Pathogenesis of septal fibrosis of the liver. (An experimental study with a new model.)

Abstract

Septal fibrosis is an important, frequent, and non-specific type of fibrosis associated with chronic liver diseases, but its pathogenesis is still poorly understood. An interesting model of septal fibrosis occurs in rats infected with the nematode Capillaria hepatica. This model was used to investigate the pathogenesis, site of origin, structure, and cell-types of septal fibrosis. Forty young adult Wistar rats were inoculated with 800 embryonated eggs of C. hepatica. Daily liver samples were obtained from the 20th to the 39th day after inoculation to cover the critical period when septal fibrosis usually starts. Routine histology, electron microscopy, immunohistochemistry, and indirect immunofluorescence were applied to the study of liver sections. Septal blood vessels were demonstrated by India ink perfusion of the portal vein system. Prominent angiogenesis was observed to precede collagen deposition. Besides angiogenesis and mesenchymal-cell mobilization, septal fibrosis was seen to originate from portal spaces and to course through acinar zone I in between sinusoids, inducing no alterations in them, with no evident participation of stellate hepatic cells. Septal fibrosis appeared as an adaptative type of response of the liver to chronic injury, which resulted in a new structure that is normal to other species and creates accessory vessels that drain portal blood into hepatic sinusoids.

Bevacizumab Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of Hepatic Stellate Cells

“…The present study demonstrates that expression of VEGF-A is up-regulated in liver fibrosis, and its expression is increased in activated HSCs [5], [6], [8], [9]. Rosmorduc et al showed that biliary cirrhosis is associated with hepatocellular hypoxia in experimental models[8].…”

“…Vascular endothelial growth factor (VEGF) is considered to be the central angiogenic factor during chronic liver injury. The present study demonstrates that expression of VEGF-A is up-regulated during liver fibrosis, and its expression is increased in activated hepatic stellate cells (HSCs) [5], [6], [8], [9].…”

An Algorithm that Predicts the Viability and the Yield of Human Hepatocytes Isolated from Remnant Liver Pieces Obtained from Liver Resections

“…The process of septal fibrosis begins with the extension of the septa between central veins through interhepatocellular space and the space of Disse on the sides of the sinusoids [22] . As fibrosis proceeds, capillarization and then venularization occurs [22] , [23] . During this process, the fenestrations in some hepatic sinusoids are lost and the development of basal laminae occur alongside the collagenization of the extravascular spaces of Disse [22] , [24] .…”

Rattus norvegicus como indicador de la circulación de Capillaria hepatica y Taenia taeniaeformis en la Plaza Minorista de Medellín, Colombia

“…Se han desarrollado algunos estudios utilizando la variedad Wistar de R. norvegicus infectada experimentalmente con C. hepatica como modelo animal, para investigar la patogénesis, el sitio de origen, la estructura y los tipos de células involucrados en la fibrosis de los tabiques (31)(32)(33)(34)(35). Asimismo, existen pruebas de una asociación significativa entre la hepatitis inducida por la infección de C. hepatica y la hipertrofia arteriolar pulmonar en roedores, que puede representar efectos de hipertensión pulmonar y llegar a afectar otros órganos como el corazón y el riñón (20).…”