Molecular Adsorbent Recirculating System Sessions Research Articles

Bleeding complications associated with the molecular adsorbent recirculating system: a retrospective study.

BackgroundThe molecular adsorbent recirculating system (MARS) is a hepatic replacement system that supports excretory liver function in patients with liver failure. However, since MARS has been employed in our hospital, bleeding complications have occurred in many patients during or after MARS. The objective of this study was to determine how MARS affects coagulopathy and identify specific factors associated with bleeding complications.MethodsWe retrospectively analyzed data from 17 patients undergoing a total of 41 MARS sessions. Complete blood count, coagulation profiles, and blood chemistry values were compared before and after MARS. To identify pre-MARS factors associated with increased bleeding after MARS, we divided patients into bleeder and non-bleeder groups and compared their pre-MARS laboratory values.ResultsMARS significantly reduced bilirubin and creatinine levels. MARS also increased prothrombin time and reduced platelet and fibrinogen, thus negatively impacting coagulation. Pre-MARS hemoglobin was significantly lower in the bleeder group than in the non-bleeder group (P=0.015). When comparing the upper and lower 33% of MARS sessions based on the hemoglobin reduction rate, hemoglobin reduction was significantly greater in MARS sessions involving patients with low pre-MARS international normalized ratio of prothrombin time (PT-INR) and factor V (P=0.038 and P=0.023, respectively).ConclusionsMARS could appears to alter coagulation-related factors such as factor V and increase the risk of bleeding complications particularly in patient with low hemoglobin. However, individual differences among patients were large, and various factors, such as low hemoglobin, PT-INR, and factor V levels, appear to be involved.

Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: A national multicenter study.

Background and AimThe molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real‐life use are lacking.MethodsThis was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives.ResultsA total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 μmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury–hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44–54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1‐year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant‐free survival.ConclusionOur study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF.

Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity

Background:Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues.Methods:We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus ⩽ 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality.Results:Three RCTs suitable for the meta-analysis (n = 285, ACLF patients = 165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p = 0.001; 30-day survival: 73.9% versus 64.3%, p = 0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p = 0.001; 30-day survival: 73.3% versus 58.5%, p = 0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy.Conclusion:HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials.

Treatment of patients with chronic liver failure according to disease etiology

Aim. Improving the efficiency of treatment of patients with chronic liver failure by optimizing the application of extracorporeal detoxification methods.Methods. The study included 292 patients with chronic liver failure (188 males and 104 females). The main causes of chronic liver failure were nutritional factor (alcohol abuse), viral liver diseases, and the combination of alcoholic and viral factors. All patients regardless of the disease etiology were divided into groups. Patients in group 1 received standard conservative therapy, aimed at relieving the symptoms of chronic liver failure. Patients in group 2 were additionally administered plasma exchange, in group 3 - PE and high-volume venovenous hemofiltration, and in group 4 - sessions of molecular adsorbent recirculating system (MARS).Results. Mortality of patients with chronic liver failure on conservative treatment accounted for 84.0% and was 1.5-2.1 times higher than in other groups (53% in plasma exchange group, 52% when using plasma exchange and high-volume venovenous hemofiltration and 40.6% in MARS group), these differences being statistically significant when compared with group 1 (χ2 from of 18.3 to 23.4, p 0.05). Indicators, reflecting the time of 50% mortality of patients with chronic liver failure of different etiology, suggest that in chronic liver failure of alcoholic origin plasma exchange and a combination of plasma exchange and high-volume venovenous hemofiltration are the most effective, and in chronic liver failure of viral and mixed etiology the best results are obtained when using MARS.Conclusion. The effectiveness of treatment of patients with chronic liver failure depends on the etiology of the disease: in alcoholic chronic liver failure plasma exchange and a combination of plasma exchange and high-volume venovenous hemofiltration are most rational, and in chronic liver failure of viral and mixed etiology MARS sessions are rational.

