Morphological findings in the liver of children with cystic fibrosis: A light and electron microscopical study

Abstract

Liver tissue from five children with cystic fibrosis, obtained through percutaneous liver biopsies, have been investigated via light and electron microscopy. None of the patients had clinical evidence of liver disorder, and their blood chemistry was mainly normal. Light microscopy showed slight fibrosis in three cases, more advanced fibrosis in one case and focal cirrhotic changes in one case. All patients had fatty infiltration in the hepatocytes and glycogen in the nuclei of these cells. Electron microscopy showed an increase in the number of Ito cells around the portal tracts and also fibrosis in all patients. In the majority of hepatocytes, no evident necrosis was seen. Hypertrophy of the smooth endoplasmic reticulum and the Golgi apparatus were noted. Large lysosomes containing lipofuscin and lipids were also present. No direct evidence of cholestasis could be seen in the hepatocytes. The bile canaliculi were not dilated and did not contain bile plugs. No bile pigment was seen in the cells, and direct evidence of cholestasis was thus not found in the hepatocytes. Other organelles, such as the rough endoplasmic reticulum, peroxisomes and mitochondria, had a normal appearance. Bile ducts, even when seen in fibrotic portal tracts, were not dilated. The ultrastructural findings cannot explain the basis for the liver cell damage. Cholestasis does not seem to be a presumable etiological factor as judged from the findings in the present study.

PDGF-Mediated Chemoattraction of Hepatic Stellate Cells by Bile Duct Segments in Cholestatic Liver Injury

“…Our study provides the first demonstration that dynamic interactions between bile duct epithelial cells and HSC may occur. This mechanism can be proposed to explain the accumulation of HSC within collagen depositions around bile ducts in the absence of marked necrosis and inflammation, as described in electronmicroscopical studies of liver tissue in cystic fibrosis liver disease (Hultcrantz et al, 1986;Lindblad et al, 1992). In this study we also demonstrate potent inhibiting effects of STI571 on HSC response to PDGF-BB in vitro, indicating that this compound could have antifibrogenic properties by blocking the effect of PDGF-BB in vivo.…”

A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis-associated liver disease

“…1,21,24 In our material, there was a tendency for younger patients to have more inflammatory cells and bile duct proliferation than older patients. This is in agreement with previous observations of a higher incidence of active liver disease in younger patients.…”

Serum markers of hepatic fibrogenesis in cystic fibrosis liver disease

“…Traditional measures of liver function do not correlate with severity of liver fibrosis [3,4] and diagnosis is frequently not made until complications such as portal hypertension are established. Liver biopsy remains the standard for diagnosis, however, it is invasive and potentially confounded by sampling error as CFLD which, when established is a focal biliary cirrhosis [5], progressing to multilobular cirrhosis [6]. Hence the challenge exists to develop a sensitive, reliable non-invasive assay to identify patients with CF who are at risk of developing significant liver disease and to monitor progression or response to therapy [7].…”