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

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: PDFF 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, PDFF 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 PDFF 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. Energy 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.