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Vitamin D is Not Associated With Severity in NAFLD: Results of a Paired Clinical and Gene Expression Profile Analysis

Patel, Yuval A MD1; Henao, Ricardo PhD2; Moylan, Cynthia A MD, MHS1; Guy, Cynthia D MD3; Piercy, Dawn L FNP-BC, MS1; Diehl, Anna Mae MD, FAASLD1; Abdelmalek, Manal F MD, MPH, FAASLD1

American Journal of Gastroenterology: November 2016 - Volume 111 - Issue 11 - p 1591–1598
doi: 10.1038/ajg.2016.406
ORIGINAL CONTRIBUTIONS: LIVER
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OBJECTIVES: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is complex. Vitamin D (VitD) has been implicated in NAFLD pathogenesis because it has roles in immune modulation, cell differentiation and proliferation, and regulation of inflammation. We evaluated the association of VitD levels, hepatic gene expression for VitD metabolizing genes, and NAFLD histological severity.

METHODS: Two adult cohorts, controls (n=39) and NAFLD (n=244), who underwent liver biopsy were compared. Two-sidedt-tests or Wilcoxon’s rank-sum tests for continuous predictors and chi-squared tests or Fisher’s exact tests for categorical variables were used to analyze the association of VitD and NAFLD. Generalized linear models were used to analyze the association of VitD levels and VitD metabolizing genes with histological severity of NAFLD while adjusting for potential confounders and correcting for multiple comparisons.

RESULTS: NAFLD patients were more likely than controls to have higher HbA1c (6.5±1.2 vs 5.9±1.0;P=0.009), a risk factor for VitD deficiency. However, no difference in VitD levels was observed between groups. VitD levels did not correlate with the severity of hepatic steatosis, lobular or portal inflammation, or ballooned hepatocytes after adjusting for confounding factors. Furthermore, no association was noted between VitD deficiency or differential expression of genes involved in VitD metabolism and severity of hepatic fibrosis or any other histologic feature of NAFLD.

CONCLUSIONS: Neither VitD deficiency, nor hepatic expression of VitD-related genes, associate with the presence or histologic severity of NAFLD in patients. Hence, despite preclinical evidence implicating VitD in NAFLD pathogenesis, VitD deficiency does not appear to be associated with NAFLD severity in humans.

1Division of Gastroenterology and Hepatology, Durham, North Carolina, USA

2Department of Electrical and Computer Engineering, Durham, North Carolina, USA

3Department of Pathology, Duke University, Durham, North Carolina, USA

Correspondence: Manal F. Abdelmalek, MD, MPH, FAASLD, Duke University Medical Center, Division of Gastroenterology, P.O. Box 3913, Durham, North Carolina 27710, USA. E-mail: manal.abdelmalek@duke.edu

SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/A949

Received 08 April 2016; accepted 28 July 2016

Guarantor of the article: Manal F. Abdelmalek, MD, MPH, FAASLD.

Specific author contributions: Study conception and design, interpretation of data, drafting, review and revision of the manuscript, final approval of version submitted: Yuval Patel; biostatistical analysis of clinical and gene expression data, interpretation of data, drafting, review and revision of the manuscript, final approval of version submitted: Ricardo Henao; performance of gene expression analysis, analysis and interpretation of data, review and revision of the manuscript, final approval of version submitted: Cynthia Moylan; review of liver biopsy histology for grading and staging according to NASH CRN Criteria, review and revision of the manuscript, final approval of version submitted: Cynthia D. Guy; study conception and acquisition of vitamin D levels in patient evaluated in Duke NAFLD Clinics, review and revision of the manuscript, final approval of version submitted: Dawn L. Piercy; secured funding for gene expression analysis, analysis and interpretation of data, critical review and revision of the manuscript, final approval of version submitted: Anna Mae Diehl; secured funding for ancillary study and analysis, study conception and design, interpretation of data, drafting, review and revision of the manuscript, final approval of version submitted: Manal F. Abdelmalek.

Financial support: Dr Yuval Patel is supported by National Institutes of Health (NIH) T32 grant (5T32DK007568-25). The acquisition of hepatic gene expression data in NAFLD was supported for an American Recovery and Reinvestment Act (ARRA) grant from the National Institute on Alcohol Abuse and Alcoholism (5RC2AA019399: AMD, principal investigator). Dr Diehl, Dr Abdelmalek and Ms Dawn Piercy receive funding support from the National Institutes of Health/ National Institute of Diabetes and Digestive and Kidney Diseases (NIH/ NIDDK grant # U01-DK57149). Dr Cynthia Moylan is supported by a Junior Faculty Development Grant from the American College of Gastroenterology. Support for the analysis of data for this ancillary study was provided by the Duke NAFLD Research Program in the Duke Division of Gastroenterology and Hepatology.

Potential competing interests: None.

© The American College of Gastroenterology 2016. All Rights Reserved.
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