Complications due to long-term administration of immunosuppressive therapy increase the morbidity and mortality of liver transplant recipients. Discontinuation of immunosuppressive drugs in recipients spontaneously developing operational tolerance could substantially lessen this burden. However, this strategy results in the development of rejection in a high proportion of recipients who require lifelong immunosuppression. Thus, there is a need to identify predictive factors of successful drug withdrawal and to define the clinical and histological outcomes of operationally tolerant liver recipients. Methods. We enrolled 102 stable liver transplant recipients in an immunosuppression withdrawal trial in which drugs were gradually discontinued over a 6-9 month period. Patients with stable graft function and no signs of rejection in a liver biopsy conducted 12 months after cessation of immunosuppressive therapy were considered operationally tolerant. Results. Out of the 98 recipients who completed the study, immunosuppression discontinuation was successful in 41 recipients and rejection occurred in 57. Rejection episodes were mild and were resolved in all cases. Development of tolerance was independently associated with time elapsed since transplantation, recipient age, and male gender. No histological damage was apparent in protocol biopsies performed after successful drug withdrawal.

PBMC gene expression profiling was assessed by DNA microarray in liver trasplanted patients groups: A group of inmunetolerant patients (TOL ;n=20), a group of non inmunotolerant (NonTOL; n=25). Finally from these two groups (Tolerant pTOL=12 and Non Tolerant pNonTOL=14 ) a sample is obtained a year after weaning

'frma' function of the Bioconductor package (v2.6) 'frma' in R.2.11.1

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi