title: Extracorporeal liver perfusion system for artificial liver support across a membrane.
abstract: BACKGROUND
  An extracorporeal porcine liver perfusion (ECPLP) system circumvents the limitations of hepatocyte based bio-artificial liver, but its clinical application has been limited so far due to the potential risk of transmission of porcine endogenous retroviruses. The aim of this study was to develop an ECPLP model that can provide artificial hepatic support across a semi-permeable membrane, which has the potential to block porcine viruses due to its pore size.
  
  
  METHODS
  Livers from white landrace pigs were perfused with normothermic oxygenated blood using Medtronic BP560 centrifugal pump (Medtronic, Inc., Minneapolis. MN). This ECPLP system was used to support a "surrogate" patient across the filter Evaclio-EC4A. Function of liver was measured by indocyanine green retention at 15 min (ICGR15). Clearance of galactose, ammonia, and para-aminobenzoic acid infused into the "surrogate" patient circulation was calculated to assess liver support across the membrane. The study was designed as test (n = 15) versus control (n = 5), with control experiments having no liver in the circuit.
  
  
  RESULTS
  For the test experiments, we perfused 15 livers with mean hepatic artery pressure of 87 mm Hg and flows of 1.2 L/min. ICGR15 in test experiments was 11%. Ammonia clearance was 945 mg/min/kg, galactose metabolic rate was 111.7 mg/min/Kg, and the hippurate ratio was 91% in the test. In contrast, the control experiments did not show any significant change in the concentration of any of these compounds.
  
  
  CONCLUSIONS
  Our ECPLP model was able to provide hepatic support in an experimental setting across a hollow fiber filter. Further work on an anhepatic animal is needed prior to application in human trials.
authors.affiliation: Department of Hepatobiliary Pancreatic Surgery, University Hospitals of Leicester, Leicester, United Kingdom. jaibikhchandani@creighton.edu
authors.forename: Jai
authors.initials: J
authors.lastname: Bikhchandani
authors.forename: Matthew
authors.initials: M
authors.lastname: Metcalfe
authors.forename: Severine
authors.initials: S
authors.lastname: Illouz
authors.forename: Florian
authors.initials: F
authors.lastname: Puls
authors.forename: Ashley
authors.initials: A
authors.lastname: Dennison
mesh_terms: D000641:Ammonia / Q000493:pharmacokinetics; D000818:Animals; D020077:Endogenous Retroviruses; D005112:Extracorporeal Circulation / Q000295:instrumentation* / Q000379:methods*; D005690:Galactose / Q000493:pharmacokinetics; D008102:Liver Circulation; D017114:Liver Failure, Acute / Q000378:metabolism / Q000628:therapy; D019164:Liver, Artificial / Q000821:virology*; D008567:Membranes, Artificial; D008955:Models, Cardiovascular; D010477:Perfusion / Q000295:instrumentation / Q000379:methods; D034421:Sus scrofa; D014777:Virus Diseases / Q000517:prevention & control* / Q000635:transmission
chemical_list: D008567:Membranes, Artificial; D000641:Ammonia; D005690:Galactose