Use of the cytosorb adsorber in patients with acute-on-chronic liver failure

ABSTRACT CytoSorb is a hemoadsorptive column used to remove high concentrations of proinflammatory cytokines in septic shock. Data on CytoSorb application in acute-on-chronic liver failure

(ACLF) is lacking. This retrospective observational study analyzed 21 ACLF patients admitted to ICUs at the Vienna General Hospital who received CytoSorb adsorber therapy between 2017 and

2023. Median ICU length of stay was 8 days (IQR: 3–13), the ICU survival rate was 23.8% (n = 5). Significant decreases in bilirubin (median peak: 20.7 mg/dL to median post-treatment: 10.8 

mg/dL; − 47.8%; _p_ < 0.001), procalcitonin (1.34 to 0.74 pg/mL; − 44.6%; _p_ < 0.001), interleukin-6 (385 to 131 ng/mL; − 66.0%; _p_ = 0.0182)—but also of platelets (72 to 31 G/L; − 

56.9%; _p_ = 0.0014) and fibrinogen (230 to 154 mg/dL; − 33.0%; _p_ = 0.0297) were detected. ICU survivors had a trend towards a stronger relative decrease in bilirubin (− 76.1% vs. − 

48.2%), procalcitonin (− 90.6% vs. − 23.5%), and IL-6 (− 54.6% vs. − 17.8%) upon CytoSorb treatment. Moreover, no serious CytoSorb-attributed complications were detected. In conclusion, use

of CytoSorb adsorber in ACLF patients results in a significant decrease in bilirubin and proinflammatory cytokines, while platelets and fibrinogen were also lowered. Prospective trials are

warranted to investigate the impact of CytoSorb on clinical outcomes of ACLF patients with high proinflammatory cytokine levels. SIMILAR CONTENT BEING VIEWED BY OTHERS A CLINICAL STUDY OF

NON-BIOARTIFICIAL LIVER DPMAES SUPPORT SYSTEM IN HEPATITIS B-RELATED ACUTE-ON-CHRONIC LIVER FAILURE Article Open access 20 January 2024 SUCCESSFUL ELIMINATION OF BILIRUBIN IN CRITICALLY ILL

PATIENTS WITH ACUTE LIVER DYSFUNCTION USING A CYTOKINE ADSORBER AND ALBUMIN DIALYSIS: A PILOT STUDY Article Open access 13 May 2021 A MATCHED CASE-CONTROL STUDY ON THE EFFECTIVENESS OF

EXTRACORPOREAL CYTOKINE ADSORPTION IN CRITICALLY ILL PATIENTS Article Open access 18 August 2023 INTRODUCTION Acute-on-chronic liver failure (ACLF) is a syndrome that may occur in patients

with cirrhosis experiencing acute decompensation and is characterized by the development of hepatic and/or extra-hepatic organ failure(s), resulting in excessive short-term mortality1. It

has been demonstrated that systemic inflammation is the hallmark of ACLF driving disease development and progression1,2,3,4,5,6,7,8. The underlying mechanisms leading to systemic

inflammation in ACLF are only partly understood and depend on the specific precipitating event, which may be identified in up to 60% of cases7. Inflammation is associated with the release of

damage-associated (DAMPs) or pathogen-associated molecular patterns (PAMPs), resulting in oxidative stress triggering immune-mediated tissue damage, mitochondrial dysfunction, renal

hypoperfusion, and subsequently, single or multiple organ failures3,9. In line, Monteiro and colleagues recently demonstrated the impact of the inflammasome, as assessed by the

pro-inflammatory cytokines interleukin (IL)-1α and IL-1β, on ACLF outcome10. Therefore, amelioration of systemic inflammation, e.g., by clearance of pro-inflammatory cytokines, may be an

important therapeutic goal in ACLF patients in order to promote liver regeneration or as a bridging therapy to liver transplantation5,11,12. The CytoSorb adsorber is an extracorporeal blood

purification tool (hemoadsorber) that may be used together with continuous dialysis to remove excessive inflammatory mediators (i.e., cytokines), as well as to lower elevated bilirubin and

myoglobin levels13. Regarding liver-related indications, there is some data on the use of CytoSorb in patients with isolated hyperbilirubinemia and case series on liver failure14. However,

there is no data on the use of CytoSorb in the specific setting of ACLF. Previously, extracorporeal liver support devices failed to improve the prognosis of patients with ACLF15.

