Antifibrotic Strategy in the Treatment of Chronic Liver Diseases

Introduction. Chronic liver disease (CLD) is a continuous and progressive process of hepatic fibrosis, disruption of liver tissue architecture and formation of regeneration nodules. Transforming growth factor beta (TGF-β) and its isoforms trigger a signaling cascade that is closely associated with liver fibrosis, cirrhosis and subsequent progression to hepatocellular carcinoma (HCC). Aim. To analyze current scientific publications on the pathogenesis of chronic liver disease and outline the possibilities of influencing its fibrotic component. Materials and methods. Search and selection of publications, systematic reviews and current recommendations were conducted using the PubMed and Google Scholar databases. Abstracts of publications were examined and articles that did not meet the study criteria were excluded. Full texts of selected articles were examined for compliance with the study criteria. Results. A new strategy against TGF-ß is to selectively block its latent activation precisely in those places where this regulatory factor is overexpressed. The activity of integrin αvß6, expressed on epithelial cells, increases as a result of damage and catalyzes the in situ activation of extracellular matrix-bound latent TGF-ß in the local microenvironment. The introduction of antibodies against αvß6 and other antifibrotic strategies prevent the development of fibrosis, while maintaining basal TGF-ß signaling necessary for homeostasis. The results obtained in the course of the studies allow us to consider the antifibrotic strategy as a promising direction for the treatment of chronic liver diseases associated with the formation of pathological fibrous tissue. Conclusions. Pharmacological focus on TGF, a key factor regulating stellate cell activity and a predictor of collagen formation, has demonstrated significant therapeutic potential in hepatitis and fibrosis – pathological conditions with a confirmed risk of HCC.