Molecular Mechanism and Treatment of Viral Hepatitis-Related Liver Fibrosis

International Journal of Molecular Sciences

Tung-Hung Su¹  Jia-Horng Kao¹ 

[1]Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002, Taiwan

[2] E-Mail:

关键词: hepatitis B;    hepatitis C;    hepatocellular carcinoma;    myofibroblast;    hepatic stellate cells;    antiviral therapy;    nucleos(t)ide analogs;    interferon;    molecular target agent;    macrophage;   

DOI  :  10.3390/ijms150610578

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.