Abstract
Liver fibrosis refers to the process underlying the development of chronic liver diseases, wherein liver cells are repeatedly destroyed and regenerated, which leads to an excessive deposition and abnormal distribution of the extracellular matrix such as collagen, glycoprotein and proteoglycan in the liver. Liver fibrosis thus constitutes the pathological repair response of the liver to chronic injury. Hepatic fibrosis is a key step in the progression of chronic liver disease to cirrhosis and an important factor affecting the prognosis of chronic liver disease. Further development of liver fibrosis may lead to structural disorders of the liver, nodular regeneration of hepatocytes and the formation of cirrhosis. Hepatic fibrosis is histologically reversible if treated aggressively during this period, but when fibrosis progresses to the stage of cirrhosis, reversal is very difficult, resulting in a poor prognosis. There are many causes of liver fibrosis, including liver injury caused by drugs, viral hepatitis, alcoholic liver, fatty liver and autoimmune disease. The mechanism underlying hepatic fibrosis differs among etiologies. The establishment of an appropriate animal model of liver fibrosis is not only an important basis for the in-depth study of the pathogenesis of liver fibrosis but also an important means for clinical experts to select drugs for the prevention and treatment of liver fibrosis. The present study focused on the modeling methods and fibrosis characteristics of different animal models of liver fibrosis, such as a chemical-induced liver fibrosis model, autoimmune liver fibrosis model, cholestatic liver fibrosis model, alcoholic liver fibrosis model and non-alcoholic liver fibrosis model. In addition, we also summarize the research and application prospects concerning new organoids in liver fibrosis models proposed in recent years. A suitable animal model of liver fibrosis and organoid fibrosis model that closely resemble the physiological state of the human body will provide bases for the in-depth study of the pathogenesis of liver fibrosis and the development of therapeutic drugs.
Highlights
Liver fibrosis is a pathophysiological process caused by a variety of pathogenic factors that induce the abnormal proliferation of connective tissue in the liver
Researchers have successfully developed a number of hepatic fibrosis models using different experimental animals and different methods
Due to the complexity of the pathogenesis of human liver fibrosis and differences in the genetic background between human and other animal species, there is no modeling method that can perfectly replicate the process of human liver fibrosis
Summary
Liver fibrosis is a pathophysiological process caused by a variety of pathogenic factors that induce the abnormal proliferation of connective tissue in the liver. After 12-week oral administration of TAA in rats, bile duct fibrosis was induced, characterized by tubular hyperplasia surrounded by fibrous tissue (Hata et al, 2013) Both CCl4 and TAA can cause lipid oxidative damage in liver cells. The same CCl4 vapor exposure combined with chronic alcohol feeding resulted in extensive liver fibrosis in rats at week 5 and micronodular cirrhosis at week 10 This animal model simulates how some chronic liver damage in humans may be due to the presence of other hepatotoxins in the environment that play a role in enhancing the effects of alcohol (Hall et al, 1991). A modified choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) rapidly induces liver fibrosis in mice This model will contribute to a better understanding of human NASH disease and may be useful for the development of effective treatments (Matsumoto et al, 2013). Mouse models carrying human apolipoprotein E∗ 3-leiden and cholesterol ester transfer protein, fed a “Western” diet, lead to liver inflammation and fibrosis that are highly dependent on genetic background and have a large overlap of pathways between human diseases (Hui et al, 2018)
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