32 results on '"Nobili, Valerio"'
Search Results
2. Pediatric Intestinal Pseudo-obstruction: Impact of Neonatal and Later Onset on Clinical and Nutritional Outcomes
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Diamanti, Antonella, Fusaro, Fabio, Caldaro, Tamara, Capriati, Teresa, Candusso, Manila, Nobili, Valerio, and Borrelli, Osvaldo
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- 2019
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3. Similarities and Differences in Allocation Policies for Pediatric Liver Transplantation Across the World
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Fischler, Björn, Baumann, Ulrich, D’Agostino, Daniel, D’Antiga, Lorenzo, Dezsofi, Antal, Debray, Dominique, Durmaz, Ozlem, Evans, Helen, Frauca, Esteban, Hadzic, Nedim, Jahnel, Jörg, Loveland, Jerome, McLin, Valérie, Ng, Vicky L., Nobili, Valerio, Pawłowska, Joanna, Sharif, Khalid, Smets, Francoise, Verkade, Henkjan J., Hsu, Evelyn, Horslen, Simon, and Bucuvalas, John
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- 2019
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4. Wilsonʼs Disease in Children: A Position Paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition
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Socha, Piotr, Janczyk, Wojciech, Dhawan, Anil, Baumann, Ulrich, D’Antiga, Lorenzo, Tanner, Stuart, Iorio, Raffaele, Vajro, Pietro, Houwen, Roderick, Fischler, Björn, Dezsofi, Antal, Hadzic, Nedim, Hierro, Loreto, Jahnel, Jörg, McLin, Valérie, Nobili, Valerio, Smets, Francoise, Verkade, Henkjan J., and Debray, Dominique
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- 2018
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5. Pediatric Nonalcoholic Fatty Liver Disease: Current Thinking
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Nobili, Valerio and Socha, Piotr
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- 2018
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6. Early and Late Factors Impacting Patient and Graft Outcome in Pediatric Liver Transplantation: Summary of an ESPGHAN Monothematic Conference
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McLin, Valérie A., Allen, Upton, Boyer, Olivia, Bucuvalas, John, Colledan, Michele, Cuturi, Maria-Cristina, d’Antiga, Lorenzo, Debray, Dominique, Dezsofi, Antal, Goyet, Jean de Ville de, Dhawan, Anil, Durmaz, Ozlem, Falk, Christine, Feng, Sandy, Fischler, Björn, Franchi-Abella, Stéphanie, Frauca, Esteban, Ganschow, Rainer, Gottschalk, Stephen, Hadzic, Nedim, Hierro, Loreto, Horslen, Simon, Hubscher, Stefan, Karam, Vincent, Kelly, Deirdre, Maecker-Kolhoff, Britta, Mazariegos, George, McKiernan, Patrick, Melk, Anette, Nobili, Valerio, Ozgenç, Funda, Reding, Raymond, Sciveres, Marco, Sharif, Khalid, Socha, Piotr, Toso, Christian, Vajro, Pietro, Verma, Anita, Wildhaber, Barbara E., and Baumann, Ulrich
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- 2017
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7. The Use of Probiotics in Pediatric Nonalcoholic Fatty Liver Disease: Teachable Moment or Missed Opportunity?
