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Multicenter Study
. 2023 Aug 3:14:1213441.
doi: 10.3389/fendo.2023.1213441. eCollection 2023.

Pancreatic steatosis and iron overload increases cardiovascular risk in non-alcoholic fatty liver disease

David Marti-Aguado  1   2 , Amadeo Ten-Esteve  2   3 , Carlos Manuel Baracaldo-Silva  4 , Ana Crespo  5 , Elena Coello  6 , Víctor Merino-Murgui  1 , Matias Fernandez-Paton  2 , Clara Alfaro-Cervello  7   8 , Alba Sánchez-Martín  7 , Mónica Bauza  9 , Ana Jimenez-Pastor  2   10 , Alexandre Perez-Girbes  4 , Salvador Benlloch  5   11 , Judith Pérez-Rojas  9 , Víctor Puglia  12 , Antonio Ferrández  7   8 , Victoria Aguilera  6   11 , Mercedes Latorre  13 , Cristina Monton  1 , Desamparados Escudero-García  1   8 , Ignacio Bosch-Roig  14 , Ángel Alberich-Bayarri  2   10 , Luis Marti-Bonmati  2   4
Affiliations
Multicenter Study

Pancreatic steatosis and iron overload increases cardiovascular risk in non-alcoholic fatty liver disease

David Marti-Aguado et al. Front Endocrinol (Lausanne). .

Abstract

Objective: To assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases.

Method: A prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated.

Results: In total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis (p<0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits (p<0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD.

Conclusion: Pancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD.

Keywords: cardiovascular risk; iron overload; magnetic resonance imaging (MRI); non-alcoholic fatty liver disease (NAFLD); pancreatic steatosis; proton density fat fraction (PDFF).

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Conflict of interest statement

AJ-P is employee of Quibim SL. AA-B is CEO and shareholder of Quibim SL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Participant flowchart, schematic overview of diagnostic techniques and organ distribution of MRI assessed steatosis and iron overload.
Figure 2
Figure 2
Scatterplots of MRI parameters in the liver versus pancreas. (A) Proton density fat fraction (PDFF), and (B) transverse relaxometry (R2*). The gray line represents the linear regression fit and the dotted lines the 95% confidence interval.
Figure 3
Figure 3
Box and whisker plots of MRI markers of (A) proton density fat fraction (PDFF, expressed as percentages) and (B) transverse relaxometry (R2*, expressed as s-1) versus histologic grades. (A) Dark-yellow boxes correspond to liver PDFF and light-yellow boxes to pancreas PDFF. (B) Dark-blue boxes correspond to liver R2* and light-blue boxes to pancreas R2*.
Figure 4
Figure 4
Prevalence (%) of moderate-to severe hepatic and pancreatic steatosis depending on the number metabolic risk factors. The metabolic traits considered were obesity, arterial hypertension, type-2 diabetes mellitus, and dyslipidemia.
Figure 5
Figure 5
Mean hepatic and pancreatic transverse relaxometry (R2*) across groups of serum ferritin values: normal iron metabolism (≤200 ng/mL women, ≤300 ng/mL men), metabolic hiperferritinemia (>200/300 - 550 ng/mL) and dysmetabolic iron accumulation (>550 ng/mL).
Figure 6
Figure 6
Prevalence (%) of high-risk cardiovascular disease (ASCVD score). The 37% high-risk CVD prevalence in the study sample significantly increased when pancreatic steatosis and iron overload was present. The CVD risk heat map is also stratified by the presence of moderate-to-severe liver steatosis and hepatic iron overload.
See this image and copyright information in PMC

References

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