Application of the “two-hit” hypothesis in animal models of alcoholic liver disease

Alcoholic liver disease （ALD） poses a serious threat to the health of drinkers worldwide， and establishing appropriate animal models of ALD is an important foundation for conducting disease-related research. Due to the physiological and pathophysiological differences between rodents and humans， alcohol feeding alone is difficult to induce a model that closely matches the disease manifestations in humans， and therefore， the “two-hit” hypothesis （ combining alcohol with another liver injury factor to induce the expected state of liver injury） has been widely used. This article classifies the more commonly used and effective “two-hit” regimens into three major categories of special diets， chemical substances， and genetic engineering， which are divided into high-fat diet， high-iron diet， carbon tetrachloride， lipopolysaccharide， and genetic engineering for further analysis. Although these five “two-hit” models have their own advantages and disadvantages， they can nearly cover the disease spectrum of ALD. In the future， the development of ALD animal models can focus on narrowing the pathophysiological differences in alcohol-induced liver injury between animals and humans and simulating more complex drinking patterns in humans.