Differential transcriptome patterns for acute cellular rejection in recipients with recurrent hepatitis C after liver transplantation

Abstract

Histopathological evaluation of the liver via biopsy remains the standard procedure for the diagnosis of both acute cellular rejection (ACR) and recurrent hepatitis C (RHC) after liver transplantation. Nevertheless, it is often difficult to diagnose ACR in hepatitis C virus–positive recipients because of changes in common and overlapping with RHC. The aim of this study was to identify potential target genes for ACR in recipients with RHC. We analyzed 22 liver biopsy samples obtained from 21 hepatitis C virus–positive recipients. The clinicopathological diagnosis based on biopsy examination was ACR‐predominant with superimposed RHC in 9 samples (ACR group) and RHC without ACR (non‐ACR group) in 13. Using oligonucleotide microarrays, we compared the transcriptional changes in the 2 groups and selected 2206 genes that were significantly modulated in ACR. We analyzed the regulatory networks in ACR with Ingenuity Pathway Analysis software, and we confirmed with quantitative real‐time polymerase chain reaction the reproducibility of caspase 8, apoptosis‐related cysteine peptidase and bone morphogenetic protein 2 up‐regulation in another group of validation samples, representing 2 genes from the core network as the target genes for ACR. Our results demonstrated novel transcriptome patterns for ACR with concurrent RHC that were distinct from those of recipients with only RHC, suggesting that gene expression profiling may be useful in the diagnosis of ACR in recipients with hepatitis C. Liver Transpl 15:1738–1749, 2009. © 2009 AASLD.

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

“…In contrast, one of the major findings of the present study concerns the relationship between ISG expression in the graft and subsequent development of acute rejection. We and others [21][22][23]; being based on protocol biopsies, however, the present data suggest that ISG activation precedes and may be causally related to acute rejection. This hypothesis is supported by the observation that, by virtue of its immune-stimulating properties, interferon alpha treatment of recurrent hepatitis C may facilitate rejection [24].…”

MicroRNA Signature of Intestinal Acute Cellular Rejection in Formalin-Fixed Paraffin-Embedded Mucosal Biopsies

“…Recent advances in genetic information using high throughput microarray analysis has revealed that there are quite different transcriptome patterns according to the rejection status after solid organ transplantation (5)(6)(7)(8). We already revealed that small bowel allografts undergoing ACR show distinct mRNA expression profiles involving immune, inflammatory and apoptosis genes reflect the histopathological changes in bowel biopsies and provided novel insights into these pathways operative in alloreactive inflammation (9).…”

Significance of Alanine Aminopeptidase N (APN) in Bile in the Diagnosis of Acute Cellular Rejection After Liver Transplantation

“…Thus, it would be ideal to have an accurate, reproducible, and noninvasive method to diagnose the cause of allograft dysfunction after liver transplantation. We approached this issue previously using transcriptome analysis of liver biopsy and peripheral blood using both an animal model [19] and human samples [20,21] and identified candidate markers associated with ACR. These studies should be continued for further validation of these candidate genes in liver and peripheral blood.…”