Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis-A randomized pilot study.

Abstract

Non-alcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease. Vitamin E (VE), an anti-oxidant, has shown improvement in NAFLD activity score (NAS) but not fibrosis. Pentoxiphylline (PTX), ananti-TNF-alpha agent, has been reported to reduce hepatic inflammation and fibrosis. We evaluated combination of these drugs in NASH patients. In a prospective study, consecutive histologically proven patients with NASH were randomized to receive either PTX, 400mg thrice daily and VE 400IU twice daily (group PTVE, n = 36) or VE alone (group VE, n = 33). Clinical, dietary and biochemical follow-up was done till 12months. Primary end-point was change in alanine aminotransferase (ALT) levels. RESULTS: Both groups were comparable at baseline. On a strict diet and lifestyle modification regimen, both groups had similar reduction in body mass index and waist circumference. There was asimilar reduction in ALT levels in the two groups. Metabolically, patients in PTVE group had greater reduction in fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) than VE group (p = 0.05). Tumor necrosis factor alpha (TNFα) levels were also significantly lower in PTVE group from 6months onwards. Twelve (10%) patients had repeat liver biopsy (7 in group PTVE, 5 in group VE) with no difference in reduction of NAS score (p = 0.45). However, there was a significant fibrosis regression in PTVE compared to VE group (p = 0.003). These data show greater efficacy of a combination of PTX and VE in achieving fibrosis regression compared to VE alone with better metabolic homeostasis and amelioration of the pro-inflammatory status. Clinical Trials Registry no. NCT01384578.