Treatment of non-alcoholic steatohepatitis patients with vitamin D: a double-blinded, randomized, placebo-controlled pilot study

Abstract

Background: Non-alcoholic steatohepatitis (NASH) is defined by liver inflammation and consecutive fibrotic damage caused by a deposition of fat in the liver. No licensed medical treatments exist and lifestyle modification is difficult to incorporate into everyday life. We investigated the efficacy and safety of a 48-week treatment with vitamin D3 in NASH patients.

Methods: Histologically determined NASH patients with elevated alanine aminotransferase (ALT) and decreased 25-OH vitamin D level at baseline received vitamin D3 or placebo orally over a 48-week period. The primary endpoint of this study was the change in ALT from baseline to the end-of-treatment. Steatohepatitis was categorized according to the Steatosis, Activity and Fibrosis Score and disease activity was assessed using the NAFLD activity score.

Results: Serum 25-OH vitamin D levels significantly increased only in the vitamin D3 group over the 48-week treatment phase indicating compliance. In contrast to placebo, patients in the vitamin D group had markedly decreased ALT levels after the end-of-treatment phase. A significant decrease during treatment with vitamin D was also observed for cytokeratin-18 fragments compared with placebo. The study was not powered to detect changes in histological score, hence only descriptive results for histopathological characteristics are available.

Conclusions: Treatment with 2100 IE vitamin D q.d. over 48 weeks was well tolerated and led to a significant improvement of serum ALT levels in patients with hypovitaminosis D and histology-proven NASH as the primary endpoint together with a trend toward reduction of hepatic steatosis, which was not significant due to a small number of available biopsy specimens.

Keywords:

• NAFLD
• NASH
• drug therapy
• vitamin D

Acknowledgments

The authors appreciate the continued support of the team at the Clinical Trials Center, Zurich Hospital University, as well as all study staff contributing at the different study centers. We are grateful to the participating patients and their families.

Disclosure statement

AG served as an advisor and/or speaker to Alexion, BMS, Gilead, Intercept, Novartis and Falk. He holds an unrestricted research grant from Novartis. BM has received consulting honoraria from Abbvie, BMS, Gilead, Janssen, Merck, Intercept and MSD and grant support from Gilead. JFD served as an advisor and/or speaker to Abbvie, Bayer, BMS, Falk, Genfit, Gilead, Intercept, Lilly, Merck and Novartis. He holds an unrestricted research grant from Bayer. All other authors do not have any disclosures to report.

Additional information

Funding

The study medication (vitamin D3 2100 IU daily) and placebo were produced and provided by Antistress AG, Rapperswil-Jona, Switzerland. The trial was partly funded by the Velux Foundation and the University of Zurich, both Zurich, Switzerland.