Alcoholic liver disease: Utility of animal models

Abstract

Alcoholic liver disease (ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

Keywords: Steatohepatitis, Cirrhosis, Hepatocellular carcinoma, Alcoholic liver disease, Reactive oxygen species

Core tip: Alcoholism is now considered a global health issue. Although significant progress has been made in our understanding of the mechanisms and pathology of alcoholic liver disease (ALD), many features of ALD remain unidentified - requiring further investigation with improved animal models that more effectively emulate human ALD. In this Review, we provide an update on the prevalence, current and emerging experimental models, as well as the pathophysiology of ALD.