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Ballestri et al. Metab Target Organ Damage 2023;3:1 https://dx.doi.org/10.20517/mtod.2022.23 Page 17 of 22

Figure 2. “A tale of two pathways”. It is hypothesized that a “long pathway” (blue arrows) leads from steatosis (NAFL) to CVD
events through subclinical atherosclerotic burden associated with traditional CVD risk factors. In contrast, a “short pathway”
(black arrows) could more directly associate fibrosing NASH with CVD events, possibly through multiple hepatic prothrombogenic
factors, fetuin-A, and specific lipidomic signatures. (reprinted, with permission). CVD: Cardiovascular disease; HIF: hypoxia-
inducible factor; ICAM-1: intracellular adhesion molecule-1; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic
steatohepatitis; VCAM: vascular adhesion molecule-1; VEGF: vascular endothelial growth factor.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study, wrote the first draft of the
manuscript and performed data analysis and interpretation: Ballestri S, Lonardo A
Performed data acquisition and provided administrative, technical, and material support: Di Girolamo M,
Baldelli E, Capitelli M
Performed study revision and editing: Ballestri S, Mantovani A, Lonardo A

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.