Research Article Details
| Article ID: | A22771 |
| PMID: | 24320032 |
| Source: | Curr Pharm Des |
| Title: | The metabolic syndrome and chronic liver disease. |
| Abstract: | The prevalence of the metabolic syndrome (MetS), a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder is not only associated with a higher risk of appearance of type 2 diabetes and cardiovascular events, but impacts on the liver in different ways. Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of MetS, and is characterized by triglyceride accumulation and a variable degree of hepatic injury, inflammation, and repair. In the presence of significant hepatocellular injury and inflammation, the picture is defined 'nonalcoholic steatohepatitis' (NASH), that has the potential to progress to advanced fibrosis and cirrhosis. Diagnosis of NASH is based on a liver biopsy, and active search for noninvasive tests is ongoing. Progression of steatohepatitis to advanced fibrosis or cirrhosis has been shown in at least one third of patients followed with paired biopsies. Presence of NASH is associated with lower life expectancy, both due to liver-related death and to an increase in cardiovascular events. The appearance of NAFLD is mainly dependent on increased flow of fatty acids derived from an excess of lipolysis from insulin-resistant adipose tissue. Development of NASH is based on lipotoxicity and is influenced by signals derived from outside the liver and from intrahepatic activation of inflammatory and fibrogenic pathways. The presence of the MetS is also associated with worse outcomes in patients with cirrhosis due to any causes, and has complex interactions with hepatitis C virus infection. Moreover, MetS poses a higher risk of development of hepatocellular carcinoma, not necessarily through the development of NASH-related cirrhosis. In conclusion, the presence of metabolic alterations has a severe and multifaceted impact on the liver, and is responsible for a higher risk of liver-dependent and -independent mortality. |
| DOI: | 10.2174/1381612819666131206111352 |
| 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 |
| 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 |
| 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | 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 |