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Nobili, Valerio and Cucchiara, Salvatore
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- 2017
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8. Pediatric NAFLD
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Putignani, Lorenza, primary, Alisi, Anna, additional, and Nobili, Valerio, additional
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- 2016
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9. A 4‐Polymorphism Risk Score Predicts Steatohepatitis in Children With Nonalcoholic Fatty Liver Disease
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Nobili, Valerio, primary, Donati, Benedetta, additional, Panera, Nadia, additional, Vongsakulyanon, Apirom, additional, Alisi, Anna, additional, Dallapiccola, Bruno, additional, and Valenti, Luca, additional
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- 2014
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10. LPIN1 rs13412852 Polymorphism in Pediatric Nonalcoholic Fatty Liver Disease
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Valenti, Luca, primary, Motta, Benedetta Maria, additional, Alisi, Anna, additional, Sartorelli, Rita, additional, Buonaiuto, Giulia, additional, Dongiovanni, Paola, additional, Rametta, Raffaela, additional, Pelusi, Serena, additional, Fargion, Silvia, additional, and Nobili, Valerio, additional
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- 2012
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11. Endotoxin and Plasminogen Activator Inhibitor‐1 Serum Levels Associated With Nonalcoholic Steatohepatitis in Children
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Alisi, Anna, primary, Manco, Melania, additional, Devito, Rita, additional, Piemonte, Fiorella, additional, and Nobili, Valerio, additional
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- 2010
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12. Association of Serum Interleukin-8 Levels with the Degree of Fibrosis in Infants with Chronic Liver Disease
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Nobili, Valerio, primary, Marcellini, Matilde, additional, Giovannelli, Luigi, additional, Girolami, Elia, additional, Muratori, Flaminia, additional, Giannone, Germana, additional, Devito, Rita, additional, and De Benedetti, Fabrizio, additional
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- 2004
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13. Macrophage Markers Are Poorly Associated With Liver Histology in Children With Nonalcoholic Fatty Liver Disease.
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Kazankov K, Alisi A, Møller HJ, De Vito R, Rittig S, Mahler B, Nobili V, and Grønbæk H
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- Adolescent, Biomarkers analysis, Child, Cohort Studies, Cross-Sectional Studies, Female, Humans, Liver immunology, Liver pathology, Macrophage Activation immunology, Male, Randomized Controlled Trials as Topic, Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, Macrophages immunology, Non-alcoholic Fatty Liver Disease immunology, Non-alcoholic Fatty Liver Disease pathology, Receptors, Cell Surface analysis
- Abstract
Objectives: We have previously demonstrated associations between the macrophage activation marker soluble (s)CD163 and histology of nonalcoholic fatty liver disease (NAFLD) in adults, and elevated sCD163 levels in children with obesity with NAFLD. Macrophage activation has, however, not been investigated in children with biopsy-proven NAFLD, which was the objective of the present study., Methods: We used in-house enzyme-linked immunosorbent assays to measure sCD163 and the novel macrophage marker soluble mannose receptor (sMR) in a cross-sectional (n = 155) pediatric NAFLD cohort, and a cohort of NAFLD children (n = 36) undergoing a randomized trial by the probiotic VSL#3. We included 56 healthy nonobese children for comparison., Results: Levels of sCD163 and sMR were higher in both of the NAFLD cohorts compared with controls (P < 0.001). In the cross-sectional cohort, sCD163 only showed trends toward association with ballooning (rho = 0.14, P = 0.08) and portal inflammation (rho = 0.17, P = 0.08). sMR showed similar associations with liver histology. In the VSL#3 cohort, sCD163 correlated inversely with steatosis (rho = -0.35, P = 0.04), and lobular (rho = -0.57, P < 0.001) and portal inflammation (rho = -0.38, P = 0.02); sMR was not associated with any histological scores. Neither sCD163 nor sMR changed significantly during intervention, and without association with NAFLD resolution., Conclusions: The macrophage activation markers sCD163 and sMR showed poor associations with liver histology in 2 different cohorts of children with biopsy-proven NAFLD, and none of the markers decreased during successful intervention. These results are in contrast with studies of adult NAFLD and may suggest a possibility of different roles for macrophages in the pathogenesis of adult and pediatric NAFLD.
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- 2018
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14. The Health Care Transition of Youth With Liver Disease Into the Adult Health System: Position Paper From ESPGHAN and EASL.
