Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey.

Lei Cai,Qing Peng,Lei Feng,Zhi Zhang,Yi Gao,Guolin He,Mingxin Pan,Jun Weng,Jiasheng Qin,Zesheng Jiang,Yang Li

doi:10.1155/2016/3518989

Abstract

Models using large animals that are suitable for studying artificial liver support system (ALSS) are urgently needed. Presently available acute liver failure (ALF) models mainly involve pigs or dogs. Establishment of current surgical ALF models (hepatectomy/devascularization) requires either very good surgical skills or multistep processes—even multiple stages of surgery. Therefore, it is necessary to develop a simplified surgical method. Here we report a novel simplified surgical ALF model using cynomolgus monkeys. Six monkeys underwent portal-right renal venous shunt combined with common bile duct ligation and transection (PRRS + CBDLT). Postoperatively, the monkeys had progressively increased listlessness, loss of appetite, and obvious jaundice. Blood biochemistry levels (Amm, ALT, AST, TBiL, DBiL, ALP, LDH, CK, and Cr) and prothrombin time (PT) were significantly increased (all P < 0.01) and albumin (ALB) was markedly reduced (P < 0.01) compared with baseline values. Histological examination of liver specimens on postoperative day 10 revealed cholestasis and inflammation. PRRS + CBDLT produced ALF that closely correlated with clinical situations. Compared with other surgical or drug ALF models, ours was simplified and animals were hemodynamically stable. This model could provide a good platform for further research on ALSS, especially regarding their detoxification functions.

Highlights

Acute liver failure (ALF) is a serious clinical disease known for its aggressive progression and poor prognosis
A portal-right renal venous shunt combined with common bile duct ligation and transection was successfully completed (Figure 1(d))
heart rate (HR), blood pressure (BP), and central venous pressure (CVP) were stable throughout the procedure except

Summary

Introduction

Acute liver failure (ALF) is a serious clinical disease known for its aggressive progression and poor prognosis. Significant treatment improvements have been achieved in recent years, its mortality is still very high [1, 2]. Liver transplantation is an effective therapeutic approach for ALF. Its application has been limited in clinical practice for various reasons, including lack of organ availability, high cost, high technical requirements, and immunological rejection [3, 4]. An artificial liver support system (ALSS) could be used as a bridge between liver failure and liver transplantation [5]. Before ALSS goes into clinical trials, establishment of an ideal experimental model in a large animal is desperately needed to test the feasibility, functionality, and safety [6, 7]

Methods

Results

Discussion

Conclusion