Liver Support With Albumin Dialysis Reduces Hepatitis C Virus Viremia and Facilitates Antiviral Treatment of Severe Hepatitis C Virus Recurrence After Liver Transplantation.

Patients with severe hepatitis C virus (HCV) recurrence after liver transplantation (LT) present an ominous prognosis, rarely achieving sustained virological response (SVR). Dialysis procedures may transiently decrease the HCV viral load, but the effect of albumin dialysis is currently unknown. Here, we evaluated the impact of albumin dialysis using the Molecular Adsorbent Recirculating System (MARS) used as a co-adjuvant antiviral treatment for severe HCV recurrence after LT. Thirteen patients (11 males, median age 48 years) with fibrosing cholestatic hepatitis or METAVIR fibrosis score ≥ F3 with severe portal hypertension underwent three consecutive MARS sessions. Antiviral therapy was initiated in 11 patients within 24 h after the MARS sessions. A contemporary cohort of seven patients who did not follow the MARS protocol is shown for comparison. MARS treatment resulted in consistent decreases of viral load from 7.59 log10 IU/mL [6.15-8.90] to 6.79 log10 IU/mL [5.18-7.84] (P = 0.003) as well as in decreases of serum bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The overall rate of SVR was 0% in the Control group and 54.6% in patients initiating antiviral therapy within 24 h after MARS. Survival at 1 and 3 years was, respectively, 93% and 70% in patients undergoing MARS, compared with 29% and 14% in the Control group (P = 0.001). No major adverse events related to MARS treatment were observed. In conclusion, the use of MARS may facilitate the achievement of SVR and improve the prognosis of patients with severe HCV-recurrence after LT by reducing viral load and improving liver function prior to antiviral therapy.

Albumin Dialysis with Mars in Post-Hepatectomy Liver Failure (PHLF): Experiences from Two HPB Centers

Aim: To study the impact of molecular adsorbent recirculating system (MARS) treatment on the outcome of patients with post-hepatectomy liver failure (PHLF). Patients and methods: Records of all patients treated with MARS due to PHLF between January 2003 and December 2013 at the intensive care units of Karolinska University Hospital (KH), Stockholm, Sweden, and Hospital Clinic (HC), Barcelona, Spain, were reviewed retrospectively. Results: Thirteen patients with PHLF were treated with MARS. Four patients suffered from PHLF secondary to serious post-operative complications and none of them survived. The remaining nine patients fulfilled the 50:50 Balzan criteria for PHLF. In these patients, MARS was commenced on post-operative day (POD) 3-21 (median 8) with a median of three cycles per treatment (range 2-6). In four patients who survived 90 days the treatment was started on POD 7-19 (median 8) with a median of six treatment cycles (range 4-6). In the non-surviving secondary PHLF patients, MARS was started first on POD 17-39 (median POD 32) with a median of 2 completed treatment sessions (range 1-4). No specific complications related to the use of MARS were observed. Conclusion: The use of MARS in PHLF seems to be feasible and safe and may be a therapeutic option in primary PHLF. Our data suggest that in order to achieve beneficial effects, MARS treatment should be initiated as early as possible in patients with PHLF and a minimum of four consecutive MARS sessions should be administered. Prospective research protocols are needed to further investigate this hypothesis.

Extracorporeal Detoxification for Hepatic Failure Using Molecular Adsorbent Recirculating System: Depurative Efficiency and Clinical Results in a Long‐Term Follow‐Up

Acute liver failure and acute-on-chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty-four patients with life-threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23-82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32-62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36-54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1-year follow-up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17-29); direct bilirubin RRs was 28% (21-35), and indirect bilirubin RRs was 8% (3-21). Ammonia RRs was 34% (12-86). Conjugated cholic acid RRs was 58% (48-61); chenodeoxycholic acid RRs was 34% (18-48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9-7.9) versus 7.9 ng/mL (3.2-14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End-stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan-Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In conclusion, MARS was clinically well tolerated by all patients and significantly reduced hepatic toxins. Better survival rates were linked to an OLT program, but patients' clinical characteristics on starting MARS therapy were the main factors predicting survival. The role of HGF should be evaluated in larger clinical trials.

