ALD management remains a significant challenge for clinicians. Effective treatments are warranted to prevent or reverse alcohol-induced liver damage to complement or supplant behavioral interventions. 

Metabolic syndrome is greatly seen in patients with ALD which accelerates its progression and increases liver disease mortality. But the Current rodent models of ALD do not assess the contribution of the western diet to ALD pathology. 

Thus a group of researchers developed a rodent model of ALD that integrates the impact of the western diet and alcohol; the WASH-diet model. This model combined chronic alcohol intake with the metabolic burden of the western diet to quantify the combined effect high fat, cholesterol, and fructose and alcohol abuse.

They demonstrated the WASH diet, either chronically or in small time-restricted bouts, accelerated ALD pathology with severe steatohepatitis, elevated inflammation and increased fibrosis compared to mice receiving chronic alcohol alone. The researchers demonstrated that the WASH diet significantly exacerbates ALD pathogenesis and produces pronounced steatohepatitis, inflammation and fibrosis contrasting to that the LD-ethanol diet.

Feeding mice on the LD-base diet high fat and fructose meal pellets even in once-daily intake, promotes more severe hepatic dyslipidemia contrasting the LD-ethanol diet alone. This is of particular interest as the consumption of fast food rich in saturated fat and fructose is commonly associated with binge drinking. 

They further validated their WASH-diet model as an in vivo system for testing the efficacy of experimental ALD treatments. This model also conserved the efficacy of the inverse-agonist SR9238, which inhibits both non-alcohol and alcohol-induced steatohepatitis progression. 

The study showed the most pronounced synergistic effect of alcohol and high fat on steatosis in the WASH model, which suggests the importance of disrupted hepatic lipid metabolism as a pathophysiological component to ALD.

Thus the study demonstrated the usefulness of the WASH-diet for in vivo pre-clinical assessment of novel therapies. The psychological challenges and the high rate of recidivism for alcohol addiction make utilizing hepatoprotective treatments increasingly important.

Source: Sengupta M, Abuirqeba S, Kameric A, Cecile-Valfort A, Chatterjee A, Griffett K, et al. (2021) A two-hit model of alcoholic liver disease that exhibits rapid, severe fibrosis. PLoS ONE 16(3): e0249316. https://doi.org/10.1371/journal.pone.0249316