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.
To review the potential benefit of drugs used in clinical practice, those entering phase II trials, and compounds being investigated in pre-clinical studies.
A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed.
Vitamin E and pioglitazone have shown efficacy in non-alcoholic steatohepatitis (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. Peroxisome proliferator-activator receptors 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 inhibitors reducing apoptosis and fibrosis.
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.
S. A. Townsend, P. N. Newsome. First published: 4 July 2017. DOI: 10.1111/apt.14210.
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