Modifications of intracranial pressure after molecular adsorbent recirculating system treatment in patients with acute liver failure: case reports

Cerebral dysfunction may be fatal in patients with acute liver failure (ALF); intracranial pressure (ICP) monitoring may be mandatory to direct measures to prevent further cerebral edema. Recently the introduction of dialysis with the molecular adsorbent recirculating system (MARS) has improved the outcomes among patients with ALF. The aim of this study was to evaluate ICP changes after MARS treatment among patients with ALF. METHODS: Three patients -- 14, 18 and 16 years old -- were admitted to the ICU for acute liver failure induced by HBV in two cases and by acetaminophen in the other one. Because of Glasgow Coma Score (GCS) <8, they were intubated and ventilated to protect the airway and maintain moderate hypocapnia. Invasive monitoring of intracranial pressure MARS treatments were performed in all patients. RESULTS: The patients received MARS treatments every day after their admission to liver transplantation. After MARS therapy the ICP decreased on average from 21 to 7 mm Hg. Significant hemodynamic modifications were not observed and their neurological conditions improved. CONCLUSION: MARS treatment improved the clinical pictures of these patients increasing the available time to obtain an urgent liver graft.     

肝衰竭人工肝治疗过程中低血压原因分析及护理

分析人工肝治疗肝衰竭中低血压原因并总结护理经验。226例次肝衰竭患者在人工肝治疗中发生低血压49例次,发生率为21.68%。有效循环血量减少、失血是最主要因素。上机前对病情实施系统评估,勿仓促上机;个性化调节各参数和使用抗凝剂;术中严密监测,准确判断病情变化;及时有效的干预,是维持患者血流动力学稳定、保证治疗顺利完成、提高抢救成功率的重要措施。     

Clinical experience with molecular adsorbent recirculating system (MARS) in patients with drug-induced liver failure

The molecular adsorbent recirculating system (MARS) is a novel extracorporeal technique for liver support. We report the clinical results in a group of fourteen patients with drug-induced liver failure. Fourteen patients, aged 22-83 years, with acute or subacute liver failure [mean Child-Turcotte-Pugh (CTP) score 11 (range 8-15)] due to the intake of various drugs (diet pill overdose-2; Chinese traditional medicine (CTM)-4; antibiotic, paracetamol, tuberculostatic, or vasodilator abuse-8) were treated with one to seven sessions of MARS. Beneficial effects such as the improvement of encephalopathy and prothrombin activity, as well as a reduction of bilirubin and ammonia were recorded during MARS treatments. Thirteen out of fourteen patients survived the hospitalization (93%), and two of the discharged patients died during the follow-up of 6-12 months. The overall survival rate was about 79%. MARS therapy can contribute to the improved treatment of drug-induced liver failure patients.     

Molecular adsorbent recirculating system for acute and acute-on-chronic liver failure: a meta-analysis.

Molecular adsorbent recirculating system (MARS) is an important option for patients with liver failure to give them additional time for recovery or to serve as a "bridge" to transplantation. However, its effect on survival for such patients is not well known. Our aim was to assess the treatment effects of MARS on patients with acute and acute-on-chronic liver failure. The outcomes measure evaluated was survival. We searched Medline (1966-2002) and EMBASE (1974-2002) using the terms liver failure, liver support systems, and MARS. Our search was extended to the Cochrane Controlled Trials Registry Database, published abstracts from 5 international conferences, Teraklin (the manufacturer of MARS), known contacts, and bibliographies from each full-published report. We included trials published in English and non-English languages. Eligible studies were randomized and nonrandomized controlled trials, which compared the treatment effects of MARS with standard medical treatment. Of the 206 articles screened, 4 randomized controlled trials including 67 patients were analyzed. Two nonrandomized trials with 61 patients were used for explorative analysis. The methodology, population, intervention, and outcomes of each selected trial were evaluated by duplicate independent review. Disagreements were resolved by consensus. In the primary meta-analysis, MARS treatment did not appear to reduce mortality significantly compared with standard medical treatment [relative risk (RR), 0.56; 95% confidence interval (CI), 0.28-1.14; P = .11]. Only 1 of the 4 randomized trials analyzed showed significant reduction in mortality. Sensitivity analysis of 3 peer-reviewed trials did not reduce mortality significantly with MARS treatment (RR, 0.72; 95% CI, 0.37-1.40; P = .33). Subgroup analysis of 2 trials for acute liver failure and another 2 trails for acute-on-chronic liver failure also did not reveal any benefit to survival with MARS treatment. In contrast, explorative analysis of 2 nonrandomized trials showed a significant survival benefit with MARS treatment (RR, 0.36; 95% CI, 0.17-0.76; P = .007). This was possibly related to bias in the selection of patients in the nonrandomized trials. In conclusion, MARS treatment had no significant survival benefit on patients with liver failure when compared with standard medical therapy. However, we found only a few trials with a small number of patients for the analysis, allowing for the possibility of false negative and erroneous conclusions. Well-conducted randomized trials are strongly recommended to define the role of MARS in the treatment of patients with liver failure.     

