Research Article Details
| Article ID: | A37463 |
| PMID: | 15625656 |
| Source: | Clin Gastroenterol Hepatol |
| Title: | A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. |
| Abstract: | BACKGROUND & AIMS: Insulin resistance and oxidative stress contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH). We conducted a pilot study for the following reasons: (1) to test the hypothesis that a combination of an antioxidant (vitamin E) and an insulin sensitizer (pioglitazone) would be superior to vitamin E alone for the treatment of NASH, and (2) to define the effects of these interventions on insulin-sensitive metabolic functions and correlate the effects with changes in liver histology. METHODS: A randomized prospective trial was performed to compare the efficacy and safety of vitamin E alone (400 IU/day) vs. vitamin E (400 IU/day) and pioglitazone (30 mg/day) in nondiabetic, noncirrhotic subjects with NASH. Metabolic functions were assessed by a 2-step, hyperinsulinemic (10 and 40 mU/m2/min) euglycemic clamp. RESULTS: A total of 10 patients were randomized to each arm. Two patients on combination therapy discontinued treatment; one because of pregnancy and the other because of hepatotoxicity. Treatment with vitamin E only produced a significant decrease in steatosis (mean grade, 2.2 vs. 1.4; P < .02). Compared with baseline, combination therapy produced a significant decrease in steatosis (mean, 2.3 vs. 1; P < .002), cytologic ballooning (1.3 vs. 0.2; P < .01), Mallory's hyaline (0.7 vs. 0.2; P < .04), and pericellular fibrosis (1.2 vs. 0.6; P < .03). Although vitamin E had no significant effects, combination therapy produced a significant increase in metabolic clearance of glucose and a decrease in fasting free fatty acid (FFA) and insulin. The decrease in fasting FFA and insulin independently predicted improvement in hepatic steatosis and cytologic ballooning. CONCLUSIONS: A combination of vitamin E and pioglitazone produces a greater improvement in NASH histology. The improvement in steatosis and cytologic ballooning are related to treatment-associated decreases in fasting FFA and insulin levels. |
| DOI: | 10.1016/s1542-3565(04)00457-4 |
| 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 | |
|---|---|---|---|---|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D388 | Vitamin E | Supplement | DB00163 | NR1I2; ALOX5; DGKA | Anti-inflammatory | Under clinical trials | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | 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 |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | 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 |