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

Sanjaya Satapathy, Sanjay Garg, Ranjeet Chauhan, Puja Sakhuja, Veena Malhotra, Barjesh C. Sharma, Shiv K. Sarin

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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.

Original languageEnglish (US)
Pages (from-to)1946-1952
Number of pages7
JournalAmerican Journal of Gastroenterology
Volume99
Issue number10
DOIs
StatePublished - Oct 1 2004

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Pentoxifylline
Tumor Necrosis Factor-alpha
Glucose Intolerance
Hypertriglyceridemia
Therapeutics
Serum
Fatigue
Insulin Resistance
Fasting
Diabetes Mellitus
Triglycerides
Body Mass Index
Antioxidants
Cholesterol
Lipids
Inhibition (Psychology)
Non-alcoholic Fatty Liver Disease
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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Beneficial effects of tumor necrosis factor-α inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. / Satapathy, Sanjaya; Garg, Sanjay; Chauhan, Ranjeet; Sakhuja, Puja; Malhotra, Veena; Sharma, Barjesh C.; Sarin, Shiv K.

In: American Journal of Gastroenterology, Vol. 99, No. 10, 01.10.2004, p. 1946-1952.

Research output: Contribution to journalArticle

Satapathy, Sanjaya ; Garg, Sanjay ; Chauhan, Ranjeet ; Sakhuja, Puja ; Malhotra, Veena ; Sharma, Barjesh C. ; Sarin, Shiv K. / Beneficial effects of tumor necrosis factor-α inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. In: American Journal of Gastroenterology. 2004 ; Vol. 99, No. 10. pp. 1946-1952.
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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.",
author = "Sanjaya Satapathy and Sanjay Garg and Ranjeet Chauhan and Puja Sakhuja and Veena Malhotra and Sharma, {Barjesh C.} and Sarin, {Shiv K.}",
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AU - Garg, Sanjay

AU - Chauhan, Ranjeet

AU - Sakhuja, Puja

AU - Malhotra, Veena

AU - Sharma, Barjesh C.

AU - Sarin, Shiv K.

PY - 2004/10/1

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N2 - 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.

AB - 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.

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