The effect of molecular adsorbent recirculating system treatment on survival,native liver recovery,and need for liver transplantation in acute liver failure patients*

Acute liver failure (ALF) is a medical emergency. Molecular adsorbent recirculating system (MARS), an artificial liver support system, can partly compensate for the detoxifying function of the liver by removing toxins from blood. To analyze the efficacy of MARS treatment, the outcomes of 113 ALF patients, treated with MARS between 2001 and 2007, were compared with a historical control group of 46 ALF patients treated without MARS between 1995 and 2001. Overall survival of transplanted patients was 94% in the MARS group and 77% in the control group (P = 0.06). Without transplantation, survival was 66% and 40% (P = 0.03), respectively. However, the etiological distribution of ALF differed significantly between the groups. In ALF patients with unknown etiology, groups were comparable at baseline; 91% and 69% of transplanted patients survived the MARS and control groups and the native liver recovered in 20% and 8% of the patients, respectively. Of the originally nonencephalopathic patients of unknown etiology, 36% underwent liver transplantation in the MARS group compared to 100% in the control group. Interpretation of the results was difficult in toxic etiology patients on account of differing baseline statuses. MARS treatment might partly explain the trend toward increased survival of ALF patients with unknown etiology.     

Acute liver failure due to leptospirosis successfully treated with MARS (molecular adsorbent recirculating system) dialysis

Background Leptospirosis is a re-emerging infectious disease, which may lead to multiple organ failure (MOF)and death. Case presentation We report the first case of severe leptospirosis complicated with acute renal and liver failure, successfully treated with albumin dialysis––molecular adsorbent recirculating system (MARS). Despite antibiotic therapy, optimum medical supportive treatment and timely initiated haemodialysis, the outcome was complicated by severe liver failure: hepatic encephalopathy grade III, hypoglycemia, prominent hyperbilirubinemia (TBIL 31.3 mg/dl, DBIL 28.6 mg/dl)and hepatic cytolysis (ALT 535 IU/l, AST 179 IU/l) and prolongation of the prothrombine time (68.4 sec). The patient underwent two sesions of albumin dialysis with the MARS procedure with complete recovery of hepatic and renal function. Conclusion Albumin dialysis may confer a significant survival benefit on patients with leptospirosis-induced acute liver failure (ALF).     

Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system

Coagulopathy is a life-threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell-free dialysis technique, on the blood coagulation of cirrhotic patients. From February 2002 to July 2002, nine patients--five males (55.5%) and four females (44.4%), age 47-70 yr (median 56)--underwent 12 courses (4-7 sessions each) of MARS. Patients were treated for the following indications: six (66.6%) acute-on-chronic hepatic failure, three (33.3%) intractable pruritus. Platelet count, prothrombin time (PT), international standardized ratio and thromboelastography were measured before and after each MARS session. Coagulation factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand, lupus anticoagulant, protein C, protein S, antithrombin III, plasminogen, alpha 2 antiplasmin, D-dimer, fibrin monomers, complement, and C(1) inactivator were measured before and at the end of each MARS treatment. We found a statistically significant difference (p < 0.05) in the platelet count, PT, all the thromboelastograph variables (reaction and constant time, alpha angle, and maximal amplitude), factor VIII, von Willebrand, and D-dimer, when measured before and after MARS. Previous reports have shown amelioration of blood coagulation following MARS treatments. However, we document that MARS induces coagulopathy through a platelet-mediated mechanism, whereby platelet may be mechanically destroyed during the passage of blood through the filters and lines. An alternative postulated mechanism is an immune-mediated platelet disruption - coagulopathy.     

Molecular adsorbent recirculating system treatment for acute hepatic failure in patients with hepatitis B undergoing chemotherapy for non-Hodgkin's lymphoma

Hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface (HBsAg) antigen-positive patients treated with chemotherapy. Because the hepatitis is related to HBV virological reactivation, application of effective antiviral therapy, such as Lamivudine, has been attempted. Despite the use of these antiviral agents at the time of clinical hepatitis, some HBsAg-positive patients still develop hepatic failure and die. We used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock, Germany) to treat 5 HBsAg-positive lymphoma patients with acute hepatic failure due to chemotherapy despite lamivudine treatment. Before and after each treatment we monitored the parameters of neurological status (EEG, cerebral CT and Glasgow coma score), hemodynamic parameters, acid-base equilibrium and blood gases as well as hepatic and renal function. The inclusion criteria were these of the King's College Hospital. Statistical analysis by Student t method showed significant results (P < .01). Three of 5 patients are alive without signs of reactivation of viral or hematological diseases at 1 year follow-up. The 2 patients died because MARS treatment was started too late, with Glascow coma score grade IV, hemodynamic instability, and mechanical ventilator assistance. Despite the limited number of cases, we believe that MARS can be applied to patients with a high tolerance and yield good results, but the treatment has to start at the first signs of hepatic failure.     

应用分子吸附循环系统治疗急性肝功能衰竭的经验

目的 探讨急性肝功能衰竭患者等待肝移植期间应用分子吸附循环系统的治疗效果.方法 本组共有16例急性肝功能衰竭患者在等待肝移植期间接受了分子吸附循环系统治疗.结果 16例患者经治疗临床症状及体征明显改善:凝血酶原时间、总胆汁酸、丙氨酸转氨酶、天冬氨酸转氰酶、肌酐和血氨水平明显降低(P＜0.05);肿瘤坏死因子α、一氧化氮和白细胞介素10等细胞因子水平有所下降,但无统计学意义(P＞0.05);序贯性脏器衰竭评估的计分由9.91±1.09降至6.64±1.76,Glascow昏迷评分由7.29±2.06升至13.26±2.14.16例患者中14例成功过渡到肝移植治疗,13例痊愈出院.治疗成功率为81.25%.结论 分子吸附循环系统是治疗肝功能衰竭安全而有效的辅助方法,帮助急性肝功能衰竭患者顺利渡过肝移植等待期.     

The role of molecular adsorbent recirculating system dialysis for extracorporeal liver support in children

The majority of children with acute, acute-on-chronic, and progressive chronic liver failure require liver transplantation. Since organ availability is limited, extracorporeal liver support systems are increasingly applied to bridge the time until transplantation. At present, four different devices are available: the molecular adsorbent recirculating system (MARS), Prometheus dialysis, plasma exchange combined with hemodialysis (PE/HD), and single-pass albumin dialysis (SPAD). Randomized trials in adults have demonstrated efficient toxin removal, improved portal hypertension, hemodynamic stability, and improved hepatic encephalopathy compared with standard medical therapy. None of the liver support systems has yet been evaluated systematically in children. Knowledge of the specific indications and technical features of the different devices is essential if applied in children. MARS combines albumin dialysis with conventional hemodialysis and allows for efficient removal of water and protein-bound toxins without exogenous protein delivery and the associated infectious and allergic risks. It has successfully been applied in children with otherwise intractable cholestatic pruritus and with liver failure. The benefits, however, need to be balanced against the costs and the risk of volume and nitrogen overload if repeated plasma infusion is required. In cases of active bleeding, plasma exchange in combination with hemodialysis should be preferred.     

