Noninvasive liver biomechanical mapping identifies a pre-fibrotic niche and early conditions favoring HCC development
Author Block: V. Koch1, L. D. Grünewald1, J. Gotta1, S. Mahmoudi1, R. Hammerstingl1, K. Eichler1, O. Darwish2, T. Vogl1, R. Sinkus2; 1Frankfurt/DE, 2Paris/FR
Purpose: The rise in metabolic syndrome is driving diffuse liver disease and HCC, often without advanced fibrosis. Identifying at-risk individuals in the pre-fibrotic stage is challenging. This study developed and validated a 3D MRE–based biomechanical imaging framework for early liver disease detection and characterization of HCC-related alterations in non-fibrotic livers.
Methods or Background: In this prospective study, 3D MRE was consecutively performed in 193 participants (mean age, 56 years; 83 women) with suspected or confirmed liver disease, including 73 biopsy-confirmed cases (38%) and 26 HCCs (14%). 20 healthy volunteers served as controls. The complex shear modulus was decomposed into classical stiffness (|G*|), shear wave attenuation (α), and phase angle (Y), yielding a two-dimensional “biomechanical fingerprint” of liver tissue. Biomechanical parameters were correlated with histopathology, blood biomarkers, and clinical characteristics.
Results or Findings: We identified three biomechanical regions: healthy tissue, a pre-fibrotic niche with inflammation but near-normal stiffness, and fibrotic/cirrhotic tissue. In the pre-fibrotic niche, α was markedly reduced despite preserved stiffness, accompanied by decreased E-cadherin and early α-smooth muscle actin upregulation. An α threshold <50 m⁻¹ was linked to higher HCC risk, even without fibrosis, and the biomechanical continuum mirrored gradual changes in clinical and molecular biomarkers (FIB-4, ASAT, PDFF, platelet count).
Conclusion: Our findings show that 3D MRE allows organ-specific, noninvasive mapping of liver disease and identifies a biomechanical state permissive to HCC before fibrosis. This approach extends elastography beyond fibrosis staging and enables early, individualized HCC risk stratification.
Limitations: This study has limitations, including predominance of fatty liver disease, reliance on biopsy with inherent variability, reduced biopsy numbers due to MRI eligibility, and its observational, hypothesis-generating design. Technical constraints (single frequency, single vendor, research transducer) and reliance on presumed F0 in most healthy volunteers may limit reproducibility.
Funding for this study: This work was supported by the German Doktor Robert Pfleger Foundation, the Wilhelm Vaillant Foundation, the French Integrated Cancer Research Center “SiRIC InsiTu” (INCa-DGOS-INSERM-ITMO Cancer_18008), and the French National Research Agency RHU Operandi (ANR-21-RHUS-0012).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The institutional ethics review board approved this prospective, cross-sectional, single-center study that complies with the Declaration of Helsinki.