Jérôme Dumortier1, Eduardo Couchonnal2, Florence Lacaille3, Christine Rivet2, Dominique Debray4, Olivier Boillot5, Alain Lachaux6, Oanez Ackermann7, Emmanuel Gonzales8, Barbara E Wildhaber9, Emmanuel Jacquemin8, Valérie McLin9. 1. Department of digestive diseases, Edouard-Herriot hospital, hospices civils de Lyon, 69437 Lyon, France; University of Lyon, 69008 Lyon, France. Electronic address: jerome.dumortier@chu-lyon.fr. 2. Department of pediatric hepatogastroenterolgy and nutrition, Femme-Mère-Enfant hospital, hospices civils de Lyon, 69677 Lyon, France. 3. Pediatric hepatology unit, National reference centre for rare pediatric liver diseases, department of pediatric gastroenterology and hepatology, Necker Enfants-Malades hospital, assistance publique-hôpitaux de Paris, 75015 Paris, France. 4. Pediatric hepatology unit, National reference centre for rare pediatric liver diseases, department of pediatric gastroenterology and hepatology, Necker Enfants-Malades hospital, assistance publique-hôpitaux de Paris, 75015 Paris, France; University Paris V, 75006 Paris, France. 5. Department of digestive diseases, Edouard-Herriot hospital, hospices civils de Lyon, 69437 Lyon, France; University of Lyon, 69008 Lyon, France. 6. University of Lyon, 69008 Lyon, France; Department of pediatric hepatogastroenterolgy and nutrition, Femme-Mère-Enfant hospital, hospices civils de Lyon, 69677 Lyon, France. 7. Pediatric hepatology and pediatric liver transplantation unit, National reference centre for rare pediatric liver diseases, hepatinov, Bicêtre hospital, assistance publique-hôpitaux de Paris, 94270 Le Kremlin Bicêtre, France. 8. Pediatric hepatology and pediatric liver transplantation unit, National reference centre for rare pediatric liver diseases, hepatinov, Bicêtre hospital, assistance publique-hôpitaux de Paris, 94270 Le Kremlin Bicêtre, France; University of Paris-Sud 11, 91400 Paris, France. 9. Swiss center for liver disease in children, university hospitals Geneva, 1205 Geneva, Switzerland.
Abstract
BACKGROUND: During the past decade, mTOR inhibitors (mTORi), everolimus and sirolimus, have been increasingly used after adult liver transplantation (LT). The aim of the present study was to describe the use of mTORi in pediatric LT recipients. METHODS: All pediatric LT recipients who received mTORi before December 2017 from 4 European pediatric LT centers were included and analyzed. RESULTS: The present retrospective study included 30 patients; 21 were male (70%), median age was 9.3 years (range: 1.2-17.1 years) at mTORi introduction. Main indications for mTORi introduction were pre-existing liver malignancy (43.3%), calcineurin inhibitor (CNI) nephrotoxicity (26.7%), or rejection (23.4%). At last follow-up, mTORi CNIs were withdrawn in 10 patients (10/29, 34.5%). The median dose of mTORi was 1.8 mg/day (range: 0.3-5.0) or 0.058 mg/kg/day (range: 0.01-0.26), and the median trough level was 5.1 μg/L (range: 1.0-15.5). After a median follow-up of 2.8 years (range: 0.2-10.0), 50.0% of the patients presented with at least one adverse event. The main adverse events included hyperlipidemia, proteinuria, dermatitis, and mucitis. Overall mTORi discontinuation rate was 23.3% (10.0% because of adverse event). Introduction of mTORi had no significant impact on renal function. CONCLUSION: Our results suggest that mTORi can be used in pediatric LT recipients in different clinical situations, both to reinforce immunosuppressive therapy, and to reduce CNI and related toxicity.
BACKGROUND: During the past decade, mTOR inhibitors (mTORi), everolimus and sirolimus, have been increasingly used after adult liver transplantation (LT). The aim of the present study was to describe the use of mTORi in pediatric LT recipients. METHODS: All pediatric LT recipients who received mTORi before December 2017 from 4 European pediatric LT centers were included and analyzed. RESULTS: The present retrospective study included 30 patients; 21 were male (70%), median age was 9.3 years (range: 1.2-17.1 years) at mTORi introduction. Main indications for mTORi introduction were pre-existing liver malignancy (43.3%), calcineurin inhibitor (CNI) nephrotoxicity (26.7%), or rejection (23.4%). At last follow-up, mTORi CNIs were withdrawn in 10 patients (10/29, 34.5%). The median dose of mTORi was 1.8 mg/day (range: 0.3-5.0) or 0.058 mg/kg/day (range: 0.01-0.26), and the median trough level was 5.1 μg/L (range: 1.0-15.5). After a median follow-up of 2.8 years (range: 0.2-10.0), 50.0% of the patients presented with at least one adverse event. The main adverse events included hyperlipidemia, proteinuria, dermatitis, and mucitis. Overall mTORi discontinuation rate was 23.3% (10.0% because of adverse event). Introduction of mTORi had no significant impact on renal function. CONCLUSION: Our results suggest that mTORi can be used in pediatric LT recipients in different clinical situations, both to reinforce immunosuppressive therapy, and to reduce CNI and related toxicity.