Cirrhosis is a very serious, gradual liver disease characterized by the overproduction of collagen and scarring, which together may result in liver failure or hepatocellular cancer. It typically develops based on fibrosis, which may be reversible when diagnosed in its initial stages. Viral hepatitis, alcohol, non-alcoholic fatty liver disease, and drug-induced hepatotoxicity are some of the etiologies of the disease. It is worth noting that about half of the cases of hepatic damage in patients are known to be caused by drug-induced liver injury. The existence of the pathophysiological complexity and therapeutic reactions of cirrhosis requires experimental models that are reliable. This review gives insight into the different in vivo, ex vivo, and operative animal models employed to cause hepatic injury by application of chemicals, drugs, dietary, and bile duct ligation particulars. The focus is on the mechanistic understanding of the actions of hepatotoxic substances, their involvement in oxidative stress, mitochondrial pathology, and the inflammatory process. Each model is critically discussed in terms of its advantages, limitations, and translational relevance.Additionally, this work highlights emerging alternatives, such as organ-on-a-chip systems, 3D co-cultures, and hepatic bioengineered tissues, as solutions that aim to reduce animal use and increase physiological relevance. The review also discusses biomarkers, histopathological endpoints, and important molecular players in hepatic fibrosis and cirrhosis. The review also examines data from preclinical studies of hepatoprotective substances and modulators of fibrosis, as it facilitates the integration of data from various experimental platforms. The next steps involve personalized pathology based on decellularized liver scaffolding and patient cells, aiming to better determine clinical outcomes and treatment responses.
Mehra et al. (Wed,) studied this question.