Research Article Details
| Article ID: | A49865 |
| PMID: | 35614896 |
| Source: | Visc Med |
| Title: | Diagnostic and Therapy of Nonalcoholic Fatty Liver Disease: A Narrative Review. |
| Abstract: | Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing and strongly associated with the metabolic syndrome, especially with obesity. A subtype, nonalcoholic steatohepatitis (NASH), might progress to advanced fibrosis and cirrhosis. NASH patients have an increased all-cause mortality. First and foremost are malignancies, followed by cardiovascular diseases. Summary: The NAFLD fibrosis score and noninvasive liver stiffness measurement (transient hepatic elastography) are essential components for the diagnostic risk assessment of NAFLD patients. Other steatoses (alcohol, genetic disorders, drugs, toxins, malnutrition, etc.) must be considered in the differential diagnosis. So far, there is no approved liver-specific drug therapy with a proven effect on NAFLD for patients without diabetes mellitus. Obeticholic acid (FXR agonist), cenicriviroc (a dual inhibitor of the chemokine receptors (CCR), CCR2 and CCR5), acetyl-CoA carboxylase inhibitors, and several thyroid hormone analogs are the most advanced substances in clinical development in ongoing phase 2 and 3 studies. Key Messages: Weight loss, physical training, and the screening and treatment of risk factors represent the cornerstones of NAFLD therapy. Treatment with glucagon-like peptide 1 analogs (e.g., liraglutide, semaglutide) and sodium-dependent glucose transporter 2 inhibitors can be recommended in patients with diabetes and NASH. |
| DOI: | 10.1159/000519611 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S09 | Bariatric surgery | Metabolic surgery | -- | -- | 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T24 | C-C chemokine receptor type 2 | CCR2 | antagonist | GPCR | P41597 | CCR2_HUMAN | Details |
| T17 | Farnesoid X-activated receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| T25 | C-C chemokine receptor type 5 | CCR5 | antagonist | GPCR | P51681 | CCR5_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | 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 | |
|---|---|---|---|---|---|---|---|
| D068 | Cenicriviroc | Chemical drug | DB11758 | CCR2 inhibitor; CCR5 inhibitor | Anti-fibrosis | Failed in clinical trials | Details |
| D327 | Semaglutide | Chemical drug | DB13928 | GLP1R agonist | Antidiabetic drug | Under clinical trials | Details |
| D207 | Liraglutide | Biological drug | DB06655 | GLP1R activator; GLP1R agonist; GCG receptor antagonist activity | Improve insulin resistance | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D155 | Glucagon | Biological drug | DB00040 | GCGR agonist | Antidiabetic drug | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |