Removal of Benzodiazepine-like Substances as a Cause of Improvement of Hepatic Encephalopathy during Albumin Dialysis

Peszynski, P.; Stange, Jan; Mitzner, Steffen; Klammt, Sebastian; Majcher-Peszynska, Jolanta; Wacke, R.; Drewelow, Bernd; Schmidt, Ralf

doi:10.1055/s-2001-919049

Cited by 8 publications

(4 citation statements)

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“…Furthermore, dialysis using this type of membrane and albumin in the dialysate solution increased the removal of a number of substances having a high albumin affinity including bile acids (24), benzodiazepines (25), copper (26), middle‐chain fatty acids (27), arachidonic acid (28), tryptophane (21), IL‐6 (29), and TNF‐α(29). In addition, reduction of aromatic amino acids associated with an increase of branched‐chain amino acids was observed in patients with liver failure who were treated with MARS (21).…”

Section: Results From Laboratory Investigationsmentioning

confidence: 99%

The Molecular Adsorbents Recycling System as a Liver Support System Based on Albumin Dialysis: A Summary of Preclinical Investigations, Prospective, Randomized, Controlled Clinical Trial, and Clinical Experience from 19 Centers

Stange¹,

Hassanein²,

et al. 2002

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Artificial liver support aims to prolong survival time of patients with liver failure by detoxification. Albumin as a molecular adsorbent in dialysis solution is capable of attracting even tightly albumin-bound toxins from blood into the dialysate if a specific dialysis membrane is used and if the albumin's binding sites are on-line-purified by a sorbent/dialysis-based recycling system (i.e., molecular adsorbents recycling system, or MARS). The MARS technology has been shown to remove water-soluble and albumin-bound toxins and to provide renal support in case of renal failure. Fourteen centers have reported that MARS treatment improved mental status of patients with liver failure and hepatic encephalopathy. In treating liver failure and cholestasis, MARS was associated with hemodynamic stabilization, improvement of hepatic and kidney function, and disappearance of pruritus. In hepatic failure and hepatorenal syndrome, a prospective, randomized, controlled trial of MARS treatment was able to prolong survival time significantly. MARS has been used in 26 patients with acute liver failure or primary graft dysfunction. Nineteen centers reporting on 103 patients have shown that MARS treatment is safe, easy to handle, feasible, and effective.

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Section: Results From Laboratory Investigationsmentioning

confidence: 99%

The Molecular Adsorbents Recycling System as a Liver Support System Based on Albumin Dialysis: A Summary of Preclinical Investigations, Prospective, Randomized, Controlled Clinical Trial, and Clinical Experience from 19 Centers

Stange¹,

Hassanein²,

et al. 2002

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“…8,12 All survivors (Table 2) did not undergo substitution of plasma proteins at the time of hospital discharge. Therefore, data from column 8 in Table 2 should represent the function of the liver itself.…”

