Non-alcoholic fatty liver disease (NAFLD) has a more progressive form, non-alcoholic steatohepatitis (NASH). In both conditions, inflammation is a key driver of the pathogenesis. Current treatments mostly focus on promoting weight loss (through encouraging lifestyle changes, or, if necessary, bariatric surgery) and improving comorbidities through pharmacotherapy, such as type 2 diabetes. This is because creating drugs to target NASH specifically has proven a challenge; many recent trials which showed promising results in early research phases were not as successful as imagined in clinical trials (this includes compounds such as elafibrinor, aldafermin and others). There are, however, promising ongoing Phase 3 trials currently, such as for obeticholic acid, which functions as an FXR agonist, and resmetiron, an agonist for the hepatic thyroid hormone receptor. These trials are currently showing positive effects, with hopes for the future pharmacotherapy of NASH.
This review by Wiering L & Tacke F aimed to understand the importance of inflammation and anti-inflammatory therapies for NASH and NAFLD.
NAFLD and NASH are complex pathologies. Although it is highly challenging to develop a pharmacological therapy for these conditions, and many trials have been terminated due to such challenges, there are currently ongoing Phase 3 trials which hold great promise to deliver a drug treatment for NAFLD and NASH.