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Liver failure: basis of benefit of therapy with the molecular adsorbents recirculating system

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Abstract

Accumulation of albumin-bound toxins is known to occur in liver failure, and to variable extents is responsible for the associated end-organ dysfunctions (kidney, circulation, brain). The toxin-binding and scavenging functions of albumin are exploited in albumin dialysis for removal of these toxins. The extracorporeal liver support device known as molecular adsorbents recirculating system (MARS) is based on dialysis across an albumin-impregnated membrane, using 20% albumin as dialysate. Charcoal and anion exchange resin columns in the circuit help cleanse and regenerate the dialysate. Clinical studies over the last few years have demonstrated proven reduction in hyperbilirubinaemia, along with an improvement in encephalopathy, systemic haemodynamics and renal function in liver failure patients, as well as apparent improvement in survival. The results of larger controlled clinical trials, as well as studies investigating the pathophysiological basis of its effect, are awaited.

Introduction

Liver failure may occur acutely without any underlying liver disease (acute liver failure, ALF), as an acute decompensation of chronic liver disease (‘acute-on-chronic’ liver failure, ACLF) or as a chronic decompensation of end-stage liver disease. In addition to the central hepatic failure, all the types are characterized by manifestations of end-organ dysfunctions, of which the most important are disturbances of circulation, renal and cerebral functions. In contrast to chronic decompensation of end-stage liver disease, ALF and ACLF have the potential of reversibility. An extracorporeal supportive therapy which can tide over the acute crisis (and, especially in ALF, act as a bridge to liver transplantation) is possibly life-saving (Sen et al., 2002, Sen et al., 2002), and the search for an effective liver support system continues. Essentially, two types are under development: bio-artificial devices, which use hepatocytes to perform the functions of the failing liver; and artificial devices, of which the one being tried extensively at present is the molecular adsorbents recirculating system (MARS), based on the principles of albumin dialysis.

Section snippets

Pathophysiology of liver failure

The mechanisms underlying the development of the multi-organ dysfunction of liver failure are complex, and as yet poorly understood. However, early studies demonstrating that cross-circulation between baboons and men with hepatic coma made the baboons sick (Abouna, 1968) led to the a ‘toxin hypothesis’ which suggests that most of the associated organ impairment is due to the accumulation of a variety of toxins as a result of impaired hepatic metabolism/detoxification. While ammonia, protein

Therapy: molecular adsorbents recirculating system (MARS)

Because most of the relevant toxins in liver failure are albumin bound, conventional haemodialysis/haemofiltration cannot effectively remove them. This has led to the development of an extracorporeal liver support system known as the molecular adsorbents recirculating system (Teraklin AG, Rostock, Germany). Using a hollow fibre dialysis module the patient’s blood is dialyzed across an albumin-impregnated polysulfone membrane with a pore size of 50 kDa, while at the same time maintaining a

Conclusion

MARS is an exciting tool for the treatment of liver failure, with its consistent effects in improving hyperbilirubinaemia and HE, along with some improvement of renal functions. Most importantly, survival may also be improved, but it has to be remembered that most of the studies till date have been small, and the majority uncontrolled. Also, very little is known about the exact mechanism by which MARS brings about these improvements. Currently, two multi-centre randomized controlled trials are

Conflict of interest statement

None of the authors have any financial conflict of interest with respect to MARS or Teraklin AG. We are, however, involved as part of a European multi-centre randomized controlled trial investigating the role of MARS in ‘acute-on-chronic’ liver failure.

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