Abstract
Background: Non-alcoholic fatty liver disease is the fastest growing cause of liver disease in the Western world, yet there is no approved pharmacotherapy. While lifestyle modifications remain the mainstay of treatment, only a proportion of individuals are able to make or sustain them, and so more treatment options are required.
Aim: To review the potential benefit of drugs used in clinical practice, those entering phase II trials, and compounds being investigated in preclinical studies.
Methods: A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed.
Results: Vitamin E and pioglitazone have shown efficacy in NASH, but long-term safety concerns, specifically bladder cancer and osteoporosis with pioglitazone, have limited their use. GLP-1 analogues and SGLT-2 inhibitors are currently approved for use in diabetes, have shown early efficacy in NASH and also have beneficial cardiovascular effects. PPARα/δ and FXR agonists have potent effects on lipogenesis, inflammation and fibrosis respectively, with their efficacy and safety being currently tested in phase 3. As inflammation and apoptosis are key features of NASH agents modulating these pathways are of interest; CCR2/5 antagonists downregulate inflammatory pathways and reduce fibrosis with caspase and apoptosis signal-regulating kinase 1 (ASK1) inhibitors reducing apoptosis and fibrosis.
Conclusions: Rising demand and an improved understanding of NASH pathophysiology has led to a surge in development of new therapies. Tailoring pharmacotherapy to the dominant pathogenic pathway in a given patient along with use of combination therapy is likely to represent the future direction in treatment of patients with NASH.
Aim: To review the potential benefit of drugs used in clinical practice, those entering phase II trials, and compounds being investigated in preclinical studies.
Methods: A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed.
Results: Vitamin E and pioglitazone have shown efficacy in NASH, but long-term safety concerns, specifically bladder cancer and osteoporosis with pioglitazone, have limited their use. GLP-1 analogues and SGLT-2 inhibitors are currently approved for use in diabetes, have shown early efficacy in NASH and also have beneficial cardiovascular effects. PPARα/δ and FXR agonists have potent effects on lipogenesis, inflammation and fibrosis respectively, with their efficacy and safety being currently tested in phase 3. As inflammation and apoptosis are key features of NASH agents modulating these pathways are of interest; CCR2/5 antagonists downregulate inflammatory pathways and reduce fibrosis with caspase and apoptosis signal-regulating kinase 1 (ASK1) inhibitors reducing apoptosis and fibrosis.
Conclusions: Rising demand and an improved understanding of NASH pathophysiology has led to a surge in development of new therapies. Tailoring pharmacotherapy to the dominant pathogenic pathway in a given patient along with use of combination therapy is likely to represent the future direction in treatment of patients with NASH.
| Original language | English |
|---|---|
| Journal | Alimentary Pharmacology & Therapeutics |
| DOIs | |
| Publication status | Published - 4 Jul 2017 |
Bibliographical note
Manuscript ID APT-0529-2017.R2. Accepted/in press.Keywords
- Vitamin E
- pioglitazone
- non-alcoholic fatty liver disease (NAFLD)
- liver fibrosis
- liver
- liver function tests
- liver biopsy
ASJC Scopus subject areas
- General Medicine
Access to Document
- Townsend_&_Newsome_New_treatments_in_non-alcoholic_fatty_liver_disease_APT_2017
This is the peer reviewed version of the following article: Townsend SA, Newsome PN. Review article: new treatments in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017;46:494–507. https://doi.org/10.1111/apt.14210, which has been published in final form at 10.1111/apt.14210 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.