Research Article Details
| Article ID: | A23638 |
| PMID: | 23607264 |
| Source: | Hepatol Res |
| Title: | Efficacy of probucol for the treatment of non-alcoholic steatohepatitis with dyslipidemia: An open-label pilot study. |
| Abstract: | AIM: Oxidative stress plays a pivotal role in the transition from simple steatosis to non-alcoholic steatohepatitis (NASH). Probucol is a lipid-lowering agent with strong antioxidant properties, and is reported to be effective for the treatment of NASH in several studies. The aim of the present study was to evaluate the efficacy of probucol for the treatment of NASH with dyslipidemia. METHODS: Twenty-six patients with biopsy-proven NASH accompanied by dyslipidemia were treated with 500 mg of probucol daily for 48 weeks. Body mass index, visceral fat area, liver function tests, serum lipids, fibrosis markers, ferritin, adiponectin, leptin, urinary 8-hydroxy-2'-deoxyguanosine (U-8OHdG) and elasticity were measured periodically during the study. Follow-up liver biopsy was performed in 18 patients. RESULTS: Serum levels of aminotransferases, total cholesterol and U-8OHdG significantly decreased (P < 0.01). Levels of hemoglobin A1c (HbA1c), the Homeostasis Model of Assessment - Insulin Resistance index and serum levels of ferritin, type IV collagen 7S and hyaluronic acid significantly decreased (P < 0.05). The serum levels of adiponectin tended to be increased. Liver stiffness significantly decreased from 8.8 ± 6.8 to 6.6 ± 4.0 kPa (P < 0.01). Non-alcoholic fatty liver disease activity scores were significantly improved from 4.2 ± 1.4 to 3.4 ± 1.6 (P < 0.05) and fibrotic stages tended to be improved from 1.6 ± 0.8 to 1.3 ± 1.1, respectively. No adverse effects of this treatment were noted. CONCLUSION: Probucol improved clinical and histological findings probably through its ability to reduce insulin resistance and oxidative stress. Probucol therapy was safe and effective for Japanese NASH patients with dyslipidemia. |
| DOI: | 10.1111/hepr.12135 |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | 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 |