Animal models of liver failure: from model development to translational therapeutic applications

Liver failure (LF) represents a severe clinical syndrome associated with rapid deterioration of hepatic function, high mortality, and limited therapeutic options. Despite extensive research efforts, the complex pathogenesis of LF remains incompletely understood, and effective therapeutic strategies remain limited. Animal models have therefore become indispensable platforms for elucidating disease mechanisms, dissecting pathological processes, and evaluating potential therapeutic interventions. In this review, we systematically summarize major animal models for liver failure research, covering surgical, toxin-induced, drug-induced, metabolic, immune-mediated, ethanol-associated, and gene-editing approaches. We discuss their mechanisms, modeling strategies, advantages, limitations, and translational relevance, with emphasis on their ability to recapitulate key pathological features of human LF. We also discuss recent therapeutic advances assessed in LF models and highlight future perspectives. Finally, we discuss current challenges and future directions, including humanized models, organoid-based platforms, multi-omics integration, artificial intelligence-assisted optimization, and standardized evaluation systems. By integrating current advances and unresolved challenges, this review underscores the importance of refining LF animal models to enhance mechanistic investigations and improve the clinical translation of emerging therapies.