Meta-Analysis
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: http://creativecommons.org/licenses/by-nc/4.0/
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. gmullin1@jhmi.edu
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
Processing time: 79 Days and 15.4 Hours
Abstract
AIM

To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD).

METHODS

Two individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant.

RESULTS

A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies.

CONCLUSION

Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD.

Keywords: Vitamin D; 25-hydroxyvitamin D; Liver fibrosis; Meta-analysis; Nonalcoholic fatty liver disease; Non-alcoholic steatohepatitis

Core tip: Non-alcoholic fatty liver disease (NAFLD) is a condition that can progress to cirrhosis, hepatic failure, and liver cancer. Vitamin D sufficiency is impaired in the advanced stages of liver disease and in NAFLD. However, our systematic review of the literature and meta-regression confirms that the serum 25-hydroxyvitamin D levels in patients with NAFLD are not associated with the severity of hepatic fibrosis.