title: Detection of HCV antigens in liver graft: relevance to the management of recurrent post-liver transplant hepatitis C.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna-Sant'Orsola-Malpighi Hospital, Bologna, Italy. albgrassi@yahoo.com
authors.forename: Alberto
authors.initials: A
authors.lastname: Grassi
authors.forename: Chiara
authors.initials: C
authors.lastname: Quarneti
authors.forename: Matteo
authors.initials: M
authors.lastname: Ravaioli
authors.forename: Francesco
authors.initials: F
authors.lastname: Bianchini
authors.forename: Micaela
authors.initials: M
authors.lastname: Susca
authors.forename: Antonia
authors.initials: A
authors.lastname: D'Errico
authors.forename: Fabio
authors.initials: F
authors.lastname: Piscaglia
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Tamè
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.forename: Gianluca
authors.initials: G
authors.lastname: Grazi
authors.forename: Silvia
authors.initials: S
authors.lastname: Galli
authors.forename: Daniela
authors.initials: D
authors.lastname: Zauli
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Pinna
authors.forename: Francesco B
authors.initials: FB
authors.lastname: Bianchi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ballardini
mesh_terms: 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
chemical_list: D018936:Hepatitis C Antigens