Molecular Mechanism and Treatment of Viral Hepatitis-Related Liver Fibrosis

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.

Changes in liver stiffness and its associated factors during oral antiviral therapy in Chinese patients with chronic hepatitis B

“…The ultimate goal regarding the treatment of CHB is to block the advancement of chronic liver injury to the stages of cirrhosis, hepatic decompensation and/or hepatocellular carcinoma (HCC). However, it is now commonly known that liver cirrhosis can be reversed by treatment with nucleoside/nucleotide analogs (NAs), particularly in the early stage (2,3).…”

Sorafenib and its derivative SC-1 exhibit antifibrotic effects through signal transducer and activator of transcription 3 inhibition

“…A comprehensive understanding of the molecular mechanisms involved in HSC activation, proliferation, and fibrosis-related gene expression will provide invaluable insight to ameliorate fibrosis progression of liver diseases with various etiology (5,6).…”

Role of antiviral therapy in patients with chronic hepatitis B or C virus in preventing the development of hepatocellular carcinoma

“…[39][40][41] Treatment with entecavir and tenofovir can reduce the risk of HCC. [42][43][44][45] The treatment effect was significant in patients with cirrhosis, [36] whereas a significant HCC risk reduction in non-cirrhotic patients was noticeable only in some reports. [45,46] Finally, there is an increasing evidence to suggest that antiviral therapy may reduce recurrence and also improve survival on post-hepatectomy outcome for hepatitis B-related HCC.…”