adsorbent re-circulating system for the treatment of liver failure complicated with hepatic encephalopathy.

BACKGROUND/AIMS: To evaluate the use of plasma exchange (PE) combined with the molecular adsorbent re-circulating system (MARS) for the treatment of liver failure complicated with hepatic encephalopathy. METHODOLOGY: A prospective randomized controlled study was conducted to compare the therapeutic effect of MARS treatment (MARS group, n=60) with that of PE combined with MARS treatment (PE+MARS group, n=60) in patients with liver failure complicated with hepatic encephalopathy. RESULTS: The serum total bilirubin and blood ammonia levels were significantly decreased compared with pretreatment levels after 3 days of both the MARS treatment (p=0.0001, p<0.001) and PE+MARS treatment (both p<0.0001) and the Glasgow coma scale score was significantly increased (both p<0.0001). The 30-day mortality rate was 10.0% (6/60) in the MARS group and 11.7% (7/60) in the PE + MARS group. The per capita cost of treatment was significantly lower in the PE + MARS group than in the MARS group (p=0.0003). CONCLUSIONS: Both MARS and PE + MARS therapy can safely and effectively be used to treat liver failure complicated with hepatic encephalopathy, but PE + MARS therapy reduces serum total bilirubin level more effectively and is more cost-effective.

Albumin for end-stage liver disease.

Albumin has been widely used in patients with cirrhosis in an attempt to improve circulatory and renal functions. The benefits of albumin infusions in preventing the deterioration in renal function associated with large-volume paracentesis, spontaneous bacterial peritonitis, and established hepatorenal syndrome in conjunction with a vasoconstrictor are well established. While some of these indications are supported by the results of randomized studies, others are based only on clinical experience and have not been proved in prospective studies. The paucity of well-designed trials, the high cost of albumin, the lack of a clear-cut survival benefit, and fear of transmitting unknown infections make the use of albumin controversial. The recent development of the molecular adsorbent recirculating system, an albumin dialysis, is an example of the capacity of albumin to act by mechanisms other than its oncotic effect. Efforts should be made to define the indications for albumin use, the dose required, and predictors of response, so that patients gain the maximum benefit from its administration.

Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Molecular Adsorbents Recirculating System dialysis in children with cholestatic pruritus.

BACKGROUND: Cholestatic pruritus may severely compromise quality of life. The Molecular Adsorbents Recirculating System (MARS) allows removal of pruritogenic substances without exposure to foreign proteins. Pediatric data, however, are scant. METHODS: We retrospectively analyzed the efficacy of MARS in three boys with severe cholestatic pruritus. They received a total of 135 MARS sessions during 8, 4, and 13 months prior to liver transplantation. Total serum bilirubin and bile acids were monitored, and pruritus was assessed by a numerical rating scale (NRS 0 = no pruritus, 10 = maximal pruritus). RESULTS: MARS sessions were initially performed three times weekly at a mean duration of 6.3 ± 1.4 h. Sessions could be reduced to once weekly and once every other week in two patients. Pre-MARS plasma bile acid concentrations averaged 207 ± 67 µmol/l. They declined to 67 ± 9%, 48 ± 3%, 38 ± 14%, and 37 ± 5% of baseline within 2, 4, 6 and 8 h of therapy, respectively (all p < 0.05). The average interdialytic increase of plasma bile acids was 34 ± 33 µmol/l per day. Mean NRS score decreased from 6.5 ± 2.3 to 3.3 ± 2.9 (p < 0.01). Skin lesions from itching disappeared. All MARS treatments were well tolerated. CONCLUSION: MARS dialysis substantially reduces cholestatic pruritus in children refractory to pharmacological treatment.

[Evaluation of extracorporeal liver support systems in the treatment of liver failure. A systematic review]. / Evaluación de los sistemas de soporte hepático extracorpóreo en el tratamiento de la insuficiencia hepática. Revisión sistemática.

OBJECTIVE: To evaluate the safety and efficacy of the MARS and Prometheus extracorporeal liver support systems in the treatment of liver failure. DESIGN: We performed a systematic review of the literature from January 1999 to June 2009 in the Medline, Embase, HTA, DARE, NHSEED, Cochrane Library Plus, Clinical Trials Registry and HSRPROJ databases. Study selection was based on a series of previously established inclusion criteria related to the study design, population, type of intervention, language, and outcome measures. PATIENTS AND INTERVENTIONS: Patients with acute liver failure or acute exacerbations of chronic liver failure treated with the MARS or Prometheus systems. OUTCOME MEASURES: Data on safety, long-term survival, clinical effects and biochemical and hemodynamic variables. RESULTS: We selected 22 studies evaluating the safety and efficacy of the MARS and Prometheus systems. Adequate evaluation of these techniques was hampered by the heterogeneity of the studies and their methodological limitations. CONCLUSIONS: Extracorporeal liver support systems are able to purify both hydrosoluble and protein-bound substances. However, current data show that only the MARS system reduces mortality in acute liver failure and in acute exacerbations of chronic liver failure, although this reduction is non-significant. These techniques can be considered safe, with adverse effects similar to those of the control group. Their main indication is severe liver failure, for short periods while the liver recovers or a liver transplant becomes available.

Efficacy and safety of anticoagulation with heparin versus heparin plus epoprostenol in patients undergoing extracorporeal liver support with Prometheus.

Anticoagulation for extracorporeal liver support is delicate due to underlying coagulation disorders in patients with liver failure and to the associated elevated bleeding risk. To date, there has been no detailed report on anticoagulation issues in patients treated with Prometheus, a device based on the principle of fractionated plasma separation and adsorption. We studied 17 patients from two centers treated with Prometheus, comparing standard anticoagulation with heparin (15 treatments) and a combination of heparin and the synthetic prostacyclin epoprostenol (22 treatments). Standard coagulation tests, proteins C and S, and thrombin-antithrombin (TAT) complex were determined, and adverse events were recorded. All but two treatments could be completed as scheduled, although filter exchange due to filter clotting was required in 24% of the treatments. Three out of 17 patients developed severe bleeding complications within 24 h of treatment. There were no overt thrombotic events. Addition of epoprostenol neither reduced coagulation-related adverse events nor improved standard coagulation parameters. Protein C, but not protein S, showed a significant reduction (23 +/- 18%) after Prometheus treatments, but levels rebounded to baseline within 18 h. TAT levels--a measure for activation of coagulation--were only altered by Prometheus in patients where TAT was already elevated before treatment. In conclusion, anticoagulation of Prometheus with heparin is feasible but still associated with a relatively high frequency of filter clotting and a considerable risk of severe bleeding in this high-risk patient population. As addition of epoprostenol did not prove beneficial, other strategies, such as regional anticoagulation with citrate, should be further evaluated.

[The role of biliary decompression and correction of dysbiosis in the treatment of obstructive jaundice].

The article providing in-depth analysis of pathogenesis of obstructive jaundice shows that this disease is manifest not only as changes at the hepatic level (cholestasis, cholehemia, cholangitis, cholangio- and lymphovenous shunts, hepatic encephalopathy) but also as marked dysbiotic disturbances due to anacholia and toxic metabolites that cause bacterial translocation and endotoxemia complicating liver insufficiency. Based on the literary data and original observations, a new scheme for the treatment of obstructive jaundice is proposed including simultaneous correction of both components of hepatoenteric turnover, also, it permits to improve the outcome of the postoperative period.