MARS therapy, the bridging to liver retransplantation — Three cases from the Hungarian liver transplant program

Besides orthotopic liver transplantation (OLT) there is no long-term and effective replacement therapy for severe liver failure. Artificial extracorporeal liver supply devices are able to reduce blood toxin levels, but do not replace any synthetic function of the liver. Molecular adsorbent recirculating system (MARS) is one of the methods that can be used to treat fulminant acute liver failure (ALF) or acute on chronic liver failure (AoCLF). The primary non-function (PNF) of the newly transplanted liver manifests in the clinical settings exactly like acute liver failure. MARS treatment can reduce the severity of complications by eliminating blood toxins, so that it can help hepatic encephalopathy (HE), hepatorenal syndrome (HRS), and the high rate mortality of cerebral herniation. This might serve as a bridging therapy before orthotopic liver retransplantation (reOLT). Three patients after a first liver transplantation became candidate for urgent MARS treatment as a bridging solution prior to reOLT in our center. Authors report these three cases, fo-cusing on indications, MARS sessions, clinical courses, and final outcomes.

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.

‘Out‐patient’ albumin dialysis for cholestatic patients with intractable pruritus

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. 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. Fifteen patients who failed to respond to standard medical therapy to control pruritus were included. Three MARS (6h) 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). 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 15.7months (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 3.3months (range 2-5). No serious adverse events were recorded, but the platelet count and haemoglobin were reduced significantly. 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.

Thromboelastography to monitor clotting/bleeding complications in patients treated with the molecular adsorbent recirculating system.

Background. The Molecular Adsorbent Recirculating System (MARS) has been shown to clear albumin-bound toxins from patients with liver failure but might cause bleeding complications potentially obscuring survival benefits. We hypothesized that monitoring clotting parameters and bed-side thromboelastography allows to reduce bleeding complications. Methods. Retrospective analysis of 25 MARS sessions during which clotting parameters were monitored by a standardized protocol. Results. During MARS therapy median INR increased significantly from 1.7 to 1.9 platelet count and fibrinogen content decreased significantly from 57 fL−1 to 42 fL−1 and 2.1 g/L to 1.5 g/L. Nine relevant complications occurred: the MARS system clotted 6 times 3 times we observed hemorrhages. Absent thrombocytopenia and elevated plasma fibrinogen predicted clotting of the MARS system (ROC 0.94 and 0.82). Fibrinolysis, detected by thromboelastography, uniquely predicted bleeding events. Conclusion. Bed-side thromboelastography and close monitoring of coagulation parameters can predict and, therefore, help prevent bleeding complications during MARS therapy.

Albumin Dialysis Without Anticoagulation in High‐Risk Patients: An Observational Study

