Research Article Details
| Article ID: | A22176 |
| PMID: | 24766298 |
| Source: | Expert Opin Drug Discov |
| Title: | Evolving therapies for non-alcoholic steatohepatitis. |
| Abstract: | INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Approved therapies for this disorder, however, are still lacking. In the last decade, pathophysiological insights into this disease have been tremendous. Various aspects, such as insulin resistance, innate immunity, metabolic inflammation and the microbiota, have been characterized as major players. Indeed, at least 1 in 10 sufferers will have the disease escalate toward its inflammatory phenotype, non-alcoholic steatohepatitis (NASH). These pathways currently represent the most attractive treatment targets. Furthermore, interference with insulin resistance has shown some efficacy in the past, although more focused therapies, which also act anti-inflammatory, are needed. AREAS COVERED: In this review, the authors highlight the current most promising treatment strategies in NASH/NAFLD. EXPERT OPINION: Treatment of NAFLD is still in its infancy, although large controlled studies have demonstrated some efficacy for pioglitazone or vitamin E. The natural course of this disease demands long-term treatments besides diet and lifestyle changes. Based on the current view of NAFLD pathophysiology, effective therapies have to target metabolic inflammation, glucose and lipid metabolism. The search for agents interfering with all of these pathways has recently generated promising candidates for the treatment of NAFLD such as farnesoid X receptor, peroxisome proliferator-activated receptor-α/δ agonists or AdipoR small-molecule agonists. |
| DOI: | 10.1517/17460441.2014.911283 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D388 | Vitamin E | Supplement | DB00163 | NR1I2; ALOX5; DGKA | Anti-inflammatory | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |