Albumin dialysis has no clear effect on cytokine levels in patients with life-threatening liver insufficiency

Cytokines play a important role in life-threatening liver insufficiency. They are released within the liver in response to hepatic injury and inflammation. To study cytokine clearance during albumin dialysis treatment (Molecular Adsorbent Recirculating System [MARS]), we monitored proinflammatory (tumor necrosis factor alpha [TNF-alpha] and interleukin-8 [IL-8]) and anti-inflammatory (IL-10 and IL-6) cytokines and the lymphocyte activation marker IL-2sRalpha in 81 consecutive ICU patients displaying serious hepatic decompensation. Cytokine levels were measured before treatment and after the last MARS treatment in 49 acute liver failure (ALF) and 32 acute decompensation of chronic liver disease (AcOChr) patients who were mainly considered for liver transplantation. No significant change in cytokines was observed before versus after the last MARS treatment in the AcOChr group, and only IL-10 decreased significantly in the ALF group. Baseline levels of IL-8 and IL-6 were significantly lower and IL-10 was higher in the ALF group compared with those in the AcOChr group. TNF-alpha and IL-2sRalpha levels did not differ between the groups. After treatment, IL-8 was also significantly lower in ALF patients compared with the levels in AcOChr patients. In this study, MARS therapy did not show a clearly identifiable efficacy at removing circulating cytokines. However, the results revealed that ALF and AcOChr patients displayed different profiles of circulating cytokines.     

The effect of albumin dialysis on cytokine levels in acute liver failure and need for liver transplantation

In acute liver failure (ALF), detoxification capacity of liver cells is reduced and a variety of cytokines, immune modulators, and toxic substances are accumulating. Multiple organ failure in ALF has been associated with increased blood cytokine levels. We have used a blood purification system, molecular adsorbent recirculating system (MARS), which is based on removal of both protein bound and water-soluble substances and toxins in liver failure. In this study, we measured the effect of MARS therapy on plasma cytokine levels in 49 patients with ALF. Interleukin 6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF)alfa were determined immediately before and after the first MARS therapy and after the last session using enzyme-linked immunosorbent assays. The overall survival of these ALF patients was 82% at 6 months; the native liver recovered in 26 cases, and 14 were successfully transplanted. All three interleukins were increased before the MARS treatment but only anti-inflammatory IL-10 was reduced significantly during therapy, which in this setting could be interpreted as a positive effect. We were not able to show constant decreases in proinflammatory cytokines, but only transient effects on IL-8 and IL-6. Surprisingly TNFalfa level was normal and did not change during therapy. In theory, MARS albumin dialysis may remove toxic substances from the blood circulation and thereby improve the possibilities of the liver to recover; however, of the measured cytokines only IL-10 decreased significantly.     

The decrease in cytokine concentration during albumin dialysis correlates with the prognosis of patients with acute on chronic liver failure

BACKGROUND AND AIM: The clearance of plasma cytokines by means of albumin dialysis (MARS) has been demonstrated in various studies involving patients affected by either acute liver failure (ALF) or acute on chronic liver failure. The aim of the study was to measure the plasma levels of TNF-alpha, IL-6, and IL-1beta in patients with ALF after each MARS treatment to evaluate the relationship between variations in cytokines levels and patient prognosis. MATERIALS AND METHODS: Ten patients with ALF undergoing several MARS treatments were enrolled (group 1). Blood samples were collected before and after each MARS treatment to measure TNF-alpha, IL-6, and IL-1beta, and other hematochemical parameters. We also enrolled 10 patients with ALF who underwent standard therapy (group 2) as well as a control group of 10 healthy subjects matched for sex and age (group 3). RESULTS: MARS reduced total bilirubin levels, biliary acids, BUN, ammonia, TNF-alpha, IL-6, and IL-1beta (P < .05). Moreover, the reduction in inflammatory cytokines levels and improved prognosis were related. CONCLUSIONS: We confirmed the therapeutic efficacy of MARS treatment for ALF, which appeared to be related to removal of toxins and inflammatory cytokines determine that which patients prognosis.     

