Matrix Fibrous Proteins and Cells in Central Vein Fibrosis of Cadaveric Livers

Abstract

The central vein (CV) is defined as a hepatic vein at the center of the classic liver lobule. It has a cross‐sectional diameter not exceeding 125 μm. The endothelium lining of the vein is thin and has openings that drain every sinusoid of a liver lobule. The rim or wall of the CV is less than 2 μm in thickness with sparse matrix fibrous proteins and cells. Fibrosis of the CV (CVF), also is called perivenular fibrosis, is marked by thickening of the rim of the vein. The fibrotic tissue deposited in the CV may act like a “pervenular fibrous dam” that obliterates the sinusoidal openings into the vein, resulting in sinusoidal portal hypertension. CVF occurs early in hepatic fibrogenesis of rats induced by CCl4 or porcine serum administration. CVF often accompanies perisinusoidal fibrosis of the centrilobular area in alcoholic liver disease and nonalcoholic fatty liver disease. In the liver of elderly cadavers (mean age, 82.1±10.4), we have observed a 49.2 % incidence (31/63 livers) of CVF, but the matrix components of the fibrotic veins are not fully characterized. This study assessed fibrous proteins and cells in CVF of cadaveric livers. A total of 72 fibrotic veins out of 315 veins from 63 livers were studied. The diameters of the veins ranged from 25.4 to 123.7 μm (mean, 75.5 ± 18.3 μm). CVF was considered present when the rim thickness exceeded 9 μm (determined on Sirius red stained sections) coincident with fibrous tissue extension into the perivenous parenchyma. Immunoperoxidase staining revealed that the CV endothelium was positive for factor VIII‐related antigen, a vascular endothelial phenotypic marker. It also stained for CD31 and D34. Staining of basement membrane collagen IV was continuous around the CV endothelium, while laminin, another principal basement membrane protein, was not detected in the CV matrix. Thus, the CV appeared to lack a continuous endothelial basement membrane and a diffusion barrier between the CV circulation and perivenous parenchyma. Fibrillar collagens I, III and V and filamentous collagen VI were robust in the rim of the fibrotic vein. The codistribution of these collagens rendered thickening of the CV as well as provided strength to the CV matrix scaffold. Elastic fibers were noted occasionally among collagen bundles. Myofibroblasts, identified by a‐smooth muscle actin, were the dominant fibrogenic cells producing the fibrous matrix. Few mononuclear cells were also present. The deposition of collagenous fibrous tissue in the rim could occlude the CV endothelial openings, reducing the efficiency and increasing the resistance of sinusoidal blood flow into the CV. This may cause sinusoidal hypertension, impair hepatocyte functions and enhance disease susceptibility of the aged people.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.