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Clinical Studies and Practice

Serum vascular cell adhesion molecule-1 predicts significant liver fibrosis in non-alcoholic fatty liver disease

International Journal of Obesity volume 41, pages 1207–1213 (2017)Cite this article

Subjects

Abstract

Background:

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is strongly associated with obesity, dyslipidemia and insulin resistance. NAFLD often presents as simple steatosis (NAFL) but can progress to non-alcoholic steatohepatitis (NASH) and fibrosis. Current non-invasive biomarkers are not tailored to identify significant (⩾F2) fibrosis, although recent guidelines recommend a stringent follow-up of this patient population. We and others have reported on the role of pathological angiogenesis in the pathogenesis of NAFLD, highlighting pro-angiogenic factors as potential diagnostic markers.

Objective:

To investigate the applicability of angiogenic and endothelial dysfunction markers as non-invasive diagnostic tools for NASH or NASH-associated fibrosis in obese patients.

Methods:

In a prospective cross-sectional study, male patients undergoing bariatric surgery (n=61) and control patients (n=35) were recruited. Serum protein levels and visceral adipose tissue gene expression of endothelial dysfunction and angiogenic markers were analyzed by multiplex bead-based assay and quantitative RT-PCR, respectively. For validation, we recruited a second cohort of patients undergoing bariatric surgery (n=40) and a cohort of NAFLD patients from our outpatient clinic (n=30).

Results:

We identified serum vascular cell adhesion molecule-1 (VCAM-1) as an independent predictor for ⩾F2 fibrosis (median 14.0 vs 8.7 ng ml−1 in patients with and without significant fibrosis; P<0.0001) with an area under the receiver-operating characteristics (AUROC) curve of 0.80. The cutoff point of 13.2 ng ml−1 showed a sensitivity of 80% and specificity of 83%. In line with these results, VCAM-1 visceral adipose tissue gene expression was also elevated in patients with fibrosis (P=0.030). In the bariatric surgery and clinical validation cohorts, VCAM-1 displayed similar AUROCs of 0.89 and 0.85, respectively.

Conclusions:

VCAM-1 levels are able to accurately predict significant (⩾F2) fibrosis in NAFLD patients.

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Acknowledgements

We thank Petra van Wassenhove and Hilde Devlies for their excellent technical assistance, Elien Glorieus for her accurate management of the patient database, and Roos Coolman from the Statistics unit for her helpful advice. Guarantor of the article: Anja Geerts. SL, SR and XV received a research grant from the Fund for Scientific Research Flanders (FWO15/ASP/146, FWO14/ASP/200 and 1700214N, respectively). HVV is a senior clinical researcher of the FWO Flanders.

Author contributions

SL, LD, BL and AG conceived and designed the study; SL, FVdV, MB, YVN, MP and AH were involved in data acquisition; SL, LD, SR, CVS, BL and AG were involved in the data analysis and interpretation; SL drafted the paper; LD, XV, HVV, BL and AG critically revised the manuscript for intellectual content.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium

    S Lefere, L Devisscher, S Raevens, X Verhelst, C Van Steenkiste, H Van Vlierberghe & A Geerts

  2. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium

    F Van de Velde, M Bekaert & B Lapauw

  3. Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium

    Y Van Nieuwenhove

  4. Department of Pathology, Ghent University Hospital, Ghent, Belgium

    M Praet & A Hoorens

  5. Department of Gastroenterology and Hepatology, Maria Middelares Hospital, Ghent, Belgium

    C Van Steenkiste

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Lefere, S., Van de Velde, F., Devisscher, L. et al. Serum vascular cell adhesion molecule-1 predicts significant liver fibrosis in non-alcoholic fatty liver disease. Int J Obes 41, 1207–1213 (2017). https://doi.org/10.1038/ijo.2017.102

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