Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice?

Seidita, Aurelio; Buscemi, Carola; Di Liberto, Diana; Pistone, Mirco; Maestri, Salvatore; Cavallo, Giorgia; Cosenza, Salvatore; Spagnuolo, Gabriele; Giuliano, Alessandra; Carlisi, Daniela; Pratelli, Giovanni; Mandreucci, Francesca; Carroccio, Antonio

doi:10.3390/ijms262411782

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Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice?

by

Aurelio Seidita

^1,2,3,†

,

Carola Buscemi

^1,2,†,

Diana Di Liberto

^4,*

,

Mirco Pistone

^1,2,

Salvatore Maestri

^1,2,

Giorgia Cavallo

^1,2,

Salvatore Cosenza

^1,2,

Gabriele Spagnuolo

^1,2,

Alessandra Giuliano

²

,

Daniela Carlisi

⁴

,

Giovanni Pratelli

⁴

,

Francesca Mandreucci

^1,2 and

Antonio Carroccio

^1,2,*

¹

Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90133 Palermo, Italy

²

Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy

³

Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90133 Palermo, Italy

⁴

Institute of Biochemistry, Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(24), 11782; https://doi.org/10.3390/ijms262411782

Submission received: 10 November 2025 / Revised: 2 December 2025 / Accepted: 4 December 2025 / Published: 5 December 2025

(This article belongs to the Special Issue Liver Fibrosis: Molecular Pathogenesis, Diagnosis and Treatment)

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Abstract

The role of hepatic stellate cells (HSCs) in the development of liver fibrosis and portal hypertension has already been largely clarified. Activation of HSCs might lead to self-increased proliferation and enhanced contractile activity, causing their transdifferentiation into myofibroblasts (activated HSCs), which drive the release of proinflammatory mediators, collagen, proteoglycans, and other extracellular matrix components, responsible for liver fibrosis and portal hypertension development. A possible mechanism for the pathophysiological role of HSCs in liver fibrosis might be autophagy, which breaks down the lipid droplets in quiescent HSCs, releasing fatty acids and providing the energy required for their activation into myofibroblasts. An ever-growing body of scientific evidence indicates that renin–angiotensin system (RAS) blockade can inhibit the evolution of fibrosis in patients with chronic liver diseases, and especially metabolic dysfunction-associated steatotic liver disease (MASLD), although the use of both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has not yet been officially identified as a potential fibrosis treatment. More recently, researchers have shown that overexpression of ACE2, induced by ACE inhibitor (ACEI) activity and leading to the degradation of angiotensin (ANG) II into ANG 1-7, inhibition of autophagy and consequent HSC activation, might prevent liver fibrosis development. This review aims to summarize recent pre-clinical studies and to identify a common thread underlying the latest scientific evidence in this field.

Keywords: renin-angiotensin-aldosterone system; angiotensin-converting enzyme inhibitors; hepatic stellate cells; autophagy; liver fibrosis

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MDPI and ACS Style

Seidita, A.; Buscemi, C.; Di Liberto, D.; Pistone, M.; Maestri, S.; Cavallo, G.; Cosenza, S.; Spagnuolo, G.; Giuliano, A.; Carlisi, D.; et al. Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice? Int. J. Mol. Sci. 2025, 26, 11782. https://doi.org/10.3390/ijms262411782

AMA Style

Seidita A, Buscemi C, Di Liberto D, Pistone M, Maestri S, Cavallo G, Cosenza S, Spagnuolo G, Giuliano A, Carlisi D, et al. Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice? International Journal of Molecular Sciences. 2025; 26(24):11782. https://doi.org/10.3390/ijms262411782

Chicago/Turabian Style

Seidita, Aurelio, Carola Buscemi, Diana Di Liberto, Mirco Pistone, Salvatore Maestri, Giorgia Cavallo, Salvatore Cosenza, Gabriele Spagnuolo, Alessandra Giuliano, Daniela Carlisi, and et al. 2025. "Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice?" International Journal of Molecular Sciences 26, no. 24: 11782. https://doi.org/10.3390/ijms262411782

APA Style

Seidita, A., Buscemi, C., Di Liberto, D., Pistone, M., Maestri, S., Cavallo, G., Cosenza, S., Spagnuolo, G., Giuliano, A., Carlisi, D., Pratelli, G., Mandreucci, F., & Carroccio, A. (2025). Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice? International Journal of Molecular Sciences, 26(24), 11782. https://doi.org/10.3390/ijms262411782

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Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice?

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