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Biological and Non-biological Elimination Therapy of Acute Liver Failure. Experimental Study on Large Laboratory Animal


Authors: M. Ryska 1,2;  E. Lásziková 2,3;  T. Pantoflíček 1,2;  E. Kieslichová 4;  O. Ryska 2,5;  J. Pražák 6;  E. Koblihová 1,2;  J. Skibová 4
Authors‘ workplace: Chirurgická klinika 2. LF UK a ÚVN, Praha 1;  Centrum buněčné terapie a tkáňových náhrad 2. LF UK, Praha 2;  Oddělení anesteziologie a resuscitace ÚVN, Praha 3;  IKEM, Praha 4;  Chirurgická klinika 1. LF UK a IPVZ ILF, FN Na Bulovce, Praha 5;  Klinika anesteziologie, resuscitace a intenzivní péče 2. LF UK a FNM, Praha 6
Published in: Čas. Lék. čes. 2008; 147: 367-375
Category: Original Article

Overview

Background.
Development of biological and non–biological artificial liver devices in the previous 20 years enabled effective treatment of acute liver failure (ALF) of patients waiting for liver transplantation or for spontaneous liver parenchyma regeneration. Aim of the study was the evaluation of the effectiveness of biological (BAL – bioartificial liver) and non–biological (FPSA – Fractionated plasma separation and adsorption) methods in the treatment of experimental ALF on large laboratory animal. 

Methods and Results.
Surgical model of ALF with liver devascularization in pigs (weight 25–40 kg) was provided following monitoring of ALF markers (AST, ALT, bilirubin, ammoniac, glycaemia, INR) including intracranial pressure (ICP). Control group included animals without treatment of ALF. Results of both experimental groups were compared and statistically worked-out with that of controls by T-test and Mann-Whitney non–parametric test by EXCEL and QUATRO. BAL group: 10 pigs (weight 30 ± 5 kg) with ALF were treated by BAL with isolated hepatocytes. When plasma bilirubin was compared, significant differences (p < 0.05) in 6 and 9 hours interval were found favouring BAL group (18.1 vs. 13.1, 22.9 vs. 13.2 mmol/l). The value of ICP in both groups was no significant. Prometheus group: 14 pigs weight 35 kg (35 ± 5 kg) with the identical ALF were treated by Prometheus (FPSA). Level of serum bilirubin in experimental group when compared to control group was significantly lower (p < 0.01) at 6 hour interval 12.81 ± 6.54 vs. 29.84 ± 9.99 at 9 hour 11.94 ± 4.14 vs. 29.95 ± 12.36 and at 12 hour 13.88 ± 6.31 vs. 26.10 ± 12.23 mmol/l. No significant difference in serum ammonia level was found. ICP was significantly different from 9 hour to 12 hour interval in favour of FPSA group (p < 0.01): 9 hour 19.1 ± 4.09 vs. 24.1 ± 2.85, 10 hour 21.9 ± 3.63 vs. 25.1 ± 2.19, 11 hour 22.5 ± 3.98 vs. 26.3 ± 3.50 and 12 hour 24.0 ± 4.66 vs. 29.8 ± 5.88 mm Hg. 

Conclusions.
Significant improvement of bilirubin and ICP levels resulting from the treatment with fractionated plasma separation and adsorption (Prometheus) were observed in the case of experimental ALF. Except the bilirubin levels, bioartificial liver provided by O. liver Performer with isolated hepatocytes did not bring any significant improvement of laboratory markers, including ICP. 

Key words:
acute liver failure, large laboratory animal, bioartificial liver, FPSA, monitoring.


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