Ryska M, Lásziková E, Pantoflícek T, Kieslichová E, Ryska O, Prazák J, Koblihová E, Skibová J
Chirurgická klinika 2. LF UK a UVN Praha.
Cas Lek Cesk. 2008;147(7):367-75.
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.
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.
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 ALE 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.
在过去20年中，生物和非生物人工肝装置的发展使等待肝移植或等待肝实质自发再生的急性肝衰竭（ALF）患者得到了有效治疗。本研究的目的是评估生物（BAL - 生物人工肝）和非生物（FPSA - 血浆成分分离吸附）方法在大型实验动物实验性急性肝衰竭治疗中的有效性。
在监测急性肝衰竭标志物（AST、ALT、胆红素、氨、血糖、INR）包括颅内压（ICP）后，建立猪（体重25 - 40 kg）肝去血管化急性肝衰竭手术模型。对照组包括未治疗急性肝衰竭的动物。通过T检验以及使用EXCEL和QUATRO进行的曼 - 惠特尼非参数检验，将两个实验组的结果与对照组进行比较并进行统计学分析。BAL组：10头急性肝衰竭猪（体重30±5 kg）接受了含分离肝细胞的生物人工肝治疗。比较血浆胆红素时，在6小时和9小时时间段发现显著差异（p < 0.05），有利于BAL组（18.1对13.1，22.9对13.2 mmol/L）。两组的颅内压值无显著差异。普罗米修斯组：14头体重35 kg（35±5 kg）的相同急性肝衰竭猪接受了普罗米修斯（FPSA）治疗。与对照组相比，实验组血清胆红素水平在6小时时间段（12.81±6.54对29.84±9.99）、9小时时间段（11.94±4.14对29.95±12.36）和12小时时间段（13.88±6.31对26.10±12.23 mmol/L）显著更低（p < 0.01）。未发现血清氨水平有显著差异。从9小时到12小时时间段，颅内压有显著差异，有利于FPSA组（p < 0.01）：9小时19.1±4.09对24.1±2.85，10小时21.9±3.63对25.1±2.19，11小时22.5±3.98对26.3±3.50，12小时24.0±4.66对29.8±5.88 mmHg。
在实验性急性肝衰竭病例中，观察到血浆成分分离吸附（普罗米修斯）治疗使胆红素和颅内压水平有显著改善。除胆红素水平外，由O. liver Performer提供的含分离肝细胞的生物人工肝未使包括颅内压在内的实验室指标有任何显著改善。