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Vajro P, Fischler B, Burra P, Debray D, Dezsofi A, Guercio Nuzio S, Hadzic N, Hierro L, Jahnel J, Lamireau T, McKiernan P, McLin V, Nobili V, Socha P, Smets F, Baumann U, and Verkade HJ
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- Adolescent, Adult, Age Factors, Chronic Disease, Humans, Young Adult, Liver Diseases therapy, Transition to Adult Care organization & administration
- Abstract
Background: Medical advances have dramatically improved the long-term prognosis of children and adolescents with once-fatal hepatobiliary diseases. However, there is no generally accepted optimal pathway of care for the transition from paediatric care to the adult health system., Aim: The purpose of this position paper is to propose a transition process for young people with paediatric onset hepatobiliary diseases from child-centred to adult-centred healthcare services., Methods: Seventeen ESPGHAN/EASL physicians from 13 countries (Austria, Belgium, France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Spain, Sweden, Switzerland, and United Kingdom) formulated and answered questions after examining the currently published literature on transition from childhood to adulthood. PubMed and Google Scholar were systematically searched between 1980 and January 2018. Quality of evidence was assessed by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) system. Expert opinions were used to support recommendations whenever the evidence was graded weak. All authors voted on each recommendation, using the nominal voting technique., Results: We reviewed the literature regarding the optimal timing for the initiation of the transition process and the transfer of the patient to adult services, principal documents, transition multi-professional team components, main barriers, and goals of the general transition process. A transition plan based on available evidence was agreed focusing on the individual young people's readiness and on coordinated teamwork, with transition monitoring continuing until the first year of adult services.We further agreed on selected features of transitioning processes inherent to the most frequent paediatric-onset hepatobiliary diseases. The discussion highlights specific clinical issues that will probably present to adult gastrointestinal specialists and that should be considered, according to published evidence, in the long-term tracking of patients., Conclusions: Transfer of medical care of individuals with paediatric onset hepatobiliary chronic diseases to adult facilities is a complex task requiring multiple involvements of patients and both paediatric and adult care providers.
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- 2018
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15. Elevated Hemoglobin Level Is Associated With Advanced Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease.
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Giorgio V, Mosca A, Alterio A, Alisi A, Grieco A, Nobili V, and Miele L
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- Biomarkers blood, Child, Erythrocyte Count, Erythrocyte Indices, Female, Hematocrit, Humans, Liver Cirrhosis blood, Liver Cirrhosis pathology, Male, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease diagnosis, Retrospective Studies, Hemoglobins metabolism, Liver Cirrhosis diagnosis, Non-alcoholic Fatty Liver Disease pathology, Severity of Illness Index
- Abstract
Objectives: Hemoglobin (Hb) and red blood cell distribution width (RDW) have been reported to be a risk marker of metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). No study exists on pediatric populations. We aimed to determine the association between hematological parameters, and the severity of disease in children with biopsy-proven NAFLD., Methods: A total of 117 children (85 boys, mean age 12 years) with ultrasound evidence of NAFLD undergoing liver biopsy for diagnosis of nonalcoholic steatohepatitis (NASH), were prospectively enrolled between January 2011 and May 2013 in the setting of a tertiary care center. Children were screened for routine hematological and metabolic parameters, and causes of liver steatosis other than nonalcoholic were excluded, before liver biopsy was performed., Results: A total of 41 NAFLD (boys 29, mean age 11.2 years) and 76 NASH (boys 56, mean age 12.8 years) children were studied. Alanine transaminase levels were significantly higher in NASH group compared with NAFLD group (P = 0.05), and homeostatic model assessment of insulin resistance and triglycerides levels (P = 0.03 and 0.02, respectively). Regarding hematological components: red cell count, Hb, hematocrit, and RDW values were all significantly higher in NASH group compared with NAFLD group (P < 0.05 for each parameter)., Conclusions: Children with NASH were more likely to have high levels of RDW compared to those with steatosis only. Moreover, NASH was associated with higher red cell count, Hb, and hematocrit. If confirmed in future follow-up studies, hematological parameters may be introduced in algorithms for NASH risk prediction.
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- 2017
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16. Hepatitis E in Children: A Position Paper by the ESPGHAN Hepatology Committee.
