Beneficial effects of tumor necrosis factor-α inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis

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 (HOMA_IR) improved (5.1 ± 3.4 vs 2.6 ± 2, p = 0.046) and the serum TNF-αreduced significantly after therapy (22.15 ± 2.49 vs 17 ± 2.58 pg/ml, p = 0.011). The drug was well tolerated. Conclusion: 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- α.