Research Article Details
| Article ID: | A15478 |
| PMID: | 28883965 |
| Source: | Trop Dis Travel Med Vaccines |
| Title: | Hepatic steatosis in HCV-infected persons in the direct-acting antiviral era. |
| Abstract: | Hepatitis C virus (HCV) infects 130-170 million people worldwide. Recently, direct-acting antivirals have been shown to eradicate HCV infection in 90-95 % of non-cirrhotic patients depending on genotype, treatment experience, and regimen used. Similar rates are achieved among compensated cirrhotics, although longer treatment duration and/or ribavirin may be required. HCV uses host lipid metabolism for its lifecycle and can cause hepatic steatosis and insulin resistance. Hepatic steatosis, defined as excessive triglyceride deposition in hepatocytes, affects approximately half of HCV-infected individuals. Genetic factors and co-morbidities can drive further steatosis, which in turn can instigate fibrosis and progression to cirrhosis and hepatocellular carcinoma. Polymorphisms in genes that modulate lipid deposition in hepatocytes such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane six superfamily member 2 (TM6SF2) predispose people to steatosis. Metabolic syndrome, obesity, and insulin resistance are increasing worldwide and further contribute to hepatic steatosis, and alcohol has long been recognized as a cause of lipid deposition in the liver. HIV and antiretroviral drugs, but not HBV, may further drive hepatic steatosis. While many of these factors limit response to interferon-based regimens for treating HCV, responses to direct-acting antivirals appear not to be impaired. The effect of HCV eradication on hepatic steatosis and progression to fibrosis, cirrhosis, and hepatocellular carcinoma warrants further study in the era of direct-acting antivirals. |
| DOI: | 10.1186/s40794-016-0038-5 |
| 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 |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |