Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease worldwide that can manifest as nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). Compared with NAFL, NASH poses a substantially higher risk of progression to advanced liver disease, cirrhosis and hepatocellular carcinoma (HCC). Given the lack of directed pharmacological therapies and the complex, multifactorial disease aetiology and pathology, NAFLD is expected to become the leading cause of end-stage liver disease in the coming decades.
Preclinical research aimed at elucidating the molecular mechanisms driving disease and identifying reliable biomarkers and potential treatments is critical and has gained significant attention in recent years. Several animal models attempt to mirror the histopathology and pathophysiology of each stage of human NAFLD, including the development of NASH and fibrosis, up to HCC development. Most in vivo studies use mouse models owing to their relatively low cost, short lifespan and ease of genetic manipulation, which allow for a level of experimental control that is not possible with human studies. Independent of each model’s inherent advantages and disadvantages, making a mistake when choosing, performing, or even analyzing results for a particular animal NASH model may jeopardize our ability to obtain accurate results or draw firm conclusions.
Here, we discuss some mistakes commonly made in NASH preclinical research. We also consider the challenges and opportunities when selecting animal models for the study of NAFLD.