Despite the rising prevalence of nonalcoholic fatty liver disease (NAFLD), the underlying disease pathophysiology remains unclear. The need is great for an efficient and reliable ‘human’ in vitro model to study NAFLD and the progression to nonalcoholic steatohepatitis (NASH), which will soon become the leading indication for liver transplantation. Here, we review the recent developments in the use of 3D liver organoids as a model to study NAFLD and NASH pathophysiology and possible treatments. Various techniques that are currently used to make liver organoids are discussed, such as the use of induced pluripotent stem cells vs. primary cell lines and human vs. murine cells. Moreover, methods for inducing lipid droplet accumulation and fibrosis to model NAFLD are explored. Finally, the limitations specific to the 3D organoid model for NAFLD/NASH are reviewed, highlighting the need for further development of multilineage models to include hepatic nonparenchymal cells and immune cells. The ultimate goal is to be able to accurately recapitulate the complex liver microenvironment in which NAFLD develops and progresses to NASH.

Background: Early allograft disfunction (EAD) can be used as a tool to asses function of the liver after transplantation. Currently, most accepted EAD definition can be defined using a number of criteria including but not limited to total bilirubin > 10 mg/dL on post-operative day 7, INR > 1.6 on post-operative day 7, and ALT or AST > 2000 IU/L within the first post-operative 7 days. EAD is associated with mortality and morbidity after liver transplantation which leads to decreased recipient survival rates. It is considered a precursor step in the pathway to eventual graft loss.    Methods: We have performed a literature review to understand what risk factors increase, including donor and recipient demographics as well as recipients’ MELD (Model for End Stage Liver Disease) scores, which predicts patients’ disease severity. We also compared the incidence of EAD between our center and the literature.     Results: We found that incidence of EAD was between 23-40% (Table 2). It is higher when livers from donation after circulatory death (DCD) donors were used, as expected.    Reference (year)  Number of patients  Incidence of EAD   Ekser et al (2019)  n = 2008  29%  Olthoff et al (2010)  n = 300  23%  Wadei et al (2015)  n = 1325  27%  Lee et al (2014)  n = 205   39.5% (DCD donors)      Risk factors that can result in an increase occurrence of EAD were; (i) donor age, (ii) liver stenosis, (iii) expanding criteria for donor livers, (iv) prolonged warm ischemia time (WIT) and (v) cold ischemia time (CIT). Histologically, hepatocellular damage that is shown as coagulative necrosis can be seen immediately after reperfusion.     Conclusions: During our literature review, potential strategies have been discovered to help prevent EAD including pharmacological treatment using glucose, antioxidants, anti-inflammatories, and apoptotic drugs. Although none of them significantly prevented the occurrence of EAD, it was clear that there are many tools that can be used to attempt to prevent EAD in order to offer a better outcome in patients undergoing liver transplantation.