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Fischler B, Baumann U, Dezsofi A, Hadzic N, Hierro L, Jahnel J, McLin V, Nobili V, Smets F, Verkade H, and Debray D
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- Acute Disease, Child, Chronic Disease, Hepatitis E etiology, Hepatitis E transmission, Humans, Immunocompetence, Immunocompromised Host, Organ Transplantation, Postoperative Complications diagnosis, Postoperative Complications immunology, Postoperative Complications therapy, Hepatitis E diagnosis, Hepatitis E therapy
- Abstract
Background: Hepatitis E virus (HEV) is endemic in large parts of the developing world. Waterborne transmission of genotypes 1 or 2 commonly causes acute hepatitis, which is usually self-limited in healthy individuals. In addition, acute HEV infections also occur outside endemic areas, mostly related to foodborne transmission of HEV genotype 3. A growing number of publications in the last decade have reported chronic infection progressing to cirrhosis in immunosuppressed patients. It has also been suggested that HEV transmission may occur via contaminated blood products. This publication aims to provide recommendations for diagnosis, prevention, and treatment of HEV infection, particularly in children after solid organ transplantation., Methods: A systematic PubMed literature search on HEV infection from 1990 to January 2016 was performed focusing on pediatric studies. The existing body of evidence was reviewed and recommendations were agreed upon following discussion and unanimous agreement by all members of the ESPGHAN Hepatology Committee during a consensus meeting in January 2016. In the absence of randomized controlled studies these recommendations were considered to be expert opinions., Key Recommendations: Immunocompetent children with increased transaminases and/or extrahepatic manifestations should be considered for testing for evidence of HEV infection. Immunocompromised children with increased aminotransferases should be repeatedly tested for HEV and may require therapeutic intervention.
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- 2016
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17. Plasma Cytokeratin-18 Level As a Novel Biomarker for Liver Fibrosis in Children With Nonalcoholic Fatty Liver Disease.
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Mandelia C, Collyer E, Mansoor S, Lopez R, Lappe S, Nobili V, and Alkhouri N
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- Biomarkers blood, Biopsy, Child, Cross-Sectional Studies, Decision Support Techniques, Disease Progression, Female, Humans, Liver Cirrhosis blood, Liver Cirrhosis pathology, Logistic Models, Male, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease diagnosis, Sensitivity and Specificity, Keratin-18 blood, Liver pathology, Liver Cirrhosis diagnosis, Non-alcoholic Fatty Liver Disease pathology
- Abstract
Objectives: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the obesity epidemic and affects approximately 10% of children in the US. The presence of hepatic fibrosis may be the most important factor in determining the prognosis of NAFLD. Noninvasive methods to identify the presence of fibrosis in children with NAFLD are greatly needed. Hepatocyte apoptosis activates hepatic stellate cells and plays a central role in fibrosis progression in NAFLD. The aim of the present study was to evaluate the use of plasma cytokeratin-18 (CK18) fragment levels, a marker of hepatocyte apoptosis, as a noninvasive biomarker in detecting liver fibrosis in pediatric NAFLD., Methods: Consecutive children with biopsy-proven NAFLD were included and blood samples and anthropometric measurements were collected at the time of the biopsy. NAFLD activity score was calculated (0-8) and fibrosis stage was scored (0-4). We measured plasma CK18 levels using the M30-Apoptosense enzyme-linked immunosorbent assay kit., Results: A total of 201 subjects were enrolled in the study. The mean age was 10.7 ± 2.5 years, and 37 % were boys. Sixty-eight percent of the patients had any fibrosis, with 56% having F1, 6% having F2, and 6 % having F3. CK18 levels were found to be significantly higher in subjects with any fibrosis compared with those without fibrosis (304.6 ± 124.8 vs 210.4 ± 70.9, P < 0.001). CK18 level revealed good accuracy for prediction of any fibrosis (F1-F3) with AUROC of 0.75. Multivariate logistic regression was performed to assess whether CK18 in combination with another clinical factor could improve accuracy of prediction of fibrosis. Together, CK18 with waist circumference percentile generated an area under the receiver operating characteristics curve of 0.842 for prediction of any fibrosis., Conclusions: CK18 is a promising noninvasive biomarker for fibrosis in NAFLD in children. A fibrosis prediction model that includes CK18 and waist circumference percentile should be validated in other populations.
