Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis

Background and Aim: Inhibition of tumor necrosis factor (TNF)-alpha is a logical approach to manage patients with non-alcoholic steatohepatitis (NASH). Pentoxifylline reduces TNF-alpha and alanine aminotransferase (ALT) levels in patients with NASH. The aim of the present paper was to study if pentoxifylline can improve histological injury in patients with NASH. Methods: Nine patients (mean age 31.6 +/- 7.2 years) with histologically proven NASH and with persistently elevated ALT (> 1.5 times) were given pentoxyfylline at a dosage of 400 mg t.i.d. for 12 months. Besides biochemical assessment, a repeat liver biopsy was performed and the degree of inflammation and fibrosis was compared. Results: After 12 months of therapy a significant reduction in ALT (111 +/- 53 IU/L vs 45 +/- 19 IU/L, P = 0.003) and aspartate aminotransferase (AST) (61 +/- 27 IU/L vs 33 +/- 12 IU/L, P = 0.005) levels was observed. Steatosis and lobular inflammation each reduced in 55% and six (67%) patients down-staged on Brunt's staging (P = 0.009). Four out of six patients with baseline fibrosis had reduction in their fibrosis stage. Conclusions: Long-term pentoxyfylline therapy effectively achieves sustained biochemical improvement. This correlates well with histological resolution of the disease.