Technology Insight: artificial extracorporeal liver support—how does Prometheus® compare with MARS®?

Abstract

Artificial extracorporeal liver support or 'liver dialysis' has been used in patients with severe liver failure with increasing frequency since the Molecular Adsorbents Recirculating System (MARS), a variant of albumin dialysis, was introduced in 1999. Nevertheless, liver dialysis must still be thought of as experimental because its contribution to improved patient survival has not been proven in large randomized trials. Prometheus is a novel device for fractionated plasma separation via an albumin-permeable filter that was developed to improve removal of albumin-bound toxins. Initial studies have proven clinical use of Prometheus to be feasible and safe. Head-to-head comparisons of Prometheus and MARS have shown treatment with the former to be more efficient with respect to removal of most albumin-bound and water-solved markers. As controlled studies with clinical end points are lacking, it is not known whether the observed greater detoxification capacity of Prometheus will translate into clinical benefit; two small studies indicate that there might be a beneficial effect in hepatic encephalopathy and pruritus. In a recent randomized comparison of MARS and Prometheus, however, hemodynamic improvement was observed in response to MARS, but not Prometheus, treatment. A large randomized controlled trial investigating the effect of Prometheus on survival--the HELIOS study--has been initiated. First results are expected in 2008 and will be crucial to establishing a role for Prometheus in the field of extracorporeal liver support.

Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions

“…More specifically, upon presence of microbes or any form of tissue damage (e.g., hypoxia, ischemia or toxic agent), both a local proinflammatory and anti-inflammatory reaction are simultaneously initiated in an attempt to confine and control invading microbes locally, destroy damaged tissue and repair damage. If the initiating infectious or noninfectious factors overwhelm the local response or the local response becomes exaggerated, spilling of proinflammatory mediators into the systemic circulation results in recruitment of a systemic response, which we recognize clinically as the systemic inflammatory response (SIRS) [16][17][18]. The severity of the disease syndrome resulting from this cascade of systemic mediators depends on the balance of SIRS and the compensatory anti-inflammatory syndrome [29,31].…”

“…By contrast, the MELD score-based allocation system relies on a 'sickest first' policy and therefore offers the opportunity for AoCLF patients to receive an allograft based upon disease severity. Moreover, this policy also raised the issue of bridging AoCLF patients to 'salvage' transplantation, which brings us to the second reason, which, more specifically, is a growing interest and focus on artificial liver support devices [1,2,[12][13][14][15][16][17]. This increased attention has further sharpened the duality of the therapeutic perspective between AoCLF and end-stage liver disease.…”

Pharmaceutically Important Pre- and Posttranslational Modifications on Human Serum Albumin

“…Due to its intrinsic ability to bind molecules, albumin has been used in blood purification techniques such as single-pass albumin dialysis, 81,82) the molecular adsorbent recirculating system, 83,84) and the Prometheus systems. 85,86) The molecular adsorbent recirculating system of albumin dialysis is a high-flux dialysis setting using HSA as a molecular adsorbent to the dialysate with subsequent recirculation of the dialysate over sorbents. It is a useful tool to treat acute liver failure and decompensated chronic liver disease, and to provide a bridge for patients to liver transplantation.…”

Emerging Therapies for Extracorporeal Support

“…Possible benefits also need to be assessed in regard to their impact on bridging to liver transplantation and on major complications, namely bleeding and infection. A large randomized trial, the HELIOS study, studying the effect of Prometheus on 1- and 3-month survival in acute-on-chronic liver failure, is expecting to publish its first results within a year [22]. Currently, these techniques should remain experimental and are contraindicated in the presence of uncontrolled coagulopathy, uncontrolled sepsis and severe gastrointestinal bleeding.…”

“…1c) [22]. The hydrophobic toxins pass the albumin-permeable filter between the two circuits and, therefore, a fraction of the patient’s plasma is filtered and the patient’s own albumin loads the second circuit.…”