E Balzano

Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function.

We present the 12‐month results of a prospective trial of conversion from calcineurin inhibitors (CNI) to everolimus (EVL) in maintenance liver transplant (LT) recipients. Forty (M:F = 28:12; 54.9 ± 11 years) patients were enrolled at a mean interval of 45.5 ± 31.2 months from transplantation. Conversion was with EVL at a dosage of 0.75 mg b.i.d., withdrawal of antimetabolites, and a 50%‐per‐week reduction of CNI to a complete stop within 4 weeks. The treatment success was conversion to EVL monotherapy at 12 months while failure was presence of CNI, death, and graft loss. Indication to conversion was deteriorating renal function in 36 (90%). At 12 months, patient‐ and graft survival were 100% and the success rate was 75% (30/40). Ten patients (25%) were failures: four (10%) for acute rejection; three hepatitis C virus‐RNA positive patients (7.5%) for hypertransaminasemia; one (2.5%) for acute cholangitis; and two (5%) due to persistent pruritus and oral ulcers. In patients on EVL monotherapy, at 12 months the mean change of calculated creatinine clearance (cCrCl) was 4.03 ± 12.6 mL/min and the only variable correlated with the probability of improvement was baseline cCrCl (P < 0.0001). Conversion from CNI to EVL is feasible in 75% of the cases and associated with improvement in renal function for patients with higher baseline cCrCl.

Risk analysis of ischemic‐type biliary lesions after liver transplant using octogenarian donors

The use of octogenarian donors to increase the donor pool in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk of ischemic‐type biliary lesions (ITBL). The aim of this study was to investigate retrospectively the role of a number of different pre‐LT risk factors for ITBL in a selected population of recipients of octogenarian donor grafts. Between January 2003 and December 2013, 123 patients underwent transplantation at our institution with deceased donor grafts from donors of age ≥80 years. Patients were divided into 2 groups based on the presence of ITBL in the posttransplant course. Exclusion criteria were retransplantations, presence of vascular complications, and no availability of procurement liver biopsy. A total of 88 primary LTs were included, 73 (83.0%) with no posttransplant ITBLs and 15 (17.0%) with ITBLs. The median follow‐up after LT was 2.1 years (range, 0.7‐5.4 years). At multivariate analysis, donor hemodynamic instability (hazard ratio [HR], 7.6; P = 0.005), donor diabetes mellitus (HR, 9.5; P = 0.009), and donor age–Model for End‐Stage Liver Disease (HR, 1.0; P = 0.04) were risk factors for ITBL. Transplantation of liver grafts from donors of age ≥80 years is associated with a higher risk for ITBL. However, favorable results can be achieved with accurate donor selection. Donor hemodynamic instability, a donor history of diabetes mellitus, and allocation to higher Model for End‐Stage Liver Disease score recipient all increase the risk of ITBL and are associated with worse graft survival when octogenarian donors are used. Liver Transplantation 22 588‐598 2016 AASLD.

The impact of everolimus on renal function in maintenance liver transplantation

We retrospectively investigated the impact on renal function (RF) of conversion from calcineurin inhibitors (CNI) to everolimus (EVL) monotherapy in orthotopic liver transplant (OLT) recipients. Between January 2006 and July 2007, 70 deceased donor OLT recipients including 51 men and 19 women of overall mean age of 55.9 +/- 11 years were enrolled into a program of conversion to EVL monotherapy at a mean interval of 45 +/- 35.9 months from transplantation (range, 7-192 months). The indication for conversion was deteriorating RF in 64 (91.4%). Efficacy failure was defined as the persistence of CNI, EVL discontinuation, death, graft loss, loss to follow-up, or need for dialysis at 12 months. Twelve months after switching, 53 patients (75.7%) were on EVL monotherapy. Their mean change in creatinine clearance (CrCl) from baseline (day 1 before EVL introduction) to endpoint (12 months) was 5.8 +/- 13.1 mL/min. On univariate and multivariate analyses, the clinical variable correlated with the greatest probability of improvement was the baseline CrCl (P < .0001). Conversion from CNI to EVL monotherapy was successful in 75.7% of cases with improvement in RF correlated with baseline CrCl. These data supported preemptive minimization of CNI in the posttransplant course, seeking to delay the decline in RF.

