Expression of Connective Tissue Growth Factor in the Human Liver with Idiopathic Portal Hypertension

Hiroyasu Morikawa,Susumu Shiomi,Akihiro Tamori,Daiki Habu,Shuhei Nishiguchi,Masaru Enomoto,Norifumi Kawada

doi:10.2119/2006-00093.morikawa

Hiroyasu Morikawa, Susumu Shiomi + Show 5 more

Open Access

https://doi.org/10.2119/2006-00093.morikawa

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Abstract

Idiopathic portal hypertension (IPH) is a disorder of unknown etiology, clinically associated with portal hypertension in the absence of cirrhosis. This study was designed to delineate the characteristics of IPH RNA expression in liver specimens from patients with IPH. Liver specimens from patients with IPH and patients without liver diseases underwent cDNA expression analysis and in situ hybridization studies. Connective tissue growth factor (CTGF) levels in serum were examined in 76 patients with IPH, 84 patients with hepatitis C virus infection (including those with cirrhosis), and 38 healthy volunteers. Among 588 genes sorted on macroarray, seven up-regulated genes, including CTGF, were detected. In situ hybridization studies showed that positive reactions for CTGF mRNA were most intense in the epithelial cells of proliferating bile ducts within portal tracts in patients with IPH. In the liver parenchyma, there was no appreciable staining of hepatocytes, sinusoidal endothelial cells, or hepatic stellate cells (HSCs), and there were few positive signals for CTGF mRNA in normal liver. The serum CTGF level in patients with IPH was significantly higher than the value in healthy volunteers. Six (8%) of the 76 patients with IPH had serum CTGF levels greater than 80 ng/mL, far exceeding the level of any patient with cirrhosis. In conclusion, overexpression of CTGF is one of the most important features of IPH.

Highlights

Idiopathic portal hypertension (IPH), or Banti’s syndrome, is relatively frequent in several Asian countries, including Japan and India, as compared with the prevalence in the United States and Europe [1,2,3]
The first part of our study demonstrated that Connective tissue growth factor (CTGF) mRNA was overexpressed in the liver of patients with IPH
In biliary atresia [25,26] and liver cirrhosis [23,24,29] accompanied by fibrosis, CTGF is highly expressed in liver tissue

Summary

Introduction

Idiopathic portal hypertension (IPH), or Banti’s syndrome, is relatively frequent in several Asian countries, including Japan and India, as compared with the prevalence in the United States and Europe [1,2,3]. Because IPH is characterized by prominent portal fibrosis despite no fibrotic changes in the liver parenchyma, this disease has been referred to as hepatoportal sclerosis [4] or noncirrhotic portal fibrosis [2]. Portal hypertension without hepatic cirrhosis is considered to result from increased portal venous flow associated with splenomegaly and from increased portal vascular resistance [5]. The principal pathological changes in IPH are moderate portal fibrosis, destruction of intrahepatic terminal portal radicles, and parenchymal atrophy of the liver secondary to portal malperfusion [6,7,8]. IPH is not associated with hepatic injury, perisinusoidal fibrosis in the liver parenchyma, or pseudonodule formation. Accumulated evidence indicates that IPH is an entirely distinct disease from liver cirrhosis. IPH has been associated with chronic abdominal infection [9], abnormal T-cell activation by continuous antigen stimulation [10], immunological abnormalities initiated by HLA-DR antigen expression by the portal tract microvasculature [11,12], expo-

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