Research Article Details
| Article ID: | A01260 |
| PMID: | 34811578 |
| Source: | Handb Exp Pharmacol |
| Title: | NAFLD and NASH: The Metabolically Diseased Liver. |
| Abstract: | Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease, with a global prevalence of approximately 24% in the general population. It is caused by fat accumulation in the liver secondary to insulin resistance, visceral obesity, and/or features of metabolic syndrome. A genetic susceptibility contributes to the phenotype, accounting for a more severe course of liver disease and the observed clinical variability. In fact, despite liver steatosis being considered a relatively benign entity, inflammation related to oxidative stress and lipid-derived damage may lead to non-alcoholic steatohepatitis (NASH), which constitutes the progressive disease. Accumulation of hepatic fibrosis can lead to cirrhosis and provide the environment for hepatocellular carcinoma. Obese and diabetic individuals represent a well-acknowledged high risk population. The assessment of liver fibrosis plays a crucial role in clinical setting, as liver-related mortality increases parallel to fibrosis stage. A liver biopsy is currently considered the reference standard for the diagnosis of NASH and the fibrosis stage, but many non-invasive tools are used with the aim of replacing histology for diagnosis and prognosis purposes. Blood based scores and liver stiffness are the most widely used and validated tools to assess liver fibrosis. Management of NAFLD resides on environmental interventions, including diet and physical activity to induce weight loss, and avoiding harmful nutrients, including fructose-sweetened beverages and high glycemic index foods, that are directly implied in liver injury. Multiple trials with investigational drugs are currently explored to treat fibrosing NASH, with promising results and it can be expected that a liver direct therapy aiming at steatohepatitis and fibrosis will become available soon. |
| DOI: | 10.1007/164_2021_561 |
| 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 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D142 | Fructose | Chemical drug | DB04173 | -- | Intravenous nutrition drug | Under clinical trials | Details |