Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain
Bilbao I(1), Salcedo M(2), Angel Gómez M(3), Jimenez C(4), Castroagudín J(5), Fabregat J(6), Almohalla C(7), Herrero I(8), Cuervas-Mons V(9), Otero A(10), Rubín A(11), Miras M(12), Rodrigo J(13), Serrano T(14), Crespo G(15), De la Mata M(16), Bustamante J(17), Gonzalez-Dieguez M(18), Moreno A(19), Narvaez I(20), Guilera M(21); EVEROLIVER study group.
(1) Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Hospital Vall d'Hebrón. Barcelona, Spain.
(2) Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Hospital Gregorio Marañón. Madrid, Barcelona, Spain.
(3) Hospital Virgen del Rocio. Sevilla.
(4) Hospital Doce de Octubre. Madrid.
(5) Hospital Universitario. Santiago de Compostela.
(6) Hospital de Bellvitge. Barcelona.
(7) Hospital del Rio Hortega. Valladolid.
(8) Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Clinica Universidad de Navarra, Barcelona, Spain.
(9) Hospital Puerta de Hierro. Madrid.
(10) Hospital Universitario. A Coruña.
(11) Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Hospital La Fe. Valencia, Barcelona, Spain.
(12) Hospital Virgen de la Arrixaca. Murcia.
(13) Hospital Carlos Haya. Málaga.
(14) Hospital Clínico Lozano Blesa. Zaragoza.
(15) Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Hospital Clínic Barcelona, Barcelona, Spain.
(16) Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Hospital Reina Sofía. Córdoba, Barcelona, Spain.
(17) Hospital de Cruces. Bilbao.
(18) Hospital Central de Asturias. Oviedo.
(19) Hospital Nuestra Señora de la Candelaria. Tenerife.
(20) Hospital Infanta Cristina. Badajoz.
(21) Novartis Farmacéutica. Barcelona.
A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC) (30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications.
During the first year of treatment, mean (standard deviation) everolimus trough levels were 5.4 (2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (MDRD-4) increase of 10.9 mL (baseline mean 45.8 [25.3] vs. 57.6 [27.6] mL/min/1.73 m2 ) at 3 months after everolimus initiation (P<0.0001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (< 1 year).
Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively.
Everolimus is a viable option for the treatment of renal dysfunction and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy.
CITATION Liver Transpl. 2015 May 19. doi: 10.1002/lt.24172.