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- 2016
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18. Pediatric NAFLD: the Future role of Patient-Tailored Probiotics Therapy.
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Putignani L, Alisi A, and Nobili V
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- Child, Evidence-Based Medicine, Forecasting, Humans, Non-alcoholic Fatty Liver Disease therapy, Probiotics therapeutic use
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Purpose of Review: Clinical evidence of the use of probiotics in pediatric NAFLD, framed within gut microbiota response, is herein discussed., Recent Findings: The assistance of a new microbiological approach in probiotics' design is playing a central role in NAFLD clinical management. Experimental studies demonstrated the effect of gut microbiota manipulation in NAFLD and recent clinical evidence reported their beneficial effect in pediatric patients., Summary: Epidemiology suggests that NAFLD is the most frequent pediatric chronic liver disease evolving from simple steatosis to a more severe form that may progress toward fibrosis. The goal of pharmacological treatment of NAFLD-related fibrosis is to stop and eventually to reverse liver damage, but no drug tested so far seem to be able to reach this endpoint. A few encouraging clinical studies demonstrated an improvement of hepato-metabolic milieu under probiotic treatment suggesting that they could exert an anti-fibrotic activity.Currently, new insights onto probiotics can be deduced by ad hoc generated NAFLD gut microbiota profiles. These functional maps may unveil gut ecosystem dynamics under probiotics' treatment, selecting the most appropriate for NAFLD gut microbiota amelioration.
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- 2016
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19. Serum Bile Acid Levels in Children With Nonalcoholic Fatty Liver Disease.
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Jahnel J, Zöhrer E, Alisi A, Ferrari F, Ceccarelli S, De Vito R, Scharnagl H, Stojakovic T, Fauler G, Trauner M, and Nobili V
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- Adolescent, Adult, Case-Control Studies, Child, Child, Preschool, Disease Progression, Female, Humans, Liver Cirrhosis etiology, Male, Non-alcoholic Fatty Liver Disease complications, Young Adult, Bile Acids and Salts blood, Liver pathology, Liver Cirrhosis blood, Non-alcoholic Fatty Liver Disease blood
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Objective: Because the prevalence of obesity in children is increasing, the frequency of pediatric nonalcoholic fatty liver disease (NAFLD) is growing. A reliable noninvasive biomarker for monitoring progression of liver fibrosis would be useful. In cirrhotic persons serum bile acid (BA) levels are significantly elevated. We hypothesized that BA levels and composition in pediatric NAFLD vary depending on the stage of fibrosis., Methods: Children with NAFLD were compared with controls and classified by stages of fibrosis (NAFLD-F0, n = 27; NAFLD-F≥1, n = 65) based on liver-biopsy findings. Fasted metabolic and cholestasis status was assessed by several blood tests. BA profiles were measured by tandem mass spectrometry and compared with healthy controls (n = 105)., Results: Compared with controls, all of the NAFLD patients were overweight and showed significantly elevated glucose, insulin, aspartate transaminase, and alanine transaminase levels. Total serum BAs were lower in nonfibrotic NAFLD children than in a control cohort (1.73 vs 3.6 μmol/L) because low glycine-conjugated BA levels were incompletely compensated by increases in taurine-conjugated or unconjugated BA. In patients with fibrotic NAFLD, BA levels were lower than in controls (2.45 vs 3.6 μmol/L) but higher than in nonfibrotic patients (2.45 vs 1.73 μmol/L), and the BA pattern resembled that of healthy controls. Fibroblast growth factor 19 levels were significantly lower in both NAFLD groups than in controls (P ≤ 0.001) and were positively correlated with ursodeoxycholic acid levels., Conclusions: Our data indicate that serum BA levels decrease in early NAFLD and increase during progression to fibrosis. Given that BA levels are increased in cirrhotic adults, we postulate a continuous rise as NAFLD advances. BA may have a value as a noninvasive biomarker in pediatric NAFLD progression.
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- 2015
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20. Indications and limitations of bariatric intervention in severely obese children and adolescents with and without nonalcoholic steatohepatitis: ESPGHAN Hepatology Committee Position Statement.