Plasma proinflammatory and anti-inflammatory cytokine and catecholamine concentrations as predictors of neurological outcome in acute stroke patients

PURPOSE: Proinflammatory and anti-inflammatory cytokines may play a pivotal role in cerebral inflammation, which is implicated in the development of brain injury. Systemic cytokine release is mediated by the sympathetic nervous system and catecholamines. The aim of this study was to investigate which parameters, among plasma levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-alpha) and the levels of the catecholamines, epinephrine and norepinephrine, contribute to the clinical outcome in acute stroke patients. METHODS: Thirty-seven acute stroke patients (ischemic, n = 19; hemorrhagic, n = 18) were enrolled. All of them were admitted to our hospital within 8 h after stroke onset. Neurological status was evaluated by a modified National Institute of Health Stroke Scale (mNIHSS) on admission and by a modified Rankin Scale (mRS) at 1 month. An mRS score of 3 or more at 1 month was considered to indicate poor outcome. Serum samples for the cytokine and catecholamine measurements were collected on admission. Plasma levels of IL-1beta, IL-6, IL-10, and TNF-alpha were determined by an enzyme-linked immunosorbent assay (ELISA) method and epinephrine and norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection (HPLC-EC). RESULTS: In the ischemic stroke patients, poor outcome was noted in 9 (47%). There were no significant differences in cytokine or catecholamine concentrations between patients with poor and good outcomes, and there was no association between clinical outcome and cytokine and catecholamine concentrations. In the hemorrhagic stroke patients, poor outcome was noted in 10 (56%). IL-6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02-1.54). CONCLUSION: In ischemic stroke, plasma cytokines and catecholamines were not predictors of neurological outcome at 1 month. In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome.     

Cytokine Level Modifications: Molecular Adsorbent Recirculating System Versus Standard Medical Therapy

Introduction

Acute-on-chronic liver failure (ACLF) is a systemic inflammatory reaction, which is characterized by a predominantly proinflammatory cytokine profile, causing the transition from stable cirrhosis to ACLF. The aim of the present study was to evaluate the changes in several cytokines associated with inflammatory liver disease and liver regeneration among 15 ACLF patients treated with the Molecular Adsorbent Recirculating System (MARS) compared with 15 patients treated with standard medical therapy (SMT). The subjects showed various disease etiologies but similar values for Model End-stage Liver Disease scores.

Methods

In the MARS group, 15 (10 male and 5 female) patients were treated with MARS (Gambro). The number of MARS applications was nine; the length of applications was 8 hours. In the SMT group; 15 (10 male and 5 female) patients were treated with SMT. The patients were monitored for 30 days from inclusion with a survival follow-up at 3 months. Statistical results were calculated with SPSS14.0 (SPSS Inc, Chicago, Ill). A P < .07 was considered significant.

Results

In the MARS group, we observed significant changes in the levels of Interleukin (IL)-6, IL-1, IL-10, and tumor necrosis factor (TNF)-α in association with improved hepatocyte growth factor. Patient survival at 3 months was 60%. The SMT group showed only a significant change in TNF-α (P = .03). Patient survival at 3 months was 30%.

Conclusion

The MARS liver support device corrected pathophysiologies of ALF and may be used to enhance spontaneous recovery or as a bridge to transplantation.     

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.     

Inflammation is an important determinant of levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) in acute liver failure.

Acute liver failure (ALF) is characterized by rapid progressive organ failure and poor outcome. The pathophysiology of multiorgan dysfunction in ALF remains unclear but increased systemic inflammatory response is believed to be an important determining factor. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, results from proteolysis and the liver is a major site for its metabolism. ADMA has been shown to independently predict outcome in multiorgan failure associated with severe liver dysfunction. In this study, we tested the hypothesis that proinflammatory cytokine driven responses are important in modulating ADMA levels in patients with acetaminophen-induced ALF. Blood samples were collected from 10 ALF patients (grade IV encephalopathy) from admission until the time of transplantation or death, and assayed for cytokines and ADMA. A total of 8 patients required treatment for raised intracranial pressure and all patients were managed with standard of care, including full mechanical ventilation and veno-venous hemofiltration. ADMA levels were markedly higher in ALF patients compared to age-matched controls (P < 0.001) and correlated with the levels of proinflammatory cytokines. In pretransplantation patients undergoing hepatic venous catheterization, we demonstrated no significant uptake of ADMA across the failing liver. However, following liver transplantation, ADMA levels reduced acutely. A timed study of ADMA levels during transplantation demonstrated a slight increase during the anhepatic phase but a marked and sustained reduction in ADMA following liver reperfusion. In conclusion, our data show a significant correlation between ADMA levels and proinflammatory cytokines, supporting a hypothesis that proinflammatory cytokines may regulate ADMA metabolism in ALF.     

