Metabolic syndrome before liver transplantation: does it have an impact on post liver transplantation outcome?

Introduction: metabolic syndrome (MS) and cardiovascular risk factors are common in liver transplant (LT) candidates and recipients. Cardiovascular events and de novotumors are increasingly common causes of mortality inliver transplant recipients. The aims of this study were i)to assess the prevalence of MS in LT recipients and itsgrowth over the years, and ii) to determine if the presenceof MS pre-LT is associated with a higher risk of post-LTcardiovascular events (CVE), de novo tumors, or early andlate survival.Patients and methods: a retrospective study was performedthat included LT recipients from January 2012 to December2017. Baseline features (MS before LT and at 1year post-LT)and outcomes (CVE, de novo tumors and survival) wererecorded. Results: a total of 483 recipients were included, MS waspresent in 20 % of pre-LT subjects with an increasingprevalence over time, from 16 % in 2012 to 34 % in 2017(p = 0.025). One-year post-LT, an additional 12 % had developed de novo MS. At a median of 56 months of follow-up,13 % developed a CVE and 9 % a de novo tumor. One and5-year survival rates were 91 % and 83 % in those with preLT MS, and 93 % and 85 % in those without it (p = 0.94). Thepresence of MS before LT was independently associatedwith a higher risk of post-LT CVE (HR: 2.66, 95 % CI: 1.6-4.4,p < 0.001) but not with de novo tumors (p = 0.94) nor earlyand late survival (p = 0.58 and p = 0.87).Conclusion: pre-LT MS is increasing among LT candidatesand is associated with a higher risk of post-LT morbidity(CVE) yet without affecting mortality. (AU)

Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study.

BACKGROUND AND AIM: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. METHODS: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. RESULTS: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. CONCLUSION: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.

Metabolic syndrome before liver transplantation: does it have an impact on post liver transplantation outcome?

INTRODUCTION: Metabolic syndrome (MS) and cardiovascular risk factors are common in liver transplant (LT) candidates and recipients. Cardiovascular events and de novo tumors are increasingly common causes of mortality in liver transplant recipients. The aim of this study were (i) assess the prevalence of MS in LT recipients and its growth over the years and (ii) determine if the presence of MS pre-LT is associated with a higher risk of post-LT cardiovascular events (CVE), de novo tumors or early and late survival. PATIENTS AND METHODS: A retrospective study was performed that included LT recipients from January 2012 to December 2017. Baseline features (MS before LT and at 1year post-LT) and outcomes (CVE, de novo tumors and survival) were recorded. RESULTS: 483 recipients were included, MS was present in 20% of pre-LT with an increasing prevalence over time, from 16% in 2012 to 34% in 2017 (p=0.025). One-year post-LT, an additional 12% had developed de novo MS. At a median of 56-months follow-up, 13% developed a CVE and 9% a de novo tumor. One and 5-yr survival rates were 91% and 83% in those with pre-LT MS and 93% and 85% in those without (p=0.94).The presence of MS before LT was independently associated with a higher risk of post-LT CVE (HR: 2.66 IC (95%): 1.6-4.4 p< 0.001), but not with de novo tumors (p=0.94) nor early and late survival (p=0.58 and p=0.87). CONCLUSION: Pre-LT MS is increasing among LT candidates and is associated with a higher risk of post-LT morbidity CVE yet without affecting mortality. .

Recomendaciones de uso de everolimus en el trasplante hepático / Recommendations of everolimus use in liver transplant

Los fármacos inhibidores de la mTOR, everolimus (EVL) y sirolimus, son inmunosupresores con muy poco efecto nefrotóxico, limitado al desarrollo de proteinuria en algunos casos. En la prevención del rechazo agudo EVL combinado con tacrolimus a dosis reducidas tiene una eficacia y seguridad comparables a la inmunosupresión estándar con tacrolimus. La aplicación temprana de una inmunosupresión basada en EVL con minimización de la exposición al inmunosupresor calcineurínico en trasplantados hepáticos permite mejorar los resultados de la función renal, con tasas similares de eficacia y seguridad, tanto en el período de novo como de mantenimiento. En pacientes con disfunción renal establecida la introducción de EVL permite minimizar la exposición al inmunosupresor calcineurínico, con la consiguiente mejoría en la función renal. Aunque no hay evidencia suficiente para recomendar su uso para prevenir la recurrencia del hepatocarcinoma y la progresión de tumores de novo, es práctica clínica habitual utilizarlos en este contexto (AU)

Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles. In patients with established kidney failure, initiating EVL may enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing to the improved renal function of these patients. Although there is not sufficient evidence to recommend their use to prevent the recurrence of hepatocellular carcinoma and the progression of de novo tumours, they are used in this context in routine clinical practice (AU)

Recommendations of everolimus use in liver transplant. / Recomendaciones de uso de everolimus en el trasplante hepático.

Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles. In patients with established kidney failure, initiating EVL may enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing to the improved renal function of these patients. Although there is not sufficient evidence to recommend their use to prevent the recurrence of hepatocellular carcinoma and the progression of de novo tumours, they are used in this context in routine clinical practice.