Section: Discussionmentioning

confidence: 99%

Liver Support by Extracorporeal Blood Purification: A Clinical Observation

Stange

Mitzner

Klammt

et al. 2000

Liver Transplantation

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131

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Liver failure associated with excretory insufficiency and jaundice results in an endogenous accumulation of toxins involved in the impairment of cardiovascular, kidney, and cerebral function. Moreover, these toxins have been shown to damage the liver itself by inducing hepatocellular apoptosis and necrosis, thus creating a vicious cycle of the disease. We report a retrospective cohort study of 26 patients with acute or chronic liver failure with intrahepatic cholestasis (bilirubin level > 20 mg/dL) who underwent a new extracorporeal blood purification treatment. A synthetic hydrophilic/hydrophobic domain-presenting semipermeable membrane (pore size < albumin size, 100-nm thick) was used for extracorporeal blood detoxification using dialysis equipment. The opposite side was rinsed with ligandin-like proteins as molecular adsorbents that were regenerated online using a chromatography-like recycling system (molecular adsorbent recirculating system [MARS]). Bile acid and bilirubin levels, representing the previously described toxins, were reduced by 16% to 53% and 10% to 90% of the initial concentration by a single treatment of 6 to 8 hours, respectively. Toxicity testing of patient plasma onto primary rat hepatocytes by live/dead fluorescence microscopy showed cell-damaging effects of jaundiced plasma that were not observed after treatment. Patients with a worsening of Child-TurcottePugh (CTP) index before the treatments showed a significant improvement of this index during a period of 2 to 14 single treatments with an average of 14 days. After withdrawal of MARS treatment, this improvement was sustained in all long-term survivors. Ten patients represented a clinical status equivalent to the United Network for Organ Sharing (UNOS) status 2b (group A1), and all survived. Sixteen patients represented a clinical status equivalent to UNOS status 2a, and 7 of these patients survived (group A2), whereas 9 patients (group B) died. We conclude that in acute excretory failure caused by a chronic liver disease, this treatment provides a therapy option to remove toxins involved in multiorgan dysfunction secondary to liver failure. (Liver Transpl 2000;6: 603-613.)

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“…Dialysis using this special membrane was able to remove the majority of the molecules with high albumin affinity, namely bilirubin, bile acids, tryptophan, middle and shortchain fatty acids, aromatic amino acids TNFα , IL-6, arachidonic acid, copper and benzodiazepines [22][23][24][25][26]. In particular, studies aimed to determine the clearances of these substances have demonstrated that a 6 h MARS treatment is theoretically able to completely remove bile acids from more than 12 L of plasma and bilirubin from 3 L of plasma [2].…”

Section: Results On Laboratory Parametersmentioning

confidence: 99%

Advances in Extracorporeal Detoxification by MARS Dialysis in Patients with Liver Failure

Campli

Verme

Andrisani

et al. 2003

CMC

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Although liver transplantation has become standard procedure for patients with liver failure, a number of issues in the management of these patients remains to be addressed. Alternative approaches have been tested, such as hepatocytes containing liver-support systems and filtration devices. However, the replacement of detoxification has been difficult, as the majority of toxins accumulating in liver failure is albumin-bound. Albumin dialysis (MARS system) is characterized by the specific removal of albumin-bound toxins through an innovative membrane transport. In particular, the albumin acts as a specific molecular adsorbent that is regenerated on line in a recycling system. Nowadays MARS represents the most frequently used liver support system. This treatment has been shown to remove albumin-bound molecules, such as bilirubin, bile acids, aromatic amino acids and copper. The removal of these toxins is clinically accompanied with an improvement of liver, cardiovascular and renal functions and hepatic encephalopathy. In several trials MARS was found to improve the clinical situation in patients with acute exacerbation of chronic liver failure and acute hepatic failure, but also in hepatorenal syndrome and primary graft non function or chronic rejection after liver transplantation. In summary, a critical analysis of the literature confirms that MARS device can be a safe therapeutic choice to achieve a better clinical outcome, and, sometimes, a survival advantage in patients with liver failure, even if a multi-center randomized trial is the only reliable way to enforce today's results. Further advances in the MARS components will definitively state whether albumin dialysis may represent the future in the field of artificial liver devices.

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Removal of Benzodiazepine-like Substances as a Cause of Improvement of Hepatic Encephalopathy during Albumin Dialysis

Cited by 8 publications

References 0 publications

The Molecular Adsorbents Recycling System as a Liver Support System Based on Albumin Dialysis: A Summary of Preclinical Investigations, Prospective, Randomized, Controlled Clinical Trial, and Clinical Experience from 19 Centers

The Molecular Adsorbents Recycling System as a Liver Support System Based on Albumin Dialysis: A Summary of Preclinical Investigations, Prospective, Randomized, Controlled Clinical Trial, and Clinical Experience from 19 Centers

Liver Support by Extracorporeal Blood Purification: A Clinical Observation

Advances in Extracorporeal Detoxification by MARS Dialysis in Patients with Liver Failure

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