title: Clinical experience with a porcine hepatocyte-based liver support system.
abstract: The only clinically proven effective treatment of fulminant hepatic failure (FHF) is orthotopic liver transplant (OLT). However, many patients die before an organ becomes available. Thus, there is a need for development of an extracorporeal liver support system to "bridge" these patients either to OLT or spontaneous recovery. We developed a bioartificial liver (BAL) based on plasma perfusion through a circuit of a hollow-fiber cartridge seeded with matrix-anchored porcine hepatocytes to treat patients with severe acute liver failure. Two groups of patients were studied. Group 1 (n = 12): patients with FHF. All patients were successfully "bridged" to OLT. "Bridge" time to OLT was 21-96 hr (mean: 39.3 hr). All patients were discharged neurologically intact. Reversal of decerebration was noted in all 11 deep stage 4 coma patients. There was reduction in intracranial pressure (ICP mmHg, 18.2 +/- 2.2 to 8.5 +/- 1.2; p < 0.004) and increase in cerebral perfusion pressure (CPP mmHg, 71.1 +/- 4.0 to 84.7 +/- 2.6; p < 0.006). Laboratory values pre- and post-BAL treatment: glucose (mg/dl) 122 +/- 11 to 183 +/- 21, p < 0.002; ammonia (mumol/l) 155.6 +/- 13.2 to 121.6 +/- 9.5, p < 0.02; total bilirubin (mg/dl) 21.6 +/- 2.8 to 18.2 +/- 2.2, p < 0.001; PT (sec) 23.2 +/- 1.7 to 21.9 +/- 1.0, p < 0.3. Group II (n = 8): patients with chronic liver failure experiencing acute exacerbation. Two patients survived and later underwent OLT. Six patients (not OLT candidates) died 1-14 days after last BAL treatment. Laboratory values pre- and post-treatment: ammonia (mumol/l) 201 +/- 47 to 143 +/- 25, p < 0.06; total bilirubin (mg/dl) 22.8 +/- 5.2 to 19.5 +/- 4.4, p < 0.01; PT (sec) 22.5 +/- 2.0 to 21.8 +/- 1.1, p < 0.6.
  
  
  CONCLUSIONS
  our clinical experience with the BAL suggests that it may serve as "bridge" to OLT in patients with FHF primarily by reversing intracranial hypertension, but it is not a substitute for OLT in patients with end-stage liver disease who are non-transplant candidates.
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, UCLA School of Medicine, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Chen
authors.forename: W R
authors.initials: WR
authors.lastname: Hewitt
authors.forename: F D
authors.initials: FD
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Eguchi
authors.forename: E
authors.initials: E
authors.lastname: Kahaku
authors.forename: Y
authors.initials: Y
authors.lastname: Middleton
authors.forename: J
authors.initials: J
authors.lastname: Rozga
authors.forename: A A
authors.initials: AA
authors.lastname: Demetriou
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002469:Cell Separation; D002648:Child; D005260:Female; D006501:Hepatic Encephalopathy / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008099:Liver / Q000166:cytology*; D017114:Liver Failure, Acute / Q000401:mortality / Q000628:therapy*; D016031:Liver Transplantation / Q000401:mortality / Q000592:standards*; D019164:Liver, Artificial; D008297:Male; D008875:Middle Aged; D013552:Swine; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers