Research Article Details
| Article ID: | A35864 |
| PMID: | 19540686 |
| Source: | Gastroenterol Clin Biol |
| Title: | [Nonalcoholic fatty liver disease: 30 years research changed NASH]. |
| Abstract: | Since the first description of nonalcoholic steatohepatitis (NASH) in 1980, much progress has been made towards its individualisation as a liver disease with potentially serious consequences. The identification of insulin resistance as a major determinant of steatogenesis and possibly of liver disease progression helped to identify a cause of this condition, which was amenable to therapeutic intervention and prompted screening for liver injury in patients with metabolic risk factors. The demonstration that steatohepatitis can coexist with other liver diseases with a detrimental effect on liver fibrosis helped this condition to be recognized as an independent hepatic disease no longer depending on exclusion of other chronic liver conditions. The robust increase in liver-related mortality, the fact that cirrhosis is a frequent and independent cause of death, as well as the significant decrease in overall mortality clearly showed the potential for severity of steatohepatitis. The data showing that steatohepatitis worsens insulin resistance and increases the risk for cardiovascular events and mortality forged the concept of extrahepatic complications of fat. Future research should focus on devising non-invasive strategies for screening of patients at risk, on understanding the natural history and risk factors of cirrhosis and hepatic carcinogenesis, and on optimizing therapeutic strategies integrating diet and lifestyle changes with targeted pharmacological agents. |
| DOI: | 10.1016/j.gcb.2009.05.001 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | 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 | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |