Phase 1/2a Trial of a Bioartificial Liver Support System (LifeLiver) for Acute Liver Failure Patients

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Abstract

Bioartificial liver (BAL) support offers a potential means of improving survival of acute liver failure (ALF) patients by providing partial liver function until a suitable donor liver is found or the native liver undergoes regeneration. Previous studies have suggested that ALF patients treated using BAL maintain a more stable medical condition, which may positively influence outcome after liver transplant (LT). This clinical trial was conducted to evaluate the safety and efficacy of the LifeLiver BAL system in ALF patients.

Patients with evidence of acute liver failure exhibiting hepatic encephalopathy grade 2 or worse who were listed for deceased donor liver transplant were eligible for enrollment. Hepatocytes were harvested from 3~4 weeks old male pigs weighing 4 to 10 kg, raised in a sterile environment. The isolate hepatocytes were cultured to form spheroids and were then mixed with 1.5% alginate solution and placed in a high content/speed immobilization apparatus and dropped into 100mM calcium solution. The Ca-alginate-immobilized hepatocyte spheroid beads were packed within the bioreactor of the BAL system. BAL treatment was continued for up to 12 hours.

Six patients were given BAL treatment and were included in the safety analysis. Adverse events related to BAL treatment included coagulopathy (increased INR), pneumonia, sepsis and disease progression. One patient developed upper gastrointestinal tract bleeding and sepsis following BAL treatment and eventually died while waiting for transplant. No evidence of porcine endogenous retrovirus (PERV) were seen.

Five patients completed the study per protocol and were included in the efficacy analysis. Four patients showed apparent decrease in serum ammonia levels and MELD scores during BAL treatment. Hepatic encephalopathy either decreased or remained stable throughout the BAL treatment period in 4 patients.

The LifeLiver BAL support system showed safety and efficacy in ALF patients with hepatic encephalopathy. Two patients were successfully bridged to liver transplantation.

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