Detection of HCV antigens in liver graft: relevance to the management of recurrent post-liver transplant hepatitis C.
The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic diagnosis and influence the clinical management of post-liver transplantation (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients with post-LT liver disease were studied. Histologic coding was: hepatitis (126), rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and 74% of cases after more than 180 days. Overall, HCV-Ag were detected more frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical diagnosis of recurrent hepatitis (RHC) was made despite inconclusive histopathologic diagnosis. Multivariate analysis identified the percentage of HCV-Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P = 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive hepatocytes >/=50% as the only independent predictor for nonresponse (P < 0.001) in 26 patients treated with alpha-interferon plus ribavirin. In conclusion, HCV reinfection occurs early post-LT, reaching its peak within 6 months. Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of hepatitis when the histologic features are not conclusive. A high number of infected cells, independently from the genotype, represents a negative predictive factor of response to antiviral treatment.
Grassi
Alberto
A
Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna-Sant'Orsola-Malpighi Hospital, Bologna, Italy. albgrassi@yahoo.com
Quarneti
Chiara
C
Ravaioli
Matteo
M
Bianchini
Francesco
F
Susca
Micaela
M
D'Errico
Antonia
A
Piscaglia
Fabio
F
Tamè
Maria Rosa
MR
Andreone
Pietro
P
Grazi
Gianluca
G
Galli
Silvia
S
Zauli
Daniela
D
Pinna
Antonio D
AD
Bianchi
Francesco B
FB
Ballardini
Giorgio
G
D000328:Adult; D000368:Aged; D003937:Diagnosis, Differential; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis; D006526:Hepatitis C / Q000175:diagnosis / Q000276:immunology* / Q000601:surgery*; D018936:Hepatitis C Antigens / Q000032:analysis*; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D012008:Recurrence; D012680:Sensitivity and Specificity; D013997:Time Factors
D018936:Hepatitis C Antigens