Research Article Details
| Article ID: | A37487 |
| PMID: | 15571584 |
| Source: | Am J Gastroenterol |
| Title: | A pilot trial of pentoxifylline in nonalcoholic steatohepatitis. |
| Abstract: | OBJECTIVES: Tumor necrosis factor alpha (TNF alpha) contributes to liver damage and insulin resistance among patients with nonalcoholic steatohepatitis (NASH). Pentoxifylline inhibits TNF alpha production. We therefore conducted a 12-month pilot trial to assess the efficacy and safety of pentoxifylline (1,600 mg/day) among 20 patients with NASH. METHODS: Patients had biopsy-confirmed NASH with other causes of liver disease and secondary causes of NASH excluded. Patients who drank more than 40 gm of ethanol weekly were also excluded. Pentoxifylline (400 mg q.i.d.) was given for 12 months. Liver enzymes and adverse events were monitored every 3 months until completion. RESULTS: The 20 patients had a mean age of 50 +/- 11 yr. Eleven (55%) were female, 14 were obese (body mass index > or =30 kg/m(2)), and 7 (35%) were diabetic. At baseline, median steatosis grade was 2 (range 1-3), median necroinflammatory grade was 1 (1-2), and median fibrosis stage was 2 (0-4). Nine patients withdrew from the study, primarily because of nausea. No serious adverse events occurred. Alanine and aspartate aminotransferase levels were significantly lower at 12 months compared to baseline (84 +/- 64 vs 138 +/- 76, p= 0.002 and 58 +/- 37 vs 102 +/- 62, p= 0.003, respectively). Bilirubin did not change significantly from baseline (0.8 +/- 0.4 vs 0.8 +/- 0.3, p= 0.95), nor did alkaline phosphatase (193 +/- 68 vs 180 +/- 53, p= 0.62) or albumin (4.0 +/- 0.2 vs 4.2 +/- 0.3, p= 0.41). CONCLUSIONS: Aminotransferase levels among patients with NASH improve with administration of pentoxifylline. Strategies to overcome side effects will be needed for future trials. |
| DOI: | 10.1111/j.1572-0241.2004.40064.x |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| 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 |
| 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 |