Molecular absorbent recirculating system for the treatment of acute liver failure in surgical patients

The Molecular Adsorbent Recirculating System (MARS) represents an attractive artificial liver support system for the treatment of liver insufficiency. However, neither indications for MARS treatment (i.e., after extended liver resection) nor criteria for discontinuation of therapy have been evaluated. Therefore, we analyzed the clinical data of all our surgical patients who received MARS treatment for acute liver failure (n = 7). The aim of the study was to identify prognostic indicators for survival. Four of 174 patients resected for hepatic malignancy at our institution received a total of 13 MARS treatments. Two additional patients were successfully bridged to orthotopic liver transplantation with seven MARS treatments and one patient was MARS supported after liver transplantation of a steatotic graft with three MARS treatments. Five of the seven patients survived and were dismissed an average of 31 days, ranging from 17 to 47 days, after the final MARS treatment. No technical complications or adverse effects were observed during the MARS treatments. Important prognostic factors for hepatic recovery and survival were indocyanin green plasma disappearance rates greater than 5%/min and an increase in clotting factor V levels after each MARS treatment. We conclude that MARS therapy can be an effective treatment of postoperative liver insufficiency in the surgical hepatobiliary unit. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

Catholic university experience with molecular adsorbent recycling system in patients with severe liver failure

BACKGROUND AND AIM: Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. MATERIALS: Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin > or =10 mg/dL and at least one of the following: hepatic encephalopathy (HE) > or =II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin > or =5 mg/dL and HE > or =I grade for acute patients. RESULTS: MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. CONCLUSIONS: Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.     

Treatment of refractory cholestatic pruritus with molecular adsorbent recirculating system (MARS)

Pruritus is a common complication of cholestatic liver diseases or liver graft dysfunction. Current medical therapies lack efficacy. The molecular adsorbent recirculating system (MARS) represents an interesting therapeutic option. Our objective was to report our experience in the management of four patients with intractable pruritus with MARS. PATIENTS AND METHODS: The MARS treatment cycle included three consecutive treatments, each of 8 hours duration. The four patients with intractable pruritus who were treated had primary biliary cirrhosis/autoimmune hepatitis overlap syndrome (n = 1), ductopenic allograft rejection (n = 2), or posttransplant cholestatic HCV recurrence (n = 1). Intensity of pruritus was documented 24 hours before as well as 24 hours, 7 and 30 days after MARS therapy, and at the end of follow-up. We measured complete blood cell counts, glucose, BUN, creatinine, sodium, potassium, AST, ALT, GGT, alkaline phosphatase, bilirubin, prothrombin activity, and activated partial thromboplastin time. RESULTS: MARS therapy was well tolerated. Patient 1 experienced temporal relief of pruritus, but needed another MARS cycle because of relapse. Patient 2 experienced partial and temporary relief of pruritus, was listed for retransplantation, and received a liver graft 2 months later. Patient 3 showed a dramatic reduction in the degree of pruritus with MARS. Pruritus in patient 4 decreased promptly with MARS therapy and conversion of immunosuppression to tacrolimus, thereby avoiding retransplantation. CONCLUSION: MARS therapy is a promising, safe therapeutic option to treat refractory pruritus caused by cholestatic liver disorders.     

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.     

