A Randomized Controlled Trial Comparing Efficacy of Pentoxifylline and Pioglitazone on Metabolic Factors and Liver Histology in Patients with Non-alcoholic Steatohepatitis.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) involves increased hepatic macrosteatosis due to increased insulin resistance and non-hepatic processes including oxidative stress, apoptosis, and increased pro-inflammatory cytokines. Present study compared the efficacy of pentoxifylline and pioglitazone therapy in improving the metabolic factors and liver histology in patients with NASH.

METHODS: Sixty consecutive biopsy proven NASH patients aged 18-70 years with ALT > 1.2 times the upper limit of normal were randomized to receive either pentoxifylline 1200 mg/day in three divided doses orally every day or pioglitazone (30 mg/day) daily for 6 months. All the patients were also instructed to reduce their calorie intake by 500 kcal/day as well as to perform modest exercise (brisk walking) regularly at least 5 days per week. Before and after treatment, liver function tests, serum insulin, C-peptide levels, TNF-α, adiponectin, leptin levels, HOMA-IR and hepatocyte injury and fibrosis scores on liver histology were assessed.

RESULTS: Both pentoxifylline and pioglitazone were effective in improving transaminases, insulin resistance (HOMA-IR) and adiponectin levels significantly. TNF-α levels improved with either of the drugs but did not achieve significant levels. Both the drugs improved the markers of acute liver injury. However, only steatosis improved significantly with either of the drugs. Patients treated with pioglitazone had significant improvement in lobular inflammation, portal inflammation and Brunts grade. Brunts grade improved significantly with pioglitazone as compared to pentoxifylline at the end of the therapy.

CONCLUSIONS: Pioglitazone shows better improvement in both metabolic factors and liver histology in patients with NASH compared to pentoxifylline.