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Clinical nutrition

Vitamin D deficiency: prevalence and association with liver disease severity in pediatric nonalcoholic fatty liver disease

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Abstract

Background/Objectives

To determine associations between serum 25-hydroxyvitamin D (25(OH)-D) concentrations and histologic nonalcoholic fatty liver disease (NAFLD) severity.

Subjects/Methods

Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD. Serum 25(OH)-D concentrations were used to define vitamin D deficiency (≤20 ng/ml), insufficiency (21–30 ng/ml), and sufficiency (≥31 ng/ml).

Results

In all, 234 patients (78% non-Hispanic, median age 14 years) were included. The majority (n = 193) were either vitamin D insufficient (50%) or deficient (32%). Eighty-four patients (36%) reported taking vitamin D supplements at the time of biopsy; serum 25(OH)-D concentrations were not higher in those supplemented. There were no differences in the demographic, clinical, and laboratory characteristics of the three vitamin D status groups. Severity of steatosis, ballooning, lobular/portal inflammation, and NAFLD activity score were also not different between the groups. The proportion of patients with significant fibrosis (stage ≥ 2) was higher in those with insufficiency (29%) compared to those who were sufficient (17%) or deficient (15%, p = 0.04). After controlling for important covariates selected from age, body mass index, ethnicity, vitamin D supplementation, and season, the insufficient group had increased odds of a higher fibrosis score compared to the sufficient group (adjusted OR, 2.04; 95%CI, 1.02–4.08).

Conclusions

Vitamin D deficiency and insufficiency are common in children with NAFLD, but not consistently related with histologic disease severity. Prospective longitudinal studies are needed to determine optimal dosing strategies to achieve sufficiency and to determine whether adequate supplementation has an impact on histology.

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Funding

SD was funded in part by NIH R21 AA022742; RO1 DK 113196; RO1 GM119174; P50 AA024333; UO1 AA021890, UO1AA026975, UO1 DK061732 and the Mikati Foundation Grant. SO was funded by NIH T32 DK007727. SAX was funded in part by R01 DK100429.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Toshifumi Yodoshi, Sarah Orkin, Ana Catalina Arce-Clachar, Kristin Bramlage, Stavra A. Xanthakos & Marialena Mouzaki

  2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Ana Catalina Arce-Clachar, Lin Fei, Stavra A. Xanthakos & Marialena Mouzaki

  3. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Chunyan Liu & Lin Fei

  4. Division of Gastroenterology, Departments of Gastroenterology, Hepatology and Pathobiology, Cleveland Clinic, Cleveland, OH, USA

    Faris El-Khider & Srinivasan Dasarathy

Authors
  1. Toshifumi Yodoshi
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  2. Sarah Orkin
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  3. Ana Catalina Arce-Clachar
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  4. Kristin Bramlage
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  5. Chunyan Liu
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  6. Lin Fei
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  7. Faris El-Khider
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  8. Srinivasan Dasarathy
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  9. Stavra A. Xanthakos
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  10. Marialena Mouzaki
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Contributions

MM was responsible for designing the protocol, writing the protocol and report, conducting the research, extracting and analyzing data, interpreting results, updating reference lists and creating the “Summary of findings” tables. SAX was responsible for designing the protocol, writing the protocol and report, conducting the research, extracting and analyzing data, interpreting results, and provided feedback on the report. TY was responsible for designing the protocol, writing the protocol and report, conducting the research, extracting and analyzing data, interpreting results, updating reference lists and creating the “Summary of findings” tables. SO was responsible for designing the protocol, writing the protocol and report, conducting the research, extracting and analyzing data, interpreting results, and provided feedback on the report. ACA-C was responsible for designing the protocol, writing the protocol and report, conducting the research, extracting and analyzing data, interpreting results, and provided feedback on the report. KB was responsible for designing the protocol, writing the protocol and report, conducting the research, extracting and analyzing data, interpreting results, and provided feedback on the report. CL was responsible for conducting the research, analyzing data, interpreting results, and arbitrating potentially eligible studies, and provided feedback on the report. LF was responsible for conducting the research, analyzing data, interpreting results, and arbitrating potentially eligible studies, and provided feedback on the report. SD was responsible for designing the protocol, writing the protocol and report, conducting the research, interpreting results, and provided feedback on the report. FE-K was responsible for designing the protocol, writing the protocol and report, conducting the research interpreting results, and provided feedback on the report. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Marialena Mouzaki.

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Yodoshi, T., Orkin, S., Arce-Clachar, A.C. et al. Vitamin D deficiency: prevalence and association with liver disease severity in pediatric nonalcoholic fatty liver disease. Eur J Clin Nutr 74, 427–435 (2020). https://doi.org/10.1038/s41430-019-0493-y

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