Hepatology International

, Volume 12, Issue 2, pp 97–106 | Cite as

Targeting incretin hormones and the ASK-1 pathway as therapeutic options in the treatment of non-alcoholic steatohepatitis

  • Alexander J. Kovalic
  • Sanjaya K. Satapathy
  • Naga Chalasani
Review Article


Non-alcoholic fatty liver disease (NAFLD) is currently one of the leading forms of chronic liver disease, and its rising frequency worldwide has reached epidemic proportions. NAFLD, particularly its progressive variant NASH (non-alcoholic steatohepatitis), can lead to advanced fibrosis, cirrhosis, and HCC. The pathophysiologic mechanisms that contribute to the development and progression of NAFLD and NASH are complex, and as such myriad therapies are under investigation targeting different pathophysiological mechanisms. Incretin-based therapies, including GLP-1RAs and DPP-4 inhibitors and the inhibition of ASK1 pathway have provided two such novel mechanisms in the management of this disease, and will remain focus of this review.


Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Incretin GLP-1 DPP-4 ASK1 



Adeno-associated virus vector 8


Alanine aminotransferase


Aspartate aminotransferase


Apoptosis signal-regulating kinase-1 (also known as MAP3K5)


Body mass index


Cell division cycle 25A/C


CASP8 and FADD-like apoptosis regulator (also known as c-FLIP)


CCAAT/enhancer-binding protein (C/EBP) homologous protein


Cellular repressor of E1A-stimulated genes


Computed tomography


Dickkopf-related protein 3


Dipeptidyl peptidase-4


Endoplasmic reticulum


Free fatty acid


Glucose-dependent insulinotropic polypeptide


Glucagon-like peptide-1


Glucagon-like peptide-1 receptor


Glucagon-like peptide-1 receptor agonist


Hepatocellular carcinoma


High fat diet


Hemoglobin A1c


Hepatocyte nuclear factor 4α


Homeostatic model assessment of insulin resistance


Interleukin 6


Insulin receptor substrate 1


c-Jun N-terminal kinase 1


Low density lipoprotein


Lysyl oxidase-like molecule 2


Mitogen-activated protein kinase


Mitogen-activated protein kinase kinase


Magnetic resonance imaging


MRI elastography




Non-alcoholic fatty liver disease


NAFLD activity score


Non-alcoholic steatohepatitis


Proton density fat fraction


Serine/threonine protein phosphatase 5


Peroxisome proliferator-activated receptor alpha


Randomized controlled trial


Reactive oxygen species


Type 2 diabetes mellitus


Tumor necrosis factor


TNF receptor-associated factor 1





No Grants or financial support was used in the writing of this manuscript. Dr. Chalasani has consulting agreements and research Grants with several pharmaceutical companies but none represent relevant conflict of interest for this invited review article. Dr. Satapathy has received Grant/research support from Biotest, Conatus, Genfit, Gilead Sciences, Intercept, and Shire; served on the advisory panel for Abbvie, Gilead Sciences, and Intercept; and Speakers bureau for Alexion, and Intercept pharma. None represent relevant conflict of interest for this invited review article.

Compliance with ethical standards

Conflict of interest

This review article is in compliant with general ethical considerations considered applicable for a review article. Alexander J. Kovalic, Sanjaya K. Satapathy and Naga Chalasani declare no financial conflicts of interest.


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Copyright information

© Asian Pacific Association for the Study of the Liver 2018

Authors and Affiliations

  1. 1.Department of Internal MedicineWake Forest Baptist Medical CenterWinston-SalemUSA
  2. 2.Division of Transplant Surgery, Department of SurgeryMethodist University Hospital Transplant Institute, University of Tennessee Health Science CenterMemphisUSA
  3. 3.Department of Medicine, Division of Gastroenterology and HepatologyIndiana University School of MedicineIndianapolisUSA

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