Non-alcoholic Steatohepatitis (NASH) Models for Preclinical Testing of Cell Death Inhibitors In Vitro



Jones, Shelley

Journal Title

Journal ISSN

Volume Title



Given the worldwide prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), and a substantial proportion of simple steatosis patients progressing to Non-Alcoholic Steatohepatitis (NASH), a condition associated with liver inflammation, and, further, to cirrhosis and end-stage liver failure, the development of in vitro models for NAFLD is warranted. Currently used models of this kind are overly simplistic, and incompatible with high-throughput experimentation mode which is necessary for the screening of potential therapeutics capable of the reversal of NASH phenotype. The best way to proceed forward would be with utility of liver-on-a-chip devices harboring established immortal cell lines, for example, HepG2 – a “workhorse” of liver toxicology – or its less malignant counterpart HepaRG. With an aid of these devices, many potential therapeutic compounds may be profiled either as monotherapy, or as synergistic enhancers for other potential treatments. The targeting of the necroptosis, rather than “classical” apoptosis, is a promising therapeutic option aimed at the delay of progression or even a reversal of NAFLD and other inflammation-associated liver diseases.



Non-Alcoholic Fatty Liver Disease (NAFLD), Non-Alcoholic Steatohepatitis (NASH), Apoptosis inhibitors as potential NAFLD therapeutics, In vitro NAFLD model for preclinical studies