What type of study is this?

This is a Narrative Review study (also classified as: Clinical Review, Preclinical Study).

September 10, 2025Open Access

Present and Future Perspectives in the Treatment of Liver Fibrosis

LCLucia CerritoAgostino Gemelli University Polyclinic LGLinda GalassoUniversità Cattolica del Sacro Cuore JIJacopo IaccarinoUniversità Cattolica del Sacro Cuore

Key Points

Current therapies for liver fibrosis primarily slow disease progression but rarely reverse it, signaling a need for more effective treatments.
Pharmacological interventions, including bile acids and FXR agonists, have shown promise but often come with limitations or side effects.
Microbiota-adjusting therapies such as probiotics and antibiotics could modulate liver health, requiring further clinical validation for efficacy.
Emerging therapies like gene editing and immunotherapy could redefine treatment landscapes for liver fibrosis, highlighting the importance of ongoing research.

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.

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