Research Article Details
| Article ID: | A36711 |
| PMID: | 17410287 |
| Source: | J Gastrointestin Liver Dis |
| Title: | Therapeutic options in non-alcoholic steatohepatitis (NASH). Are all agents alike? Results of a preliminary study. |
| Abstract: | AIM: The evaluation of the efficacy of ursodeoxycholic acid (UDCA), pentoxifylline, losartan, and atorvastatin in non-alcoholic steatohepatitis (NASH) treatment. METHOD: 48 patients (25 males/23 females, aged 55 +/- 7.54 years) with histologically confirmed NASH were enrolled between 2001 and 2005. The batch was divided into four groups: A (10 dyslipidemic patients, receiving atorvastatin 10 mg/day), P (13 nonhypertensive/ nondyslipidemic patients receiving pentoxifylline 400 mg bid), L (12 hypertensive patients, treated with losartan, 50 mg/day) and U (13 nonhypertensive patients receiving UDCA 15 mg/kg/day). Mean duration of treatment was 37.8 +/- 5.4 weeks. Body mass index, liver biopsy and serum level of alanine-aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were determined at inclusion and at the end of treatment. Liver biopsy samples were evaluated for necroinflammation, steatosis and fibrosis (Brunt's score). RESULTS: In group A, a significant reduction of ALT, GGT, TC and AP was noticed. Histology showed diminished steatosis, but no improvement of fibrosis and necroinflammation. In groups P and L we found a reduction of mean ALT and GGT levels and necroinflammatory score. Group U presented a significant reduction in ALT and GGT levels, without improvement in steatosis, necroinflammation or fibrosis. CONCLUSION: Atorvastatin and losartan proved to be efficient in the treatment of dyslipidemia- and hypertension-associated NASH, by improving both biochemical parameters and steatosis/ necroinflammation. Pentoxifylline showed similar efficacy in non-hypertensive/non-dyslipidemic patients, while UDCA did not improve the histological score although it improved the biochemical parameters. |
| DOI: |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 | |
|---|---|---|---|---|---|
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| 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 |
| 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 |
| D209 | Losartan | Chemical drug | DB00678 | AGTR1 antagonist&binder | Anti-fibrosis | Under clinical trials | Details |
| D020 | Atorvastatin | Chemical drug | DB01076 | DPP4 inhibitor; AHR agonist; HDAC2 inhibitor; NR1I3 ligand | Enhance lipid metabolism | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D381 | Ursodeoxycholic acid | Chemical drug | DB01586 | AKR1C2 inducer | Anti-inflammatory | 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 |