Extracorporeal treatment with large-volume plasma exchange—in order to eliminate pro-inflammatory cytokines—is explored as a promising treatment option in ACLF16. Moreover, a recently

published randomized, controlled clinical trial detected a significant decrease in biomarkers involved in the pathophysiological process of ACLF in patients treated with the liver dialysis

system DIALIVE compared to patients with standard medical treatment. Patients treated with the DIALIVE device showed an improvement in CLIF-C OF and CLIF-C ACLF scores but no significant

difference in 28-day mortality17. The results of a phase III study investigating the efficacy of plasma exchange in ACLF patients are still pending (APACHE, NCT03702920)18. Given the unmet

clinical need for supportive treatments in patients with ACLF, we aimed to investigate the impact of CytoSorb treatment on liver and extra-hepatic organ function and to evaluate potential

complications occurring during this treatment in critically ill ACLF patients. METHODS STUDY DESIGN AND SETTING We conducted a retrospective observational study of patients with ACLF

admitted to the ICU at a large tertiary center (Vienna General Hospital). Importantly, we did not include patients with acute liver failure (ALF) without pre-existing liver disease. All

adult (18 years and older) patients with ACLF receiving treatment with CytoSorb adsorber between January 1st, 2017, and January 1st, 2023, were included in this study. The diagnosis of ACLF

was defined according to the European Association for the Study of the Liver (EASL) CLIF criteria19. The observation period started from ICU admission (baseline) until ICU discharge or

death. We evaluated the effects of CytoSorb hemoadsorption on the clinical course, carefully screened for potential complications, and analyzed laboratory parameters directly prior to

CytoSorb application, after 24 h, and at the end of CytoSorb treatment (or last available in case of death). In addition, we included a control group comprising 10 patients with ACLF who

were all treated at the ICU during the respective time period 2017 to 2023 and received hemodialysis without the inclusion of the CytoSorb adsorber. HEMOADSORPTION WITH CYTOSORB ADSORBER All

included ACLF patients fulfilled an indication (i.e., acute kidney injury, hyperammonemia, and fluid- and acid–base disturbances) for hemodialysis during their respective ICU stay. The

decision for additional CytoSorb adsorber application was made by the treating physicians. Thereby, CytoSorb adsorber was always used in addition to standard intensive care treatment of ACLF

patients according to current EASL guidelines19. CytoSorb adsorber was always used with continuous venovenous hemodialysis (CVVHD; MultiFiltrate, Fresenius Medical Care) in prefilter

position and changed after 8–24 h. Anticoagulation during extracorporeal blood circulation was primarily conducted with citrate. In case of suspected citrate accumulation, the

anticoagulation regimen was switched to antithrombin III supplementation. According to our local standard operating procedures, citrate accumulation is rigorously monitored at least 3 times

daily in patients with liver failure using the total calcium to ionized calcium ratio20. Dialysis with low-molecular-weight heparin was not applied in our patient cohort, nor was dialysis

without anticoagulation21. Laboratory parameters including liver chemistry [bilirubin, aspartate transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (aP), gamma-glutamyl

transferase (GGT), and ammonia], inflammation parameters [procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP)], coagulation parameters [fibrinogen, international normalized

ratio (INR)], white blood count (WBC) and platelets were collected in all patients and analyzed prior to CytoSorb application, 24 h after the commencement of CytoSorb therapy and after

discontinuation of CytoSorb therapy (or prior to death). Overall CytoSorb treatment time and all CytoSorb adsorber changes were documented. For the evaluation of potential adverse events or

complications directly associated with CytoSorb therapy, the patient's condition and laboratory changes were closely monitored during hemoadsorption in standardized time intervals. DATA

COLLECTION Data were extracted from electronic patient charts (IntelliSpace Critical Care and Anesthesia, Philips, Amsterdam, Netherlands) that are routinely used at all ICUs at the Vienna

