Abstract: Hepatic fibrosis is a wound-healing response to various chronic stimuli, including viral hepatitis B or C infection. Activated myofibroblasts, predominantly derived from the hepatic stellate cells (HSCs), regulate the balance between matrix metalloproteinases and their tissue inhibitors to maintain extracellular matrix homeostasis. Transforming growth factor-β and platelet-derived growth factor are classic profibrogenic signals that activate HSC proliferation. In addition, proinflammatory cytokines and chemokines coordinate macrophages, T cells, NK/NKT cells, and liver sinusoidal endothelial cells in complex fibrogenic and regression processes. In addition, fibrogenesis involves angiogenesis, metabolic reprogramming, autophagy, microRNA, and epigenetic regulations. Hepatic inflammation is the driving force behind liver fibrosis; however, host single nucleotide polymorphisms and viral factors, including the genotype, viral load, viral mutation, and viral proteins, have been associated with fibrosis progression. Eliminating the underlying etiology is the most crucial antifibrotic therapy. Growing evidence has indicated that persistent viral suppression with antiviral therapy can result in fibrosis regression, reduced liver disease progression, decreased hepatocellular carcinoma, and improved chances of survival. Preclinical studies and clinical trials are currently examining several investigational agents that target key fibrogenic pathways; the results are promising and shed light on this debilitating illness.
Keywords: hepatitis B; hepatitis C; hepatocellular carcinoma; myofibroblast; hepatic stellate cells; antiviral therapy; nucleos(t)ide analogs; interferon; molecular target agent; macrophage
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Su, T.-H.; Kao, J.-H.; Liu, C.-J. Molecular Mechanism and Treatment of Viral Hepatitis-Related Liver Fibrosis. Int. J. Mol. Sci. 2014, 15, 10578-10604.
Su T-H, Kao J-H, Liu C-J. Molecular Mechanism and Treatment of Viral Hepatitis-Related Liver Fibrosis. International Journal of Molecular Sciences. 2014; 15(6):10578-10604.
Su, Tung-Hung; Kao, Jia-Horng; Liu, Chun-Jen. 2014. "Molecular Mechanism and Treatment of Viral Hepatitis-Related Liver Fibrosis." Int. J. Mol. Sci. 15, no. 6: 10578-10604.