Pathophysiology Of Liver Fibrosis Research Articles

Can we identify liver fibrosis in HCV-infected patients without a liver biopsy?

The most relevant consequence of persistent infection with the hepatitis C virus is liver fibrosis, which will evolve into cirrhosis in a significant proportion of patients. Evaluation of liver damage is commonly assessed by a liver biopsy. However, there is an increasing interest to use noninvasive methods for the diagnosis of liver fibrosis. There have been several approaches aimed at identifying liver fibrosis. The simplest ones are based on routine laboratory tests and a few well-known markers of collagen production or degradation. Different combinations of these markers allow us to correctly identify a remarkable proportion of patients at both spectrums of the disease (mild and severe fibrosis). With a better knowledge on the pathophysiology of liver fibrosis and, therefore, with the incorporation of more specific markers involved in the different steps of the fibrogenic process, accurate noninvasive diagnosis of liver fibrosis will be available in the next few years.

Contribution of sinusoidal endothelial liver cells to liver fibrosis: Expression of transforming growth factor-β1 receptors and modulation of plasmin-generating enzymes by transforming growth factor-β1

Transforming growth factor-beta 1 is an important cytokine in the pathophysiology of liver fibrosis, stimulating the production of extracellular matrix. Whether this cytokine can also control the degradation of matrix proteins in liver cells has not been investigated. Because plasmin is an important protease for the degradation of matrix glycoproteins, we investigated whether sinusoidal endothelial liver cells could contribute to fibrosing liver disease through the modulation of plasmin-generating enzymes in response to transforming growth factor-beta 1. Sinusoidal endothelial cells from guinea pig liver were investigated in pure monolayer culture. Using 125I-labelled transforming growth factor-beta, we demonstrated high-affinity binding sites on sinusoidal endothelial cells at a density of 9.3 x 10(2) per cell, and a dissociation constant of about 5.5 x 10(-11) mol/L. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the known three classes of membrane receptors for transforming growth factor-beta. Using biosynthetic labeling of proteins with 35S-methionine, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we showed that sinusoidal endothelial cells produce and secrete plasminogen activator inhibitor type 1 from the beginning of culture. Treatment of confluent cell cultures for 24 hr with transforming growth factor-beta 1 increased synthesis and release of plasminogen activator inhibitor type 1. The response was almost maximal at a concentration of 1 ng transforming growth factor-beta/ml and paralleled the increased synthesis of fibronectin. On reverse fibrin autography we proved that transforming growth factor-beta 1 stimulated the release of functionally active plasminogen activator inhibitor type 1.(ABSTRACT TRUNCATED AT 250 WORDS)