General Hospital. The system enables prospective and digital documentation of crucial patient data, including patient characteristics (age, gender, height, weight, BMI, vital signs and

comorbidities/underlying disease), laboratory tests (blood chemistry, global tests of coagulation and blood cell count) and complete information about ICU-specific parameters like fluid

balances, medication, nutrition and extracorporeal life support (mechanical ventilation, renal replacement therapy and ECMO). In order to quantify the severity of critical illness and extent

of organ dysfunction for patients admitted to the ICU, we calculated the following scores within the first 24 h upon ICU admission: simplified acute physiology score (SAPS II)22 and

sequential organ failure assessment score (SOFA)23. In addition, CLIF-C-ACLF and CLIF-C-OF scores were calculated as ACLF-specific prognostic scores24,25. Child–Pugh-Score (CPS) was

collected using laboratory data and clinical parameters at ICU admission26,27. STATISTICAL ANALYSIS Descriptive statistical analysis was used to provide a demographic overview of our patient

cohort. Continuous variables were reported as mean ± standard deviation or median (interquartile range), while categorical variables were reported as numbers (relative proportions, %).

Differences in laboratory parameters before and after CytoSorb adsorber application were compared using the Wilcoxon test for non-parametric variables. All statistical analyses were

performed using IBM SPSS Statistics 27 (IBM, New York, NY, USA) and GraphPad Prism 8 (GraphPad Software, CA, USA). ETHICAL APPROVAL AND INFORMED CONSENT The study was conducted according to

the guidelines of the Declaration of Helsinki28, and approved by the local Ethics Committee of the Medical University of Vienna (Ethics committee number: 1924/2020). Given the retrospective

design of the study, informed consent requirement was waived by the ethics committee of the Medical University of Vienna. RESULTS PATIENT CHARACTERISTICS During the study period, 21 patients

with ACLF were admitted to the ICU and received CytoSorb adsorber therapy (Supplemental Figure S1). The baseline characteristics of our patient population are depicted in Table 1. The

individual characteristics of each patient are shown in Table 2. The median age was 50 years (IQR: 35–58), and most patients were male (n = 18; 86%). SOFA and SAPS II scores at ICU admission

were 16 (IQR: 13–19) and 59 (IQR: 53–69), respectively. The most common underlying etiology of cirrhosis was alcohol-related liver disease (ALD; n = 11), followed by primary sclerosing

cholangitis (PSC, n = 4), re-cirrhosis after LTX (n = 2), autoimmune hepatitis (AIH; n = 1), porphyria (n = 1), chronic hepatitis B (n = 1) and secondary sclerosing cholangitis (n = 1). At

the time of ICU admission, most patients presented with CPS C (n = 16), while 5 patients showed CPS B. The median CPS score was 12 (IQR: 10–14). Infections (n = 12) and gastrointestinal

bleeding events (n = 8) were the main precipitating events for the development of ACLF. The median number of organ failures at ICU admission was 4 (IQR: 4–6), corresponding to a median

CLIF-C ACLF and CLIF-C OF Score of 67 (IQR: 57–76) and 15 (IQR: 14–18), respectively. We reported a median ICU length of stay (LOS) of 8 days (IQR: 3–13) and an ICU survival rate of 23.8% (n

 = 5). Additionally, we detected a 1-month survival of 23.8% (n = 5) and a 3-month survival of 19% (n = 4). Based on the CLIF-C-ACLF score, a predicted 1-month mortality of 82% and a

predicted 3-month mortality of 92.9% were determined. Detailed information on the individual patients’ courses during CytoSorb adsorber application is shown in Fig. 1 and Supplemental Figure

S2. The temporal relationship between CVVHD, CytoSorb application, outcome, and anticoagulation is depicted in Supplemental Table S1. All but one patient (95.2%) required vasopressor (i.e.,

noradrenaline) therapy during ICU stay. A detailed description of noradrenaline doses during CytoSorb treatment is depicted in Supplemental Table S2. In 10 patients, an increase in

noradrenalin dose was observed 6 h after the start of CytoSorb treatment. After discontinuation of CytoSorb therapy, 6 patients (28.6%) were resolved from vasopressors. In addition,

mechanical invasive ventilation (MIV) was conducted in 18 patients with a median length of MIV of 4 days (IQR: 2–8). Differences in baseline characteristics between survivors and

non-survivors are shown in Table 1. Survivors were younger (47 vs. 51 years), showed a lower CLIF-C-ACLF score at ICU admission (60 vs. 68.5), and had a longer ICU LOS (9 vs. 5.5 days).

