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Background: Besides standard medical therapy and critical care monitoring, extracorporeal liver support may provide a therapeutic option in patients with liver failure. However, little is known about detoxification capabilities, efficacy, and efficiency among different devices., Methods: Retrospective single-center analysis of patients treated with extracorporeal albumin dialysis. Generalized Estimating Equations with robust variance estimator were used to account for repeated measurements of several cycles and devices per patient., Results: Between 2015 and 2021 n = 341 cycles in n = 96 patients were eligible for evaluation, thereof n = 54 (15.8%) treatments with Molecular Adsorbent Recirculating System, n = 64 (18.7%) with OpenAlbumin, n = 167 (48.8%) Advanced Organ Support treatments, and n = 56 (16.4%) using Single Pass Albumin Dialysis. Albumin dialysis resulted in significant bilirubin reduction without differences between the devices. However, ammonia levels only declined significantly in ADVOS and OPAL. First ECAD cycle was associated with highest percentage reduction in serum bilirubin. With the exception of SPAD all devices were able to remove the water-soluble substances creatinine and urea and stabilized metabolic dysfunction by increasing pH and negative base excess values. Platelets and fibrinogen levels frequently declined during treatment. Periprocedural bleeding and transfusion of red blood cells were common findings in these patients., Conclusions: From this clinical perspective ADVOS and OPAL may provide higher reduction capabilities of liver solutes (i.e. bilirubin and ammonia) in comparison to MARS and SPAD. However, further prospective studies comparing the effectiveness of the devices to support liver impairment (i.e. bile acid clearance or albumin binding capacity) as well as markers of renal recovery are warranted.

Extracorporeal albumin dialysis (ECAD) represents a supplemental therapy for patients with liver failure. Most experience was gained with the molecular adsorbent recirculating system (MARS). However, the ADVanced Organ Support (ADVOS) system was recently introduced. This study aims to compare effects of MARS and ADVOS on biochemical and clinical parameters in critically ill patients with liver failure using a retrospective analysis of ECAD at Jena University Hospital. Laboratory parameters, health scoring values, and need for transfusion were recorded before and after treatment. Generalized estimating equations were used to account for repeated measurements of multiple ECAD cycles per patient. Between 2012 and 2017, n = 75 MARS and n = 58 ADVOS cycles were evaluated. Although ADVOS runs significantly longer, both devices provided comparable reduction rates of bilirubin (MARS: -48 [-80.5 to -18.5] μmol/L vs ADVOS: -35 [-87.8 to -2.0] μmol/L, P = .194), a surrogate for detoxification capacity, while urea and lactate levels were more significantly lowered by the ADVOS system. In cycles with similar treatment times, both systems provided comparable reduction rates for bilirubin, renal replacement, coagulation, and metabolic parameters. Citrate was the preferred anticoagulant in case of bleeding. Neither bleeding tendency nor fibrinogen levels or platelets were altered by the type of anticoagulation. No adverse events were reported, but two sessions (one MARS and one ADVOS) were terminated early due to filter clotting. Experience is needed in the application of ADVOS and more prospective trials comparing the detoxification capacity of ECAD devices are needed to support and enlarge the findings of the current evaluation., (© 2020 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background & Aims: Retention of bile acids in the blood is a hallmark of liver failure. Recent studies have shown that increased serum bile acid levels correlate with bacterial infection and increased mortality. However, the mechanisms by which circulating bile acids influence patient outcomes still are elusive., Methods: Serum bile acid profiles in 33 critically ill patients with liver failure and their effects on Takeda G-protein-coupled receptor 5 (TGR5), an immunomodulatory receptor that is highly expressed in monocytes, were analyzed using tandem mass spectrometry, novel highly sensitive TGR5 bioluminescence resonance energy transfer using nanoluciferase (NanoBRET, Promega Corp, Madison, WI) technology, and in vitro assays with human monocytes., Results: Twenty-two patients (67%) had serum bile acids that led to distinct TGR5 activation. These TGR5-activating serum bile acids severely compromised monocyte function. The release of proinflammatory cytokines (eg, tumor necrosis factor α or interleukin 6) in response to bacterial challenge was reduced significantly if monocytes were incubated with TGR5-activating serum bile acids from patients with liver failure. By contrast, serum bile acids from healthy volunteers did not influence cytokine release. Monocytes that did not express TGR5 were protected from the bile acid effects. TGR5-activating serum bile acids were a risk factor for a fatal outcome in patients with liver failure, independent of disease severity., Conclusions: Depending on their composition and quantity, serum bile acids in liver failure activate TGR5. TGR5 activation leads to monocyte dysfunction and correlates with mortality, independent of disease activity. This indicates an active role of TGR5 in liver failure. Therefore, TGR5 and bile acid metabolism might be promising targets for the treatment of immune dysfunction in liver failure., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure., Methods: Patients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4% albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model., Results: Sixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median -68 μmol/L, interquartile range [IQR] -107.5 to -33.5, p = 0.001; SPAD: -59 μmol/L, -84.5 to +36.5, p = 0.001). However, bile acids (MARS: -39 μmol/L, -105.6 to -8.3, p < 0.001; SPAD: -9 μmol/L, -36.9 to +11.4, p = 0.131), creatinine (MARS: -24 μmol/L, -46.5 to -8.0, p < 0.001; SPAD: -2 μmol/L, -9.0 to +7.0/L, p = 0.314) and urea (MARS: -0.9 mmol/L, -1.93 to -0.10, p = 0.024; SPAD: -0.1 mmol/L, -1.0 to +0.68, p = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10%, -0.8 to +20.9%, p < 0.001; SPAD: +7%, -7.5 to +15.5%, p = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD., Conclusions: Both procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation., Trial Registration: German Clinical Trials Register ( www.drks.de) DRKS00000371. Registered 8 April 2010.

Background: Nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are frequent comorbidities in perioperative patients. However, the predictive role of the hepatokine fetuin A was not evaluated in this collective.Objective: To study fetuin A as predictor of NAFLD/NASH in preoperative patients.Methods: 58 subjects were included. Fetuin A was studied in patients undergoing open abdominal surgery and in a subset with acute liver failure. Blood and liver specimens were sampled. NAFLD was histologically evaluated. Liver fat was additionally analyzed by an enzymatic approach, circulating fetuin A by enzyme linked-immunosorbent assay, fetuin A mRNA by reverse-transcription PCR.Results: Univariate correlation studies linked fetuin A to liver steatosis (r= 0.40,p= .029) and hepatocellular ballooning degeneration (r= 0.34,p= .026). Compared to non-NAFLD subjects fetuin A was increased in NAFLD (p= .009) and in NASH (p= .029). However, when corrected for main confounders by linear modeling, fetuin A remained related to hepatic steatosis, but not to ballooning degeneration or other NAFLD features. In support of this, biochemically analyzed liver lipids correlated with fetuin A in plasma (r= 0.34,p= .033) and with hepatic fetuin A mRNA (r = 0.54,p< .001). In addition, plasma fetuin A was related to hepatic mRNA (r = 0.32,p= .036), while circulating levels were reduced by 64% with acute liver failure (p< .001), confirming the liver as main fetuin A source.Conclusion: Fetuin A is suggested as noninvasive biomarker of hepatic steatosis in preoperative settings. [ABSTRACT FROM PUBLISHER]