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Nobili V, Vajro P, Dezsofi A, Fischler B, Hadzic N, Jahnel J, Lamireau T, McKiernan P, McLin V, Socha P, Tizzard S, and Baumann U
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- Adolescent, Adult, Child, Humans, Non-alcoholic Fatty Liver Disease etiology, Non-alcoholic Fatty Liver Disease pathology, Obesity, Morbid surgery, Weight Loss, Bariatric Surgery methods, Non-alcoholic Fatty Liver Disease surgery, Obesity, Morbid complications
- Abstract
Morbid obesity is strongly associated with nonalcoholic fatty liver disease (NAFLD), which is one of the most common causes of chronic liver disease worldwide. The present best treatment for NAFLD and nonalcoholic steatohepatitis (NASH) is weight reduction through lifestyle modification. Because of frustrating inefficiency of such a therapeutic approach, bariatric surgery is increasingly performed in adolescents as an alternative option for weight reduction. Standards of care and consensus for indications are, however, scarce. We explore the indications and limitations of bariatric surgery in children with severe obesity with and without NASH and aim to provide guidance for the exceptional indications for adolescents with extreme obesity with major comorbidity that may benefit from these controversial interventions. Present evidence suggests that bariatric surgery can decrease the grade of steatosis, hepatic inflammation, and fibrosis in NASH. Uncomplicated NAFLD is not an indication for bariatric surgery. Roux-en-Y gastric bypass is considered a safe and effective option for adolescents with extreme obesity, as long as an appropriate long-term follow-up is provided. Laparoscopic adjustable gastric banding has not been approved by the Food and Drug Administration for use in adolescents and therefore should be considered investigational. Finally, sleeve gastrectomy and other types of weight loss surgery that have grown increasingly common in adults, still need to be considered investigational. Temporary devices may be increasingly being used in pediatrics; however, future studies, including a long-term risk analysis of patients who undergo surgery, are much needed to clarify the exact indications for bariatric surgery in adolescents.
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- 2015
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21. Liver biopsy in children: position paper of the ESPGHAN Hepatology Committee.
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Dezsőfi A, Baumann U, Dhawan A, Durmaz O, Fischler B, Hadzic N, Hierro L, Lacaille F, McLin VA, Nobili V, Socha P, Vajro P, and Knisely AS
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- Biopsy adverse effects, Biopsy standards, Child, Child, Preschool, Contraindications, Europe, Gastroenterology trends, Humans, Infant, Infant, Newborn, Liver Diseases pathology, Nutritional Sciences trends, Pediatrics trends, Prognosis, Societies, Medical, Evidence-Based Medicine, Gastroenterology methods, Liver pathology, Liver Diseases diagnosis, Nutritional Sciences methods, Pediatrics methods, Precision Medicine
- Abstract
Liver biopsy (LB) is still the criterion standard procedure for obtaining liver tissue for histopathological examination and a valuable tool in the diagnosis, prognosis, and management of many parenchymal liver diseases. The aim of this position paper is to summarise the present practice of paediatric LB and make recommendations about its performance. Although histological evaluation of the liver is important in assessing prognosis and exploring treatment, noninvasive techniques (ie, imaging, laboratory markers) may replace use of liver histology. The indications for LB are changing as present knowledge of aetiologies, pathomechanism, and therapeutic options in paediatric liver disease is evolving. Adult and paediatric literature was reviewed to assess the existing clinical practice of LB with focus on the technique, indications, risk of complications, and contraindications in paediatrics. This position paper presents types of LB, indications, complications, contraindications, and an essential checklist for paediatric LB.
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- 2015
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22. Deciphering the role of ω3 fatty acids in nonalcoholic steatohepatitis.
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Valenti L and Nobili V
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- Female, Humans, Male, Fatty Liver genetics, Genotype, Lipase genetics, Liver pathology, Membrane Proteins genetics, Pediatric Obesity genetics, Polymorphism, Genetic, Receptors, G-Protein-Coupled genetics
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- 2014
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23. Genetic insight into the pathogenesis of nonalcoholic fatty liver disease.
