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Future Treatments of NASH

  • Fatty Liver Disease (SA Harrison and J George, Section Editors)
  • Published:
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Abstract

NASH is a complex metabolic disease best understood by recognizing the sources and fates of major metabolic substrates (carbohydrates and fatty acids) and how their excess can lead to lipotoxic liver injury with a histological phenotype of NASH. With this perspective, targets of therapy can be predicted. This review summarizes recent clinical trial data and where these trials fit into the substrate overload lipotoxic liver injury paradigm of NASH pathogenesis. Because NASH is likely the result of diverse environmental, genetic, and epigenetic factors that differ among patients, no single therapy is likely to be effective in all patients. Ultimately, rationally designed personalized therapy will be achieved for patients with NASH, but this will require substantial new knowledge on why patients respond to specific therapies, a goal that remains elusive. Hopefully, this gap in knowledge will be addressed by analysis of responders and non-responders in current and future clinical trials.

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Abbreviations

NASH:

Nonalcoholic steatohepatitis

NAFLD:

Nonalcoholic fatty liver disease

DNL:

De novo lipogenesis

PPAR:

Peroxisomal proliferator activated receptor

FXR:

Farnesol X receptor

SGLT2:

Sodium glucose cotransporter 2

GLP:

Glucagon-like peptide

DPP:

Dipeptidyl dipeptidase-4

FGF:

Fibroblast growth factor

CoA:

Coenzyme A

SREPBP:

Sterol response element binding protein

ACC:

Acetyl-CoA carboxylase

FAS:

Fatty acid synthetase

SCD:

Stearoyl-CoA desaturase

SAMe:

S-adenosylmethionine

PDE-4:

Phosphodiesterase-4

CCR:

Chemokine receptor

ELF:

European liver fibrosis

Loxl2:

Lysl oxidase-like protein 2

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, 3635 Vista Ave, GI/FDT-9, St. Louis, MO, 63110, USA

    Brent A. Neuschwander-Tetri

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Correspondence to Brent A. Neuschwander-Tetri.

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Conflict of Interest

BANT reports personal fees from Nimbus Therapeutics, Bristol Myers Squibb, Janssen, Conatus, Galmed, Genetech-Roche, and Boehringer-Ingelheim, and personal fees and consultancy for Receptos, Pfizer, and Zafgen, outside the submitted work.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and were in compliance with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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This article is part of the Topical Collection on Fatty Liver Disease

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Neuschwander-Tetri, B.A. Future Treatments of NASH. Curr Hepatology Rep 15, 125–133 (2016). https://doi.org/10.1007/s11901-016-0300-3

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