Expression of cystic fibrosis transmembrane conductance regulator in livertissue from patients with cystic fibrosis

The authors examined the expression of cystic fibrosis transmembrane conduc tance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examin e expression of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers in liver cryosections in 11 patients with CF-associated l iver disease, and non-CF controls with (n = 17) and without (n = 3) liver d isease. In CF patients prominent inflammatory infiltrates were not found, y et hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM-1 immunoreactivity in 3 cas es, but bile ducts were otherwise negative. In 2 patients homozygous for R7 64X and for 1112delT no CFTR immunoreactivity was detected. Bile-duct epith elial cells in patients carrying the Delta F508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the lum inal surface seen in controls. No clear relationship between CFTR expressio n and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of Delta F508 CFTR proces sing in intrahepatic biliary epithelium. ICAM-1 expression on bile-duct epi thelial cells and inflammatory infiltrates were rare findings in CF liver t issue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF-associated liver disease.