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Valenti L, Dallapiccola B, and Nobili V
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- Female, Humans, Male, Alanine Transaminase genetics, Body Mass Index, Genotype, Intracellular Signaling Peptides and Proteins genetics, Liver, Membrane Proteins genetics, Non-alcoholic Fatty Liver Disease genetics, Polymorphism, Single Nucleotide
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- 2014
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24. Serum bilirubin level is inversely associated with nonalcoholic steatohepatitis in children.
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Puri K, Nobili V, Melville K, Corte CD, Sartorelli MR, Lopez R, Feldstein AE, and Alkhouri N
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- Adolescent, Allostasis, Biopsy, Body Mass Index, Child, Fatty Liver blood, Fatty Liver etiology, Fatty Liver pathology, Hepatitis etiology, Humans, Liver pathology, Liver Cirrhosis etiology, Logistic Models, Metabolic Syndrome physiopathology, Non-alcoholic Fatty Liver Disease, Obesity physiopathology, Severity of Illness Index, Antioxidants analysis, Bilirubin blood, Fatty Liver physiopathology, Hyperbilirubinemia etiology, Liver physiopathology
- Abstract
Objectives: Oxidative stress has been implicated in the development of nonalcoholic fatty liver disease (NAFLD) and progression to the more severe form, nonalcoholic steatohepatitis (NASH), in children. We aimed to study the clinical correlation between bilirubin, a potent endogenous antioxidant with cytoprotective properties, and histopathological findings in pediatric patients with NAFLD., Methods: We included consecutive children with biopsy-proven NAFLD and obtained demographic, clinical, and histopathological data. We performed logistic regression analysis to assess the clinical factors associated with the histological features of NASH or fibrosis., Results: From a total of 302 biopsies, 67% (203) had evidence of NASH, whereas 64.2% had some degree of fibrosis (stage 1 in 51%, stage 2 in 6.3%, and stage 3 in 6.6%). Mean total bilirubin was significantly lower in the NASH group compared with the non-NASH group (0.65 ± 0.24 vs 0.73 ± 0.22 mg/dL, P = 0.007). Higher total bilirubin levels were negatively correlated with the presence of steatosis and the NAFLD activity score (P < 0.05), whereas a trend in that direction was observed for presence of fibrosis and inflammation (P = 0.051). On multivariable analysis, higher bilirubin levels were significantly associated with a decreased likelihood of a histological diagnosis of NASH on biopsy (odds ratio 0.29, 95% CI 0.10-0.85, P = 0.024)., Conclusions: In children with NAFLD, there is an inverse relation between serum bilirubin levels and the presence of NASH on biopsy. This may be secondary to the antioxidant effect of bilirubin.
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- 2013
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25. Levels of serum ceruloplasmin associate with pediatric nonalcoholic fatty liver disease.
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Nobili V, Siotto M, Bedogni G, Ravà L, Pietrobattista A, Panera N, Alisi A, and Squitti R
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- Algorithms, Biomarkers blood, Biopsy, Ceruloplasmin deficiency, Child, Cohort Studies, Copper blood, Fatty Liver diagnosis, Fatty Liver pathology, Fatty Liver physiopathology, Female, Humans, Liver immunology, Liver Cirrhosis etiology, Male, Non-alcoholic Fatty Liver Disease, Sensitivity and Specificity, Severity of Illness Index, Transferrin analysis, Ceruloplasmin analysis, Fatty Liver blood, Iron Metabolism Disorders etiology, Liver pathology, Neurodegenerative Diseases etiology
- Abstract
Objectives: Nonalcoholic fatty liver disease (NAFLD) in adolescents and children is rapidly becoming one of the most common causes of chronic liver disease worldwide. NAFLD varies from simple fatty liver to nonalcoholic steatohepatitis (NASH) with possible fibrosis. Several studies suggest that oxidative stress plays a central role in several metabolic abnormalities and cellular damage that characterize NAFLD. We investigated whether transition metals and their related proteins were related to NAFLD symptoms and their underlying processes., Methods: We measured copper, iron, ceruloplasmin (Cp) concentration and activity, transferrin (Tf), ferroxidase activity, and ferritin, and we calculated Tf saturation and Cp to Tf ratio (Cp/Tf) as an index of the activity of the antioxidant Cp-Tf system in 100 children with biopsy-proven NAFLD. Pediatric patients were grouped by nonalcoholic fatty liver disease score (NAS) ≥ 5 (30 subjects) and NAS < 5 (70)., Results: Cp distinguished children with NAS ≥ 5 from those with NAS < 5 with an accuracy of 82%. Specifically, a receiver operator characteristics curve showed that a cutoff of 28.6 mg/dL separated NAS ≥ 5 from NAS < 5 with a specificity of 92% and a sensitivity of 76%. The Cp/Tf ratio, as well as copper concentration and Cp activity, decreased in the NAS ≥ 5 group, pointing out an imbalance in metal regulation. Either copper or Cp concentrations were lower in subjects having ballooning., Conclusions: Serum antioxidant capacity owing to Cp failure is strongly associated with NAFLD-related damage. Further studies are, however, required to clarify the role of Cp in NAFLD pathogenesis and to evaluate its potential application as diagnostic marker.
