Research Article Details
| Article ID: | A20726 |
| PMID: | 25774446 |
| Source: | Curr Opin Gastroenterol |
| Title: | Nonalcoholic fatty liver disease: new treatments. |
| Abstract: | PURPOSE OF REVIEW: Nonalcoholic fatty liver disease is the most common cause of liver dysfunction in the western world because of its close association with obesity, insulin resistance and dyslipidaemia. Nonalcoholic steatohepatitis (NASH) is a particular health concern due to the increased morbidity and mortality associated with progressive disease. At present, without specific targeted pharmacological therapies, the mainstay of therapy remains weight loss through dietary modification and lifestyle change; thus, the purpose of this review is to summarize the recent evidence for current and emerging therapies in NASH. RECENT FINDINGS: Some existing medications, including pioglitazones and angiotensin receptor antagonists, may be repurposed to help treat this condition. Vitamin E may improve histology in NASH, but safety issues limit its use. Recently, a number of novel agents specifically targeting nonalcoholic fatty liver disease pathogenesis have entered clinical trials, including the farnesoid X receptor agonist obeticholic acid, which has shown significant histological improvements in steatohepatitis and fibrosis. SUMMARY: Diet/lifestyle modification remains the mainstay of treatment. For patients with NASH and advanced fibrosis, current liver-directed pharmacotherapy with vitamin E and pioglitazone offer some benefits; obeticholic acid appears promising and is currently being tested. Comorbidities must be diagnosed and treated; cardiovascular disease remains a primary cause of death in these patients. |
| DOI: | 10.1097/MOG.0000000000000175 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| 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 |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| 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 | |
|---|---|---|---|---|---|---|---|
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D388 | Vitamin E | Supplement | DB00163 | NR1I2; ALOX5; DGKA | Anti-inflammatory | Under clinical trials | Details |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | Under clinical trials | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |