Xavier Stephenne

Cliniques Universitaires Saint-Luc, Bruxelles, Brussels Capital, Belgium

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Publications (49)217.83 Total impact

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    ABSTRACT: A Belgian alpha-1-antitrypsin (AAT) deficiency registry has been established in 2003. Currently 55 patients are included. At the same time, a working group has been set up for publishing national guidelines. In 2014, several Belgian patients founded Alpha-1 Global. We hope that the integrated activities of all the stakeholders involved in AAT deficiency will permit a high quality care for all patients suffering from this disabling disease.
    COPD Journal of Chronic Obstructive Pulmonary Disease 05/2015; 12(S1):10-14. DOI:10.3109/15412555.2015.1021916 · 2.67 Impact Factor
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    ABSTRACT: To investigate predictors of clinical evolution in PFIC2patients and how they relate to bile salt export pump (BSEP) expression and it's (re)targeting. Retrospective study included 22 children with PFIC2. Clinical, biochemical, and histological characteristics were reviewed on admittance and following treatment with either ursodeoxycholic acid (UCDA) alone (10mg/Kg thrice daily) (n= 19) or with partial biliary diversion (PBD) (n=3). BSEP immunostaining was performed in 20 patients. Response to treatment was defined as normalization of pruritus, disappearance of jaundice, and alanine aminotransferase (ALT) levels<1.5 upper limit of normal [ULN]. 10 of 22 patients were responders and paired biopsies were available in six. De novo or retargeted canalicular expression of BSEP occurred in four of these six of which two exhibited baseline intracellular expression. 12 of 22 were non-responders, exhibited earlier onset of jaundice (<9 months), neonatal cholestasis, and higher ALT levels. ALT >165 IU/L produced 72% sensitivity and 55% specificity in predicting non-response. Seven patients were still responding at last follow-up (median: 20 months; range: 5-67 months). Three responders relapsed after 56, 72, and 82 months, respectively. Of nine surviving responders, median relapse-free survival time was 72 months (95% CI: 48-96 months) and 5-year relapse-free survival was 75% (95% CI: 33-100%). Intracellular BSEP at baseline was seen in 6, of which 5 were responders. Genetic analysis was performed in 17 of 22, confirming diagnosis in 13 (76%) and in 4 (24%) only heterozygous mutation was identified. De novo or retargeted canalicular expression of BSEP occurs in treatment responders. Children with late-onset presentation, lower ALT and intracellular BSEP expression are likely to respond, at least transiently to non-transplant treatment. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    Hepatology 04/2015; 62(1). DOI:10.1002/hep.27834 · 11.06 Impact Factor
  • Journal of Hepatology 04/2015; 62:S818-S819. DOI:10.1016/S0168-8278(15)31429-X · 11.34 Impact Factor
  • G Reychler · L Jacques · D Arnold · I Scheers · F Smets · E Sokal · X Stephenne
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    ABSTRACT: Chest physiotherapy is regularly prescribed for children, particularly in cystic fibrosis. Gastro-oesophageal reflux is common in this disease and is associated with certain chest physiotherapy manoeuvres. To evaluate the influence of two chest physiotherapy techniques on gastro-oesophageal reflux in children. Twenty-nine children were investigated by routine pHmetry. During the examination, they performed two chest physiotherapy manoeuvres in a seated position for 10minutes each with a 5minutes rest between them. The two manoeuvres used were a slow expiration technique (ELPr) and positive expiratory pressure (PEP). It was a prospective study and the order of manoeuvres was randomised. The pH traces were analysed blindly when all the studies had been completed. In the sample, 21% of children had gastro-oesophageal reflux during the physiotherapy session. No relationship was found between reflux during physiotherapy and pathological reflux (P=0.411) nor the physiotherapy technique used (P=0.219). The use of these two chest physiotherapy techniques in children in a seated position can produce gastro-oesophageal reflux. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.
    Revue des Maladies Respiratoires 02/2015; 32(5). DOI:10.1016/j.rmr.2015.02.004 · 0.62 Impact Factor
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    ABSTRACT: To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance. LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field. Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate. Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients. LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.