Strategies to optimize the use of marginal donors in liver transplantation

Liver transplantation is the treatment of choice for end stage liver disease, but availability of liver grafts is still the main limitation to its wider use. Extended criteria donors (ECD) are considered not ideal for several reasons but their use has dramatically grown in the last decades in order to augment the donor liver pool. Due to improvement in surgical and medical strategies, results using grafts from these donors have become acceptable in terms of survival and complications; nevertheless a big debate still exists regarding their selection, discharge criteria and allocation policies. Many studies analyzed the use of these grafts from many points of view producing different or contradictory results so that accepted guidelines do not exist and the use of these grafts is still related to non-standardized policies changing from center to center. The aim of this review is to analyze every step of the donation-transplantation process emphasizing all those strategies, both clinical and experimental, that can optimize results using ECD.

A single-staggered dose of calcineurin inhibitor may be associated with neurotoxicity and nephrotoxicity immediately after liver transplantation

Abstract:  The aim of the present work was to assess the incidence of neuro‐nephrotoxicity after a single‐staggered dose of calcineurin inhibitors (CI) with different immunosuppressive approaches. From January to December 2006, all liver transplantation (LT) recipients at risk of renal or neurological complications treated with extracorporeal photopheresis (ECP) + mycophenolate mofetil + steroids and staggered introduction of CI (ECP group) were compared with a historical control group on standard CI‐based immunosuppression. The ECP group included 24 patients with a mean model for end‐stage liver disease (MELD) score of 19.9 ± 11.1. The control group consisted of 18 patients with a mean MELD score of 12.5 ± 5.2 (p = 0.012). In the ECP group CI were introduced at a mean of 9.2 ± 6.2 d (4–31 d) after LT. Five patients in the ECP group presented acute neuro‐nephrotoxicity after the first CI administration on post‐transplant d 4, 5, 6, 6, and 14. Overall patient survival at one, six, and 12 months was 100%, 95.8%, and 95.8% in the ECP group vs. 94.4%, 77.7%, and 72.2% in the control group (p < 0.001). In conclusion, we showed that CI toxicity may occur after a single‐staggered dose administration, ECP seems to be a valuable tool for managing CI‐related morbidity regardless of the concomitant immunosuppressive regimen, being associated with a lower mortality rate in the early post‐transplant course.

Dual aortic and portal perfusion at procurement prevents ischaemic-type biliary lesions in liver transplantation when using octogenarian donors: a retrospective cohort study

Several risk factors for ischaemic‐type biliary lesions (ITBL) after liver transplantation (LT) have been identified, but the role of portal vein perfusion at graft procurement is still unclear. This was a prospective study on double aortic and portal perfusion (DP) of liver grafts stratified by donors decade (<60 yo; 60–69 yo; 70–79 yo and ≥80 yo) versus similar historical cohorts of primary, adult grafts procured with single aortic perfusion (SP) only. The primary study aim was to assess the role of DP on the incidence of ITBL. There was no difference in the incidence of overall biliary complications according to procurement technique for recipients of grafts <80 years. A higher incidence of ITBL was observed for patients receiving grafts ≥80 years and perfused through the aorta only (1.9 vs. 13.4%; P = 0.008). When analysing octogenarian grafts, donor male gender (HR = 6.4; P = 0.001), haemodynamic instability (HR = 4.9; P = 0.008), and type‐2 diabetes mellitus (DM2) (HR = 3.0; P = 0.03) were all independent risk factors for ITBL, while double perfusion at procurement (HR = 0.1; P = 0.04) and longer donor intensive care unit (ICU) stay (HR = 0.7; P = 0.04) were protective factors. Dual aortic and portal perfusion has the potential to reduce post‐transplant ITBL incidence for recipients of octogenarian donor grafts. Larger series are needed to confirm this preliminary experience.