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