David Bihari

Equipment review: the molecular adsorbents recirculating system (MARS).

The molecular adsorbents recirculating system (MARS®) is a form of artificial liver support that has the potential to remove substantial quantities of albumin-bound toxins that have been postulated to contribute to the pathogenesis of liver cell damage, haemodynamic instability and multi-organ failure in patients with acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF). These toxins include fatty acids, bile acids, tryptophan, bilirubin, aromatic amino acids and nitric oxide. Data from controlled clinical trials are limited so far. One of two studies performed on small numbers of patients with AoCLF suggest a survival benefit, but no controlled data are available in the ALF setting. Our preliminary experience with MARS therapy, instituted late in the clinical course of five patients with severely impaired liver function, including three with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease, indicates some clinical efficacy. However, the overall survival rate (1 of 5; 20%) remained poor. More data obtained from larger cohorts of patients enrolled in randomised controlled studies will be required in both the AoCLF and ALF settings to identify categories of liver failure patients who might benefit most from MARS treatment, to ascertain the most appropriate timing of intervention and to determine the overall impact on outcome, including cost-effectiveness.

THIS ARTICLE HAS BEEN RETRACTED: An Australian Experience With the Molecular Adsorbents Recirculating System (MARS)

Abstract:  The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin‐bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi‐organ failure in patients with acute liver failure and acute‐on‐chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre‐existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/β‐hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in‐hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi‐organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.

An Australian experience with the molecular adsorbents recirculating system (Mars).

Abstract:  The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin‐bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi‐organ failure in patients with acute liver failure and acute‐on‐chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre‐existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/β‐hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in‐hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi‐organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.

Nitric-oxide-lowering effect of terlipressin in decompensated cirrhosis: comparison to the molecular adsorbent recirculating system and correlation with clinical status.

Systemic vasodilatation and arterial hypotension, refractory to adrenergic vasopressors, portend a poor prognosis in patients with decompensated cirrhosis. The production of large amounts of nitric oxide, consequent to endotoxin-induced tumour necrosis factor (TNF)-α-mediated upregulation of inducible nitric oxide synthase (iNOS), has been suggested to be central to this phenomenon. Terlipressin has recently been shown in an animal model of cirrhosis to suppress endotoxin-induced TNF-α-mediated upregulation of iNOS, thereby preventing overproduction of nitric oxide and restoring normal vascular tone. We present the first evidence that this effect of terlipressin may also occur clinically, in a patient with Child-Pugh class C cirrhosis, endotoxaemia, a raised circulating TNF-α concentration, and marked systemic vasodilatation with refractory arterial hypotension. Beneficial effects of terlipressin on circulating nitrate and nitrite concentrations, haemodynamic status, plasma renin levels and indocyanine green clearance were comparable to those of the molecular adsorbent recirculating system (MARS). Our findings suggest that terlipressin may be the vasopressor agent of choice in patients with decompensated cirrhosis and provide a rationale for combination terlipressin and MARS therapy when the therapeutic response to either treatment alone is suboptimal.

THIS ARTICLE HAS BEEN RETRACTED: An Australian Experience With the Molecular Adsorbents Recirculating System (MARS): Australian Experience with MARS

Abstract:  The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin‐bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi‐organ failure in patients with acute liver failure and acute‐on‐chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre‐existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/β‐hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in‐hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi‐organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.