Hepatic fibrosis occurs in response to persistent liver damage and is characterized by an excessive accumulation of extracellular matrix. When the damage is prolonged, there is a chronic inflammation and persistent hepatic fibrosis eventually leads to cirrhosis, where in addition to the scar, there is an important vascular remodeling associated with portal hypertension and, if decompensated, leads to death or can develop hepatocellular carcinoma. We have been studying the pharmacologic functions of adenosine, finding that a derivative of this nucleoside, IFC-305, shows hepatoprotective effects in a CCl4-induced rat cirrhosis model where it reverses liver fibrosis through modulation of fibrosis-related genes and by ameliorating hepatic function. Furthermore, this compound has the property to rescue cell cycle inhibition in vivo, prevents hepatic stellate cell activation, modulates anti-inflammatory macrophage polarization, and favors a chromatin context that could decrease the genomic instability and characteristics of cirrhosis, enabling the recovery of gene expression profile. Here we show results that contribute to the comprehension of molecular and cellular mechanism of cirrhosis, give the opportunity to suggest biomarkers to the early diagnostic of this pathology, and constitute the fundaments to suggest IFC-305 as a coadjuvant for treatment of this disease.
Part of the book: Liver Cirrhosis