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 (μmol/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 (μmol/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. Conclusion: 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.