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Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease is associated with heterogeneous pattern of fat infiltration in skeletal muscles

  • Gastrointestinal
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To evaluate the association between fat infiltration in skeletal muscles (myosteatosis) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD).

Methods

In a cross-sectional cohort of 72 histologically proven NAFLD patients (n = 38 with non-alcoholic steatohepatitis; NASH), among which 20 had HCC diagnosed on biopsy, we used proton density fat fraction (PDFF) at MRI to evaluate myosteatosis in skeletal muscles (mean fat fraction and first order radiomic-based pattern) at the third lumbar level, namely in erector spinae (ES), quadratus lumborum (QL), psoas, oblique, and rectus muscles.

Results

PDFFES was 70% higher in patients with HCC when compared to those without HCC (9.6 ± 5.5% versus 5.7 ± 3.0%, respectively, p < 0.001). In multivariate logistic regression, PDFFES was a significant predictor of the presence of HCC (AUC = 0.72, 95% CI 0.57–0.86, p = 0.002) independently from age, sex, visceral fat area, and liver fibrosis stage (all p < 0.05). The relationship between PDFFES and HCC was exacerbated in patients with NASH (AUC = 0.79, 95% CI 0.63–0.86, p = 0.006). In patients with NASH, radiomics features of heterogeneity such as energy and entropy in any of the paraspinal muscles (i.e., ES, QL, or psoas) were independent predictors of HCC. EnergyES identified patients with HCC (n = 13) in the NASH population with AUC = 0.92 (95% CI 0.82–1.00, p < 0.001).

Conclusion

In patients with NAFLD, and more specifically in those with NASH, the degree and heterogeneity of myosteatosis is independently associated with HCC irrespective of liver fibrosis stage.

Clinical relevance statement

Our data suggest that myosteatosis could be used as a biomarker of HCC in the ever-expanding NAFLD population and pave the way for further investigation in longitudinal studies.

Key Points

• HCC in patients with non-alcoholic fatty liver disease, and more specifically in those with non-alcoholic steatohepatitis, is independently associated with severe fatty infiltration (myosteatosis) of paravertebral skeletal muscles.

• Association between myosteatosis and HCC is independent from liver fibrosis stage.

• Histogram-based radiomics features of myosteatosis predicts the risk of HCC in patients with non-alcoholic steatohepatitis.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AUC:

Area under the receiver operating characteristic curve

BMI:

Body mass index

HCC:

Hepatocellular carcinoma

MRI:

Magnetic resonance imaging

NAFL:

Non-alcoholic fatty liver

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

PDFF:

Proton density fat fraction

ROI:

Region of interest

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Funding

This work was supported by a Ph.D. fellowship from FRIA (FNRS, Belgium) (grant number 31618719 (to M.N.)), by a post-doctoral fellowship of Bpifrance (grant PSPC HECAM to A.A.)), and by an FNRS PDR grant (T.0141.19 (to I.A.L.)). The study was performed by a laboratory member of France Life Imaging network (grant ANR-11-INBS-0006).

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Author notes

  1. Maxime Nachit and Marco Dioguardi Burgio contributed equally.

Authors and Affiliations

  1. Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium

    Maxime Nachit & Isabelle Leclercq

  2. Department of Imaging and Pathology, KU Leuven, Louvain, Belgium

    Maxime Nachit

  3. Laboratory of Imaging Biomarkers, Center of Research On Inflammation, Université Paris Cité, Inserm, Paris, France

    Marco Dioguardi Burgio, Anton Abyzov, Philippe Garteiser, Valérie Vilgrain & Bernard E. Van Beers

  4. Department of Radiology, Beaujon University Hospital Paris Nord, AP-HP, Clichy, France

    Marco Dioguardi Burgio, Valérie Vilgrain & Bernard E. Van Beers

  5. Team “From Inflammation to Cancer in Digestive Disease”, Center of Research on Inflammation, Université Paris Cité, Inserm, Paris, France

    Valérie Paradis

  6. Department of Pathology, Beaujon University Hospital Paris Nord, AP-HP, Clichy, France

    Valérie Paradis

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  1. Maxime Nachit
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Contributions

M.N. conceived and designed the study; M.D.B., VV, and BVB recruited the patients and carried out data collection in human studies. M.N. and AA analyzed and interpreted the data. VP analyzed liver biopsies. IL and BVB critically discussed the study design, data, and manuscript for scientific content. M.N., M.D.B., IL, and BVB wrote the manuscript, with contribution from all authors.

Corresponding author

Correspondence to Maxime Nachit.

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Guarantor

The scientific guarantor of this publication is Maxime Nachit.

Conflict of interest

The authors have no conflict of interest to disclose.

Statistic and biometry

The authors thank Lieven Desmet (Louvain Institute of Data Analysis and Modeling in economics and statistics, Louvain-la-Neuve, Belgium) for assistance for statistical analyses.

Informed consent

Informed consent was waived because of the retrospective nature of the study.

Ethical approval

This retrospective study (project no. 2017–030) obtained local IRB approval.

Study subjects or cohorts overlap

Some patients were reported in https://link.springer.com/article/10.1007/s00330-021-08261-6. The paper is unrelated to the present work.

Methodology

• retrospective study

• performed at one institution

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Nachit, M., Dioguardi Burgio, M., Abyzov, A. et al. Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease is associated with heterogeneous pattern of fat infiltration in skeletal muscles. Eur Radiol 34, 1461–1470 (2024). https://doi.org/10.1007/s00330-023-10131-2

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