CHANGES IN LABORATORY PARAMETERS The median number of CytoSorb applications per patient was 4 (IQR: 2.5–8), with a median CytoSorb therapy duration of 64 h (IQR: 42.5–130). We found a

significant decrease in bilirubin levels during and after CytoSorb therapy (median peak: 20.7 mg/dL to median post-treatment: 10.8 mg/dL; – 47.8%; _p_ < 0.001; Fig. 2). Interestingly,

these changes were already observed after 24 h of CytoSorb treatment (median peak: 20.7 mg/dL to median 24 h-treatment: 13.8 mg/dL; – 33.3%; _p_ < 0.001; Fig. 2a). Except for a

significant decrease in GGT levels after 24 h (median peak: 47 U/L to median post 24 h-treatment: 32 U/L; – 31.9%; _p_ = 0.0018), we did not find a clear trend for the remaining liver

chemistries. WBC, CRP, PCT, and IL-6 were monitored as surrogate parameters for systemic inflammation. While CytoSorb therapy did not affect WBC and CRP levels, we observed a significant

decline in PCT levels (median peak: 1.34 ng/mL to median 24 h-treatment: 1.09 ng/mL; – 18.4%; _p_ < 0.001) 24 h after first CytoSorb adsorber therapy (Fig. 3a). There was also a relevant

but non-significant trend regarding the decline in IL-6 levels after 24 h of CytoSorb therapy (median peak: 385 pg/mL to median 24 h-treatment: 327 pg/mL; – 15.2%; _p_ = 0.0599).

Importantly, after total CytoSorb therapy, both PCT (median peak: 1.34 ng/mL to median post-treatment: 0.74 ng/mL; – 44.9%; _p_ < 0.001) and IL-6 (median peak: 385 pg/mL to median

post-treatment: 131 ng/mL; – 66.1%; _p_ = 0.0182) showed a significant decrease (Fig. 3b). In addition, the 5 ICU survivors tended to have a stronger initial decrease in bilirubin (– 76.1%

vs. – 48.2%), procalcitonin (– 90.6% vs. – 23.5%), and IL-6 (– 54.6.3% vs. – 17.8%) upon CytoSorb treatment compared to non-survivors. In order to analyze if the aforementioned changes in

laboratory parameters were achieved by the addition of CytoSorb adsorber to CVVHD and not by conventional hemodialysis alone, we also evaluated laboratory changes in patients with ACLF and

CVVHD without inclusion of the CytoSorb adsorber. The basic characteristics of this control group are depicted in Supplemental Table S3–S4. As seen in Supplemental Table S5, CVVHD without

CytoSorb had no significant impact on the investigated laboratory parameters. In the control group, we detected a noticeable but not statistically significant decrease in median ammonia

levels after 24 h and at CVVHD discontinuation. FEASIBILITY, SAFETY, AND COMPLICATIONS OF CYTOSORB THERAPY IN ACLF PATIENTS We found a significant decrease in platelet counts during and

after CytoSorb therapy (median peak: 72 G/L to median post-treatment: 31 G/L; – 56.9%; _p_ = 0.0014; Fig. 4). These changes could already be detected 24 h after the start of CytoSorb

treatment (median pre-treatment: 72 G/L to median 24 h-treatment: 44 G/L; – 38.9%; _p_ = 0.043). Concerning global coagulation tests, we observed a significant increase in INR after 24 h of

CytoSorb therapy (median pre-treatment: 2.5 to median 24-treatment: 3.2; 28%; _p_ = 0.0215). In addition, fibrinogen levels showed a significant decrease during the course of CytoSorb

therapy (median pre-treatment: 230 mg/dL to median post-treatment: 154 mg/dL; 33%; _p_ = 0.0297). We did not observe any bleeding or other complications (i.e., allergic reactions) attributed

to treatment with the CytoSorb adsorber in our ACLF patient cohort. In all patients, the CytoSorb adsorber was combined with CVVHD using regional citrate anticoagulation by local standards.

