Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system

Abstract

Aim: To establish a highly reproducible animal model of acute liver failure (ALF), for assessing the effect of bioartificial liver support system (BALSS).

Methods: A two-phase complete liver devascularization procedure was performed in eight loco-hybrid pigs. Blood biochemical index and liver biopsy were studied every 2 h after surgery, and survival time was recorded. The BALSS constructed with high volume recirculating technique was a hollow fiber circulating system consisting of a hepatocyte reactor-hollow fiber module inoculated with microcarrier-adhering hepatocytes, and a double pump, heparinized, thermostabilized, micro-capsulized activated carbon-adsorbing plasmapheresis system. Twelve pigs undergoing two-phase surgery were randomized into: control group (perfused without hepatocytes, n = 6) and treatment group (perfused with hepatocytes, n = 6). Intergroup liver biochemical indexes, survival time, and liver pathological changes were analyzed at regular intervals.

Results: Two-phase surgery was performed in all the experimental pigs, and there was no obvious difference between their biochemical indexes. After 3 h of phase II surgery, ammonia (Amm) increased to (269+/-37) micromol/L. After 5 h of the surgery, fibrinogen (Fib) decreased to (1.5+/-0.2) g/L. After 7 h of the surgery, ALT, AST, Tbil and PT were (7.6+/-1.8) nka/L, (40+/-5) nka/L, (55+/-8) micromol/L and (17.5+/-1.7) nka/L respectively. After 9 h of surgery, ALB and Cr were (27+/-4) g/L and (87+/-9) micromol/L. After 13 h of surgery, BUN was (3.5+/-0.9) micromol/L. All the above values were different from those determined before surgery. Survival time of pigs averaged 13.5+/-1.4 h. ALF pigs in the other group were treated with BALSS. The comparison analysis between the treated and control animals showed the changes of Tbil, PT, Alb, BUN, Cr, Fib, and Amm (P<0.01), but there was no change of ALT and AST. The survival time was statistically different (P<0.01), and there was no significant difference in histological changes.

Conclusion: The porcine ALF model established by two-phase devascularized surgery is valid and reproducible. The hollow fiber BALSS can meet the needs of life support and is effective in treating ALF.

Figure 1

Pattern of BAL circulating system.

Figure 2

Liver histology observation at 0 h (A), 1 h (B), 4 h (C), 7 h (D) after liver devascularization, and death of pigs (E) under light microscope.

Figure 3

Electronic microscopy observation of hepatocytes at 0 h (A) and 4 h (B).

Figure 4

Changes of ALT (A), AST (B), Tbil (C), Alb (D), Amm (E), BUN (F), Cr (G), PT (H), and Fib (I).