The Advanced Organ Support (ADVOS) hemodialysis system fulfills its intended purpose: Analysis of data from 282 patients from the Registry on Extracorporeal Multiple Organ Support (EMOS)

As many as 30% of critically ill patients in intensive care units experience acute liver dysfunction with hyperbilirubinemia as a part of multiorgan failure that is associated with poor outcome. This retrospective cohort study was aimed at comparing CytoSorb and ADVOS in terms of bilirubin removal and overall survival among critically ill patients with hyperbilirubinemia ≥ 7mg/dL. At the University Hospital Essen, between January 2021 and March 2024, 71 patients were treated with CytoSorb integrated in a continuous veno-venous hemodiafiltration (CVVHDF) circuit, and 71 patients were treated with ADVOS. Each therapy session lasted 24h. We separately analyzed the subgroup of patients with acute-on-chronic liver failure (ACLF), in which 31 patients were treated with CytoSorb and 66 patients were treated with ADVOS. The first single sessions of both CytoSorb with CVVHDF and ADVOS were associated with a statistically significant decrease in total serum bilirubin levels (Cytosorb, 20 to 14mg/dL, p < 0.0001; ADVOS, 16 to 14mg/dL, p < 0.0001), but the percentage bilirubin reduction was more pronounced for CytoSorb treatment (26% vs. 17%, p = 0.0002). The number of days of treatment was similar for both groups (3 vs. 4, p = 0.07). After completion of therapy, serum levels of total bilirubin had decreased significantly; 19.9 to 11.3mg/dl (p < 0.0001) in the CytoSorb group and 16.3 to 14.0mg/dL (p = 0.003) in the ADVOS group. The relative bilirubin reduction was significantly higher after application of CytoSorb than after treatment with ADVOS (35% (IQR 19,54) vs. 15% (IQR - 11;54), p < 0.0001). Regarding patients with ACLF, relative reduction of bilirubin after the first session as well as after the completion of liver support was significantly higher among patients who were treated with CVVHDF and CytoSorb than among those patients who received ADVOS. The relative removal of creatinine and urea nitrogen was significantly higher after ADVOS treatment than after CytoSorb with CVVHDF treatment considering all critically ill patients as well as ACLF patients. Seven-day or in-hospital mortality rates were high among critically ill patients and patients with ACLF in both liver support groups. Our results showed that CytoSorb and CVVHDF treatment performed better than ADVOS in bilirubin removal among critically ill patients with hyperbilirubinemia caused by acute liver dysfunction and in the subgroup of patients with ACLF. ADVOS was more efficient in eliminating creatinine and urea nitrogen than was CVVHDF with CytoSorb. Additional prospective randomized controlled trials are warranted to investigate the efficacy of hemoperfusion with CytoSorb for liver disease indications among critically ill patients. Not applicable.

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

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

Sarcopenia should be evaluated in patients with acute-on-chronic liver failure and candidates for liver transplantation

BackgroundPrevalence of multiple organ failure (MOF) in critically ill patients is increasing and associated mortality remains high. Extracorporeal organ support is a cornerstone in the management of MOF. We report data of an advanced hemodialysis system based on albumin dialysis (ADVOS multi device) that can regulate acid–base balance in addition to the established properties of renal replacement therapy and albumin dialysis systems in critically ill patients with MOF.Methods34 critically ill patients with MOF received 102 ADVOS treatment sessions in the Department of Intensive Care Medicine of the University Medical Center Hamburg-Eppendorf. Markers of metabolic detoxification and acid–base regulation were collected and blood gas analyses were performed. A subgroup analyses were performed in patients with severe acidemia (pH < 7.2).ResultsMedian number of treatment sessions was 2 (range 1–9) per patient. Median duration of treatment was 17.5 (IQR 11–23) hours per session. Treatment with the ADVOS multi-albumin dialysis device caused a significant decrease in bilirubin levels, serum creatinine, BUN and ammonia levels. The relative elimination rate of bilirubin was concentration dependent. Furthermore, a significant improvement in blood pH, HCO3− and PaCO2, was achieved during ADVOS treatment including six patients that suffered from severe metabolic acidosis refractory to continuous renal replacement therapy. Delta pH, HCO3− and PaCO2 were significantly affected by the ADVOS blood flow rate and pH settings. This improvement in the clinical course during ADVOS treatments allowed a reduction in norepinephrine during ADVOS therapy. Treatments were well tolerated. Mortality rates were 50% and 62% for 28 and 90 days, respectively.ConclusionsIn this case series in patients with MOF, ADVOS was able to eliminate water-soluble and albumin-bound substances. Furthermore, the device corrected severe metabolic and respiratory acid–base disequilibrium. No major adverse events associated with the ADVOS treatments were observed.

