Borgogna Cinzia, Toniutto Pierluigi, Smirne Carlo, Azzimonti Barbara, Rittà Massimo, Avellini Claudio, Fabris Carlo, Landolfo Santo, Gariglio Marisa, Pirisi Mario
DPMSC, Medical Liver Transplantation Unit, University of Udine, Udine, Italy.
Histopathology. 2009 Jun;54(7):837-46. doi: 10.1111/j.1365-2559.2009.03311.x.
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.
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.
Acute allograft rejection and recurrence of HCV infection in the liver allograft appear to intersect in the IFN system pathways.
检验以下假设，即干扰素（IFN）系统通路的激活可能将肝移植受者中丙型肝炎病毒（HCV）复发与急性细胞排斥反应联系起来。
在这项回顾性研究中，分析了28例接受首次肝移植的成年患者（14例HCV阳性和14例HCV阴性）的移植肝活检标本。11份活检标本显示有急性细胞排斥反应（班夫排斥活动指数评分≥3）。对标本进行两种IFN诱导蛋白MxA和IFI16以及CD45的免疫染色。MxA的主要反应模式为肝细胞性，而IFI16在肝细胞和炎症区域均有表达。肝细胞中MxA中度至强表达与排斥反应评分呈正相关（P<0.01）、供者年龄≤45岁（P<0.05）以及活检当天天冬氨酸转氨酶水平>40 U/L（P<0.05），与IFI16+/CD45+细胞对门管区的浸润呈负相关（P<0.005）以及与复发性丙型肝炎超过伊沙克2期的进展时间呈负相关（P<0.01）。多因素分析显示，肝细胞中MxA表达与移植肝排斥反应和供者年龄独立相关。
肝移植中的急性移植排斥反应和HCV感染复发似乎在IFN系统通路中存在交集。
