Transcriptome at the Time of Hepatitis C Virus Recurrence May Predict the Severity of Fibrosis Progression After Liver Transplantation

Allograft gene expression analysis may provide insights into the mechanisms involved in liver damage during hepatitis C virus recurrence (HCVrec) after orthotopic liver transplantation (OLT) and allow the identification of patients who have a higher risk of developing severe disease. Forty-three OLT recipients with hepatitis C virus (HCV) were evaluated. Genome-wide gene expression analysis was performed with formalin-fixed, paraffin-embedded (FFPE) liver biopsy samples obtained from 21 OLT recipients with HCV at the time of clinical HCVrec, which was defined as increased alanine aminotransferase levels and detectable HCV RNA levels in serum. Patients were classified into 3 groups according to the severity of the fibrosis in the liver biopsies at 36 months post-OLT : group 1 (G1) for mild fibrosis (F0-F1), group 2 for moderate fibrosis (F2), and group 3 (G3) for severe fibrosis (F3-F4). No significant differences were observed between the groups with respect to donor age, histology during HCVrec, treated episodes of acute cellular rejection, or immunosuppression therapy. The results were validated in the remaining 22 OLT recipients with HCV using quantitative real-time polymerase chain reaction. Fifty-seven beadtypes showed significantly different expression (P < 0.001) between the groups during HCVrec. In G3, the gene expression of interleukin-28RA (IL-28RA), IL-28, and angiotensin-converting enzyme was up-regulated. Samples from G1 and G3 were used to determine whether a multigenetic classifier could be derived to predict the group class. The final model included the intercept and 9 bead types. Pairwise scatter plots of these 9 bead types revealed that G1 and G3 were well separated with respect to each gene. Our analysis has demonstrated the utility of a set of molecular markers indicating HCVrec severity early after OLT. Liver Transpl 17:824-835, 2011. (C) 2011 AASLD.