An In vitro Model of Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition1. The incidence and prevalence of this condition is rising rapidly due to the trend towards high fat diets and an increase in obesity levels.

Stage 1: The first stage of the disease is known as ‘fatty liver’ or ‘steatosis’ where abnormal levels of fat in the liver are observed. This stage can have no symptoms and with weight loss through dietary changes and exercise it can be reversible.

Stage 2: If levels of fat in the liver continue to rise, this can lead to a condition known as NASH (non-alcoholic steatohepatitis) where the abnormal fat levels lead to inflammation and eventually scarring of the liver. Progression to NASH occurs in approximately 10-20% of patients with NAFLD2.

Stage 3: As scar tissue builds up, this damage can eventually progress to advanced fibrosis and cirrhosis of the liver. As well as an increased susceptibility to liver failure, NAFLD-related cirrhosis increases the risk of liver cancer.

There is growing evidence that NAFLD can increase the risk of drug-induced liver injury (DILI). It is also thought that certain drugs may increase the progression of the disease. These reports are of concern as, due to the underlying condition, on average a greater number of drugs are administered to obese individuals compared to non-obese individuals, therefore, individuals with obesity may be at greater risk from these adverse effects2. In vitro models of NAFLD are now being developed in order to test the effects of new chemical entities and existing drugs on this condition.

Cyprotex are currently developing a 3D fatty liver model for this purpose. The model uses HepaRG cells cultured in the presence of fatty acids to mimic the effects of fatty liver. High content imaging has been used to confirm fat accumulation within the HepaRG cells as shown in the images below.

 

 

 

 

 

1Bertot LC and Adams LA (2016) The natural course of non-alcoholic fatty liver disease. Int J Mol Sci 17(5); 774.

2Massart J et al., (2017) Role of non-alcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity. J Clin Transl Res 3(Suppl 1); 212-232.

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