Therapeutic options in non-alcoholic steatohepatitis (NASH). Are all agents alike? Results of a preliminary study

Abstract

Aim: The evaluation of the efficacy of ursodeoxycholic acid (UDCA), pentoxifylline, losartan, and atorvastatin in non-alcoholic steatohepatitis (NASH) treatment.

Method: 48 patients (25 males/23 females, aged 55 +/- 7.54 years) with histologically confirmed NASH were enrolled between 2001 and 2005. The batch was divided into four groups: A (10 dyslipidemic patients, receiving atorvastatin 10 mg/day), P (13 nonhypertensive/ nondyslipidemic patients receiving pentoxifylline 400 mg bid), L (12 hypertensive patients, treated with losartan, 50 mg/day) and U (13 nonhypertensive patients receiving UDCA 15 mg/kg/day). Mean duration of treatment was 37.8 +/- 5.4 weeks. Body mass index, liver biopsy and serum level of alanine-aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were determined at inclusion and at the end of treatment. Liver biopsy samples were evaluated for necroinflammation, steatosis and fibrosis (Brunt's score).

Results: In group A, a significant reduction of ALT, GGT, TC and AP was noticed. Histology showed diminished steatosis, but no improvement of fibrosis and necroinflammation. In groups P and L we found a reduction of mean ALT and GGT levels and necroinflammatory score. Group U presented a significant reduction in ALT and GGT levels, without improvement in steatosis, necroinflammation or fibrosis.

Conclusion: Atorvastatin and losartan proved to be efficient in the treatment of dyslipidemia- and hypertension-associated NASH, by improving both biochemical parameters and steatosis/ necroinflammation. Pentoxifylline showed similar efficacy in non-hypertensive/non-dyslipidemic patients, while UDCA did not improve the histological score although it improved the biochemical parameters.