Research Article Details
| Article ID: | A23113 |
| PMID: | 24030232 |
| Source: | Dig Dis |
| Title: | Liver complications in inflammatory bowel diseases. |
| Abstract: | Diseases of the liver and the biliary tract are commonly observed in patients with inflammatory bowel diseases (IBD). Besides primary sclerosing cholangitis (PSC), drug-induced hepatotoxicity and non-alcoholic fatty liver disease (NAFLD) are the most frequent liver complications in IBD. PSC is a chronic inflammatory and commonly progressive disorder of unknown etiology associated with fibrosis and stricture development in the intrahepatic and extrahepatic biliary tree. Interestingly, this form of liver disease is mainly associated with ulcerative colitis. Development of PSC is highly relevant for IBD patients as cholestasis-associated problems increase over time resulting in biliary strictures, cholangitis, cholangiocarcinoma and importantly these patients also have a higher risk to develop colon cancer. Another major aspect regarding IBD and liver disease refers to drug-induced hepatotoxicity. Clinically, most relevant is liver toxicity caused by immunosuppressants such as azathioprine. Azathioprine and its derivate 6-mercaptopurine can cause a spectrum of liver injuries ranging from asymptomatic elevated liver enzymes to cholestasis and nodular regenerative hyperplasia. The third common IBD-associated liver disease is NAFLD, and first studies suggest that NAFLD might appear in IBD patients independent of classical risk factors such as obesity or insulin resistance. Overall, liver complications are observed in 10-20% of IBD patients, and therefore physicians have to be familiar with these complications to improve and to optimize patient care. |
| DOI: | 10.1159/000353377 |
| 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 |
| 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 | |
|---|---|---|---|---|---|
| I11 | 5295 | Intestinal disease | A gastrointestinal system disease that is located_in the intestine. http://en.wikipedia.org/wiki/Human_gastrointestinal_tract | disease of anatomical entity/gastrointestinal system disease | Details |
| 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 |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |