 Introduction: Immunosuppressive treatment IS has several and frequents adverse effects; among them are: severe infections, diabetes mellitus, arterial hypertension, osteoporosis, neurologic disorders, renal failure, dyslipemias, increased cardiovascular risk, cancer, etc. After 5 years, 18 of liver receptors develop renal failure, the risk of developing cancer is three times higher after LT and 30 of liver graft receptors previously infected by hepatitis C virus HCV have cirrhosis 5 years after LT, probably because of the effect of IS on viral kinetics. An ideal situation would be that liver transplant recipients receive enough IS to inhibit the immune response against the allograft, while avoiding an excessive effect over the capacity of the immune system to recognize pathogens, tumoral cells and minimizing the adverse effects or even more, the indefinite graft acceptance in the complete absence of IS, concept that in clinic in called operational tolerance OT. OT occurs in around 20 of liver recipients. So although the potential benefit is important it affects just a small fraction of liver recipients. A different but related strategy has been evaluated in several trials in the past, and consist in to change from an IS based on calcineurin inhibitors CNI to another less intense based on mofetil mycophenolate MMF, which is known to have less adverse effects, preserve renal function and do not affect the function and proliferation of T regulatory cells, which are involved in the development of OT. In a recent study in press, the investigators performed an IS withdrawal to over a hundred liver recipients and the investigators found that those who were classified as operationally tolerant 40 where those with a longer time elapsed since LT to IS withdrawal, those who received lower doses of CNI and those who received MMF monotherapy. The investigators were able also to discriminate between operationally tolerant liver recipients and those who developed a rejection based on its differential gene expression evaluated by whole genome microarray just before the ISwithdrawal. 