Development and validation of a primate model for liver fibrosis.

INTRODUCTION

Many liver diseases involve liver fibrosis. Most preclinical studies of liver fibrosis are carried out in small animals such as rodents, and thus lack direct potential for extrapolation to human diseases. The aim of the current study was to develop a primate model for liver fibrosis with greater relevance to translational research.

METHODS

Liver fibrosis was induced in adult male healthy rhesus monkeys using repeated CCl4 treatment (40% in olive oil, 1.5 ml/kg once every 3 days via peritoneal injection, subcutaneous injection or gastric gavage). Liver biopsy was conducted at various time points for histologic examination. Blood samples were taken for standard liver function test.

RESULTS

Gastric gavage was the optimal approach for establishing stably liver fibrosis without animal loss due to toxicity. The progression of fibrosis appeared to involve epithelial to mesenchymal transition and hepatic ductular reaction.

CONCLUSION

Repeated CCl4 gavage in rhesus monkeys results in stable liver fibrosis. Such a model may be an effective platform for future studies of human liver fibrosis.