In our ACLF cohort, citrate accumulation was suspected in 6 (28.6%) patients, and in all of these cases, citrate anticoagulation was replaced by substituting antithrombin III (Fig. 1 and

Supplemental Table S1)21. In these patients, antithrombin III anticoagulation was continued for the remaining CVVHD circuits. DISCUSSION Here we provide first observational data on the use

of the CytoSorb adsorber as supportive therapy in ACLF patients. Importantly, we detected a significant reduction of bilirubin after 24 h and at the end of CytoSorb application in all ACLF

patients. In addition, CytoSorb therapy also led to a significant decrease in PCT and IL-6 levels after CytoSorb application, indicating a potential benefit by ameliorating the systemic

proinflammatory state in ACLF. We also found a significant decrease in platelets and alterations in the plasmatic coagulation, but did not detect bleeding and other complications directly

attributed to CytoSorb use. The integration of CytoSorb in an extracorporeal circuit to modulate hyperinflammation (‘cytokine storm’) in sepsis represents a novel therapeutic approach first

introduced in 200829,30,31. CytoSorb treatment has been approved in Europe since 2011 and is authorized for use as an additional treatment for all indications associated with elevated

cytokine levels. In animal studies, CytoSorb treatment was able to reduce inflammation-related molecules such as IL-6, IL-10, and TNF- α32,33. _Brouwer _et al. demonstrated reduced 28-day

mortality in septic patients treated with CytoSorb31. Supporting data for the use of CytoSorb in the setting of ACLF are derived from patients with ALF (i.e., notably a different setting)

occurring in patients with sepsis and systemic inflammation. Importantly, systemic inflammation is a key risk factor for the development and progression of ACLF6,8. Therapy with CytoSorb

adsorber in ACLF patients is used with the rationale to ameliorate a hyperinflammatory state and thereby promote liver regeneration5,11,12. While we did not find any clear trend regarding

CRP and WBC during and after CytoSorb treatment, we detected a significant decline in PCT and IL-6 levels13. Importantly, the declines in PCT and IL-6 levels were already evident as early as

24 h after the start of CytoSorb application, i.e., in a critical early phase of ACLF. This finding argues for a direct effect of the CytoSorb adsorber on these proinflammatory parameters.

However, in our study, the reported decrease in IL-6 was rather small compared to in vitro data34. An explanation for the discrepancy between in vitro experiments and clinical application

might be the constant hyperinflammatory response during ACLF, especially at the beginning of the disease course. In this regard, the observed small decrease of IL-6 by CytoSorb therapy might

indicate a successful dampening of hyperinflammation that would have otherwise happened. Similar effects could already be seen in a study investigating the effects of CytoSorb hemoperfusion

on systemic inflammation in humans in vivo35. We also found a significant decrease in bilirubin levels during hemoadsorption, confirming data from other studies analyzing the effects of

CytoSorb in different settings14,36,37,38,39. Again, these effects could already be achieved as early as 24 h after the commencement of CytoSorb therapy. According to recent data, the impact

of CytoSorb treatment on bilirubin removal is even more effective compared to MARS13,40. However, the removal of further clinically relevant metabolites accumulating during liver failure by

the CytoSorb adsorber is still unclear and under debate. Effects on hyperammonemia have been reported mainly in ex vivo studies40,41. However, recent data from one clinical report indicate

that CytoSorb does not directly affect ammonia levels, and the elimination may be mainly achieved through simultaneously applied hemodialysis42. Interestingly, we found a more pronounced

decrease in median ammonia levels in the control group, which only received CVVHD. However, the sample size was small, and the results were not statistically significant. It is yet not clear

how CytoSorb application influences ammonia levels in patients with ACLF. Recent data suggests that the decrease in ammonia levels is a primary effect of hemodialysis, which is a

perquisition for CytoSorb use43. However, we do not think CytoSorb negatively affects serum ammonia levels. Therefore, the observed difference in the clearance of ammonia levels between the

CytoSorb group and the control group is likely due to the small sample size in both subgroups. Further studies are needed to investigate the impact of CytoSorb therapy on hyperammonemia and

encephalopathy during liver failure. Nevertheless, our findings suggest that hemoadsorption with CytoSorb might support blood detoxification during ACLF. Besides standard medical treatment,

there is considerable interest in extracorporeal liver support systems for patients with liver failure15,44. Artificial liver support devices, such as MARS, Prometheus, and single-pass

albumin dialysis (SPAD), led to an amelioration of laboratory parameters in ACLF. However, no consistent improvement in survival was found compared to standard medical treatment15,44. A

prospective, randomized controlled trial reported no benefit in laboratory chemistries and outcome in ACLF patients treated with ELAD45. Potential positive effects were reported in ALF

