A pilot trial of pentoxifylline in nonalcoholic steatohepatitis.

OBJECTIVES: Tumor necrosis factor alpha (TNF alpha) contributes to liver damage and insulin resistance among patients with nonalcoholic steatohepatitis (NASH). Pentoxifylline inhibits TNF alpha production. We therefore conducted a 12-month pilot trial to assess the efficacy and safety of pentoxifylline (1,600 mg/day) among 20 patients with NASH.

METHODS: Patients had biopsy-confirmed NASH with other causes of liver disease and secondary causes of NASH excluded. Patients who drank more than 40 gm of ethanol weekly were also excluded. Pentoxifylline (400 mg q.i.d.) was given for 12 months. Liver enzymes and adverse events were monitored every 3 months until completion.

RESULTS: The 20 patients had a mean age of 50 +/- 11 yr. Eleven (55%) were female, 14 were obese (body mass index > or =30 kg/m(2)), and 7 (35%) were diabetic. At baseline, median steatosis grade was 2 (range 1-3), median necroinflammatory grade was 1 (1-2), and median fibrosis stage was 2 (0-4). Nine patients withdrew from the study, primarily because of nausea. No serious adverse events occurred. Alanine and aspartate aminotransferase levels were significantly lower at 12 months compared to baseline (84 +/- 64 vs 138 +/- 76, p= 0.002 and 58 +/- 37 vs 102 +/- 62, p= 0.003, respectively). Bilirubin did not change significantly from baseline (0.8 +/- 0.4 vs 0.8 +/- 0.3, p= 0.95), nor did alkaline phosphatase (193 +/- 68 vs 180 +/- 53, p= 0.62) or albumin (4.0 +/- 0.2 vs 4.2 +/- 0.3, p= 0.41).

CONCLUSIONS: Aminotransferase levels among patients with NASH improve with administration of pentoxifylline. Strategies to overcome side effects will be needed for future trials.