Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain

Antoniadis, Nikolaos; Goulis, Ioannis; Fouzas, I.; Vasiliadis, Themistoklis; Akriviadis, Evangelos; Papanikolaou, Vasilios

doi:10.1002/lt.24345

Cited by 2 publications

(4 citation statements)

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“…In several randomized controlled trials, survival benefits have been reported for solid cancers [79,80,81]. Regarding HCC, Everolimus is used in clinical studies for patients with advanced HCC, after liver transplantation and TACE [82,83,84,85]. Synergistic effects have been described for the application of Everolimus and calcineurin inhibitors to avoid HCC recurrence after liver transplantation [84,85] and for the combination of Everolimus with radiation [86].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding HCC, Everolimus is used in clinical studies for patients with advanced HCC, after liver transplantation and TACE [82,83,84,85]. Synergistic effects have been described for the application of Everolimus and calcineurin inhibitors to avoid HCC recurrence after liver transplantation [84,85] and for the combination of Everolimus with radiation [86]. However, low response rates have been reported in patients that were treated with single-agent Everolimus [79,80,81].…”

Section: Discussionmentioning

confidence: 99%

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A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis

Kroh

Walter

Schüler

et al. 2019

IJMS

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Non-alcoholic steatohepatitis (NASH) has become a major risk factor for hepatocellular cancer (HCC) due to the worldwide increasing prevalence of obesity. However, the pathophysiology of NASH and its progression to HCC is incompletely understood. Thus, the aim of this study was to generate a model specific NASH-derived HCC cell line. A murine NASH-HCC model was conducted and the obtained cancer cells (N-HCC25) were investigated towards chromosomal aberrations, the expression of cell type-specific markers, dependency on nutrients, and functional importance of mTOR. N-HCC25 exhibited several chromosomal aberrations as compared to healthy hepatocytes. Hepatocytic (HNF4), EMT (Twist, Snail), and cancer stem cell markers (CD44, EpCAM, CK19, Sox9) were simultaneously expressed in these cells. Proliferation highly depended on the supply of glucose and FBS, but not glutamine. Treatment with a second generation mTOR inhibitor (KU-0063794) resulted in a strong decrease of cell growth in a dose-dependent manner. In contrast, a first generation mTOR inhibitor (Everolimus) only slightly reduced cell proliferation. Cell cycle analyses revealed that the observed growth reduction was most likely due to G1/G0 cell cycle arrest. These results indicate that N-HCC25 is a highly proliferative HCC cell line from a NASH background, which might serve as a suitable in vitro model for future investigations of NASH-derived HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis

Kroh

Walter

Schüler

et al. 2019

IJMS

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“…Combined with a low dose of CNIs or without CNIs, everolimus prevents the rejection of organ transplants and significantly improves the renal function . Accumulating evidence states that everolimus is more efficient and safer than the conventional immunosuppressive therapy among LT patients in preserving the renal function . Two systematic reviews have been published on this phenomenon.…”

Section: Introductionmentioning

confidence: 99%

“…1 Accumulating evidence states that everolimus is more efficient and safer than the conventional immunosuppressive therapy among LT patients in preserving the renal function. [7][8][9][10] Two systematic reviews have been published on this phenomenon. Tang et al 11 combined four randomized controlled trails in 2015 and concluded that early introduction of everolimus combined with low-dose CNIs in de novo LT patients decreases the risk of acute graft rejection, improves the renal function and increases the risk of infection.…”

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confidence: 99%

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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Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain

Cited by 2 publications

References 4 publications

A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis

A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis

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

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