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Review

Present and Future Perspectives in the Treatment of Liver Fibrosis

1
Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy
2
CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Rome, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(9), 1321; https://doi.org/10.3390/ph18091321
Submission received: 5 August 2025 / Revised: 28 August 2025 / Accepted: 1 September 2025 / Published: 3 September 2025
(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

Abstract

Background/Objectives: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption of liver tissue, with transforming growth factor-β (TGF-β) signaling and inflammatory mediators as central pathways. Current therapies primarily target the underlying causes, which may halt disease progression but rarely reverse established fibrosis. This review aims to outline current and emerging therapeutic strategies for liver fibrosis, informing both clinical practice and future research directions. Methods: A narrative synthesis of preclinical and clinical evidence was conducted, focusing on pharmacological interventions, microbiota-directed strategies, and innovative modalities under investigation for antifibrotic activity. Results: Bile acids, including ursodeoxycholic acid and derivatives, modulate HSC activity and autophagy. Farnesoid X receptor (FXR) agonists, such as obeticholic acid, reduce fibrosis but are limited by adverse effects. Fatty acid synthase inhibitors, exemplified by denifanstat, show promise in metabolic dysfunction-associated steatohepatitis (MASH). Additional strategies include renin–angiotensin system inhibitors, omega-3 fatty acids, and agents targeting the gut–liver axis. Microbiota-directed interventions—probiotics, prebiotics, symbiotics, antibiotics (e.g., rifaximin), and fecal microbiota transplantation—are emerging as potential modulators of barrier integrity, inflammation, and fibrogenesis, though larger clinical trials are required. Reliable non-invasive biomarkers and innovative trial designs, including adaptive platforms, are essential to improve patient selection and efficiently evaluate multiple agents and combinations. Conclusions: Novel modalities such as immunotherapy, gene editing, and multi-targeted therapies hold additional potential for fibrosis reversal. Continued translational efforts are critical to establish safe, effective, and accessible treatments for patients with liver fibrosis.
Keywords: liver fibrosis; hepatic stellate cells (HSC); transforming growth factor-β (TGF-β); farnesoid X receptor (FXR) agonists; gut–liver axis liver fibrosis; hepatic stellate cells (HSC); transforming growth factor-β (TGF-β); farnesoid X receptor (FXR) agonists; gut–liver axis

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MDPI and ACS Style

Cerrito, L.; Galasso, L.; Iaccarino, J.; Pizzi, A.; Termite, F.; Esposto, G.; Borriello, R.; Ainora, M.E.; Gasbarrini, A.; Zocco, M.A. Present and Future Perspectives in the Treatment of Liver Fibrosis. Pharmaceuticals 2025, 18, 1321. https://doi.org/10.3390/ph18091321

AMA Style

Cerrito L, Galasso L, Iaccarino J, Pizzi A, Termite F, Esposto G, Borriello R, Ainora ME, Gasbarrini A, Zocco MA. Present and Future Perspectives in the Treatment of Liver Fibrosis. Pharmaceuticals. 2025; 18(9):1321. https://doi.org/10.3390/ph18091321

Chicago/Turabian Style

Cerrito, Lucia, Linda Galasso, Jacopo Iaccarino, Alessandro Pizzi, Fabrizio Termite, Giorgio Esposto, Raffaele Borriello, Maria Elena Ainora, Antonio Gasbarrini, and Maria Assunta Zocco. 2025. "Present and Future Perspectives in the Treatment of Liver Fibrosis" Pharmaceuticals 18, no. 9: 1321. https://doi.org/10.3390/ph18091321

APA Style

Cerrito, L., Galasso, L., Iaccarino, J., Pizzi, A., Termite, F., Esposto, G., Borriello, R., Ainora, M. E., Gasbarrini, A., & Zocco, M. A. (2025). Present and Future Perspectives in the Treatment of Liver Fibrosis. Pharmaceuticals, 18(9), 1321. https://doi.org/10.3390/ph18091321

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