Early activation of interferon-stimulated genes in human liver allografts: relationship with acute rejection and histological outcome.

Abstract:

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

journal_name

J Gastroenterol

authors

Minisini R,Giarda P,Grossi G,Bitetto D,Toniutto P,Falleti E,Avellini C,Occhino G,Fabris C,Pirisi M

doi

10.1007/s00535-011-0440-8

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

1307-15

issue

11

eissn

0944-1174

issn

1435-5922

journal_volume

46

pub_type

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