Search for Transcriptional Biomarkers in a Conversion Protocol From Calcineurin Inhibitors to Mycophenolate Mofetil

Summary

As is well known, immunosuppressive treatment (IS) after liver transplantation has several and frequents adverse effects that limit the survival of the graft and recipients. Because of that, it is desirable that these recipients were able to receive a mild IS regime with a better safety profile. An attempt to get that aim has been evaluated in several trials in the past, and consist in to change the IS regime from an calcineurin inhibitors (CNI) based to another less intense and with less adverse effects based on mycophenolate mofetil (MMF), which is known to have a better safety profile. The success rate of this strategy(i.e. complete conversion in absence of rejection) has a wide range from 100% to 50% approximately. However it is accepted that this strategy is associated with the improvement of several adverse effects of CNIs such as renal failure and dyslipemia. This study's aim is to perform IS conversion from CNI to MMF monotherapy and look for transcriptional biomarkers employing a whole genome expression study performed with microarrays at baseline on liver tissue and/or PBMCs to try to find a differential gene expression able to correlate with a successful conversion and thus, to generate a set of transcriptional biomarkers potentially able to predict the result of the IS conversion on an independent cohort of liver recipients.

Timeline

Start

2011-02

Primary completion

2014-03

Completion

2014-03

Publications

• Background Mells G, Neuberger J. Long-term care of the liver allograft recipient. Semin Liver Dis. 2009 Feb;29(1):102-20. doi: 10.1055/s-0029-1192059. Epub 2009 Feb 23.
• Background Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007 Dec 20;357(25):2601-14. doi: 10.1056/NEJMra064928. No abstract available.
• Background Martinez-Llordella M, Lozano JJ, Puig-Pey I, Orlando G, Tisone G, Lerut J, Benitez C, Pons JA, Parrilla P, Ramirez P, Bruguera M, Rimola A, Sanchez-Fueyo A. Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients. J Clin Invest. 2008 Aug;118(8):2845-57. doi: 10.1172/JCI35342.
• Background Demirkiran A, Sewgobind VD, van der Weijde J, Kok A, Baan CC, Kwekkeboom J, Tilanus HW, Metselaar HJ, van der Laan LJ. Conversion from calcineurin inhibitor to mycophenolate mofetil-based immunosuppression changes the frequency and phenotype of CD4+FOXP3+ regulatory T cells. Transplantation. 2009 Apr 15;87(7):1062-8. doi: 10.1097/TP.0b013e31819d2032.
• Background Farkas SA, Schnitzbauer AA, Kirchner G, Obed A, Banas B, Schlitt HJ. Calcineurin inhibitor minimization protocols in liver transplantation. Transpl Int. 2009 Jan;22(1):49-60. doi: 10.1111/j.1432-2277.2008.00796.x.
• Norero B, Serrano CA, Sanchez-Fueyo A, Duarte I, Torres J, Ocquetau M, Barrera F, Arrese M, Soza A, Benitez C. Conversion to mycophenolate mofetil monotherapy in liver recipients: Calcineurin inhibitor levels are key. Ann Hepatol. 2017 Jan-Feb 2017;16(1):94-106. doi: 10.5604/16652681.1226820.

Drugs

Indications

No indication recorded.