Hepatic inflammation and progressive liver fibrosis in chronic liver disease

Table 2 Promising anti-fibrotic agents in chronic liver disease

Anti-fibrotic agent	Possible anti-fibrotic actions	Clinical experiences
Anti-oxidants
-acetylcysteine	Inhibits NF-κB activity[195]Limits pro-inflammatory genes[195]Reduces iNOS and NO activity[196]Decreases hepatocyte apoptosis[195]	Reduced hepatic fibrosis and inflammation in NASH[191]
S-adenosyl-L- methionine (SAMe)	Increase mitochondrial glutathione[197]Inhibit NF-κB activity[197]Reduce ROS production[197]Impair iNOS and NO production[197]Limit HSC activation[197]	Decreased mortality and LT in alcoholic cirrhosis[190]Hastened decline of viral load and increased early response in HCV non-responders[192]
Vitamin E	Reduce TGF-β in animals and humans[199,200]Decrease oxidant stress on hepatocytes[198]Limit collagen deposition[198]	Decreased hepatic fibrosis in NAFLD[201]Prevented progressive hepatic fibrosis in NAFLD[202]
Angiotensin inhibitors
Losartin	Limit angiotensin II production by HSC[208]Decrease expression of pro-fibrotic genes[170]Limit NADPH-oxidase and oxidative stress[170]Reduce TGF-β and pro-collagen production[214]Decrease extracellular matrix[210,212,213]	Small trial in chronic hepatitis C[170]Impeded pro-fibrotic and NADPH oxidase genes[170]Reduced oxidative stress[170]Decreased inflammatory and fibrosis scores in 50%[170]

HCV: Hepatitis C virus; HSC: Hepatic stellate cells; iNOS: Inducible nitric oxide synthase; LT: Liver transplantation; NADPH: Nicotinamide adenine dinucleotide phosphate; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; NF-κB: Nuclear factor kappa-light-chain enhancer of activated B cells; NO: Nitric oxide; ROS: Reactive oxygen species; TGFβ: Transforming growth factor beta.