Mollecular hepatic stellate cells targets in antifibrotic therapy

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Article Title:	Mollecular hepatic stellate cells targets in antifibrotic therapy
Authors:	Dr. Alin Gabriel Ionescu, Conf. Univ. Dr. Cristin Constantin Vere, Dr. Costin Teodor Streba, Dr. Liliana Streba, Prof. Univ. Dr. Ion Rogoveanu
Affiliation:	University of Medicine and Pharmacy, Craiova
Abstract:	Hepatic stellate cells (HSC) activation as a result of liver injury, followed by their proliferation and the increase of extracellular matrix (ECM) synthesis, is the main phenomenon in the development of liver fibrosis. In case of chronic liver injury, the negative consequences generated by liver fibrosis on hepatic function and morphology may lead to hepatic insufficiency and portal hypertension. Liver cirrhosis is considered a precancerous stage prior to the development of hepatocellular carcinoma (HCC). Initiation of HSCs activation consists in rapid changes in protein synthesis, followed by alterations in cellular phenotype, amplifying HSCs response to inflammatory cytokines and local stimuli. By blocking activated HSCs response to inflammatory cytokines and growth factors stimulation, antifibrotic therapies aim to inhibit their proliferation, trigger their apoptosis, reduce the collagen synthesis and increase ECM degradation. Future therapeutic strategies target the development of oral drugs with high antifibrotic potential, as well as a series of therapeutic agents with parenteral administration and reduced side effects. Also, a special attention should be given to gene therapy that alters HSCs phenotype and inhibits exacerbated collagen synthesis. In the same time, prophylactic and neoadjuvant therapy for HCC aims to block activated HSCs expression of growth and nuclear factors involved in carcinogenesis.
Keywords:	hepatic stellate cells, liver fibrosis, antifibrotic therapy, hepatocellular carcinoma, carcinogenesis
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*Correspondence:	Conf. Univ. Dr. Cristin Constantin Vere, University of Medicine and Pharmacy Craiova, Faculty of Medicine, Department of Internal Medicine, no. 2-4 Petru Rares St., 200349, Dolj, Romania, Tel. +40-(251)- 522 458, Fax. +40-(251)- 593 077, email: vere_cristin@yahoo.com