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.

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

Severe hypercapnia, especially when associated with acidosis, should be avoided or actively managed, as it is an independent risk factor in critically ill patients. The ADVOS multi hemodialysis system offers the potential to correct acidosis and hypercapnia through customizable pH and bicarbonate content within the dialysate fluid. The aim of this work is to analyze the exact timing for pH correction and the main factors leading to it in patients with multiple organ failure (MOF) and hypercapnic acidosis treated with ADVOS. Patients with MOF and metabolic or hypercapnic acidosis (pH < 7.35) were included over a study period of 13months. All patients received at least one treatment with ADVOS hemodialysis system for at least 24h. The primary outcome was the time to blood pH ≥ 7.35. 24 patients with a median age of 61years and a median SOFA score of 15 points were included. The results of 134 ADVOS sessions, with a median of 5 sessions per patient, were analyzed. Median time to blood pH ≥ 7.35 was 4h; a significant blood pH increase within 24h was reached in all patients (7.21 before vs. 7.39 after, p < 0.01). A single session of ADVOS corrected blood pH and supported the reduction of pCO2 with a median CO2 removal of 55mL/min in patients with multiple organ failure and hypercapnic acidosis.

Background: Acute on chronic liver failure (ACLF) is typically characterized by a rapid progression of liver failure in patients with liver cirrhosis and it is triggered by a precipitant factor, usually a bacterial infection (BI). Considering the low accuracy of the inflammation biomarkers in liver cirrhosis, presepsin and procalcitonin have demonstrated a good diagnostic performance for BI. Understanding the key prognostic factors that influence patient outcomes can significantly impact clinical decision-making and improve patient care in ACLF which can lead to lower mortality rates. Aim: To evaluate the prognostic factors associated with 30-day mortality in patients with alcohol-related liver cirrhosis and ACLF. Methods: This retrospective study on 227 patients diagnosed with ACLF and alcohol-related liver cirrhosis analyzed the prognostic role of presepsin and procalcitonin serum levels. Results: The survival analysis according to the grade of ACLF showed that more than 80% of patients with ACLF grade 1 survived after 30 days, with a mean estimated time of death of 29 ±0.44 days (95 % CI: 28.17-29.92) compared to ACLF grade 2 (24.9±1.064 days; 95 % CI: 22.82-26.99) and ACLF grade 3 (21.05±1.17 days; 95 % CI: 18.75-23.34), with a mean overall survival on entire cohort of 25.69±0.52 days (95 % CI: 24.65-26.73). Presepsin (OR: 4.008, CI 95:3.130-6.456, p=0.001) and procalcitonin (OR: 3.666, CI 95:2.312-5.813, p=0.001) were the most significant factors associated with 30-day mortality. In ACLF grade 2, presepsin provides a better prediction of mortality at the cutoff value of 1050 pg/mL (Sensitivity 72%, Specificity 69%) than procalcitonin (AUC=0.727 95% CI 0.594-0.860, p<0.002) whereas in ACLF grade 3, a cutoff of 1450 pg/mL (Sensitivity 89%, Specificity 91%) presepsin had a more significant accuracy of mortality prediction (AUC=0.93 95% CI 0.81-0.99, p<0.001) than procalcitonin (AUC=0.731 95% CI 0.655-0.807, p<0.001). Conclusion: ACLF is associated with a high mortality rate and the risk of death increases with the grade of ACLF. Presepsin and procalcitonin serum levels are good prognostic factors for 30-day mortality and should be used in clinical practice to stratify the risk and provide and early and efficient treatment in patients with ACLF.

Living Donor Liver Transplantation for Acute on Chronic Liver Failure Based on EASL-CLIF Diagnostic Criteria

Acute on chronic liver failure (ACLF) is a syndrome occurring in patients with chronic liver disease with or without cirrhosis characterised by acute hepatic decompensation and one or more extra...

