Expression of cytokine-dependent immune adhesion molecules by hepatocytes and bile duct cells in chronic hepatitis C.
OBJECTIVE
The pathogenesis of liver cell injury in chronic hepatitis C is poorly understood. To test whether immune-mediated mechanisms might be involved in the pathogenesis of liver cell injury during infection by hepatitis C virus, the expression of cytokine-dependent immune molecules by hepatocytes and bile duct cells during chronic hepatitis C was studied.


METHODS
In 35 patients, expression of class I and II HLA antigens, intercellular adhesion molecule (ICAM) 1, and lymphocyte function antigen (LFA) 3 was studied by immunohistochemistry and scored by a semiquantitative grading system. Statistical analysis was performed using Spearman's test and t test.


RESULTS
Class I HLA antigens were induced on hepatocytes in 20 cases. In all cases, HLA-DR, ICAM-1, and/or LFA-3 were detected on hepatocytes in piecemeal necrosis and intralobular clusters. Bile duct cells expressed HLA-DR in 32 cases and ICAM-1 and LFA-3 in 14 cases. Expression levels of immune molecules on hepatocytes correlated with aminotransferase activity (P < 0.035), histological activity (P < 0.001), and score of necrosis (P < 0.01). ICAM-1 expression on hepatocytes was higher in patients with intraportal lymphoid nodules (P = 0.005). Expression levels of ICAM-1 and LFA-3 on bile ducts correlated with the severity of bile duct damage (P < 0.015).


CONCLUSIONS
These results suggest the involvement of immune-mediated mechanisms in the pathogenesis of liver cell injury in chronic hepatitis C.
Mosnier
J F
JF
Laboratoire de Biologie Cellulaire, INSERM Unité 327, Faculté de Médecine Xavier Bichat, Université Paris, France.
Scoazec
J Y
JY
Marcellin
P
P
Degott
C
C
Benhamou
J P
JP
Feldmann
G
G
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001652:Bile Ducts / Q000276:immunology* / Q000473:pathology; D018968:CD58 Antigens; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006526:Hepatitis C / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged
D015703:Antigens, CD; D018968:CD58 Antigens; D016207:Cytokines; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1