Molecular mechanism and treatment of viral hepatitis-related liver fibrosis
Journal
International Journal of Molecular Sciences
Journal Volume
15
Journal Issue
6
Pages
10578-10604
Date Issued
2014
Author(s)
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. ? 2014 by the authors; licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
adefovir dipivoxil; angiotensin receptor antagonist; atorvastatin; dipeptidyl carboxypeptidase inhibitor; entecavir; fresolimumab; host factor; immunomodulating agent; lamivudine; microRNA; nintedanib; pioglitazone; pirfenidone; platelet derived growth factor; prm 151; sar 156597; simtuzumab; sorafenib; statin (protein); stx 100; telbivudine; tenofovir; tralokinumab; transforming growth factor beta; unclassified drug; antivirus agent; microRNA; protein kinase inhibitor; angiogenesis; antiviral therapy; autophagy; cell proliferation; disease course; endothelium cell; epigenetics; fibrogenesis; fibrosing alveolitis; focal glomerulosclerosis; gene mutation; genotype; hepatitis B; hepatitis C; human; inflammation; liver cell carcinoma; liver cirrhosis; liver fibrosis; macrophage; membrane vesicle; metabolic regulation; myelofibrosis; myofibroblast; natural killer cell; natural killer T cell; nonhuman; phase 2 clinical trial (topic); phase 3 clinical trial (topic); polarization; remission; review; single nucleotide polymorphism; stellate cell; T lymphocyte; virus hepatitis; virus load; CD4+ T lymphocyte; complication; cytology; Hepatitis, Viral, Human; immunology; liver cirrhosis; metabolism; Angiotensin-Converting Enzyme Inhibitors; Antiviral Agents; CD4-Positive T-Lymphocytes; Hepatic Stellate Cells; Hepatitis, Viral, Human; Humans; Liver Cirrhosis; MicroRNAs; Protein Kinase Inhibitors
Publisher
MDPI AG
Type
review