Portal and Parenchymal Alterations of the Liver in Idiopathic Portal Hypertension: A Histological and Immunochemical Study

Department of Human Pathology, Kanazawa University Graduate School of Medicine, Japan.
Pathology - Research and Practice (Impact Factor: 1.4). 02/2002; 198(9):597-603. DOI: 10.1078/0344-0338-00308
Source: PubMed

ABSTRACT Idiopathic portal hypertension (IPH) is characterized by presinusoidal portal hypertension owing to the intrahepatic, presinusoidal portal venous block, whereas the primary cause and initial vascular lesions(s) remain only speculative. In this study, a total of 97 IPH livers were histopathologically and immunohistochemically examined, placing emphasis on hepatic parenchymal fibrosis and atrophy as well as on portal tract fibrosis. Alcoholic cirrhosis and normal livers were used as controls. When compared with normal livers, the expression of connective tissue growth factor (CTGF) in periductal mononuclear cells was significant. Matrix metalloproteinase (MMP)9-positive mononuclear cells were fewer in number in the portal tract of IPH liver, when compared with alcoholic cirrhosis. These findings suggest a possible pathogenesis of collagen and elastin deposition because of increased CTGF expression and decreased MMP-9 expression in portal tracts of IPH. Sinusoidal dilatation associated with hepatocellular atrophy and apoptosis occurred frequently, but focally in 20% of the IPH cases. These changes were most often found in hyperplastic hepatocellular areas and in the perivenular areas of hepatic lobules. In these areas, pericellular fibrosis and thin fibrous septa were also frequently seen. In these fibrotic areas, there were deposited not only collagen fibers, but also elastic fibers, in which alpha-smooth muscle actin-positive sinusoidal cells, reflecting activated hepatic stellate cells, were frequently detected. It is possible that in IPH cases, continuing portal venous blood insufficiency may be responsible for hepatic parenchymal damage, which may be followed by hepatocellular apoptotic dropout and then by hepatic parenchymal atrophy and fibrosis.

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    • "Collagen a1(I) mRNA and collagen a2(I) mRNA were increased, on average, several hundred fold, as well as mRNAs encoding type V and type VIII collagens. Table 3 shows the most downregulated genes, of which MMP9 was previously reported to be downregulated in activated HSCs in vivo [13]. To verify the microarray data we assessed the expression of the selected genes by RT-PCR. "
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