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Abstract Details
Evolving Role for Pharmacotherapy in NAFLD/NASH
Clin Transl Sci. 2020 Jun 25. doi: 10.1111/cts.12839. Online ahead of print.
Suzanna L Attia1, Samir Softic123, Marialena Mouzaki4
Author information
1Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Kentucky College of Medicine, University of Kentucky, USA.
2Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.
3Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
4Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, dynamic disease that occurs across the age spectrum and can lead to cirrhosis and hepatocellular carcinoma. There are currently no FDA approved treatments for NAFLD; however, this is a field of active research. This review summarizes emerging pharmacotherapies for the treatment of adult and pediatric NAFLD. Investigated pharmacotherapies predominantly target bile acid signaling, insulin resistance and lipid handling within the liver. Three drugs have gone on to phase 3 trials for which results are available. Of those, obeticholic acid is the single agent that demonstrates promise according to the interim analyses of the REGENERATE trial. Obeticholic acid showed reduction of fibrosis in adults with NASH taking 25mg daily for 18 months (n=931, reduction in fibrosis in 25% vs. 12% placebo, p<0.01). Ongoing Phase 3 trials include REGENERATE and MAESTRO-NASH, which investigates Thyroid Hormone Receptor-β (THR-β) agonist MGL-3196. Outcomes of promising phase 2 trials in adults with NASH are also available and those have investigated agents including the FGF19 analogue NGM282, the GLP1 agonist liraglutide, the FGF21 analogue Pegbelfermin, the SGLT2 inhibitor Empagliflozin, the ketohexokinase inhibitor PF-06835919, the acetyl-coenzyme A carboxylase inhibitor GS-0976 and the chemokine receptor antagonist Cenicriviroc. Completed and ongoing clinical trials emphasize the need for a more nuanced understanding of the phenotypes of subgroups within NAFLD that may respond to an individualized approach to pharmacotherapy.