Systemic liberation of interleukin-1β and interleukin-1 receptor antagonist in the perioperative phase of liver transplantation

We measured systemic serum levels of interleukin-1 receptor antagonist (IL-1ra), interleukin-1 (IL-1), tumor necrosis factor (TNF-), and interleukin-6 (IL-6) during the preoperative, anhepatic, and postreperfusional phases up to the 7th postoperative day in 60 patients undergoing orthotopic liver transplantation (LTx). In contrast to IL-1, IL-1ra, TNF-, and IL-6 showed a significant elevation in relation to the early phase after reperfusion, while TNF- displayed a high grade of scatter. In addition, IL-1ra levels were significantly elevated during the anhepatic phase. Maximum serum levels were found at 15 min after reperfusion, 120 min after reperfusion, and on the 1st postoperative day, respectively. Serum levels decreased considerably at 24 h and 7 days after reperfusion. The comparative monitoring of systemic cytokine and cytokine antagonist levels, in particular the liberation of IL-1ra and IL-6 may provide useful parameters for the development of new liver preservation theories for LTx.     

Local secretion of TNF-α from the liver does not correlate with endotoxin, IL-6, or organ function in the early phase after orthotopic liver transplantation

Hepatic ischemia/reperfusion leads to an excessive release of proinflammatory cytokines, which promotes local and remote cell damage. The value of cytokine measurement in humans for predicting graft function after orthotopic liver transplantation (OLT) remains unclear. Therefore, in this study, tumor-necrosis-factor-α (TNF-α), interleukin-6 (IL-6), and endotoxin (ET) levels were determined in the blood taken from the hepatic veins of 31 patients who underwent OLT. Peak levels of TNF-α in hepatic venous blood were measured shortly after reperfusion and were significantly higher than concentrations in the systemic circulation. IL-6 concentrations, peaking 90 min after reperfusion, only correlated with postoperative pulmonary dysfunction. ET was detectable in 21 patients, but levels did not correlate with either IL-6 or TNF-α concentrations. Additionally, serum cytokine levels did not correlate with the duration of ischemia or with histological changes seen in liver biopsies. In general, our study suggests that local secretion of cytokines does not predict liver function in the early posttransplant phase. Received: 25 October 1999 Revised: 7 July 2000 Accepted: 22 November 2000     

Value of albumin dialysis therapy in severe liver insufficiency

A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patients own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.     

血清sIL-2R、IL-6及胆汁IL-6监测对早期预测肝移植急性排斥反应的作用

目的　评价血清sIL 2R、IL 6及胆汁IL 6水平在预测肝移植急性排斥反应中的意义。方法　连续 3周监测 2 8例肝移植受者术后血清sIL 2R、IL 6及胆汁IL 6水平 ,观察其与急性排斥反应的关系。结果　在急性排斥反应 (AR)组 ,血清sIL 2R及胆汁IL 6水平在排斥发作时明显升高 ,与非排斥组比较有显著性差异 (P <0 .0 1)。当AR经激素冲击治疗逆转后 ,血清sIL 2R及胆汁IL 6下降至排斥前的水平。在AR组 ,仅有 3例受者在排斥发作时血清IL 6水平升高 ,与非排斥组相比 ,血清IL 6水平无明显差异 (P >0 .0 5 )。结论　胆汁IL 6水平有望作为预测AR敏感、较具特异性及非侵袭性的手段。同时 ,其水平还可作为观察抗排异治疗是否有效的指标。     

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.     

Albumin dialysis and Molecular Adsorbents Recirculating System (MARS) for acute Wilson's disease

