Elsevier

Journal of Hepatology

Volume 39, Issue 6, December 2003, Pages 984-990
Journal of Hepatology

Prometheus® – a new extracorporeal system for the treatment of liver failure

https://doi.org/10.1016/S0168-8278(03)00468-9Get rights and content

Abstract

Background/Aims: Extracorporeal detoxification systems for supportive therapy of liver failure have recently gained much interest. We herein report results from the first clinical application of Prometheus®, a new liver support system in which albumin-bound substances are directly removed from blood by special adsorber. In a simultaneous step, high-flux hemodialysis is performed. We assessed safety, adsorber efficiency and clinical efficacy of the Prometheus® system.

Methods: Eleven patients with acute-on-chronic liver failure and accompanying renal failure were treated with Prometheus® on 2 consecutive days for >4 h.

Results: Prometheus® treatment significantly improved serum levels of conjugated bilirubin, bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. There were no significant changes in hemoglobin and platelet levels, whereas leucocytes increased without signs of systemic infection. No treatment-related complications except a blood pressure drop in two patients with systemic infection were noted. In one patient (Child-Pugh score: 15) Prometheus® treatment could not be completed due to onset of uncontrolled bleeding 16 h after dialysis.

Conclusions: Prometheus® is a safe supportive therapy for patients with liver failure. A significant improvement of the biochemical milieu was observed already after two treatments. Prospective controlled studies with the Prometheus® system are necessary to evaluate hard clinical end-points.

Introduction

Despite recent progress, the therapeutic options in patients with liver failure are not satisfying in many aspects. Patients with acute liver failure and hepatic encephalopathy of stages 3 or 4 still have a mortality rate above 60% without liver transplantation, which is hampered by a significant worldwide shortage of available organs [1]. In patients with acute deterioration of chronic liver disease, i.e. acute-on-chronic liver failure, mortality is even higher. These patients often die on the transplantation waiting list because they cannot be upgraded to high-urgency status like patients with acute liver failure. Therefore, clinical support of liver function remains a challenge that is not yet resolved. Many therapeutic procedures with the goal to enhance removal of putative toxins have been tested in the past. Among these various extracorporeal therapies such as hemodialysis, hemofiltration, exchange transfusion, plasma exchange and charcoal perfusion have been tried alone or in combination [2], [3], [4], [5], [6]. Corrections of various biochemical parameters have been reported, but a significant improvement of patient survival has not been achieved. An obvious reason for therapy failure is that most of these techniques predominantly remove water-soluble substances such as ammonia or lactate, whereas protein-bound substances that accumulate in liver failure (such as bile acids) are removed only to a minor extend [7]. Moreover, unintended removal of growth factors delays the process of liver regeneration at least theoretically [8].

Recently, single pass albumin dialysis (SPAD) and molecular adsorbent recirculation system (MARS) were introduced in order to improve removal of protein-bound substances [9], [10], [11]. Both procedures are based on albumin dialysis: on one side of a semipermeable membrane toxin-rich blood passes by, while on the other side an albumin-enriched electrolyte solution flows in the opposite direction (counter-current flow). Due to the relatively small pore size of the high-flux membranes used, passage of large albumin molecules is hindered, while smaller compounds diffuse freely through the membrane. Thus small unbound toxins cross the membrane, bind to the albumin on the other side and are carried away. In SPAD, the albumin-rich dialysate is discharged after circulation through the dialyser, while in MARS it is regenerated in a separate circuit by using low-flux dialysis and different adsorber to wash away or to bind the toxins unloaded from albumin. This ‘regenerated’ albumin is then used again for the detoxification process.

In 1999, Falkenhagen et al. introduced fractionated plasma separation and adsorption (FPSA) [12], [13], a new type of albumin dialysis. In this system a special albumin-permeable filter with a cut-off of approximately 250,000 Dalton (250 kD) is used. Thus albumin and the protein-bound toxins pass through the membrane and are then directly removed from the blood by special adsorber within the secondary circuit. The newly developed Prometheus® system combines the FPSA method with high-flux hemodialysis (of the blood) in an extracorporeal detoxification system. We herein report results from the first clinical application of Prometheus®.

Section snippets

Study protocol and patients

The study protocol was approved by the Ethics Committee of the Medical University Hannover, where the pilot study was conducted. Study endpoints were safety, adsorber efficiency and clinical efficacy of the Prometheus® system. Written informed consent was obtained from each patient respectively from his or her legal representative. Inclusion criteria were chosen broadly, because our intention was to evaluate clinical application of Prometheus in patients with different aetiologies of liver

Safety and usability of Prometheus® therapy

Eleven patients (six men and five women, mean age 52±7 years) were enrolled between October 2001 and May 2002; eight of them (73%) were treated on the intensive care unit (ICU). Average Child-Pugh score was 12±2 points. Eight patients (73%) suffered from hyperbilirubinemia of more than 250 μmol/l. Six of the nine patients (67%) who were not mechanically ventilated presented hepatic encephalopathy of stage 2 or higher. Ascites was found in nine patients (82%). The cause of renal failure was

Discussion

The present study was designed to explore the safety and clinical utility and efficacy of the Prometheus® system – a new extracorporeal device for supportive therapy of patients with liver failure based on the FPSA method developed by Falkenhagen et al. [12], [13]. Eleven patients with severe acute-on-chronic liver failure (average Child-Pugh score 12 and mean bilirubin level >450 μmol/l) were examined. In addition, all of them had renal failure and most patients were treated on the ICU. In

Acknowledgements

We thank Fresenius Medical Care Germany for financial support of the study. We also thank Dr Alfred Krause for technical support and fruitful discussions.

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  • Cited by (0)

    The authors received funding from the manufacturers which enabled them to carry out their research.

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