Efficacy, tolerance, and safety of mammalian target of rapamycin inhibitors as rescue immunosuppressants in liver transplantation.
BACKGROUND
Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants which have the advantages, with respect to calcineurin inhibitors (CNI: cyclosporine or tacrolimus), of no nephrotoxicity and inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias.


METHODS
Twenty-two liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 7 hepatocellular carcinomas; 5 de novo malignancies; 4 renal insufficiencies; 4 chronic rejections; and 2 acute rejection episodes.


RESULTS
There were 16.7% tumor recurrences, and 25% improvements in renal function, 75% in chronic rejection, and 50% in acute rejection. There was no incidence of rejection, kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. We observed incidences of 50% for hypercholesterolemia, 31.8% for hypertriglyceridemia, 22.7% for thrombocytopenia, 18.2% for leukopenia, and 9.1% for anemia. The intercurrent infection rate was 13.6%, including oral thrush in 13.6%. Lower limb edema occurred in 13.6%, with 1 case of facial edema and 1 of alopecia.


CONCLUSIONS
mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with no incidence of rejection. Their effectiveness to control chronic rejection seems significant, but it is doubtful for steroid-resistant acute rejection episodes.
Alamo
J M
JM
Liver Transplantation Unit, Virgen del Rocío Hospital, Seville, Spain. jmalamom@terra.es
Barrera
L
L
Casado
M D
MD
Bernal
C
C
Marin
L M
LM
Suarez
G
G
Sanchez-Moreno
L
L
Jimenez
R
R
Suarez-Grau
J M
JM
Sousa
J M
JM
Cordero
E
E
Gomez-Bravo
M A
MA
D006528:Carcinoma, Hepatocellular / Q000601:surgery; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000276:immunology; D000068338:Everolimus; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011494:Protein Kinases / Q000276:immunology*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases
D007166:Immunosuppressive Agents; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus