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Association of fetuin B with markers of liver fibrosis in nonalcoholic fatty liver disease

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Abstract

Objective

The liver-derived plasma protein fetuin B is associated with nonalcoholic fatty liver disease (NAFLD) and impaired glucose homeostasis in mice. However, its association with non-invasive ultrasound- and magnetic resonance (MR)-based markers of liver fibrosis and steatosis, the enhanced liver fibrosis (ELF) score, liver biopsy, as well as rs738409 in PNPLA3, has not been elucidated in NAFLD, so far.

Design and methods

The association of circulating fetuin B and transient elastography (TE), controlled attenuation parameter (CAP), 1H-MR-spectroscopy, the ELF score, liver biopsy, as well as risk alleles in rs738409 in PNPLA3, was studied in 101 NAFLD patients as compared to 15 healthy controls.

Results

Serum fetuin B levels did not differ between NAFLD patients and controls (p = 0.863). Fetuin B was independently and negatively associated with transient elastography liver stiffness measurement (LSM) (p = 0.002), but not with the steatosis markers CAP or 1H-MR-spectroscopy. Fetuin B serum concentrations were significantly lower in individuals with LSM > 7.0 kPa as compared to patients with LSM < 7.0 kPa (p = 0.024). Furthermore, the ELF score and histologically proven fibrosis were independent and negative predictors of circulating fetuin B. Moreover, serum fetuin B significantly depended on number of rs738409 risk alleles (p = 0.026).

Conclusions

Fetuin B is independently and negatively associated with non-invasive markers of liver fibrosis and PNPLA3 status in NAFLD patients but does not show a correlation with the hepatic lipid content. Future studies need to elucidate the pathophysiological significance of fetuin B in NAFLD and its potential value as predictor for disease severity.

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Acknowledgements

We thank Yvonne Kurth (Division of Gastroenterology and Rheumatology, University Hospital Leipzig), Kilian Solty (IFB AdiposityDiseases, University of Leipzig), and Ulrike Lössner (Department of Endocrinology and Nephrology and IFB AdiposityDiseases, University of Leipzig) for technical assistance.

Funding

This work was supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001 (IFB AdiposityDiseases, MetaRot program) to T.E.

Author contributions

T.E., J.W., and T.K. wrote the manuscript and researched data. A.S., N.L., H.B., J.B., and V.K. researched data and reviewed/edited the manuscript. Guarantors: Dr. Thomas Ebert and Dr. Thomas Karlas are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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    Authors and Affiliations

    1. Department of Endocrinology and Nephrology, University of Leipzig, 04103, Leipzig, Germany

      Thomas Ebert

    2. Leipzig University Medical Center, IFB AdiposityDiseases, 04103, Leipzig, Germany

      Thomas Ebert & Nicolas Linder

    3. Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, 04103, Leipzig, Germany

      Nicolas Linder, Alexander Schaudinn & Harald Busse

    4. Division of Gastroenterology and Rheumatology, University Hospital Leipzig, 04103, Leipzig, Germany

      Joachim Berger, Volker Keim, Johannes Wiegand & Thomas Karlas

    5. Institute of Clinical Chemistry, Hannover Medical School, 30625, Hannover, Germany

      Ralf Lichtinghagen

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    Correspondence to Thomas Ebert.

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    Conflict of interest

    T.K., J.W., and V.K. received an unrestricted research grant from Echosens, Paris, France not directly related to the present study. J.W. and R.L. received lecturer fees from Siemens. The ELF score analyses were sponsored by a research grant from Siemens to J.W. Other authors declare that they have no competing interests.

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    Johannes Wiegand and Thomas Karlas contributed equally to this work.

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    Ebert, T., Linder, N., Schaudinn, A. et al. Association of fetuin B with markers of liver fibrosis in nonalcoholic fatty liver disease. Endocrine 58, 246–252 (2017). https://doi.org/10.1007/s12020-017-1417-z

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