Evaluation of a novel hybrid bioartificial liver based on a multi-layer flat-plate bioreactor

Abstract

Aim: To evaluate the efficacy and safety of a hybrid bioartificial liver (HBAL) system in the treatment of acute liver failure.

Methods: Canine models with acute liver failure were introduced with intravenous administration of D-galactosamine. The animals were divided into: the HBAL treatment group (n = 8), in which the canines received a 3-h treatment of HBAL; the bioartificial liver (BAL) treatment group (n = 8), in which the canines received a 3-h treatment of BAL; the non-bioartificial liver (NBAL) treatment group (n = 8), in which the canines received a 3-h treatment of NBAL; the control group (n = 8), in which the canines received no additional treatment. Biochemical parameters and survival time were determined. Levels of xenoantibodies, RNA of porcine endogenous retrovirus (PERV) and reverse transcriptase (RT) activity in the plasma were detected.

Results: Biochemical parameters were significantly decreased in all treatment groups. The TBIL level in the HBAL group was lower than that in other groups (2.19 ± 0.55 μmol/L vs 24.2 ± 6.45 μmol/L, 12.47 ± 3.62 μmol/L, 3.77 ± 1.83 μmol/L, P < 0.05). The prothrombin time (PT) in the BAL and HBAL groups was significantly shorter than the NBAL and control groups (18.47 ± 4.41 s, 15.5 ± 1.56 s vs 28.67 ± 5.71 s, 21.71 ± 3.4 s, P < 0.05), and the PT in the HBAL group was shortest of all the groups. The albumin in the BAL and HBAL groups significantly increased and a significantly higher level was observed in the HBAL group compared with the BAL group (27.7 ± 1.7 g/L vs 25.24 ± 1.93 g/L). In the HBAL group, the ammonia levels significantly decreased from 54.37 ± 6.86 to 37.75 ± 6.09 after treatment (P < 0.05); there were significant difference in ammonia levels between other the groups (P < 0.05). The levels of antibodies were similar before and after treatment. The PERV RNA and the RT activity in the canine plasma were all negative.

Conclusion: The HBAL showed great efficiency and safety in the treatment of acute liver failure.

Keywords: Acute liver failure; Co-culture; Flat plate bioreactor; Hybrid bioartificial liver; Nanofiber scaffold.

Figure 1

Schematic assembly of three artificial liver systems. A: Schematic assembly of non-bioartificial liver; B: Schematic assembly of bioartificial liver; C: Schematic assembly of hybrid bioartificial liver. P: Pump; RBC: Red blood cells; PS: Plasma separator; PE: Plasma component exchange column; IERC: Anionic resin adsorption column.

Figure 2

Comparisons of biochemical index between the treatment groups and the control group. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LDH: Lactate dehydrogenase; TBIL: Total bilirubin; ALB: Albumin; PT: Prothrombin time; HBAL: Hybrid bioartificial liver; BAL: Bioartificial liver; NBAL: Non-bioartificial liver; N: Normal; T0: Before treatment; D1: Day 1 after treatment; D3: Day 3 after treatment; D5: Day 5 after treatment.

Figure 3

Kaplan-Meier analysis of survival of two groups. HBAL: Hybrid bioartificial liver; BAL: Bioartificial liver; NBAL: Non-bioartificial liver.

Figure 4

Safety evaluation. A: Xenoreactive antibodies levels during bioartificial liver treatments; B: Representative results of reverse transcription-polymerase chain reaction electrophoresis with the RNA extracted from the plasma. The ladder ranged from 100 bp to 600 bp. NBAL: Hybrid bioartificial liver; BAL: Bioartificial liver; PERV: Porcine endogenous retrovirus.