Severe liver failure causes coagulopathy and high bleeding risk. Albumin dialysis with Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden) is useful for treatment. However, anticoagulation during its use is of uncertain value. We omitted heparin-saline priming and intradialytic heparin and examined its effects. Albumin dialysis was performed in critically ill patients with intermittent circuit saline flushes (2664 ± 2420 mL per treatment). A total of 12 patients (M : F = 10:2; age 49 ± 9 years) were thus treated: 6 for fulminant hepatic failure and 6 for acute-on-chronic liver failure. The overall hospitalization duration was 31 ± 30 days. A total of 44 treatment sessions were performed (average 8 ± 7 sessions per patient). Prescribed versus achieved MARS duration were 13 ± 3 versus 11 ± 4 h, P < 0.05. Twenty-three percent (10/44) of MARS sessions clotted, 11% (5/44) of treatments were electively terminated, and 2% (1/44) developed vascular catheter occlusion. Spontaneous bleeding occurred in 9% (4/44). Pre- versus post-MARS systemic and blood circuit transmembrane pressures (mm Hg), and albumin dialysate afferent and efferent pressures were all stable. Coagulation indices were (pre- vs. post-MARS): (i) prothrombin time (seconds): 36 ± 30 versus 42 ± 33, P = 0.143; (ii) activated partial thromboplastin time (seconds): 78 ± 43 versus 88 ± 45, P = 0.117; and (iii) platelet count (×10(3) /µL): 87 ± 40 versus 76 ± 48, P = 0.004. Systemic blood solute concentrations pre- versus post-MARS were: (i) serum urea (mg/dL): 22.4 ± 19.6 versus 14.0 ± 8.4, P < 0.05; (ii) serum creatinine (mg/dL): 2.8 ± 2.3 versus 1.9 ± 1.5, P < 0.05; (iii) total bilirubin (mg/dL): 29.5 ± 8.8 versus 20.5 ± 5.1, P < 0.05; and (iv) plasma ammonia (µg/dL): 186 ± 85 versus 129 ± 66, P < 0.05. Anticoagulant-free albumin dialysis remained effective despite frequent circuit clotting. This led to significant exacerbation of thrombocytopenia although bleeding risk remained low.

Comparison of the Molecular Adsorbent Recirculating System and Plasmapheresis for Patients With Graft Dysfunction After Liver Transplantation

Background Graft dysfunction after liver transplantation (OLT) is a life- threatening condition. Molecular adsorbent recirculating system (MARS) or plasmapheresis (PLP) may be effective supportive therapy of graft dysfunction for patients who cannot undergo retransplantation. The aim of this study was to compare the effects of MARS and PLP in patients with graft dysfunction after OLT. Methods Between January 2002 and July 2007, 31 OLT recipients who experienced graft dysfunction, defined as hyperbilirubinemia (>10 mg/dL) without bile duct obstruction and/or presence of hepatic encephalopathy, were treated with MARS or PLP. Biochemical and hemodynamic data and survival were compared in MARS and PLP groups. Results Fifteen patients were treated with 41 MARS sessions and 16 with 105 PLP sessions. After a single MARS session, patients showed significant reductions in creatinine, urea nitrogen, bilirubin, and ammonia. After a single PLP session, patients showed significant improvements in prothrombin time, bilirubin, alanine aminotransferase, alkaline phosphatase, and albumin. After the completion of treatment, Both MARS and PLP significantly improved bilirubin values. at 90 days there were no differences in overall survival rates; 53% in MARS versus 56% in PLP. Conclusion Both MARS and PLP are alternative supportive treatments for graft dysfunction after OLT.

Albumin Dialysis in Critically Ill Patients: Use Versus Omission of Intradialytic Heparin

Albumin liver dialysis using the Molecular Adsorbent Recirculating System (MARS) (Teraklin AG, Rostock, Germany) is used in severe acute liver failure (ALF). We hypothesized that intradialytic heparin worsens preexisting hemostatic defects without enhancing system longevity or therapeutic efficacy. This was a retrospective, single center study of 10 critically ill patients (M : F = 8:2; mean age 58.5 +/- 16.5 years old; Acute Physiology and Chronic Health Evaluation II 25.0 +/- 3.5) treated with 31 MARS sessions (intradialytically heparinized : nonheparinized = 18:13). Mortality in this cohort was 80%. All MARS circuits were primed with dilute heparinized saline before commencement. However, intradialytic, intermittent, bolus heparin was administered on an ad hoc basis with circuit saline flush where indicated. Acute renal replacement therapy was instituted where indicated. Average total intradialytic heparin used was 757 +/- 389 IU. Circuit pressures were stable with or without intradialytic heparin. Significant reductions in serum urea, creatinine, ammonia, and total bilirubin were achieved using intradialytically heparinized and nonheparinized MARS. Thrombocytopenia and elevated activated partial thromboplastin time (aPTT) were further deranged post-MARS for both circuit types, but significantly so in intradialytically heparinized MARS: pre- versus post-MARS aPTT (s) 57.8 +/- 17.6 versus 88.7 +/- 48.0, P = 0.011, and platelet count (x 10(3)/L) 102.9 +/- 61.1 versus 84.4 +/- 50.5; P = 0.009. The use of low dose, intradialytic heparin during MARS exacerbates preexisting severe coagulopathy and thrombocytopenia in patients with severe ALF without enhancing circuit function and longevity. However, the role and safety of heparinized saline prime need further investigation.