Objective: To observe baseline characteristics, ACLF (Acute on Chronic Liver Failure) grading and mortality in ACLF patients using EASL CLIF CRITERIA. Study Design: Prospective, Observational study. Setting: Medical unit 111, ward 7, Jinnah Postgraduate Medical Centre, Karachi. Period: January 2022 to June 2022. Material &amp; Methods: We prospectively analysed data of hospitalised liver cirrhosis patients at a tertiary care hospital in Karachi, Pakistan. The data was analysed in SPSS version 25. Results: There were a total of 43 ACLF patients, with the median age of IQR of 56(47-62) years, out of which 20 (46.5%) patients were male and 23 (53.5%) were females. The most common etiology of liver cirrhosis was hepatitis C 26(60.5%) followed by other etiologies nine (20.9%) and hepatitis B eight (18.6%). The most common precipitating factor was infection 19(44.2%) and the most frequent organ failure (OF) was renal failure (60.5%), followed by cerebral failure (46.5%) and other OFs. There were 24 patients in ACLF grade one, 13 in grade two and six in grade three ACLF. All six patients of ACLF grade three belonged to CTP C (Child-turcotte-pugh Cirrhosn) (100%) with 100% mortality. ACLF grade two had nine (69.2%) and ACLF grade one had eight (33.33%) CTP C patients. The in hospital mortality of ACLF was 23%. The median MELD Na of these patients was 28 (23-31), CLIF Consortium Organ Failure score was 9(8-10) and CLIF C ACLF Score was 45 (38-55). Conclusion: Highest mortality was observed in Child Pugh C and ACLF grade three in our patients. Such patients must be closely monitored and referred early for medical management and liver transplantation.

Predictors and outcome of emergent Liver transplantation for patients with acute-on-chronic liver failure

BackgroundMulti‐organ failure characterized by acute kidney injury, liver dysfunction, and respiratory failure is a complex condition associated with high mortality, for which multiple individual support devices may be simultaneously required. This review aims to appraise the current evidence for the ADVanced Organ Support (ADVOS) system, a novel device integrating liver, lung, and kidney support with blood detoxification.MethodsWe performed a literature review of the PubMed database to identify human and animal studies evaluating the ADVOS system.ResultsIn porcine models of acute liver injury and small clinical studies in humans, ADVOS significantly enhanced the elimination of water‐soluble and protein‐bound toxins and metabolites, including creatinine, ammonia, blood urea nitrogen, and lactate. Cardiovascular parameters (mean arterial pressure, cerebral perfusion pressure, and cardiac index) and renal function were improved. ADVOS clears carbon dioxide (CO2) effectively with rapid correction of pH abnormalities, achieving normalization of CO2, and bicarbonate levels. In patients with COVID‐19 infection, ADVOS enables rapid correction of acid–base disturbance and respiratory acidosis. ADVOS therapy reduces mortality in multi‐organ failure and has been shown to be safe with minimal adverse events.ConclusionsFrom the small observational studies analyzed, ADVOS demonstrates excellent detoxification of water‐soluble and protein‐bound substances. In particular, ADVOS permits the correction of metabolic and respiratory acidosis through the fluid‐based direct removal of acid and CO2. ADVOS is associated with significant improvements in hemodynamic and biochemical parameters, a trend toward improved survival in multi‐organ failure, and is well‐tolerated. Larger randomized trials are now necessary to further validate these encouraging results.

The aim - to determine the etiology and clinical features of the acute-on-chronic liver failure (ACLF) in patients with acute decompensation of liver cirrhosis (LC). Materials and methods. A retrospective analysis of the clinical features of ACLF was performed in 71 patients with LC, who died within 28 days of hospital stay. The etiology of the LC was determined, traditional clinical, laboratory and instrumental data were performed, the chronic liver failure organ failure score (CLIF OF S), chronic liver failure-consortium acute-on-chronic liver failure score (CLIF-C ACLF S), model for end stage liver disease score (MELD S) and Child-Pugh score (Ch-P S) were calculated. Results. Alcoholic genesis of LC was detected in 63.4% of patients, alcoholic in combination with metabolic (NAFLD) - in 15.5%, alcoholic in combination with viral - in 4,2%, metabolic - in 1,4%, viral - in 4, 2%, autoimmune - in 1,4%, drug - in 1,4%, unidentifiable - in 8.5%. Triggers for the development of ACLF were active alcoholism in 39.4% of patients, bacterial infection in 19.7%, esophageal bleeding in 15.5%, active HCV infection in 4.2%, autoimmune attack in 1,4%. ACLF grade 1 was revealed in 26.8%, ACLF grade 2 - in 19.7%, ACLF grade 3 - in 53.5% of patients. The frequency of organ failures were: liver - 73.2%, kidney - 54.9%, coagulation - 54.9%, cerebral - 21.6%, circulation - 18.3%, lungs - 11.3%. CLIF OF S, CLIF-C ACLF S significantly increased already at ACLF grade 2, and MELD S and Ch-P S - only at ACLF grade 3. Conclusion. The alcoholic genesis of LC was revealed in the most patients (63.4%) and active alcoholism was the trigger for ACLF development (39.4%). The most frequent clinical manifestations of ACLF were liver failure (73.2%), kidney (54.9%) and coagulation (54.9%). CLIF OF S, CLIF-C-ACLF S had better diagnostic and prognostic significance than MELD S and Ch-P S.