Research Article Details
| Article ID: | A11805 |
| PMID: | 30732664 |
| Source: | Proc Nutr Soc |
| Title: | Understanding susceptibility and targeting treatment in non-alcoholic fatty liver disease in children; moving the fulcrum. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is the most common cause of paediatric liver disease, affecting 10% of school-aged children and 44-70% of obese children and young people (CYP) in the western world. Encompassing a spectrum from simple steatosis to steatohepatitis and progressive fibrosis, the disease is rapidly becoming the most common indication for liver transplantation. The molecular pathogenesis of NAFLD remains only partially understood. Development and progression of NAFLD is influenced by genetic and nutritional factors, insulin resistance, oxidative stress, gut microbiome, bile acid metabolism and lipid/glucose handling and is closely associated with overweight and obesity. Lifestyle change is the only proven effective treatment for paediatric NAFLD, however this is difficult to achieve in many. Given that moderate or severe fibrosis is already present in 30-50% of children with NAFLD at the time of presentation, progression in CYP may be more rapid, though adequate outcome data do not yet exist in this cohort. CYP with NAFLD are an excellent population in which to study underlying mechanisms and interventions to correct disease progression as they are largely unaffected by other environmental influences such as alcohol and may represent the more severe end of the spectrum in terms of early onset. Undoubtedly genetic and epigenetic mechanisms determine a large proportion of susceptibility to the disease and potentially, identification of individuals at risk may allow for targeted therapy. This review with give a clinical perspective of paediatric NAFLD focused on identifying those at risk of progressive disease and what to consider in attempting to modify risk. |
| DOI: | 10.1017/S0029665118002914 |
| 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 |
| S10 | Liver transplantation | -- | -- | -- | 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 |
| 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 |
| 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 |