Abstract

UNRAVELLING THE PATHOGENESIS OF LIVER FIBROSIS INSIGHTS, MECHANISMS, AND THERAPEUTIC STRATEGIES

Shakir Iqbal Siddiqui*, Km. Kahkasha, Muneer Alam, Aamir Saifi and Majid Ali

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Abstract

Liver fibrosis represents a complex and dynamic process characterized by the excessive accumulation of extracellular matrix proteins, leading to liver dysfunction and eventual cirrhosis. This review aims to elucidate the intricate pathogenesis of liver fibrosis, offering insights into the underlying mechanisms and discussing emerging therapeutic strategies. The development of liver fibrosis involves a cascade of events triggered by chronic liver injury, inflammation, and the activation of hepatic stellate cells (HSCs). Various cellular and molecular pathways, including transforming growth factor-beta (TGF- β) signalling, oxidative stress, and inflammatory cytokines, contribute to the initiation and progression of fibrosis. Moreover, recent studies have highlighted the role of non-coding RNAs, epigenetic modifications, and the gut-liver axis in modulating fibrogenesis. Understanding the dynamic interplay between different cell types within the liver microenvironment is crucial for developing targeted therapies. Promising therapeutic approaches include antifibrotic agents targeting HSC activation and collagen synthesis, immunomodulatory strategies to attenuate inflammation, and interventions aimed at restoring metabolic homeostasis. Furthermore, advancements in liver imaging techniques and non-invasive biomarkers have facilitated early detection and monitoring of fibrosis progression, enabling timely intervention and personalized treatment strategies. However, challenges remain in translating preclinical findings into effective clinical therapies, emphasizing the need for multidisciplinary collaborations and innovative drug development platforms. In conclusion, this review provides a comprehensive overview of the pathogenesis of liver fibrosis, highlighting key molecular mechanisms and discussing current and emerging therapeutic avenues. By elucidating the underlying processes driving fibrogenesis, we aim to pave the way for the development of more efficacious and targeted interventions, ultimately improving patient outcomes in liver fibrosis management.

Keywords: Liver fibrosis, Pathogenesis, Mechanisms, Hepatic stellate cells, Extracellular matrix, Inflammation, Transforming growth factor-beta, Oxidative stress, non-coding RNAs, Epigenetics, Gut-liver axis, Therapeutic strategies, Antifibrotic agents, Immunomodul