Research Article Details
| Article ID: | A24135 |
| PMID: | 25755455 |
| Source: | J Clin Exp Hepatol |
| Title: | A Randomized Controlled Trial Comparing Efficacy of Pentoxifylline and Pioglitazone on Metabolic Factors and Liver Histology in Patients with Non-alcoholic Steatohepatitis. |
| Abstract: | BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) involves increased hepatic macrosteatosis due to increased insulin resistance and non-hepatic processes including oxidative stress, apoptosis, and increased pro-inflammatory cytokines. Present study compared the efficacy of pentoxifylline and pioglitazone therapy in improving the metabolic factors and liver histology in patients with NASH. METHODS: Sixty consecutive biopsy proven NASH patients aged 18-70 years with ALT > 1.2 times the upper limit of normal were randomized to receive either pentoxifylline 1200 mg/day in three divided doses orally every day or pioglitazone (30 mg/day) daily for 6 months. All the patients were also instructed to reduce their calorie intake by 500 kcal/day as well as to perform modest exercise (brisk walking) regularly at least 5 days per week. Before and after treatment, liver function tests, serum insulin, C-peptide levels, TNF-α, adiponectin, leptin levels, HOMA-IR and hepatocyte injury and fibrosis scores on liver histology were assessed. RESULTS: Both pentoxifylline and pioglitazone were effective in improving transaminases, insulin resistance (HOMA-IR) and adiponectin levels significantly. TNF-α levels improved with either of the drugs but did not achieve significant levels. Both the drugs improved the markers of acute liver injury. However, only steatosis improved significantly with either of the drugs. Patients treated with pioglitazone had significant improvement in lobular inflammation, portal inflammation and Brunts grade. Brunts grade improved significantly with pioglitazone as compared to pentoxifylline at the end of the therapy. CONCLUSIONS: Pioglitazone shows better improvement in both metabolic factors and liver histology in patients with NASH compared to pentoxifylline. |
| DOI: | 10.1016/j.jceh.2012.10.010 |
| 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 |
| 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 |
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 | |
|---|---|---|---|---|---|---|---|
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D266 | Pentoxifylline | Chemical drug | DB00806 | ADORA2A antagonist; ADORA1 antagonist; PDE4A inhibitor; PDE3B inhibitor; PDE4B inhibitor; PDE5A inhibitor; PDE8A inhibitor; PDE4C inhibitor; PDE11A inhibitor; PDE7A inhibitor; PDE7B inhibitor; PDE4D inhibitor; PDE3A inhibitor | Anti-inflammatory; Cardiovascular drug | Under clinical trials | Details |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | 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 |