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Metabolic Targets in Nonalcoholic Steatohepatitis: Treating the Disease at the Metabolic Root

  • Fatty Liver Disease (V Ajmera, Section Editor)
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Abstract

Purpose of Review

Nonalcoholic fatty liver disease (NAFLD) and its more aggressive form nonalcoholic steatohepatitis (NASH) are a leading cause of chronic liver disease worldwide. Thus far, there are no FDA-approved therapeutic options for NASH. This review discusses relevant and recent findings in the development of pharmacotherapy that targets the metabolic processes implicated in NASH.

Recent Findings

Several key drugs have been identified across various drug classes. Among inhibitors of de novo lipogenesis, the SCD-1 inhibitor aramchol and the ACC inhibitor firsocostat are the most advanced. Within nuclear hormone receptor agonists, PPARα/δ agonist elafibranor and PPARα/γ agonist saroglitazar show promise with respect to improvement in NASH histology and hepatic steatosis. Additionally, THR-β agonist resmetirom showed significant reduction in hepatic steatosis and NASH resolution. Larger studies with longer treatment duration are needed to establish safety and efficacy of these metabolic drugs.

Summary

Significant progress has been made over the past decade in testing drugs that modulate the metabolic targets responsible for NASH progression.

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Authors and Affiliations

  1. University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA

    Pankaj Aggarwal, Tamneet Singh & Naim Alkhouri

  2. The Texas Liver Institute, University of Texas Health San Antonio, 607 Camden Street, San Antonio, TX, 78215s, USA

    Naim Alkhouri

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  1. Pankaj Aggarwal
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Dr. Alkhouri has served on advisory boards for Allergan, Gilead, Intercept, Pfizer, and Zydus; he has served as a speaker for AbbVie, Alexion, Gilead, Intercept, and Simply Speaking; and has received research support from Akero, Albireo, Allergan, Axcella, BI, BMS, Celgene, Gilead, Galmed, Galectin, Genfit, Enanta, Enyo, Hanmi, Inventiva, Madrigal, Merck, Novartis, Novo Nordisk, Pfizer, Poxel and Zydus.

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Aggarwal, P., Singh, T. & Alkhouri, N. Metabolic Targets in Nonalcoholic Steatohepatitis: Treating the Disease at the Metabolic Root. Curr Hepatology Rep 19, 302–314 (2020). https://doi.org/10.1007/s11901-020-00533-x

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