Everolimus immunosuppression reduces the serum expression of fibrosis markers in liver transplant recipients

作     者：Ainhoa Fernández-Yunquera Cristina Ripoll Rafael Banares Marta Puerto Diego Rincón Ismael Yepes Vega Catalina Magdalena Salcedo 

作者机构：Department of Liver TransplantationHospital General Gregorio Mara?ón28028 MadridSpain On-Line Bio-medical Investigation Center for Hepatic and Gastrointestinal Diseases28028 MadridSpain 

出 版 物：《World Journal of Transplantation》 (世界移植杂志)

年 卷 期：2014年第4卷第2期

页      面：133-140页

学科分类：10[医学] 

基　　金：Supported by Novartis Pharma Schweiz AG 

主　　题：Everolimus Rapamycin Liver fibrosis Mammalian target of rapamycin Transplantation 

摘      要：AIM: To evaluate the expression of serum fibrosis markers in liver transplantation(LT) recipients on everolimus monotherapy compared to patients on an anti-calcineurin ***: This cross-sectional case-control study included LT patients on everolimus monotherapy(cases)(E)(n = 30) and matched controls on an anticalcineurin regimen(calcineurin inhibitors, CNI), paired by etiology of liver disease and time since LT(n = 30). Clinical characteristics, blood tests and elastography were collected. Serum levels of transforming growth factor-β(TGF-β), angiopoietin-1, tumor necrosis factor(TNF), platelet derived growth factor, amino-terminal propeptide of type Ⅲ procollagen(PⅢNP), hyaluronicacid(HA), VCM-1(ng/m L), interleukin(IL)-10, interferoninducible protein 10(IP-10), vascular endothelial growth factor and hepatocyte growth factor(HGF)(pg/m L) were determined by enzyme-linked immunosorbent assay. Expression of these markers between E and CNI was compared. Stratified analysis was done according to factors that may influence liver fibrosis. Variables are described with medians(interquartillic range) or ***: A total of 60 patients [age: 59(49-64), hepatitis C virus(HCV): n = 21(35%), time from LT: 73 mo(16-105)] were included. Patients had been on everolimus for a median of 15 mo. No differences in inflammatory activity, APRI test or liver elastography were found between the groups. No significant differences were observed between the groups in serum levels of PⅢ NP, metalloproteinase type = 1, angiopoietin, HGF, IP-10, TNF-α, IL-10 and vascular cell adhesion molecule. Patients on E had a lower expression of TGF-β [E: 12.7(3.7-133.6), CNI: 152.5(14.4-333.2), P = 0.009] and HA [E: 702.89(329.4-838.2), CNI: 1513.6(691.9-1951.4), P = 0.001] than those on CNI. This difference was maintained in the stratified analysis when recipient age is more than 50 years(TFG-β1: P = 0.06; HA: P = 0.005), in patients without active neoplasia(TFG-β1, P = 0.009; HA: P =