    Annals of Surgery 01/2015; DOI:10.1097/SLA.0000000000001094 · 8.33 Impact Factor
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    ABSTRACT: The diagnostic role of endoscopic ultrasound (EUS) in children has only recently been demonstrated, and that to a lesser extent than in adults. Data on the technique's therapeutic indications remains scarce. We therefore sought to evaluate diagnostic and interventional EUS indications, safety, and impact in children with pancreaticobiliary disorders. We retrospectively reviewed our single pediatric center records, covering a 14-year period. From January 2000 to January 2014, 52 EUS procedures were performed on 48 children (mean age: 12yrs; range: 2-17yrs) with pancreaticobiliary disorders for the following indications: suspected biliary obstruction (n = 20/52), acute/chronic pancreatitis (n = 20), pancreatic mass (n = 3), pancreatic trauma (n = 7), and ampullary adenoma (n = 2). EUS was found to have a positive impact in 51/52 procedures, enabling us to avoid endoscopic retrograde cholangiopancreatography (ERCP) (n = 13 biliary; n = 6 pancreatic), focusing instead on endotherapy (n = 7 biliary; n = 14 pancreatic) or reorienting therapy towards surgery (n = 7). EUS-guided fine-needle aspiration was carried out on 12 patients for pancreatic tumor (n = 4), pancreatic cyst fluid analysis (n = 4), autoimmune pancreatitis (n = 2), and suspicion of biliary tumor (n = 2). A total of 13 therapeutic EUS procedures (11 children) were conducted, including nine combined EUS-ERCP procedures (seven children, mean age: 8yrs, range: 4-11yrs), three EUS-guided pseudocyst drainage (two children), and one EUS-guided transgastric biliary drainage. Our study reports on a large pediatric EUS series for diagnostic and therapeutic pancreaticobiliary disorders, demonstrating the impact of diagnostic EUS and affording insights into novel EUS and combined EUS-ERCP therapeutic applications. We suggest considering EUS as a diagnostic and therapeutic tool in the management of pediatric pancreaticobiliary diseases.
    Journal of Pediatric Gastroenterology and Nutrition 01/2015; Publish Ahead of Print(2). DOI:10.1097/MPG.0000000000000692 · 2.63 Impact Factor
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    ABSTRACT: Aims • Pentamidine in nebulized form is one of the drugs listed in the primary or secondary prevention of pneumocystis carinii pneumonia in immunosuppressed patients. • This nebulization requires a nebulizer with specific characteristics. These features are the presence of a circuit with expiratory filter preventing the dissemination of droplets into the environment (pentamidine may be toxic) and secondly, to ensure a fine particle size allowing deep lung deposition. • The reference nebulizer used for pentamidine nebulization is currently the Respirgard II®, a disposable pneumatic nebulizer. Several studies remark that all nebulizers with comparable properties could be used for the nebulization. • The aim of our work is to evaluate and compare the results between the reference nebulizer Respirgard II ®, and one of these nebulizers available on the market, the Isoneb ®. • This in vitro study is the first step in the comparison of the two nebulizers. • We found no significant difference in the inhaled dose. • We observed a difference in residual solution but none in calculated lost dose. It could be explained by the drugs concentration in the cuve or by a difference of deposition in the device, in the one-way valves and in the filter positioned on the nebulizer expiratory branch. Nevertheless we have no measure to prove it. The difference in the internal volume is highly significative, it could explain a different deposition in the device. • However the effectiveness of pneumocystis carinii pneumonia prophylaxis is based on the inhaled dose and pulmonary deposition. We will have to measure the pulmonary deposition in a second study to compare the relative effectiveness of the two nebulizers. Results • In this in vitro study, we have tested the inhaled dose corresponding to the two nebulizers. • Based on our results, we can conclude that both nebulizer have similar properties. Methods • A solution of pentamidine (300mg/6mL sterile water) was nebulized by a Respirgard II® (Vital Signs, New Jersey, USA) (RII) or by an Iso-NEB® (Teleflex, Pennsylvania, USA) (Iso). • Nebulizers (Iso and RII) were connected to a dual chamber lung model (5600i Dual Adult Training/Test Lung®, Michigan Instrument Inc., Michigan, USA) simulating usual breathing pattern of an adult. Respiratory frequency and tidal volume driving by a ventilator (SERVO-I®, Maquet, Rastatt, Germany) to the lung model were 15 cycle/min, 500 mL respectively. • During the nebulization, a filter (filter 1) was interposed between the nebulizer and the lung model. The filter was weighed before the nebulization and after drying for 24 hours at ambient air. The resulting weight is the inhaled dose. We expressed the inhaled dose in percentage of the nominal dose.
    ERS ANNUAL CONGRESS 2014, Munich; 09/2014
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    ABSTRACT: The microsomal protein per gram of liver (MPPGL) is an important scaling factor in the in vitro-in vivo extrapolation of metabolic data obtained in liver microsomes. This study aimed to determine the MPPGL in 4 biliary atresia patients (0.6 - 1.6 years old) undergoing liver transplantation, as it is known that the MPPGL is affected by age and possibly by liver disease. Due to presence of bilirubin in the homogenates and microsomes, the NADPH-cytochrome reductase activity was used to determine the recovery factor, rather than methods using the dithionite difference spectrum. A mean value of 18.73 (±2.82) mg/g (geometric mean ± SD, n = 4) was observed, which is lower than the expected MPPGL based on the age of the patients (26.60 ± 0.40 mg/g). This suggests a decreased amount of microsomal protein in the livers of biliary atresia patients. Moreover, no differences in MPPGL between different zones of the liver could be detected. This article is protected by copyright. All rights reserved.
    Biopharmaceutics & Drug Disposition 07/2014; 35(5). DOI:10.1002/bdd.1895 · 2.34 Impact Factor
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  • Pediatric Critical Care Medicine 05/2014; 15:141. DOI:10.1097/01.pcc.0000449348.12742.6d · 2.34 Impact Factor
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    ABSTRACT: Current treatment of inherited liver inborn errors of metabolism in children consists in appropriate diet and drugs and, for unstable patients, final orthotopic liver transplantation. Unfortunately, liver transplantation remains not easily available because of organ shortage and imposes inherent risks and lifelong immunosuppressive therapy. Therefore alternative treatments are required. Hepatocytes transplantation and its limitations led to consider innovative alternative such as transplantation of adult derived human liver stem cells (ADLHSC). These cells present high proliferative capacity, good resistance to cryopreservation and ability to differentiate into hepatocyte-like cells displaying mature hepatocyte functions. Biodistribution of ADHLSC had never been assessed after infusion through the portal vein in patients. This information is required to determine the safety of the method. ADHLSC were efficiently labelled with 111-Indium DTPA radiotracer and SPECT imaging was used for the acquisition of whole body imaging to document short term biodistribution of ADHLSC. Following infusion through the portal vein, ADHLSC diffused homogenously throughout the liver and remained strictly within the targeted organ. Images were acquired until 5 days after infusion. At that time, no signal was observed in any other organs except the liver. Urinary excretion of 111-Indium DTPA was also monitored. For the first time, we documented the short term biodistribution of ADHLSC within the liver after infusion through the portal vein.
    Nuclear Medicine and Biology 04/2014; 41(4):371-375. DOI:10.1016/j.nucmedbio.2014.01.010 · 2.41 Impact Factor
  • Journal of pediatric gastroenterology and nutrition 03/2014; Publish Ahead of Print. DOI:10.1097/MPG.0000000000000388 · 2.63 Impact Factor
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    ABSTRACT: The transition from parent-controlled care to self-managed care represents an important challenge for adolescents with chronic conditions. We sought to gain a deeper understanding of the factors influencing the internalization of motivation to self-care in adolescent liver transplant recipients. We conducted a qualitative study using in-depth interviews with 18 young patients. We triangulated the data collected from the patients with data from parents and health care providers, and used an inductive approach to analyze the data. Our results illustrate three interrelated challenges that impact on young patients' motivation to self-care: (a) the cognitive challenge of fully understanding one's condition and personal health risks; (b) the behavioral challenge of developing independence regarding self-management issues; and (c) the psychological challenge of building a sense of self-ownership and purpose. The latter involves overcoming the trauma of survival and coming to terms with feelings of obligation, two challenges inherent to transplantation that warrant further investigation.
    Qualitative Health Research 02/2014; 24(3). DOI:10.1177/1049732314523505 · 2.19 Impact Factor
  • Mustapha Najimi · Xavier Stéphenne · Christine Sempoux · Etienne Sokal
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    ABSTRACT: To investigate the activity and expression of EAAT2 glutamate transporter in both in vitro and in vivo models of cholestasis. This study was conducted on human hepatoblastoma HepG2 cell cultures, the liver of bile duct ligated rats and human specimens from cholestatic patients. EAAT2 glutamate transporter activity and expression were analyzed using a substrate uptake assay, immunofluorescence, reverse transcription-polymerase chain reaction, and immunohistochemistry, respectively. In HepG2 cells, cholestasis was mimicked by treating cells with the protein kinase C activator, phorbol 12-myristate 13-acetate. Under such conditions, EAAT2 transporter activity was decreased both at the level of substrate affinity and maximal transport velocity. The decreased uptake was correlated with intracellular translocation of EAAT2 molecules as demonstrated using immunofluorescence. In the liver of bile duct ligated rats, an increase in EAAT2 transporter protein expression in hepatocytes was demonstrated using immunohistochemistry. The same findings were observed in human liver specimens of cholestasis in which high levels of γ-glutamyl transpeptidase were documented in patients with biliary atresia and progressive familial intrahepatic cholestasis type 3. This study demonstrates the alteration in glutamate handling by hepatocytes in liver cholestasis and suggests a potential cross-talk between glutamatergic and bile systems.
    World Journal of Gastroenterology 02/2014; 20(6):1554-64. DOI:10.3748/wjg.v20.i6.1554 · 2.37 Impact Factor
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    ABSTRACT: A 3-year-old girl suffering from ornithine carbamoyltransferase (OTC) deficiency was poorly equilibrated under conventional diet and scavenger treatment. Following unsuccessful cryopreserved hepatocyte transplantation, she received two infusions of Adult Derived Human Liver Stem/Progenitor Cells (ADHLSCs) expanded in vitro under GMP settings, the quantity being equivalent to 0.75% of her calculated liver mass. Using FISH immunostaining for the Y chromosome, the initial biopsy did not detect any male nuclei in the recipient liver. Two liver biopsies taken 100 days after ADHLSC transplantation showed 3% and 5% of male donor cells in the recipient liver, thus suggesting repopulation by donor cells. Although limited follow-up did not allow us to draw conclusions on long-term improvement, these results provide a promising proof of concept that this therapy is feasible in an OTC patient.
    10/2013; 13. DOI:10.1007/8904_2013_257
  • Journal of pediatric gastroenterology and nutrition 06/2013; DOI:10.1097/MPG.0b013e31829f12d0 · 2.63 Impact Factor
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    ABSTRACT: The success of liver cell therapy remains closely dependent on how well the infused cells can be accepted after transplantation and is directly related to their degree of immunogenicity. In this study, we investigated the in vitro immunogenic properties of isolated human hepatocytes (hHeps) and adult-derived human liver progenitor cells (ADHLPCs), an alternative cell candidate for liver cell transplantation (LCT). The constitutive expression of immune markers was first analyzed on these liver-derived cells by flow cytometry. Human liver-derived cells were then cocultured with allogeneic human adult peripheral blood mononuclear cells (PBMCs), and the resulting activation and proliferation of PBMCs was evaluated, as well as the cytokine levels in the coculture supernatant. The effect of liver-derived cells on monocyte-derived dendritic cell (MoDC) properties was further analyzed in a secondary coculture with naive CD4+ T-cells. We report that hHeps and ADHLPCs expressed human leukocyte antigen (HLA) class I and Fas but did not express HLA-DR, Fas ligand, and costimulatory molecules. hHeps and ADHLPCs did not induce T-cell activation or proliferation. Moreover, hHeps induced a cell contact-dependent production of interleukin (IL)-10 that was not observed with ADHLPCs. The IL-10 was produced by a myeloid DC subset characterized by an incomplete mature state. Furthermore, hHep-primed MoDCs induced an antigen-independent hyporesponsiveness of naive CD4+ T lymphocytes that was partially reversed by blocking IL-10, whereas nonprimed MoDCs (i.e., those cultured alone) did not. hHeps and ADHLPCs present a low immunogenic phenotype in vitro. Allogeneic hHeps, but not ADHLPCs, promote a cell contact-dependent production of IL-10 by myeloid DCs, which induces naive CD4+ T-cells antigen-independent hyporesponsiveness.
