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Impact of using different biomarkers of liver fibrosis on hepatologic referral of individuals with severe obesity and NAFLD



The purpose of this study was to estimate how many individuals with severe obesity and NAFLD should be referred to hepatologists according to the EASL–EASD–EASO guidelines and whether the choice of specific indicators of liver fibrosis would significantly impact the number of referrals.


This was a single-center retrospective study of 495 individuals with severe obesity screened at our institution between 2012 and 2018 for a bariatric surgery intervention. The guidelines were applied using the NAFLD Liver Fat Score (NLFS) to assess the presence of steatosis and the NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and Hepamet Fibrosis Score (HFS) to assess the risk of advanced fibrosis.


Three hundred and seventy-nine patients (76.6%) had evidence of liver steatosis. The application of the guidelines would lead to referral of 66.3% of patients using NFS, 31.7% using FIB-4 and 34.2% using HFS. When referrals due to abnormal liver function tests were excluded, these percentages dropped to 55.8%, 7.3% and 12.1%, respectively. The strongest inter-biomarker agreement was found between FIB-4 and HFS (κ = 0.86, 95% CI 0.815–0.910).


Strict application of the guidelines in individuals with severe obesity would probably lead to over-referral, although a great variability exists among the different scores.

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Fig. 1
Fig. 2

Data availability

The datasets are available from the corresponding author on reasonable request.



American Association for the Study of Liver Diseases


European Association for the Study of Diabetes


European Association for the Study of the Liver


European Association for the Study of Obesity






Fatty Liver Index


Hepamet Fibrosis Score


Non-alcoholic fatty liver disease


Non-alcoholic steatohepatitis


NAFLD fibrosis score


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We thank the staff of the department of Metabolic Medicine, Bariatric Surgery and Biology, Policlinico di Monza, for their helpful assistance.


The authors received no specific funding for this work.

Author information

All authors made substantial contributions to the conception and design or acquisition, analysis and interpretation of data. All authors drafted the article or revised it critically for important intellectual content. All authors approved the final version of the manuscript to be published. GP is the guarantor of this work.

Correspondence to G. Perseghin.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimantation (Institutional and National) and with the Helsinki Declaration of 1964 and later versions.

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Informed consent was obtained from all patients for being included in the study.

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Ciardullo, S., Ronchetti, C., Muraca, E. et al. Impact of using different biomarkers of liver fibrosis on hepatologic referral of individuals with severe obesity and NAFLD. J Endocrinol Invest (2020). https://doi.org/10.1007/s40618-020-01188-7

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  • Non-alcoholic fatty liver disease
  • Fibrosis-4
  • NAFLD fibrosis score
  • Screening
  • Guidelines