Beneficial Effects of Tumor Necrosis Factor-α Inhibition by Pentoxifylline on Clinical, Biochemical, and Metabolic Parameters of Patients with Nonalcoholic Steatohepatitis


    loading  Checking for direct PDF access through Ovid

Abstract

BACKGROUND:Tumor necrosis factor-α (TNF-α) has been incriminated to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Pentoxifylline, a TNF-α 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/m2, 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 (HOMAIR) improved (5.1 ± 3.4 vs 2.6 ± 2, p = 0.046) and the serum TNF-α 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 HOMAIR. These benefits are possibly mediated through suppression of TNF-α.(Am J Gastroenterol 2004;99:1946-1952)

    loading  Loading Related Articles