    Cell Transplantation 04/2013; 23(9). DOI:10.3727/096368913X666421 · 3.13 Impact Factor
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    ABSTRACT: Objectives: The management of esophageal varices (EV) in children experiencing biliary atresia (BA) remains controversial. Recent studies in children proposed initiating a prophylactic treatment in patients with severe (grade III) EV and/or EV associated with red color signs. Our study was aimed at assessing the risk of bleeding from EV in a series of patients with BA, identifying risk factors for bleeding to develop a predictive model of bleeding. Methods: This was a retrospective study including 83 eligible patients with BA. Clinical, ultrasonographic, endoscopic, and laboratory parameters were studied from the beginning of medical management up to the occurrence of upper gastrointestinal bleeding. In patients not presenting any bleeding, data were analyzed until liver transplantation, endoscopic treatment of EV was performed, or last follow-up. Risk factors were investigated using univariate and multivariate statistical analyses. Results: Seventeen of 83 patients (20%) presented gastrointestinal bleeding, with a median age of 9.5 months (6-50 months). In univariate and multivariate analyses, high-grade EV, red color signs on endoscopic examination, and low fibrinogen levels, at first endoscopy, were identified as risk factors for bleeding. When tested in >10,000 different models, these 3 variables appeared to play the most significant role in predicting bleeding. Conclusions: Our study confirmed that grade III EV and red color signs are risk factors for bleeding in patients followed up for BA. We identified low fibrinogen levels as an additional risk factor. The relevance of these 3 factors to predict bleeding from EV requires validation in a prospective study.
    Journal of pediatric gastroenterology and nutrition 12/2012; 56(5). DOI:10.1097/MPG.0b013e318282a22c · 2.63 Impact Factor
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    ABSTRACT: pT, under mono- and infratherapeutic calcineurin inhibition, may constitute an optimal condition combining graft acceptance with low IS load and minimal IS-related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr after LT, transplanted between April 1999 and June 2007 under tacrolimus-based regimens (median follow-up post-LT: 6.0 yr, range: 0.8-9.5 yr). Their current status regarding IS therapy was analyzed and correlated with initial immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough blood levels <4 ng/mL during the preceding year of follow-up, combined with normal liver function tests. The 66 children transplanted before April 2001 received a standard tacrolimus-steroid regimen. Beyond April 2001, 105 patients received steroid-free tacrolimus-basiliximab or tacrolimus-daclizumab immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute rejection episode and never received steroids. In the long term, a total of 79 recipients (47%) developed pT (n = 73) or IS-free operational tolerance (n = 6), 27 of them belonging to the 43 steroid-free patients (63%). In contrast, only 52/128 (41%) children treated with steroids subsequently developed prope/operational tolerance (p = 0.012). Steroid-free tacrolimus-based IS seems to promote long-term graft acceptance under minimal/no IS. These results constitute the first evidence that minimization of IS, including steroid avoidance, might be tolerogenic in the long term after pediatric LT.
    Pediatric Transplantation 11/2012; 17(1). DOI:10.1111/petr.12024 · 1.44 Impact Factor
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    ABSTRACT: To improve modelling and simulation of the pharmacokinetics (PK) in paediatric patients, there is a need for research on developmental and disease-specific determinants. This article describes the evaluation of the in vitro cytochrome P450 activity, an important enzyme family in drug metabolism, in children with hepatic dysfunction. The activity of 6 CYP isoforms, CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 was evaluated in thirty-one patients with different pathologies, mainly biliary atresia (n=23). A hypervariable activity was observed for all the isoforms. Compared to an average adult activity, low activities were seen for CYP1A2, 2C19, 2E1, and 3A4. For CYP2E1 and 3A4, a positive correlation between activity and abundance was observed. In this population, age, co-medication, and genotype could not be used as predictors for the CYP activity. In contrast, the Paediatric End-stage Liver Disease score was negatively correlated with the ln(activity). This suggests a decrease in CYP activity with deteriorating hepatic function. Moreover, the activity of all isoforms was correlated, demonstrating a concomitant decrease of all isoforms in young patients with liver disease. To our knowledge, this is the first study to evaluate CYP activity in children with hepatic impairment. The presented data may provide support in the further optimization of a disease-specific model in this patient population.
    Drug metabolism and disposition: the biological fate of chemicals 11/2012; 41(2). DOI:10.1124/dmd.112.048504 · 3.25 Impact Factor

Publication Stats

671 Citations
217.83 Total Impact Points

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  • 2005–2015
    • Cliniques Universitaires Saint-Luc
      • Division of Pediatric Gastroenterology
      Bruxelles, Brussels Capital, Belgium
  • 2004–2015
    • Catholic University of Louvain
      • • Laboratory of Hepatogastroenterology
      • • Laboratory of Pediatric Hepatology and Cell Therapy
      Лувен-ла-Нев, Walloon, Belgium