Hemodynamic improvement as an additional parameter to evaluate the safety and tolerability of the molecular adsorbent recirculating system in liver failure patients

BACKGROUND: The molecular adsorbent recirculating system (MARS) is an extracorporeal acute liver failure (ALF) support system method using albumin-enriched dialysate to remove albumin-bound toxins. PATIENTS AND METHODS: Since 1999 we performed 2027 MARS treatments in 191 patients: 39 fulminant hepatic failure (FHF), 16 primary nonfunction (PNF), 21 delayed function (DF), 94 acute-on-chronic liver failure (AoCHF), 7 post-hepatic resection, and 14 intractable pruritus. RESULTS: We divided the complications by the AoCHF versus the ALF populations. Among 83 ALF patients, we observed worsening of hemodynamic parameters in 16 patients: 3 with PNF, 2 with DF without retransplantation, 9 with FHF, and 2 after hepatic resection. Among 94 AoCHF patients, 42 showed hemodynamic instability requiring intensive care unit support. Our study did not note significant adverse effects (1.8%), except for infections and hemorrhage from the central venous catheter not due to MARS treatment. The thrombocytopenia was controlled through administration of platelets before the start of treatment when a patient showed a level under 30,000 mm(3). CONCLUSION: Our results confirmed that nonbiological hepatic support by MARS was safe and tolerable.     

Molecular adsorbent recirculating system in liver transplantation: Safety and efficacy

We assessed the safety and clinical efficacy of the Molecular Adsorbent Recirculating System (MARS) in liver failure patients admitted to our intensive care unit (ICU) from May 2000 to February 2006. Of 28 adult patients with bilirubin >15 mg/dL and hepatic encephalopathy (HE) grade > or =2 or hepato-renal syndrome, 22 patients were included in the study, because 6 patients were older than 65 years of age or showed recent alcohol abuse or extrahepatic malignancy. Patients were assigned to 2 groups according to whether MARS therapy was associated with a transplantation procedure: 11 patients received MARS therapy and liver transplantation (OLT group) and 11 patients received MARS therapy alone (non-OLT group). Five of 11 patients in the OLT group were listed for transplantation and 6 patients with graft failure for retransplantation. The patients in the OLT and non-OLT groups were similar in MELD, SOFA, and SAPS scores. All patients were stable and free from complications. MARS significantly reduced bilirubin, bile acids, and blood urea nitrogen (BUN) levels in both groups (P < .05), whereas a significant decrease in ammonia level was observed in the OLT group. Patient survival rates at 3 and 6 months in the OLT group were 91% and 73%, respectively, and in the non-OLT group, 9% and 9%, respectively (P < .001). MARS was safe and well tolerated, improving biochemical parameters, neurological function, and pruritus. In terms of survival, the use of MARS alone was not effective due to the high rate of multiple organ failure. Nevertheless, the association of MARS with a transplant/retransplantation procedure was highly effective.     

Pediatric liver transplantation for acute liver failure

The only proven therapy for patients unlikely to recover from acute liver failure (ALF) is liver transplantation. Correct diagnosis of these individuals and rapid referral to a transplant center are crucial. We evaluated 12 pediatric patients with ALF who underwent liver transplantation (LT) at our institution during a 3-year period. The reasons for transplantation were hepatitis A (3 patients); non-A, non-E hepatitis (3); autoimmune hepatitis (1); fulminant Wilson's disease (3); Amanita phalloides (mushroom) poisoning (1); and hepatitis B and toxic hepatitis with leflunomide treatment (1). Seven of the participants were female and five were male (mean age, 9.1 +/- 4.2 years). Three received right liver-lobe grafts, one received a whole liver graft, and the remainder received left or left-lateral liver lobe grafts. All patients recovered from hepatic coma the second postoperative day. Two patients died at postoperative days 57 and 71 due to adult respiratory distress syndrome and sepsis with multiorgan failure, respectively. One patient required retransplantation because of chronic rejection 7 months after the initial transplantation. That patient died 10 days after retransplantation because of sepsis. Nine patients were healthy at follow-up (range, 2-46 months). LT is the only treatment option for ALF in patients in countries with low organ-donation rates. In this scenario, donor preparation in a limited time frame is difficult. We have been able to decrease the duration of donor preparation to approximately 4 hours (including biopsy of the donated liver tissue).