An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

Table 1 Main AHF animal models in different species

Animal model	Species	Advantages/disadvantages
Surgical
Total/partial hepatectomy	Pig, dog, rabbit, rat, mouse	Hepatic encephalopathy; reproducible/no reversibility; no long-term survival
Total/partial devascularization	Pig, dog, rabbit, rat	Hepatic encephalopathy; reproducible/no reversibility; no long-term survival
Chemical
Acetaminophen	Pig, dog, rabbit, rat, mouse	Hepatic encephalopathy; no hazard/non-reproducible; variable interval between damage and death; species and age variability
Amanitin	Pig	Hepatic encephalopathy; specific toxic effects; large animal
Azoxymethane	Mouse	Hepatic encephalopathy; reproducible/small size; hazard
Carbon tetrachloride	Pig, rabbit, rat, mouse	Hepatic encephalopathy/non reproducible; extrahepatic toxicity; small time window before death
Concanavalin A	Rat, mouse	Hepatic encephalopathy/small size
Galactosamine	Pig, dog, rabbit, rat, mouse	Hepatic encephalopathy; biochemical markers/non-reproducible; hazard; variable interval between damage and death; species differences
Lipopolysaccharide	Rat, mouse	Hepatic encephalopathy/non-reproducible; small size; hazard; small time window before death
Thioacetamide	Rabbit, rat, mouse	Hepatic encephalopathy; reproducible; large time window before death/hazard
Viral
Rabbit hemorrhagic disease	Rabbit	Hepatic encephalopathy; reproducible; no hazard

Table 2 Main criteria for an AHF animal model (according to Terblanche and Hickman (1991)

Reversibility	Suitable treatment may reverse and improve survival
Reproducibility	Reproducible end-points are required to standardize the model
Death from liver failure	Should reflect biochemical, histological and clinical changes including death from AHF
Therapeutic window	Time for treatment should be available between insult and death
Adequate animal size	Size large enough to allow blood and tissue analysis to take place serially
Minimal hazard to personnel	Minimum risk for operators and associated staff