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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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Acknowledgments

This work has been supported in part by grants from the Ricerca Sanitaria Finalizzata program, Regione Piemonte, Italy.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Università del Piemonte Orientale “A. Avogadro”, Via G. Solaroli 17, 28100, Novara, Italy

    Rosalba Minisini, Paola Giarda, Glenda Grossi, Giuseppa Occhino & Mario Pirisi

  2. DPMSC Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy

    Davide Bitetto, Pierluigi Toniutto, Edmondo Falleti & Carlo Fabris

  3. Department of Medical and Morphological Research, University of Udine, Piazzale S. M. della Misericordia 1, 33100, Udine, Italy

    Claudio Avellini

  4. Interdisciplinary Research Center of Autoimmune Diseases, Università del Piemonte Orientale “Amedeo Avogadro”, Novara, Italy

    Mario Pirisi

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  1. Rosalba Minisini
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  2. Paola Giarda
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  3. Glenda Grossi
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Correspondence to Mario Pirisi.

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Minisini, R., Giarda, P., Grossi, G. et al. Early activation of interferon-stimulated genes in human liver allografts: relationship with acute rejection and histological outcome. J Gastroenterol 46, 1307–1315 (2011). https://doi.org/10.1007/s00535-011-0440-8

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  • DOI: https://doi.org/10.1007/s00535-011-0440-8

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