Department of Clinical and Experimental Medicine, Università del Piemonte Orientale A. Avogadro, Via G. Solaroli 17, 28100 Novara, Italy.
J Gastroenterol. 2011 Nov;46(11):1307-15. doi: 10.1007/s00535-011-0440-8. Epub 2011 Jul 23.
Innate immunity mechanisms have been shown to play a paramount role in organ transplantation. Our aim was to investigate the hypothesis that activation of the interferon system may affect clinically relevant outcomes, such as acute rejection and/or early fibrosis progression, after liver transplantation.
We studied 71 consecutive recipients (57 males; 25 with hepatitis C) who underwent two per protocol graft biopsies: the first, within 60 days after the transplant operation (median 24) and the second, after 1 year. The mRNA expression for five interferon-stimulated genes (Mx1, OAS2, PKR, IRF7A, IFI16) was measured on the first biopsy specimens. The main outcome measures were acute rejection during the first post-transplant year and fibrosis progression at the second biopsy.
On multivariate analysis, the independent predictors of gene expression were hepatitis C (Mx1, OAS2, PKR and IFI16), donor age (IFI16) and recipient gender (IRF7A) (P < .05 for all). During the first post-transplant year, 19/71 patients (27%) had acute cellular rejection. At multivariate analysis, acute cellular rejection was independently predicted by high IRF7A mRNA expression. At the end of follow-up, 25 patients had some degree of fibrosis (F2 or higher in seven cases). On multivariate analysis, hepatitis C etiology, recipient age, and OAS2 overexpression were independent predictors of early fibrosis progression.
In the early postoperative period of liver transplantation, interferon-stimulated gene activation is dependent on hepatitis C recurrence (the main factor responsible for early fibrosis progression) and donor age, and is related to the risk of acute cellular rejection.
先天免疫机制已被证明在器官移植中起着至关重要的作用。我们的目的是研究这样一种假设，即干扰素系统的激活可能会影响肝移植后临床相关的结果，如急性排斥和/或早期纤维化进展。
我们研究了 71 例连续接受者（57 名男性；25 例丙型肝炎），他们进行了两次符合方案的移植物活检：第一次在移植手术后 60 天内（中位数 24 天），第二次在 1 年后。在第一次活检标本上测量了五种干扰素刺激基因（Mx1、OAS2、PKR、IRF7A、IFI16）的 mRNA 表达。主要观察指标是移植后第一年的急性排斥反应和第二次活检的纤维化进展。
多变量分析显示，基因表达的独立预测因子是丙型肝炎（Mx1、OAS2、PKR 和 IFI16）、供体年龄（IFI16）和受体性别（IRF7A）（所有 P <.05）。在移植后第一年，71 例患者中有 19 例（27%）发生急性细胞排斥反应。多变量分析显示，急性细胞排斥反应与高 IRF7A mRNA 表达独立相关。在随访结束时，25 例患者有一定程度的纤维化（7 例为 F2 或更高）。多变量分析显示，丙型肝炎病因、受体年龄和 OAS2 过表达是早期纤维化进展的独立预测因子。
在肝移植的术后早期，干扰素刺激基因的激活依赖于丙型肝炎的复发（是早期纤维化进展的主要因素）和供体年龄，并与急性细胞排斥反应的风险相关。
