Reversal of liver fibrosis: From fiction to reality

• Published in: Baillière's best practice & research. Clinical gastroenterology Vol. 31; no. 2; pp. 129 - 141
• Main Authors: Zoubek, Miguel Eugenio, Trautwein, Christian, Strnad, Pavel
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.04.2017; Elsevier Limited
• Subjects: Animal models; Animals; Bile; Clinical trials; Disease Models, Animal; Emerging therapies; Extracellular matrix; Fibrosis resolution; Gastroenterology and Hepatology; Hepatic stellate cell; Hepatic Stellate Cells - pathology; Humans; Liver cirrhosis; Liver Cirrhosis - drug therapy; Liver Cirrhosis - therapy; Liver diseases; Liver fibrosis; Mortality; Rodents; FXR; Animal models; NAFLD; Fibrosis resolution; RAS; Liver fibrosis; BDL; LPS; DAMPs; LOXL2; HSC; TGF-β; TIMPs; Hepatic stellate cell; HBV; CB; TRAIL; DMN; VEGF; AH; HCC; AT1R; DEN; NASH; ECM; MCD; ARB; MMP; TNF-α; TAA; PDGF; CCl4; ROS; ACEi; αSMA; Emerging therapies; ALD; aHSC; HCV; TLR4; TIMP; activated hepatic stellate cell; hepatitis B virus; angiotensin-converting-enzyme inhibitor; platelet-derived growth factor; angiotensin receptor blocker; alpha smooth muscle actin; bile duct ligation; hepatocellular carcinoma; dimethylnitrosamine; Toll-like receptor 4; lysyl oxidase-like 2; alcoholic hepatitis; alcoholic liver disease; diethylnitrosamine; angiotensin II receptor type 1; tissue inhibitors of metalloproteinases; transforming growth factor-β; lipopolysaccharide; renin-angiotensin-system; non-alcoholic steatohepatitis; non-alcoholic fatty liver disease; tumor necrosis factor related apoptosis inducing ligand; cannabinoid receptor; tumor necrosis factor alpha; reactive oxygen species; hepatitis C virus; farnesoid X receptor; carbon tetrachloride; methionine and choline-deficient; CCl 4; thioacetamide; AT 1R; damage-associated molecular patterns; vascular endothelial growth factor; matrix metalloproteinase; extracellular matrix
• ISSN: 1521-6918; 1532-1916; 1532-1916
• DOI: 10.1016/j.bpg.2017.04.005

In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM. While animal models have been indispensable for our understanding of liver fibrosis, they possess several important limitations and need to be further refined. A better insight into the liver fibrogenesis resulted in a large number of clinical trials aiming at reversing liver fibrosis, particularly in patients with non-alcoholic steatohepatitis. Collectively, the current developments demonstrate that reversal of liver fibrosis is turning from fiction to reality.