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

Satapathy, Sanjay K.; Garg, Sanjay; Chauhan, Ranjeet; Sakhuja, Puja; Malhotra, Veena; Sharma, Barjesh C.; Sarin, Shiv K.
October 2004
American Journal of Gastroenterology;Oct2004, Vol. 99 Issue 10, p1946
Academic Journal
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 (55.6vs20%,p= 0.016), but serum triglyceride (182± 66vs160± 55 mg/dl,p= 0.397), cholesterol (173± 46vs162± 40 mg/dl,p= 0.440), and body mass index (BMI) (27.3± 3.1vs26± 3.1 kg/m2,p= 0.087) remained unchanged. Mean AST (66± 29vs33± 11 IU/l,p<0.0001) and ALT (109± 44vs47± 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± 3.4vs2.6± 2,p= 0.046) and the serum TNF-α reduced significantly after therapy (22.15± 2.49vs17± 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.


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