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Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD

1
Division of Gastroenterology, Women & Infants Hospital/Warren Alpert School of Medicine, Brown University, Providence, RI 02905, USA
2
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA
3
Drexel University College of Medicine, Philadelphia, PA 19129, USA
4
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, USA
*
Author to whom correspondence should be addressed.
Diseases 2018, 6(3), 83; https://doi.org/10.3390/diseases6030083
Received: 9 August 2018 / Revised: 17 September 2018 / Accepted: 17 September 2018 / Published: 19 September 2018
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Abstract

The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1) nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the potential to progress to advanced liver damage. Current treatment strategies have focused on lifestyle management of modifiable risk factors, namely weight, and on the optimization of the management of individual components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading to the development of novel drugs with the potential to effectively treat patients with NASH. Numerous clinical trials are ongoing, utilizing these experimental drugs and molecules targeting specific mechanistic pathway(s) to effectively treat NASH. Some of these mechanistic pathways targeted by experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism, inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation of fibroblast growth factor 19, agonism of selective thyroid hormone receptor-beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl-coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and further updates from ongoing clinical trials are eagerly awaited. View Full-Text
Keywords: NAFLD; NAFLD; NASH; nonalcoholic fatty liver disease; drug therapy; chemokine receptor 2 and 5; galectin-3 protein; toll-like receptor 4; fibroblast growth factor 19; selective thyroid hormone receptor-beta; apoptosis signal-regulating kinase 1; acetyl-coenzyme A carboxylase; farnesoid X receptor; inflammasomes NAFLD; NAFLD; NASH; nonalcoholic fatty liver disease; drug therapy; chemokine receptor 2 and 5; galectin-3 protein; toll-like receptor 4; fibroblast growth factor 19; selective thyroid hormone receptor-beta; apoptosis signal-regulating kinase 1; acetyl-coenzyme A carboxylase; farnesoid X receptor; inflammasomes
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Dibba, P.; Li, A.A.; Perumpail, B.J.; John, N.; Sallam, S.; Shah, N.D.; Kwong, W.; Cholankeril, G.; Kim, D.; Ahmed, A. Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD. Diseases 2018, 6, 83.

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