patients with high volume plasma exchange, while a survival benefit in ACLF patients is debated controversially15. There is a lack of data on the efficacy of CytoSorb adsorber in the

specific setting of ACLF. In a recent retrospective study of a small patient cohort with liver failure (ALF and ACLF) by _Popescu _et al.40, CytoSorb therapy was found to be equally or even

more effective in rebalancing liver functional tests in patients with liver failure compared to MARS. However, there were no differences in patient outcome40. Nevertheless, CytoSorb adsorber

is a rather cheap, easy-to-use, and readily available blood purification tool installed in conventional hemodialysis, which could also be used in smaller centers, in contrast to artificial

liver support devices, that often require significant expertise for their application38. The application of CytoSorb adsorber is generally associated with a low risk of complications46. In

our cohort of ACLF patients, platelets were significantly decreased, as reported in other studies using renal replacement therapy with CytoSorb adsorber40,47. Moreover, we detected changes

in plasmatic coagulation, including a significant decrease in fibrinogen levels and an increase in INR after the commencement of CytoSorb that may, however, also be due to liver disease

progression. We did not detect bleeding complications or other adverse effects directly associated with the use of CytoSorb adsorber therapy. In 10 patients CytoSorb application was

accompanied by increased vasopressor requirements shortly after commencement of adsorber therapy. This observation is best explained by progressive multiorgan failure and refractory shock in

ACLF grade 3 rather than a negative impact of CytoSorb adsorber on hemodynamics itself. Due to an imbalance of coagulation and risk of bleeding, regional citrate dialysis was used in all

our patients, and a switch to antithrombin III supplementation due to citrate accumulation was only rarely necessary. Nevertheless, citrate accumulation was detected in 6 patients. In our

experience, the risk for citrate accumulation is highest during the first cycle of CVVHD when the patient is still in an unstable condition. In this situation, the already limited liver

function is further compromised by circulatory/septic shock, resulting in the inability to metabolize citrate and ultimately leading to citrate accumulation20. In this regard, citrate

accumulation might also represent a negative prognostic marker for outcome in ACLF patients48. The ICU survival of our study population was rather low, with 23.8%. However, our patients were

admitted to the ICU with advanced ACLF as indicated by high CLIF-C ACLF scores and CLIF-OF scores at ICU admission corresponding to a predicted 1-month and 3-month mortality of 82% and

92.9%, respectively. 95.2% of our patients had an ACLF grade 3 before CytoSorb application. In our small study population, we observed comparable numbers with a 1-month mortality of 76.2%

and 3-month mortality of 81%. Similar outcome data concerning ACLF patients was reported in the CANONIC study (28-day = 76.7%; 90-day mortality = 79.1%)1. Overall, in patients with advanced

ACLF stages, treatment with CytoSorb adsorber might be less effective as organ failures may no longer be reversible. Therefore, close monitoring of organ function and, consequently, the

earlier application of CytoSorb adsorber in ACLF patients might represent a treatment strategy to prevent disease progression to multiorgan failure (i.e., bridge to recovery) or to enable

liver transplantation5,49,50. Indeed, liver transplantation for ACLF patients has shown very promising results, with a 1-year probability of survival after liver transplantation of 81%50.

Unfortunately, liver transplantation for ACLF patients is not established at our center. Therefore, none of our patients was even evaluated for eligibility for liver transplantation. The

present study has limitations: First, in our single center study, we only report the data of a rather small cohort, including 21 ACLF patients treated with CytoSorb adsorber. However, to our

knowledge, this is the first study to date that investigates the effects of hemoadsorption with CytoSorb in the specific setting of ACLF—while others have included patients with ALF in

other settings15,40. Second, due to the retrospective design, we had some missing laboratory values, especially for ammonia, but also for PCT and IL-6, which may therefore introduce a bias

in the interpretation of the results. Third, we acknowledge that in addition to CytoSorb therapy, patients always received standard medical treatment, including hemodialysis, according to

the EASL guidelines19. Therefore, it is unclear to what extent the laboratory changes may be allocated to hemoadsorption or standard medical treatment. However, we found significant changes

in a couple of laboratory parameters 24 h after the commencement of CytoSorb treatment, suggesting a direct effect of hemoadsorption. Fourth, due to the small number of patients in the

control group, we were not able to perform a propensity matched comparison. Future multicenter prospective trials are required to provide a more comprehensive comparison regarding the

efficacy of CVVHD + CytoSorb therapy and CVVHD alone in patients with ACLF. Nevertheless, we here present a comprehensive summary of our single center experience using CytoSorb adsorber in

