Research Article Details
| Article ID: | A19878 |
| PMID: | 26289505 |
| Source: | Niger J Clin Pract |
| Title: | Nonalcoholic fatty liver disease: Synopsis of current developments. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) which is defined as the accumulation of fat>5% of liver weight is increasingly becoming an important cause of chronic liver disease. This article tries to chronicle advances that have occurred in the understanding of the pathogenesis, pathology as well as the management of this disease. We have done a Medline search on published work on the subject and reviewed major conference proceedings in the preceding years. The Pathogenesis involves a multi-hit process in which increased accumulation of triglycerides in face of insulin resistance results in increased susceptibility to inflammatory damage mediated by increased expression of inflammatory cytokines and adipokines, oxidative stress and mitochondrial dysfunction, endoplasmic reticulum stress and gut derived endotoxemia. An interplay of multiple metabolic genetic expression and environmental factors however determine which patient with NAFLD will progress from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. The minimum criteria for diagnosis of NASH are steatosis, ballooning and lobular inflammation; fibrosis is not required. The NASH Clinical Research Network (CRN), histological scoring system is used to grade and stage the disease for standardization. The management of NAFLD consists of treating liver disease as well as associated metabolic co-morbidities such as obesity, hyperlipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM). Patient education is important as their insight and commitment is pivotal, and lifestyle modification is the first line of treatment. Improvement in liver histology in non-diabetic NASH patients has been reported with use of Vitamin E. Other liver-related therapies under investigations include pentoxyfiylins, Caspar inhibitors, Resveratrol as well as probiotics. The prognosis (both overall and liver-related mortality) for simple steatosis is not different from that of the general population however. |
| DOI: | 10.4103/1119-3077.163288 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D388 | Vitamin E | Supplement | DB00163 | NR1I2; ALOX5; DGKA | Anti-inflammatory | Under clinical trials | Details |
| D301 | Resveratrol | Chemical drug | DB02709 | ALOX15; ALOX5; AHR; NR1I2; NR1I3 | Anticancer agent | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D284 | Probiotic | Supplement | -- | -- | -- | Under clinical trials | Details |