Wilson's disease presenting as acute liver failure (ALF) is potentially fatal, and liver transplantation (LTx) is the only option. We report two patients with Wilson's disease and ALF treated with the Molecular Adsorbents Recirculating System (MARS). Both patients fulfilled criteria for poor prognosis. Because LTx was not available immediately in either case, MARS was used as a bridge to LTx. In Case 1, serum bilirubin decreased from 803 to 425 μmol/L after 3 treatments, but increased to 656 μmol/L during a break, decreasing again to 457 μmol/L with further treatment. Serum copper decreased from 53.7 μmol/L, to 35.8 μmol/L after first treatment session, and 17.4 μmol/L at treatment completion. In Case 2, MARS treatment over 2 weeks reduced serum bilirubin from 1200 to 450 μmol/L and copper from 35 to 13 μmol/L with marked improvement in encephalopathy and reduction in ammonia (59 to 34 μmol/L). Both patients were successfully bridged to LTx (days 9 and 28, respectively). Analysis of albumin-dialysate from the MARS circuit suggested that copper removal occurred mostly in the first few hours of treatment, partly being adsorbed by albumin and partly by the MARSFlux membrane (Teraklin AG, Rostock, Germany). These data suggest that MARS removes copper efficiently and can be used to bridge patients with Wilson's disease and ALF to LTx. (Liver Transpl 2002;8:962-967.)     

The calcium channel blocker nisoldipine minimizes the release of tumor necrosis factor and interleukin-6 following rat liver transplantation

Kupffer cells, when activated, release toxic cytokines such as tumor necrosis factor (TNF), which can cause tissue injury. Takei et al. have reported that nisoldipine, a calcium channel blocker which decreases phagocytotic activity by Kupffer cells, also diminishes liver and lung injury and dramatically improves survival following liver transplantation [27]. Therefore, we studied the effect of nisoldipine on the time course of TNF and interleukin-6 (IL-6) release following cold storage and liver transplantation in the rat. Livers were stored under survival and non-survival conditions in cold Euro-Collins solution in the presence or absence of nisoldipine (1.4 µM). After storage, the effluent was collected for determination of cytokines. The liver was then transplanted orthotopically and serum was collected at various time intervals for up to 5 h. In the effluent, TNF levels were very low in both the control and nisoldipine-treated groups and IL-6 was not measurable. Furthermore, when livers were stored under survival conditions and transplanted (liver stored in the cold for 4 h), serum TNF (2 U/ml) and IL-6 (350 U/ml) values were minimal in both the control and nisoldipine-treated groups. In contrast, when livers were stored under non-survival conditions and transplanted (liver stored in the cold for 10 h), TNF levels increased to 15 ± 2 U/ml, 150 min after graft reperfusion, an increase which was prevented by nisoldipine (6.5 U/ml). Serum IL-6 levels were also elevated 300 min after transplantation in livers stored for 10 h. Nisoldipine also reduced the release of this cytokine. Serum transaminases (SGOT) were elevated to values around 2000 U/l 5 h following transplantation. In the nisoldipine-treated group, values were lower between 60 and 300 min. In the lung, interstitial and alveolar edema and cellular infiltration were detectable 5 h post-operatively and were diminished by nisoldipine. These data confirmed that TNF and IL-6 release were minimal following cold storage and transplantation of livers stored under survival conditions, but were elevated transiently after transplantation under non-survival conditions. Nisoldipine prevented cytokine release, most likely by blocking the activation of Kupffer cells, which may explain how it decreases liver and lung injury very early following liver transplantation.     

The significance of serum hepatocyte growth factor levels in planning follow-up of postoperative jaundice-free patients with biliary atresia

Purpose

The aim of this study was to clarify the significance of serum hepatocyte growth factor (HGF), interleukin (IL)-6, and IL-1 receptor antagonist (ra) levels in the evaluation of disease status in jaundice-free survivors with biliary atresia after Kasai operation.

Patients and Methods

Serum concentrations of HGF, IL-6, and IL-ra were measured in 31 long-term jaundice-free patients with biliary atresia after Kasai operation and 29 controls. Patients were divided into 4 groups: group A (n = 8), normal liver function; group B (n = 9), mild liver dysfunction without portal hypertension; group C (n = 9), moderate liver dysfunction with controllable portal hypertension; and group D (n = 5), receiving liver transplantation.

Results

Serum IL-6 levels were significantly higher in patients than in controls. There was no difference in serum IL-6 levels among groups B, C, and D. Serum IL-1ra levels were elevated according to liver dysfunction. Serum HGF levels in group D were significantly higher than in controls and the other groups. Serum hyarulonic acid levels were positively correlated with serum levels of IL-1ra and HGF.

Conclusions

Elevation of serum IL-1ra and HGF levels correlated with the progression of liver fibrosis and dysfunction. In particular, serum HGF levels could be used as a predictor for requiring liver transplantation.     

Nucleosome Serum Levels in Acute Hepatic Failure and MARS Treatment

Serum nucleosomes have been suggested to be markers for cell death and apoptosis. Increased hepatocyte apoptosis can be demonstrated in acute liver failure (ALF) as well as acute-on-chronic liver failure (ACLF). We investigated the relevance of nucleosomes in the setting of acute hepatic failure. Further, we studied the effects of the molecular adsorbent recirculating system (MARS) on this marker of cell death. We measured serum nucleosome concentrations with ELISA in 12 patients with ACLF and 7 patients suffering from ALF, with 14 patients experiencing stable chronic hepatic failure (CHF) as controls. In a subset of 8 ACLF and ALF patients treated with MARS, nucleosomes were determined immediately before and after the first MARS session. Baseline nucleosome serum concentrations were significantly increased in ACLF and ALF patients as compared with CHF patients (P = .0161 and P = .0037, respectively). There was no significant difference between the ALF and ACLF groups. Moreover, serum nucleosome levels did not change significantly during MARS treatment in ALF and ACLF patients. Serum nucleosome levels therefore may be useful to discern acute from chronic hepatic failure or to monitor the course and the severity of the disease. Our results, however, warrant further larger clinical studies regarding the clearance of nucleosome in artificial liver-assist devices and to assess their role in acute hepatic failure.     

Strain-specific in vitro cytokine production profiles do not predict rat liver allograft survival

The aim of this study was to assess whether differences in cytokine production between inbred rat strains could explain differences in liver allograft survival. Splenocytes from five different strains were cultured with Concanavalin A to determine in vitro cytokine production profiles. Strain-specific TNF-, IFN-, IL-6 and IL-10 responses in naive animals were not associated with survival after rat liver transplantation. To investigate whether in vitro cytokine responses changed during the allogeneic inflammatory response, Brown Norway livers were transplanted to Lewis and Pivold Virol Glaxo recipients. During the early postoperative phase IL-6 and IL-10 (Th2-like) responses were significantly up-regulated in Lewis recipients, whereas Th2-like responses were not increased in Pivold Virol Glaxo. Our results do not support the generally held view that differential in vitro cytokine responses are related to liver allograft survival but suggest that cytokine responses are affected by the allogeneic inflammatory response after liver allografting.     

Value of albumin dialysis therapy in severe liver insufficiency

Abstract A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patient's own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.     

Management of sepsis during MARS treatment in acute on chronic liver failure

Introduction

The aim of our study was a 30-day follow-up of the use of early detection of endotoxin by the endotoxin activity assay (EAA) for patients with acute liver failure superimposed on chronic liver disease (AoCLF) and treated with polymyxin-B hemoperfusion-based (PMX-DHP) treatment and albumin dialysis in the molecular adsorbent recirculating system (MARS).

Materials and Methods

From February 2008 to July 2010, we evaluated 10 AoCLF patients experiencing systemic inflammatory response syndrome (SIRS) in association with suspected infection and an EAA-positive test (>0.60). These patients awaiting liver transplantation (OLT) showed similar Model End-Stage Liver Disease (MELD) scores (range, 19-25) and encephalopathy grade ≤ 2. Five patients received therapy to remove endotoxins with PMX-DHP with MARS treatment for liver failure (group A); the other 5 patients received MARS treatment only (group B).

Results

Two PMX-DHP treatments were performed in 4 group A patients (average EA = 0.66 [range, 0.61-0.70]) and 3 treatments for 1 patient (EA = 0.92). All 5 subjects underwent an average of 4 MARS treatments (range, 3-5). At the end of therapy, the median EA level was 0.42 (range, 0.37-0.48). As reported in the literature, we achieved a significant improvement in liver and kidney functions using MARS. Measurements of lactate, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were significantly improved among patients treated with the extracorporeal therapies. At 30 days of observation, all 5 patients treated with MARS plus PMX-DHP are alive. In group B, a mean of 7.5 MRAS treatments were performed. We observed an improvement in hemodynamic and liver functions with reduced levels of proinflammatory cytokines and lactates in 4 patients. One patient showed no improvement in clinical status with the development of sepsis and subsequent multiorgan failure after 24 days.

Conclusion

The possibility of an early diagnosis using the EAA in AoCLF patients could prevent the progression of the sepsis cascade. The use of PMX-DHP and MARS in these patients, could lead to resolution of clinical status in a short time.