Feng Lei, Wang Yi, Liu Shusong, He Guolin, Cai Lei, Qin Jiasheng, Xu Xiaoping, Jiang Zesheng, Zhou Chenjie, Gao Yi
Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, P.R. China.
State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, P.R. China.
Int J Artif Organs. 2022 May;45(5):523-532. doi: 10.1177/03913988221091286. Epub 2022 Apr 13.
Acute liver failure (ALF), which can potentially be treated with an artificial liver, is a fatal condition. The purpose of this study was to evaluate the safety and effectiveness of a novel hybrid bioartificial liver system (NHBLS) using simulated liver failure serum in vitro.
The bioreactor in experimental group was cultivated with primary porcine hepatocytes, whereas in control group was not. Next, the simulated liver failure serum was treated using the NHBLS for 10 h. Changes in albumin (ALB), total bilirubin (TBIL), ammonia (Amm), total bile acid (TBA), creatinine (Cr), and blood urea nitrogen (BUN) were measured before treatment (0 h) and every 2 h during treatment. In addition, changes in NHBLS pressures, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lidocaine metabolism were also recorded.
The NHBLS worked steadily without unexpected occurrences during the treatment. Blood culture showed no bacterial growth after 7 days, and the endotoxin level was less than 0.5 EU. The TBIL, TBA, Cr, and BUN levels in both groups were markedly lower than those at 0 h (0.05). The Amm level in experimental group was significantly lower than that in control group ( < 0.05). NHBLS pressures were also stable, and the hepatocytes in the bioreactor functioned well.
The preparation method for the simulated liver failure serum was optimized successfully, and the safety and effectiveness of the NHBLS in vitro were verified. Furthermore, the NHBLS significantly reduced the levels of Amm which can lead to hepatic encephalopathy.
急性肝衰竭（ALF）是一种致命疾病，有可能通过人工肝进行治疗。本研究旨在体外使用模拟肝衰竭血清评估新型混合生物人工肝系统（NHBLS）的安全性和有效性。
实验组生物反应器用原代猪肝细胞培养，而对照组未培养。接下来，使用NHBLS对模拟肝衰竭血清进行10小时处理。在处理前（0小时）以及处理期间每2小时测量白蛋白（ALB）、总胆红素（TBIL）、氨（Amm）、总胆汁酸（TBA）、肌酐（Cr）和血尿素氮（BUN）的变化。此外，还记录了NHBLS压力、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和利多卡因代谢的变化。
处理过程中NHBLS运行稳定，未发生意外情况。血培养显示7天后无细菌生长，内毒素水平低于0.5 EU。两组的TBIL、TBA、Cr和BUN水平均明显低于0小时时的水平（P<0.05）。实验组的Amm水平明显低于对照组（P<0.05）。NHBLS压力也稳定，生物反应器中的肝细胞功能良好。
成功优化了模拟肝衰竭血清的制备方法，验证了NHBLS在体外的安全性和有效性。此外，NHBLS显著降低了可导致肝性脑病的Amm水平。
