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

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Abstract

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

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Acknowledgements

We would like to thank our staffs Ms. Anila and Ms. Madhu for data compilation.

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Author notes

  1. Chandan Kumar Kedarisetty and Shiv Kumar Sarin are both corresponding authors

Authors and Affiliations

  1. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110 070, India

    Chandan Kumar Kedarisetty, Manoj Kumar & Shiv Kumar Sarin

  2. Departments of Hepatology, Sri Ramachandra Institute of Higher Education and Research, Chennai 600 116, India

    Chandan Kumar Kedarisetty

  3. Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi 110 070, India

    Ankit Bhardwaj & Guresh Kumar

  4. Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi 110 070, India

    Archana Rastogi & Chhagan Bihari

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  1. Chandan Kumar Kedarisetty
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Contributions

Chandan Kumar Kedarisetty: conceptualization, methodology, original draft preparation. Ankit Bhardwaj: data collection. Guresh Kumar: data analysis. Archana Rastogi: data collection. Chhagan Bihari: data collection. Manoj Kumar: conceptualization, methodology, reviewing and editing. Shiv Kumar Sarin: conceptualization, methodology, reviewing and editing.

Corresponding authors

Correspondence to Chandan Kumar Kedarisetty or Shiv Kumar Sarin.

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Conflict of interest

CKK, AB, GK, AR, CB, MK, and SKS  declare that they have no conflict of interest.

Ethics statement

The study was performed conforming to the Helsinki declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on Springer.com. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethics Committee of Institute of Liver and Biliary Sciences, New Delhi.

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Kedarisetty, C.K., Bhardwaj, A., Kumar, G. et al. Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis— A randomized pilot study. Indian J Gastroenterol 40, 41–49 (2021). https://doi.org/10.1007/s12664-020-01131-x

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  • DOI: https://doi.org/10.1007/s12664-020-01131-x

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