Research Article Details
| Article ID: | A25157 |
| PMID: | 22126026 |
| Source: | Adv Clin Chem |
| Title: | Iron overload in nonalcoholic steatohepatitis. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is a major causative agent of chronic liver disease worldwide, but the actual mechanisms responsible for liver injury remain unclear. NAFLD includes a spectrum of clinical entities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with possible evolution to cirrhosis and hepatocellular carcinoma. Iron is considered a putative element that interacts with oxygen radicals in inducing liver damage/fibrosis and insulin resistance. The role of hepatic iron in the progression of NASH remains controversial, but in some patients, iron may have a role in the pathogenesis of NASH. Though genetic factors, insulin resistance, dysregulation of iron-regulatory molecules, erythrophagocytosis by Kupffer cells may be responsible for hepatic iron accumulation in NASH, exact mechanisms involved in iron overload remain to be clarified. Iron reduction therapy such as phlebotomy or iron-restricted diet may be promising in patients with NAFLD/NASH to reduce hepatic injury as well as insulin resistance. Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of phlebotomy and/or iron-restricted diet in NAFLD/NASH. |
| DOI: | 10.1016/b978-0-12-387042-1.00006-x |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D272 | Phlebotomy | Miscellany | -- | -- | -- | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |