Christophe De Block, Belgium
Moderator of 1 Session
Presenter of 1 Presentation
Prevention and pharmacological interventions in NAFLD/NASH
Abstract
Background and Aims
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease defined by intrahepatic lipid accumulation which is strongly associated with insulin resistance (IR) and inceases the risk for type 2 diabetes mellitus (T2DM) two- to threefold. Conversely, persons with T2DM have a higher prevalence of steatohepatitis, liver fibrosis and end-stage liver disease. Prevalence and incidence of NAFLD are dramatically increasing and NAFLD is projected to be the most common cause of chronic liver disease. In addition, NAFLD independently contributes to cardiovascular disease. CVD is the most common cause of death in patients with NAFLD. Therefore, early screening and identification of NAFLD is needed. Given the high prevalence and the rising incidence of NAFLD, and its clinical importance, the absence of approved therapies is striking.
Methods
Systematic review
Results
Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy. NAFLD therapies target 4 main pathways. The first approach is targeting hepatic fat accumulation via PPAR agonists (eg, pioglitazone), medications targeting the bile acid-farnesoid X receptor axis (obeticholic acid), inhibitors of de novo lipogenesis, GLP-1 receptor agonists (lira- and dulaglutide), dual GLP-1/GIP receptor agonist (tirzepatide), and fibroblast growth factor (FGF)-21 analogues. A second approach is targeting the oxidative stress, inflammation and injury via use of antioxidants (vitamin E), medications with a target in the TNF α pathway, and immune modulators (eg. cenicriviroc). A third group has a target in the gut, including antiobesity agents. Finally, antifibrotics are tested.
Conclusions
In the next few years several medications may become available to treat patients with NAFLD across the entire spectrum of disease, although their long-term safety and efficacy remain to be established.