Research Article Details
| Article ID: | A12471 |
| PMID: | 30441981 |
| Source: | Vnitr Lek |
| Title: | Future of pharmacological treatment of non-alcoholic steatohepatitis in terms of key pathophysiological mechanisms. |
| Abstract: | Obesity reaches the dimensions of the global epidemic. It directly contributes to an increase in the prevalence of systemic diseases associated with obesity. Obesity and overweight globally cause 3.5 million deaths annually [1]. Non-alcoholic fatty liver disease has become the most common chronic liver disease in developed countries and is considered to be a liver manifestation of metabolic syndrome. The extent and burden of the disease are increasing and reaching epidemic proportions because of its close association with the epidemic of obesity and diabetes mellitus type [2]. It affects 30 % of the adult population [2]. There is an alarming increase in prevalence among children and adolescents. However, in the group of patients with high cardiometabolic risk, we can see a significantly higher prevalence of NAFLD. Prevalence in obese patients is 75 -92 %, in diabetic patients prevalence is between 60 -70 % [3]. A significant proportion of patients with NAFLD will suffer from a progressive form of the disease - non-alcoholic steatohepatitis (NASH), which is associated with the development of advanced liver fibrosis, cirrhosis, and its complications. The growing prevalence of NASH in the near future will bring the advanced cohort of our patients to the stage of an advanced liver disease. If the adverse epidemiological trend is not reversed, in the next decade the most common cause of liver transplantation will be NASH. A steadily rising trend can be seen in an increase in the number of cases of hepatocellular carcinoma causally related to NASH [4]. Treatment based on the influence of key pathogenetic mechanisms could alter the individual's future as well as the global burden arising with NASH. New molecules with anti-inflammatory and antifibrotic effects will play a key role in the future. Key words: cirrhosis - insulin resistance - metabolic syndrome - NASH. |
| DOI: |
| 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 |
| 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 |
| 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 |