Expression of the interferon-inducible proteins MxA and IFI16 in liver allografts.
OBJECTIVE
To test the hypothesis that the activation of the interferon (IFN) system pathways might link hepatitis C virus (HCV) recurrence in the liver allograft with acute cellular rejection.


RESULTS
In this retrospective study, allograft biopsy specimens from 28 adult patients (14 HCV+ and 14 HCV-) who had undergone their first liver transplantation were analysed. Eleven biopsy specimens showed acute cellular rejection (Banff rejection activity index score > or =3). Specimens were immunostained for two IFN-inducible proteins, MxA and IFI16, and for CD45. The predominant MxA reactivity pattern was hepatocytic, whereas IFI16 was expressed in both the hepatocellular and inflammatory compartments. Moderate to strong MxA expression in hepatocytes was associated positively with rejection score (P < 0.01), donor's age < or =45 years (P < 0.05) and aspartate aminotransferase levels >40 U/l on the day of biopsy (P < 0.05), and inversely with infiltration of portal triads by IFI16+/CD45+ cells (P < 0.005) and time to progression beyond Ishak stage 2 of recurrent hepatitis C (P < 0.01). On multivariate analysis, MxA expression in hepatocytes was independently associated with allograft rejection and donor's age.


CONCLUSIONS
Acute allograft rejection and recurrence of HCV infection in the liver allograft appear to intersect in the IFN system pathways.
Borgogna
Cinzia
C
DPMSC, Medical Liver Transplantation Unit, University of Udine, Udine, Italy.
Toniutto
Pierluigi
P
Smirne
Carlo
C
Azzimonti
Barbara
B
Rittà
Massimo
M
Avellini
Claudio
C
Fabris
Carlo
C
Landolfo
Santo
S
Gariglio
Marisa
M
Pirisi
Mario
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006526:Hepatitis C / Q000209:etiology; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D012008:Recurrence; D012189:Retrospective Studies; D014019:Tissue Donors; D055815:Young Adult
C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human; D019204:GTP-Binding Proteins