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Alcoholic liver disease (ALD) is a major cause of chronic liver injury worldwide.1 ,2 Clinically, jaundice and liver failure are hallmark presentations of patients with severe alcoholic hepatitis (AH) who typically have been drinking up to the time of admission or have stopped drinking within 4–6 weeks of their presentation of symptoms. The liver histology of AH has features of steatohepatitis, hepatic neutrophil infiltration, cholestasis and florid inflammation.3 Among patients with ALD, liver-related mortality is much higher in patients with AH than those with only simple steatosis.3 Current recommended treatments for AH include corticosteroids or pentoxifylline and nutritional supplements, but they only have moderate therapeutic effects.3
A major barrier preventing drug development against AH is our lack of understanding of the regulatory pathways involved in the pathogenesis of AH despite decades of research on ALD. One reason for this knowledge gap is a lack of proper animal models that reflect the exact pathogenesis of human ALD. The commonly used rodent models, including mice or rats administered with acute oral gavage, ad libitum oral alcohol in drinking water or chronic Lieber–DeCarli ethanol diet feeding, only show mild elevation of serum alanine aminotransferase (ALT) and increased hepatic levels of triglyceride (TG). These models only mimic early pathogenic changes in human ALD, and neutrophil infiltration in the liver is not evident. Dr Bin Gao's group recently developed a mouse model in which mice were fed with the Lieber–DeCarli ethanol diet for 10 days followed by an acute gavage of alcohol (hereafter referred to as Gao-binge model).4 Mice administered with Gao-binge have elevated serum ALT levels, increased hepatic TG, and more importantly, increased circulating and hepatic infiltrated neutrophils, making it possible to determine the mechanisms and role of neutrophils in AH. Indeed, using this Gao-binge model, Dr Gao's group demonstrated …
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