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

• Published in: Indian journal of gastroenterology 2021-02, Vol.40 (1), p.41-49
• Main Authors: Kedarisetty, Chandan Kumar, Bhardwaj, Ankit, Kumar, Guresh, Rastogi, Archana, Bihari, Chhagan, Kumar, Manoj, Sarin, Shiv Kumar
• Format: Article
• Language: English
• Subjects: Gastroenterology; Hepatology; Medicine; Medicine & Public Health; Original Article
• ISSN: 0254-8860; 0975-0711
• DOI: 10.1007/s12664-020-01131-x

Background and Aim 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), an anti-TNF-alpha agent, has been reported to reduce hepatic inflammation and fibrosis. We evaluated combination of these drugs in NASH patients. Methods In a prospective study, consecutive histologically proven patients with NASH were randomized to receive either PTX, 400 mg thrice daily and VE 400 IU twice daily (group PTVE, n  = 36) or VE alone (group VE, n  = 33). Clinical, dietary and biochemical follow-up was done till 12 months. 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 a similar 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 6 months 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). Conclusions 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. Trial registration Clinical Trials Registry no. NCT01384578