Therapeutic pipeline in nonalcoholic steatohepatitis
Top Cited Papers
- 10 February 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Gastroenterology & Hepatology
- Vol. 18 (6), 373-392
- https://doi.org/10.1038/s41575-020-00408-y
Abstract
Our understanding of nonalcoholic fatty liver disease pathophysiology continues to advance rapidly. Accordingly, the field has moved from describing the clinical phenotype through the presence of nonalcoholic steatohepatitis (NASH) and degree of fibrosis to deep phenotyping with a description of associated comorbidities, genetic polymorphisms and environmental influences that could be associated with disease progression. These insights have fuelled a robust therapeutic pipeline across a variety of new targets to resolve steatohepatitis or reverse fibrosis, or both. Additionally, some of these therapies have beneficial effects that extend beyond the liver, such as effects on glycaemic control, lipid profile and weight loss. In addition, emerging therapies for NASH cirrhosis would have to demonstrate either reversal of fibrosis with associated reduction in portal hypertension or at least delay the progression with eventual decrease in liver-related outcomes. For non-cirrhotic NASH, it is the expectation that reversal of fibrosis by one stage or resolution of NASH with no worsening in fibrosis will need to be accompanied by overall survival benefits. In this Review, we summarize NASH therapies that have progressed to phase II and beyond. We also discuss some of the potential clinical challenges with the use of these new therapies when approved.Keywords
This publication has 183 references indexed in Scilit:
- Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trialBMJ Open, 2013
- Should combination therapy be the paradigm for future nonalcoholic steatohepatitis clinical trials?Hepatology, 2011
- Identification of a Therapeutic Strategy Targeting Amplified FGF19 in Liver Cancer by Oncogenomic ScreeningCancer Cell, 2011
- Genome-Wide Association Study Identifies Variants Associated With Histologic Features of Nonalcoholic Fatty Liver DiseaseGastroenterology, 2010
- Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver diseaseHepatology, 2010
- Pioglitazone, Vitamin E, or Placebo for Nonalcoholic SteatohepatitisThe New England Journal of Medicine, 2010
- Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other CancersJAMA, 2009
- Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and managementHepatology, 2008
- Alternative M2 Activation of Kupffer Cells by PPARδ Ameliorates Obesity-Induced Insulin ResistanceCell Metabolism, 2008
- Design and validation of a histological scoring system for nonalcoholic fatty liver diseaseHepatology, 2005