Document Detail

Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis.
MedLine Citation:
PMID:  15447754     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been incriminated to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Pentoxifylline, a TNF-alpha inhibitor could prove useful in treating patients with NASH. METHODS: Eighteen patients (mean age, 34 +/- 7.8 yr) with histologically proven NASH and with persistently elevated ALT (>1.5 times) were given pentoxifylline at a dosage of 400 mg t.i.d. for 6 months. No lipid-lowering agent or antioxidants were concurrently advised. RESULTS: Impaired fasting glycemia, impaired glucose tolerance, diabetes mellitus, and hypertriglyceridemia were noted in 6, 35, 17, and 53% of the patients, respectively. After 6 months of therapy, fatigue improved (55.6 vs 20%, p= 0.016), but serum triglyceride (182 +/- 66 vs 160 +/- 55 mg/dl, p= 0.397), cholesterol (173 +/- 46 vs 162 +/- 40 mg/dl, p= 0.440), and body mass index (BMI) (27.3 +/- 3.1 vs 26 +/- 3.1 kg/m(2), p= 0.087) remained unchanged. Mean AST (66 +/- 29 vs 33 +/- 11 IU/l, p < 0.0001) and ALT (109 +/- 44 vs 47 +/- 20 IU/l, p < 0.0001) reduced significantly. ALT normalized in 23% at month 1 (p= 0.125), 35% at month 2 (p= 0.125), and 60% at month 6 (p= 0.008) of treatment. The insulin resistance index assessed by homeostatic metabolic assessment (HOMA(IR)) improved (5.1 +/- 3.4 vs 2.6 +/- 2, p = 0.046) and the serum TNF-alpha reduced significantly after therapy (22.15 +/- 2.49 vs 17 +/- 2.58 pg/ml, p = 0.011). The drug was well tolerated. CONCLUSIONS: In patients with NASH, pentoxifylline therapy effectively achieved significant clinical and biochemical improvement with reduction in HOMA(IR). These benefits are possibly mediated through suppression of TNF-alpha.
Sanjay K Satapathy; Sanjay Garg; Ranjeet Chauhan; Puja Sakhuja; Veena Malhotra; Barjesh C Sharma; Shiv K Sarin
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  99     ISSN:  0002-9270     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-27     Completed Date:  2004-12-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1946-52     Citation Subset:  IM    
Departments of Gastroenterology and Pathology, GB Pant Hospital, New Delhi 110-002, India.
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MeSH Terms
Fatty Liver / complications,  diagnosis,  drug therapy*,  metabolism*
Middle Aged
Pentoxifylline / therapeutic use*
Pilot Projects
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Reg. No./Substance:
0/Tumor Necrosis Factor-alpha; 6493-05-6/Pentoxifylline

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