Extracorporeal Liver Support

A 17 yo woman is admitted to the ICU with fulminant liver failure due to Wilson’s disease; her course is complicated by encephalopathy, renal failure, and circulatory collapse despite maximal medical therapy and copper chelation.

Are there any additional therapies that may be utilized to provide a bridge to recovery or transplant, and assist with copper removal?

Extracorporeal albumin dialysis systems: Single pass albumin dialysis (SPAD) and Molecular Adsorbent Recirculation System (MARS)

Background

  • Acute liver failure (ALF) and acute on chronic liver failure (AoCLF) are associated with high mortality
  • Accumulation of liver toxins (ammonia, cytokines, aromatic amino acids, endogenous benzodiazepines, heavy metals, bilirubin) are implicated in hepatic encephalopathy, cerebral edema, circulatory dysfunction, and renal failure
  • Extracorporeal systems can provide an environment to facilitate recovery or bridge to transplant (similar to renal dialysis and ECMO)
  • Goal is to prolong survival time by preventing progression of secondary organ failure

How it works

Albumin dialysis:  patient’s blood is dialyzed against an albumin-containing solution across highly permeable membrane; albumin acts as scavenging molecule to remove protein bound substances normally cleared by the liver.

Proposed Indications

  • AoCLD complicated by progressive jaundice, hepatic encephalopathy, renal dysfunction
  • Acute Liver Failure
  • Severe alcoholic steatohepatitis
  • Primary graft dysfunction after liver transplantation
  • Posthepatectomy liver failure
  • Intrahpetaic cholestasis with intractable pruritus
  • Overdoses/intoxication with protein-bound substances
  • Progressive intrahepatic cholestasis associated with heart failure, graft v host disease, etc.

SPAD: Uses standard continuous venovenous hemodialysis (CVVHD) system

  • Diluted albumin solution (4.4%) added to dialysis solution
  • Albumin rich dialysate is not recycled; discarded after “single pass,” with “clean” albumin continuously introduced to maintain binding site availability

MARS: Patient’s blood dialyzed across an albumin-impregnated high-flux dialysis membrane

  • 20% albumin solution acts as dialysate
  • Albumin dialysate cleansed via passage across two adsorbent columns (ie- dialysate recirculates within closed circuit and is regenerated) to maintain binding site availability

Evidence

  • MARS better studied than SPAD
  • Studies limited, underpowered controlled studies and case reports
  • Case reports documented for acute liver failure due to toxins, including acetaminophen, Amanita phalloides, amphetamines, antibiotics, diet pills, and allopurinol
  • Case reports also reported for acute poisonings with highly bound protein substances, due to phenytoin, lamotrigine, theophylline, calcium channel blockers, and heavy metals
  • Evidence suggests that MARS is effective; associated with improvement in hyperbilirubinemia, encephalopathy, and circulatory dysfunction
  • Few RCTs suggest MARS beneficial for biochemical profile, encephalopathy, and renal dysfunction
  • Randomized trial (n= 23):
    • AoCLF patients (mostly alcoholic cirrhosis); standard medical therapy vs MARS + standard medical therapy
    • Showed 30 day mortality reduction
    • Limited data specifically looking at patients with ALF
    • No definitive data regarding mortality

 

References

  1. Collins K, Roberts E, Adeli K, et al. Single pass albumin dialysis (SPAD) in fulminant Wilsonian liver failure: a case report.  Pediatr Nephrol 2009; 23: 1013-1016
  2. Karvellas C, Gibney N, Kutsogianis D, et al.  Bench-to-bedside review: Current evidence for extracorporeal albumin dialysis systems in liver failure.  Critical Care 2007; 11: 215-223
  3. Laleman W, Wilmer A, Evenepoel P, et al. Review article: non-biological liver support in liver failure.  Alimentary Pharm & Ther 2006; 23: 351-363
  4. Stange J. Extracorporeal liver support.  Organogenesis 2011; 7: 64-73

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