Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study

Jeng, Long Bin; Lee, Sung Gyu; Soin, Arvinder S.; Lee, Wei Chen; Suh, Kyung Suk; Joo, Dong Jin; Üemoto, Shinji; Joh, Jae‐Won; Yoshizumi, Tomoharu; Yang, Horng Ren; Song, Gi Won; López, Patricia; Kochuparampil, Jossy; Sips, C.; Kaneko, Shuhei; Levy, Gary

doi:10.1111/ajt.14623

Cited by 64 publications

(78 citation statements)

References 36 publications

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“…Everolimus (EVE), a macrocyclic lactone derivative of Sirolimus, has recently emerged as a key maintenance immunosuppressive molecule in therapies for preventing acute and chronic allograft organ rejection [1,2,3]. EVE is successfully used in combination with cyclosporine and corticosteroids both in adult and paediatric population of renal- and cardiac-transplant recipients, but far less often for lung-transplant recipients [4,5,6,7].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus

Chiesa

Dorati

Conti

et al. 2018

IJMS

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Bronchiolitis obliterans syndrome (BOS), caused by lung allograft-derived mesenchymal cells’ abnormal proliferation and extracellular matrix deposition, is the main cause of lung allograft rejection. In this study, a mild one-step ionotropic gelation method was set up to nanoencapsulate the everolimus, a key molecule in allograft organ rejection prevention, into hyaluronic acid-decorated chitosan-based nanoparticles. Rationale was the selective delivery of everolimus into lung allograft-derived mesenchymal cells; these cells are characterized by the CD44-overexpressing feature, and hyaluronic acid has proven to be a natural selective CD44-targeting moiety. The optimal process conditions were established by a design of experiment approach (full factorial design) aiming at the control of the nanoparticle size (≤200 nm), minimizing the size polydispersity (PDI 0.171 ± 0.04), and at the negative ζ potential maximization (−30.9 mV). The everolimus was successfully loaded into hyaluronic acid-decorated chitosan-based nanoparticles (95.94 ± 13.68 μg/100 mg nanoparticles) and in vitro released in 24 h. The hyaluronic acid decoration on the nanoparticles provided targetability to CD44-overexpressing mesenchymal cells isolated from bronchoalveolar lavage of BOS-affected patients. The mesenchymal cells’ growth tests along with the nanoparticles uptake studies, at 37 °C and 4 °C, respectively, demonstrated a clear improvement of everolimus inhibitory activity when it is encapsulated in hyaluronic acid-decorated chitosan-based nanoparticles, ascribable to their active uptake mechanism.

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Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus

Chiesa

Dorati

Conti

et al. 2018

IJMS

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“…Manzia et al began the study at postoperative day 1, Cillo et al began at postoperative day 7, while Masetti et al began the study at postoperative day 10. The randomization was performed for the rest of the included studies about 30 days after the surgery . Only one study followed the participants for <1 year.…”

Section: Resultsmentioning

confidence: 99%

“…The process of study inclusion is illustrated in Figure 1. A total of eight trials reported in 12 articles [7][8][9]13,14,[20][21][22][23][24][25][26] were included in the present study. De Simone et al 21 recruited the maintenance liver transplant recipients.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…The randomization was performed for the rest of the included studies about 30 days after the surgery. 8,9,14,20 Only one study 25 followed the participants for <1 year. The baseline characteristics of the included studies are listed in Table 1.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…12 However, a decreased risk of graft rejection, graft loss or overall survival was not detected. 12 Based on the several new trials 13,14 published since 2016, the present study aimed to review the current evidence and discuss the efficacy and safety of everolimus therapy on LT patients.…”

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confidence: 99%

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Efficacy and safety of everolimus treatment on liver transplant recipients: A meta‐analysis

Guan

Lin

et al. 2019

Eur J Clin Investigation

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Background Everolimus is an effective immunosuppressant in organ transplantation without impaired renal function. The present study aimed to evaluate the efficacy and safety of everolimus therapy in liver transplant recipients. Materials and methods A systematic literature search was conducted to identify the eligible studies. The quality of the included studies was assessed. The outcomes of interest were biopsy‐proven acute rejection (BPAR), graft loss, death, renal function and adverse events. Results Eight trials involving 1570 participants were included. Compared to the standard exposure to calcineurin inhibitors (CNIs), the incidences of BPAR, graft loss and death were not increased in the everolimus combined with reduced CNIs group. The renal function was significantly improved after everolimus combined with reduced CNI therapy, and the glomerular filtration rate (GFR) was estimated to be elevated by 5.59 (95% CI: 2.17‐9.01, P = .001) as compared to the standard exposure to CNIs. The risk of any adverse event was increased by everolimus combined with reduced CNI therapy (RR = 1.22, 95% CI: 1.04‐1.42, P = .01) as compared to the standard exposure to CNIs. The likelihood of infection was not associated with the regimen. Any publication bias was not identified. Conclusions Although everolimus combined with reduced CNI therapy significantly improved the renal function in liver transplant recipients, it did not influence the incidence of BPAR, graft loss and death. This regimen might be associated with an increased risk of adverse events, which needs to be elucidated further.

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Predictor of outcome after living donor liver transplantation for patients with hepatocellular carcinoma beyond the Japan criteria

Yonemura

Yoshizumi

Inokuchi

et al. 2020

Annals of Gastroent Surgery

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Background The Japan criteria (JC, maximum tumor size within 5 cm, within five tumor nodules, AFP within 500 ng/mL or within Milan criteria) have been applied to cadaveric liver transplantation (LT) for hepatocellular carcinoma (HCC) and will be used for living donor LT (LDLT) in Japan. The aim of this study was to verify the JC in LDLT and to clarify the risk factor of HCC recurrence and mortality after LDLT beyond the JC. Patients and methods Adult patients who underwent LDLT for end‐stage liver disease with HCC until October 2019 were reviewed retrospectively (n = 246). Patients were divided into two groups according to whether they were within JC (n = 203) or beyond JC (n = 43). Recurrence‐free or overall survival rates after LDLT were compared. Univariate and multivariate analyses were performed to identify risk factors of HCC recurrence and HCC‐related mortality after LDLT for patients beyond the JC. Results Patients beyond the JC had significantly poorer 5‐year recurrence‐free (50.3% vs 95.9%, P < .001) or overall (61.7% vs 98.1%, P < .001) survival rates compared with patients within the JC. A multivariate analysis revealed that des‐gamma‐carboxy prothrombin (DCP) ≥ 300 mAU/mL (hazard ratio 9.36, 95% CI; 2.41‐36.4, P = .001) was an independent risk factor for HCC recurrence and HCC‐related mortality (hazard ratio 13.8, 95% CI; 1.92‐98.6, P = .01) after LDLT in patients beyond the JC. Conclusion The outcome of LDLT for patients within the JC was favorable. Patients beyond the JC with DCP ≥ 300 mAU/mL might be contraindicated for LDLT.

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Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study

Cited by 64 publications

References 36 publications

Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus

Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus

Efficacy and safety of everolimus treatment on liver transplant recipients: A meta‐analysis

Predictor of outcome after living donor liver transplantation for patients with hepatocellular carcinoma beyond the Japan criteria

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