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. 2024 Nov;34(11):7492-7502.
doi: 10.1007/s00330-024-10798-1. Epub 2024 May 25.

Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis

Carl Edin  1   2   3 , Mattias Ekstedt  1   2 , Markus Karlsson  1   2   4 , Bertil Wegmann  2   5 , Marcel Warntjes  1   2 , Eva Swahn  1   6 , Carl Johan Östgren  2   7 , Tino Ebbers  1   2 , Peter Lundberg  1   2   4 , Carl-Johan Carlhäll  8   9   10
Affiliations

Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis

Carl Edin et al. Eur Radiol. 2024 Nov.

Abstract

Objective: In nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers.

Methods: In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistical approach.

Results: In total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2.

Conclusion: MRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling.

Clinical relevance statement: Liver fibrosis may be considered a cardiovascular risk factor in patients without cirrhosis. Further research on the mechanisms that link liver fibrosis to left ventricular concentricity may reveal potential therapeutic targets in patients with non-alcoholic fatty liver disease (NAFLD).

Key points: Previously, studies on liver fibrosis and cardiac remodeling have focused on advanced stages of liver fibrosis. Liver fibrosis is associated with left ventricular (LV) concentricity and may relate to interleukin-1 receptor type 2. Interleukin-1 signaling is a potential mechanistic interlink between early liver fibrosis and LV remodeling.

Keywords: Elastography; Interleukin-1; Magnetic Resonance; Non-alcoholic fatty liver disease; Type 2 diabetes.

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Conflict of interest statement

MW is a consultant for SyntheticMR AB and holds stock in SyntheticMR AB. The remaining authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Figures

Fig. 1
Fig. 1
A Liver elastogram from magnetic resonance elastography (3D MRE) in a 53-year-old male in the diabetes group, with a liver shear stiffness of 2.2 kPa. The position of the external transducer on the right anterior chest wall and the axial waves are schematically illustrated. The region of interest (ROI-2) for measurement of shear stiffness, located in the right liver lobe, is shown in blue (dashed). The larger region of interest (ROI-1) for defining the input region to the KIR-software is shown in orange (dotted), and the coloured overlay shows the result of the calculation within the region representing liver, on a background anatomical image. The image is presented using radiological convention. B Liver proton spectra from magnetic resonance spectroscopy, used for proton density fat fraction (PDFF) calculation, with water (H2O) resonance at 4.76 ppm and major fatty-acyl chain (-CH2-) resonance at 1.21 ppm
Fig. 2
Fig. 2
Mid-ventricular short-axis image of the left ventricle at end-diastole (A) and end-systole (B) in a participant with an LV ejection fraction of 66% and LV concentricity ratio of 1.06 g/mL
Fig. 3
Fig. 3
Quantitative native T1 map, in a mid-ventricular slice from the 3D-QALAS sequence. The region of interest is shown in red, in the septal myocardium
Fig. 4
Fig. 4
Scatterplot of LV concentricity (Y-axis) and liver stiffness (X-axis), with corresponding Pearson correlation coefficient and p value
See this image and copyright information in PMC

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