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Low vitamin D status is associated with advanced liver fibrosis in patients with nonalcoholic fatty liver disease

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Abstract

Several studies explored the association between vitamin D status and nonalcoholic fatty liver disease with contradictory results. We aimed to investigate the association between vitamin D status, inflammatory cytokines and liver fibrosis in nonalcoholic fatty liver disease patients. Two hundred nineteen nonalcoholic fatty liver disease patients and 166 age- and gender- matched healthy controls were recruited for this study. Serum 25(OH)D was measured by radioimmunoassay. Serum interleukin-8 and transforming growth factor-β1 were measured using ELISA. Serum 25(OH)D was only marginally decreased in nonalcoholic fatty liver disease patients. Interestingly, serum 25(OH)D was markedly reduced in nonalcoholic fatty liver disease patients with advanced liver fibrosis compared to nonalcoholic fatty liver disease patients with indeterminate liver fibrosis and no advanced fibrosis. Logistic regression analysis showed that there was an inverse association between serum 25(OH)D and severity of liver fibrosis in nonalcoholic fatty liver disease patients. Further analysis showed that serum interleukin-8 was elevated in nonalcoholic fatty liver disease patients, the highest interleukin-8 in patients with advanced fibrosis. An inverse correlation between serum 25(OH)D and interleukin-8 was observed in nonalcoholic fatty liver disease patients with and without liver fibrosis. Although serum transforming growth factor-β1 was slightly elevated in nonalcoholic fatty liver disease patients, serum transforming growth factor-β1 was reduced in nonalcoholic fatty liver disease patients with advanced fibrosis. Unexpectedly, a positive correlation between serum 25(OH)D and transforming growth factor-β1 was observed in nonalcoholic fatty liver disease patients with advanced fibrosis. In conclusion, low vitamin D status is associated with advanced liver fibrosis in nonalcoholic fatty liver disease patients. Interleukin-8 may be an important mediator for hepatic fibrosis in nonalcoholic fatty liver disease patients with low vitamin D status.

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Abbreviations

NAFLD:

nonalcoholic fatty liver disease

25(OH)D:

25-hydroxyvitamin D

BMI:

body mass index

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

ALP:

alkaline phosphatase

GGT:

glutamyltransferase

LDH:

lactate dehydrogenase

HDL:

high-density lipoprotein

LDL:

low density lipoprotein

OR:

odds ratio

NASH:

nonalcoholic steatohepatitis

IL-8:

interleukin-8

TGF-β:

transforming growth factor-β

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Acknowledgments

This project was supported by National Natural Science Foundation of China (81373495, 81471467), Natural Science Foundation of Anhui province (1308085MH120), Research Fund for Doctoral Program of Higher Education of China (20133420110005) and Research Fund for Fourth Affiliated Hospital of Anhui Medical University (FKY2014D05).

Author Contributions

XC and DXX conceived study. BBY collected data and carried out experiments. YHC and CZ carried out experiments and analyzed data. CES, KFH and JZ collected data. DXX and YHC wrote the paper. All authors read and approved the final manuscript.

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    Authors and Affiliations

    1. Department of Gastroenterology, Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230032, China

      Bing-Bing Yang, Chang-E Shi, Kai-Feng Hu & Ju Zhou

    2. Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China

      Xi Chen

    3. Department of Toxicology, Anhui Medical University, Hefei, 230032, China

      Yuan-Hua Chen, Cheng Zhang & De-Xiang Xu

    4. Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, China

      Yuan-Hua Chen

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    Bing-Bing Yang and Yuan-Hua Chen contributed equally to this work.

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    Yang, BB., Chen, YH., Zhang, C. et al. Low vitamin D status is associated with advanced liver fibrosis in patients with nonalcoholic fatty liver disease. Endocrine 55, 582–590 (2017). https://doi.org/10.1007/s12020-016-1152-x

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