Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2014; 20(46): 17399-17406
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17399
Hybrid bioartificial liver support in cynomolgus monkeys with D-galactosamine-induced acute liver failure
Zhi Zhang, Yi-Chao Zhao, Yuan Cheng, Guo-Deng Jian, Ming-Xin Pan, Yi Gao
Zhi Zhang, Yuan Cheng, Ming-Xin Pan, Yi Gao, Second Department of Hepatobiliary, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
Zhi Zhang, Yuan Cheng, Ming-Xin Pan, Yi Gao, Department of Hepatobiliary, Tangshan Gongren Hospital, Tangshan 063000, Hebei Province, China
Yi-Chao Zhao, Chancheng District Central Hospital, Guangdong Province, Foshan 528031, Guangdong Province, China
Guo-Deng Jian, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
Author contributions: Zhang Z and Gao Y designed and performed the experiments; Zhao YC and Pan MX evaluated and organized the experimental data; Jian GD and Zhao YC wrote the manuscript; Gao Y revised the manuscript; Zhao YC, Zhang Z and Cheng Y contributed equally to the article.
Supported by National High Technology Research and Development Program of China 863 Programs No. 2006AA02A141 and No. 2012AA020505, and the Medical Research Fund of Guangdong Province No. 2009164
Correspondence to: Yi Gao, Professor, Second Department of Hepatobiliary, Zhujiang Hospital, Southern Medical University, Guangzhoudadao 1838, Guangzhou 510282, Guangdong Province, China. gaoyi6146@163.com
Telephone: +86-20-61643207 Fax: +86-20-61643207
Received: November 3, 2013
Revised: March 14, 2014
Accepted: July 15, 2014
Published online: December 14, 2014
Abstract

AIM: To evaluate a hybrid bioartificial liver support system (HBALSS) in cynomolgus monkeys with acute liver failure.

METHODS: To establish a model of acute liver failure, 0.3 g/kg of D-galactosamine was injected intravenously into cynomolgus monkeys. Chinese human liver cells were introduced into a perfusion bioreactor to carry out hybrid bioartificial liver support treatment. Forty-eight hours after the injection, one group of cynomolgus monkeys received HBALSS care, and a second experimental group received no treatment. Clinical manifestations of all animals, survival time, liver and kidney functions and serum biochemistry changes were recorded. Simultaneous detection of the number, viability and function of hepatocytes in the hybrid bioartificial liver were also performed.

RESULTS: Forty-eight hours after the injection of D-galactosamine, serum biochemistry levels were significantly increased, whereas albumin levels and the Fischer index were significantly reduced compared to baseline (all Ps < 0.05). Of the ten monkeys in the HBALSS treatment group, five survived, with an average duration of survival of 128 ± 3 h. All cynomolgus monkeys in the control group died, with a duration of survival of 112 ± 2 h. Survival time was significantly longer with HBALSS treatment (P < 0.05). Moreover, the number, viability and function of hepatocytes were maintained at a high level with HBALSS.

CONCLUSION: The novel hybrid bioartificial liver plays a significant role in liver support by significantly reducing serum biochemistry levels and extending animal survival time.

Keywords: Acute liver failure, Chinese human liver cells, Cynomolgus monkey, Human liver cell, Hybrid bioartificial liver

Core tip: In this study, the authors evaluated the safety, efficacy, and clinical feasibility of a hybrid bioartificial liver support system (HBALSS) with Chinese human liver cells for the treatment of acute liver failure in monkeys. The bioartificial liver significantly reduced serum biochemistry levels and extended animal survival time. Furthermore, the number, viability and function of hepatocytes in the HBALSS were maintained at a high level during treatment. The results demonstrate that the novel HBALSS has the potential to be a safe, reliable bridge treatment for acute liver failure patients awaiting donor-organ availability.