Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2018; 10(1): 142-154
Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.142
Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data
Behnam Saberi, Alia S Dadabhai, Julie Nanavati, Lin Wang, Russell T Shinohara, Gerard E Mullin
Behnam Saberi, Alia S Dadabhai, Gerard E Mullin, Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Behnam Saberi, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Julie Nanavati, Welch Medical Library, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Lin Wang, Department of Epidemiology, Johns Hopkins-Bloomberg School of Public Health, Baltimore, MD 21205, United States
Russell T Shinohara, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
Author contributions: Saberi B, Dadabhai AS and Mullin GE contributed to the data evaluation, manuscript and figure preparation, editing and final submission; Shinohara RT and Wang L provided biostatistics methodology oversight, as well as data extractions, meta-analysis with pooled data figure preparation and manuscript preparation and editing; Nanavati J provided informatics methodology support, conducted the literature search, and reviewed and edited the manuscript.
Conflict-of-interest statement: None.
Data sharing statement: The authors of the following studies were contacted to obtain their approval to share data in order to systematically evaluate their data for our meta-analysis: Drs. Patel, Luger, Barchetta, Anty, Bril, and Targher.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Gerard E Mullin, MD, Associate Professor, Department of Gastroenterology and Hepatology, The Johns Hopkins Hospital, 600 N Wolfe Street, Carnegie 464B, Baltimore, MD 21287, United States.
Telephone: +1-410-5024270 Fax: +1-410-5024478
Received: November 7, 2017
Peer-review started: November 8, 2017
First decision: December 4, 2017
Revised: December 12, 2017
Accepted: January 15, 2018
Article in press: January 15, 2018
Published online: January 27, 2018
Research background

Vitamin D is a hormone and a vitamin combined that appears to effects cells throughout the body and impart abundant health benefits. There are many studies on its potential role in modifying chronic liver disease. Given the escalating prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide, we studied the literature for the association of vitamin D serum levels and progression of scar tissue formation in NAFLD.

Research motivation

The goal of a systematic review is to pull together the peer-reviewed literature and then apply standardized guidelines to extract the papers that used proper methodology. In this instance, we sorted through 337 papers to find relevant peer-reviewed manuscripts of sufficient quality to provide scientific evidence about the association between vitamin D level and hepatic fibrosis.

Research objectives

The primary objective was to determine whether there was an association of serum vitamin D and the degree of scar tissue in the liver.

Research methods

We followed international guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses in systematically analyzing the 337 articles with duplicate screening and extraction by the authors. The authors contacted investigators of previous papers to report crucial data not stated in their manuscripts. An expert biostatistician assisted with data analysis by using Cochrane RevMan 5 software.

Research results

We discovered that only six of the 337 studies presented sufficient data to be included in the meta-analysis. We did not find an association of serum vitamin D with the degree of liver scarring in NAFLD.

Research conclusions

We applied advanced methodologies to determine the relationship between stages of liver scarring and serum vitamin D levels. We observed that serum vitamin D was not associated with liver scar tissue accumulation irrespective of the phase of hepatic injury. In February 2017, we reported in World Journal of Hepatology that there was an association between the degrees of scar tissue formation in chronic Hepatitis C with the serum level of vitamin D. Given that vitamin D appears to have a strong influence on immunity and wound healing, it is still possible that supplemental vitamin D to normal levels could help prevent liver disease progression in NAFLD. Interventional trials would be best suited to explore this possibility. This study further elucidated that serum vitamin D does not appear to be associated with the stage of liver scar tissue accumulation. Application of meta-regression permits an analysis of the individual phases of liver scar tissue formation in association with the serum levels of vitamin D. This meta-analysis utilized data synthesis and statistical inquiry to study whether the degree of liver scarring is associated with serum vitamin D status, and found no association. Clinicians should bear in mind that many patients with nonalcoholic fatty liver disease are obese and have lower serum vitamin D levels than non-obese subjects due to sequestration into adipose tissues. Thus, supplementation with vitamin D3 to sufficient levels should be considered.

Research perspectives

When conducting a meta-regression, there may be crucial data that is unavailable that does require proactive investigation by researchers for analysis. Careful meta-analyses can help the scientific community to integrate evidence across studies. Systematic reviews and synthesis, as in our paper, should employ vigilance in data extraction and make efforts to contact the authors of relevant prior works to obtain further information about missing data, statistical analysis, and to clarify methods. As in our paper, acknowledgment of authors who cooperate with the provision of information for systematic review and synthesis should be noted in the resulting manuscript.