ACLF patients. CONCLUSIONS Our study supports the use of CytoSorb adsorber as a feasible and easy-to-use blood purification tool with few complications in patients with ACLF. CytoSorb

treatment led to a significant decrease in important surrogate markers of systemic inflammation and supported blood detoxification by removing bilirubin in ACLF patients. Larger randomized

controlled trials are warranted to further investigate the clinical value of CytoSorb therapy in ACLF patients. DATA AVAILABILITY Data are available from the corresponding author upon

reasonable request. ABBREVIATIONS * ACLF: Acute-on-chronic liver failure * ALD: Alcoholic liver disease * ALF: Acute liver failure * ALT: Alanine aminotransferase * aP: Alkaline phosphatase

* AIH: Autoimmune hepatitis * AST: Aspartate transferase * CRP: C-reactive protein * CVVHD: Continuous venovenous hemodialysis * CPS: Child–Pugh-score * DAMP: Damage-associated molecular

patterns * EASL: European Association for the Study of the Liver * GGT: Gamma-glutamyl transferase * ICU: Intensive Care Unit * IL-6: Interleukin-6 * INR: International normalized ratio *

IQR: Interquartile range * LOS: Length of stay * LTX: Liver transplantation * MCI: Myocardial infarction * MIV: Mechanical invasive ventilation * MOF: Multi organ failure * PAMP:

Pathogen-associated molecular patterns * PCT: Procalcitonin * Pt.: Patient * PSC: Primary sclerosing cholangitis * RC: Re-cirrhosis * SAPS II: Simplified acute physiology score * SOFA:

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610–622. https://doi.org/10.1016/j.jhep.2021.03.030 (2021). Article  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Intensive Care Unit 13H1,

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria Patrick Haselwanter, Bernhard Scheiner,

 Lorenz Balcar, Georg Semmler, Marlene Riedl-Wewalka, Monika Schmid, Thomas Reiberger, Christian Zauner & Mathias Schneeweiss-Gleixner Authors * Patrick Haselwanter View author

publications You can also search for this author inPubMed Google Scholar * Bernhard Scheiner View author publications You can also search for this author inPubMed Google Scholar * Lorenz

Balcar View author publications You can also search for this author inPubMed Google Scholar * Georg Semmler View author publications You can also search for this author inPubMed Google

Scholar * Marlene Riedl-Wewalka View author publications You can also search for this author inPubMed Google Scholar * Monika Schmid View author publications You can also search for this

author inPubMed Google Scholar * Thomas Reiberger View author publications You can also search for this author inPubMed Google Scholar * Christian Zauner View author publications You can

also search for this author inPubMed Google Scholar * Mathias Schneeweiss-Gleixner View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Concept

of the study (P.H., B.S., T.R., C.Z., M.S-G.), data collection (P.H., M.R.-W., M.S., M.S-G.), statistical analysis (P.H., B.S., G.S., M.S-G.), drafting of the manuscript (P.H., B.S., L.B.,

T.R., M.S-G.,) and revision for important intellectual content as well as approval of the final manuscript (all authors). CORRESPONDING AUTHOR Correspondence to Mathias Schneeweiss-Gleixner.

ETHICS DECLARATIONS COMPETING INTERESTS The authors have nothing to disclose regarding the work under consideration for publication. Conflicts of interests outside the submitted work: B.S.

received travel support from AbbVie, Ipsen, and Gilead; G.S. received travel support from Gilead; T.R. received grant support from Abbvie, Boehringer-Ingelheim, Gilead, Intercept, MSD, Myr

Pharmaceuticals, Philips Healthcare, Pliant, Siemens and W. L Gore & Associates; speaking honoraria from Abbvie, Gilead, Intercept, Roche, MSD, W. L Gore & Associates;

consulting/advisory board fee from Abbvie, Astra Zeneca, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Resolution Therapeutics, Siemens; and travel support from Abbvie,

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patients with acute-on-chronic liver failure. _Sci Rep_ 14, 11309 (2024). https://doi.org/10.1038/s41598-024-61658-3 Download citation * Received: 02 November 2023 * Accepted: 08 May 2024 *

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