Anticoagulation Minimization Is Safe and Effective in Albumin Liver Dialysis Using the Molecular Adsorbent Recirculating System

The molecular adsorbent recirculating system (MARS) is a blood purification device with renal and hepatic dialytic effects. This study examined the use of low-dose unfractionated heparin in MARS. This was a prospective, observational study of 15 MARS treatment sessions (mean duration per treatment cycle = 12.2 +/- 4.5 h) in four patients with severe acute decompensation of chronic liver disease (n = 3) and fulminant hepatic failure (n = 1) treated with intermittent MARS. All patients were critically ill (APACHE II 24.8 +/- 3.3). Renal dialysis was with continuous hemofiltration and/or slow low-efficiency dialysis. One MARS session was terminated because of vascular access occlusion (1/15; 6.7%). Bleeding was noted in two sessions (2/15; 13%). Twelve MARS sessions were heparin-free and three treatments were with mean heparin dose of 833 +/- 382 IU. Serum biochemical parameters pre- and post-MARS were total bilirubin (micromol/L): 409.4 +/- 141.6 versus 282.9 +/- 90, P < 0.05; plasma ammonia (micromol/L): 44.3 +/- 21.2 versus 28.8 +/- 20.2, P = 0.002; urea (mmol/L): 15.9 +/- 11.8 versus 7.9 +/- 6.6, P = 0.002; creatinine (micromol/L): 252.4 +/- 151.9 versus 150.1 +/- 96.6, P = 0.003. Pre-MARS versus post-MARS systolic (SBPs) and diastolic (DBPs) blood pressures (mm Hg) were SBP = 129.2 +/- 27.7 versus 124 +/- 25, P = 0.838; and DBP = 60.7 +/- 15.3 versus 56 +/- 13, P = 0.595. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count (Plt) pre- and post-MARS were PT(s): 22 +/- 7.9 versus 23.8 +/- 10.2, P = 0.116; aPTT (s): 64.5 +/- 40.9 versus 85.5 +/- 50.6, P = 0.092; and Plt (x10(3)/mm(3)): 87 +/- 67.6 versus 68.8 +/- 39, P = 0.098. MARS priming with heparin saline was safe. Heparin-minimized MARS did not compromise circuit function and longevity in extended intermittent MARS.

Artificial liver support with the molecular adsorbent recirculating system: activation of coagulation and bleeding complications

Numerous, mostly uncontrolled, observations suggest that artificial liver support with the Molecular Adsorbent Recirculating System (MARS) improves pathophysiologic sequelae and outcome of acute and acute-on-chronic liver failure. MARS is felt to be safe, but extracorporeal circuits may activate coagulation. To assess the frequency of and risk factors for activation of coagulation during MARS treatment. Retrospective analysis of coagulopathy/bleeding complications observed during 83 consecutive MARS sessions in 21 patients (11 men; median age 46 years; median three sessions per patient; median duration of session 8 h). Nine clinically relevant episodes of coagulopathy/bleeding were observed in eight patients, forced to premature cessation of MARS in seven and ended lethal in four. Four complications occurred during the first, five during later (third to seventh) MARS sessions and two bleeders tolerated further sessions without complications. Coagulation parameters worsened significantly also during MARS sessions not associated with bleeding (P< or =0.004). In univariate analysis, patient's age, vasopressor therapy, pretreatment INR, fibrin D-dimer and fibrinogen concentrations, but not severity of underlying disease (MELD, Child-Pugh, SAPS II scores), were significantly associated with coagulopathy (P<0.05). Only patient's age, fibrin D-dimer level and INR were retained in a multivariate model correctly classifying 98% of sessions without, but only 33% with complications. Coagulation is frequently activated during MARS therapy, potentially leading to bleeding complications and mortality.

Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience

The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin-bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong. From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients. The cause of liver failure included acute liver failure (n = 2), acute on chronic liver failure (n = 12), posthepatectomy liver failure (n = 4), and posttransplantation allograft failure (n = 4). MARS treatment showed significant reduction in total bilirubin level, serum ammonia level and blood urea, and nitrogen (P < 0.001 for all three parameters). Five patients (22.7%) were able to bridge to transplantation and one patient (4.5%) made a spontaneous recovery. The 30-day mortality rate was 72.7%. Our results indicated that MARS can effectively improve serum biochemistry and is suitable for temporarily supporting patients with liver failure where transplantation is not immediately available. There is, however, no clear evidence showing that MARS can increase survival, improve the chance of transplantation or assist liver regeneration. Future studies in the form of randomized-controlled trials are crucial to characterize the true potential of this treatment.

A Modeling Study of Bilirubin Kinetics During Molecular Adsorbent Recirculating System Sessions

This work presents a quantitative description, by means of a mathematical model, of bilirubin removal during Molecular Adsorbent Recirculating System sessions. The model includes four compartments: two for the patient, and two for the albumin circuit. Equations in each compartment express mass preservation, mass exchange between compartments, and bilirubin-albumin binding kinetics. Model development and validation are based on in vivo data of bilirubin concentration acquired in eight sessions at different times during the session. The accuracy of the model in reproducing real data is high (error in blood = -0.3 +/- 0.93 mg/dL), if three parameters, representing the depurative efficacy of the system (the dialysance of the blood filter and the initial and final clearance of the depurative elements in the albumin circuit), are estimated on each single session. However, model accuracy is only slightly deteriorated (error in blood = -0.4 +/- 0.99 mg/dL) if a single set of parameters (fixing the three parameters at their mean values) is adopted. These results suggest that the model may be used a priori (i.e., using a single set of parameters) to achieve a satisfactory prediction of the overall bilirubin removal, as well as a posteriori for the estimation of device parameters. The latter use may allow the investigation of the dependence of these parameters on the operative and clinical conditions, in the effort to arrive at a rationalization and optimization of the treatment.

Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus

Intractable pruritus is more common in cholestatic liver diseases and may be the presenting symptom and/or major complaint of hepatitis C and/or hepatitic C virus—related cirrhosis. From September 2000 to May 2002, three patients affected by intractable pruritus secondary to hepatitis C cirrhosis that failed medical treatment were treated with a molecular adsorbent recirculating system (MARS). MARS is an artificial liver support system that aims to clear the blood of metabolic waste products normally metabolized by the liver. Each patient underwent seven MARS sessions. Liver function tests, the 36-Item Short Form quality-of-life test, visual analog scale for itching, and bile acid measurement in the serum, albumin circuit and ultrafiltrate were performed before and after each MARS session. Moreover, at hospital admission, each patient underwent a psychological workup and abdominal imaging study. Subjective improvement in pruritus and quality of life, along with a decrease in serum bile acid concentration, was observed in every patient; no patient underwent retreatment and/or liver transplantation up to a 9-month follow-up. One patient died 201 days after MARS treatment. Although we observed a decreased level of serum bile acids, one cannot conclude that this was the mechanism of action for the reduction in pruritus intensity in patients in our series. Different toxins and/or a placebo effect might have had a role in this setting. (Liver Transpl 2003;9:437-443.))