Extracorporeal Detoxification Using the Molecular Adsorbent Recirculating System for Critically Ill Patients with Liver Failure

Abstract

Abstract.Liver failure resulting from different causes and its concomitant complications represent difficult-to-treat conditions with high mortality rates, despite improved therapeutic modalities in intensive care medicine. The accumulation of albumin-bound metabolites that are normally cleared by the liver, such as bilirubin and bile acids, contributes substantially to the development of multiorgan dysfunction in these clinical situations. The molecular adsorbent recirculating system (MARS) represents a cell-free, extracorporeal, liver assistance method for the selective removal of albumin-bound substances. Moreover, it enables the removal of excess water and water-soluble substances via an inbuilt dialysis step. Since 1993, >400 patients have been treated in 53 centers in Europe, the United States, and Asia. Diseases treated with MARS included acute exacerbation of chronic hepatic failure, hepatorenal syndrome, acute hepatic failure, and primary nonfunction/poor function after liver transplantation and major liver resection. Treatments were well tolerated. No severe adverse events were observed. Six- to 8-h MARS treatments resulted in significant (P< 0.05) removal of bilirubin, bile acids, tryptophan, shortand middle-chain fatty acids, aromatic amino acids, and ammonia. Clearance rates for strongly albumin-bound substances were between 10 and 60 ml/min. The removal of albumin-bound toxins resulted in decreases in hepatic encephalopathy, increases in mean arterial pressure, and improvements in kidney and liver function. In the first randomized clinical trial of the MARS method for treatment of the hepatorenal syndrome, significant prolongation of survival was observed for the MARS-treated group. It is concluded that the MARS method can contribute to the treatment of critically ill patients with liver failure and different underlying diseases.

Bifidobacterium longum BL-10 with Antioxidant Capacity Ameliorates Lipopolysaccharide-Induced Acute Liver Injury in Mice by the Nuclear Factor-κB Pathway

“…Acute liver injury (ALI) is a term used to characterize hepatocyte necrosis and significant liver function impairment that occur in a short period without the presence of basic hepatopathy . Cases of severe illness may also have acute liver failure (AHF) or multiple organ dysfunction syndrome . Previous research has demonstrated that inflammation and oxidative stresses, namely the expression of the cyclooxygenase-2 (COX-2) gene and the activation of nuclear factor κB (NF-κB), were the primary causes of ALI .…”

“…1 Cases of severe illness may also have acute liver failure (AHF) or multiple organ dysfunction syndrome. 2 Previous research has demonstrated that inflammation and oxidative stresses, namely the expression of the cyclooxygenase-2 (COX-2) gene and the activation of nuclear factor κB (NF-κB), were the primary causes of ALI. 3 Moreover, the activated NF-κB signal pathway stimulates the release of inflammatory substances from the hepatic salivary cells, such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6).…”

Evolution of Electrospinning in Liver Tissue Engineering

“…The remaining mostly die with the want of a fully functional liver. Given the increasing burden of patients with end-stage liver diseases and the resulting dearth of suitable donor organs, scientists worldwide have been exploring other options, such as extracorporeal temporary liver assist devices [ 22 , 23 , 24 ], tissue engineering approaches, 3D printing and cell-based therapies, to combat liver diseases and most of these have also shown promising results in pre-clinical studies. The fabrication of scaffolds, implantable devices, cell encapsulated hydrogels and 3D printed liver tissues are being investigated under the umbrella of liver tissue engineering [ 25 , 26 ].…”

Adsorbents with High Selectivity for Uremic Middle Molecular Peptides Containing the Asp-Phe-Leu-Ala-Glu Sequence

“…9 The accumulation of metabolites in the human body is thought to be toxic and contributes to many pathological changes in patients with organ failure. 10,11 These toxins could be eliminated by hemodialysis or hemoperfusion; for example, low-density lipoprotein could be removed by adsorbents with sulfonic and cholesterol groups. 12 According to the middle molecule hypothesis, 13 middle-molecular-weight toxins ranging from 500 to 5000 Da are the main toxic substances that accumulate in uremic patients, and middle molecular peptides have been assumed to be one type of major uremic toxin.…”