Les nouveaux traitements de la stéatohépatite non-alcoolique

Non-alcoholic steatohepatitis (NASH) is a liver disease responsible for complications and mortality from hepatic (fibrosis, cirrhosis, hepatocellular carcinoma) and extrahepatic (insulin resistance, cardiovascular diseases) causes. Currently, there is no approved treatment for this indication. However, a weight loss of 5 to 10 % of the initial body weight is able to improve liver histology. However, it is difficult to achieve in all patients or ineffective/not indicated if the disease is diagnosed at an irreversible cirrhosis stage. Different drugs available in the dysmetabolic context are presented (statins, metformin, etc.) with their impact on liver disease. Recently, numerous agents have shown modest but positive results. Several compounds tested in phase 2 trials are explained in this article, including FXR or TGR5 agonists, PPARα/δ/γ agonists, recombinant FGF21, FGF19 analog, thyroid receptor agonist β1, GLP-1 agonists, inhibitors of lipogenesis, CCR2/5 antagonist… The most advanced results concern the interim analysis of the phase 3 study on obeticholic acid (FXR agonist) which notably confirmed a regression of hepatic fibrosis with this treatment. Four other compounds are also currently tested in phase 3 trials. The multi-mechanistic strategy of a combination therapy is also discussed. Other therapeutic approaches such as obesity surgery, microbiota modulation and bariatric endoscopy are exposed.