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- 2013
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26. Viral hepatitis in children.
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Nel E, Sokol RJ, Comparcola D, Nobili V, Hardikar W, Gana JC, Abarca K, Wu JF, Chang MH, and Renner JK
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- Child, Humans, Prevalence, Global Health, Hepatitis, Viral, Human epidemiology
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- 2012
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27. Children unresponsive to hepatitis B virus vaccination also need celiac disease testing.
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Vajro P, Paolella G, and Nobili V
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- Humans, Celiac Disease diagnosis, Duodenum pathology, HLA-DQ Antigens blood, Immunoglobulin A blood, Transglutaminases immunology
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- 2012
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28. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee.
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Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, Baumann U, Durmaz O, Lacaille F, McLin V, and Nobili V
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- Adolescent, Child, Disease Progression, Fatty Liver complications, Female, Gastroenterology, Genetic Predisposition to Disease, Humans, Liver pathology, Liver Cirrhosis complications, Liver Cirrhosis diagnosis, Liver Cirrhosis physiopathology, Liver Function Tests, Male, Non-alcoholic Fatty Liver Disease, Obesity complications, Obesity diagnosis, Obesity epidemiology, Prevalence, Risk Factors, United States epidemiology, Fatty Liver diagnosis, Fatty Liver epidemiology
- Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents in the United States, and most probably also in the rest of the industrialized world.As the prevalence of NAFLD in childhood increases with the worldwide obesity epidemic, there is an urgent need for diagnostic standards that can be commonly used by pediatricians and hepatologists. To this end, we performed a PubMed search of the adult and pediatric literature on NAFLD diagnosis through May 2011 using Topics and/or relevant Authors as search words. According to the present literature, NAFLD is suspected based on the association of fatty liver combined with risk factors (mainly obesity), after the exclusion of other causes of liver disease. The reference but imperfect standard for confirming NAFLD is liver histology. The following surrogate markers are presently used to estimate degree of steatosis and liver fibrosis and risk of progression to end-stage liver disease: imaging by ultrasonography or magnetic resonance imaging, liver function tests, and serum markers of liver fibrosis.NAFLD should be suspected in all of the overweight or obese children and adolescents older than 3 years with increased waist circumference especially if there is a NAFLD history in relatives. The typical presentation, however, is in children ages 10 years and older. The first diagnostic step in these children should be abdominal ultrasound and liver function tests, followed by exclusion of other liver diseases. Overweight/obese children with normal ultrasonographic imaging and normal liver function tests should still be monitored due to the poor sensitivity of these tests at a single assessment.Indications for liver biopsy include the following: to rule out other treatable diseases, in cases of clinically suspected advanced liver disease, before pharmacological/surgical treatment, and as part of a structured intervention protocol or clinical research trial.
- Published
- 2012
- Full Text
- View/download PDF
29. Biochemical parameters and anthropometry predict NAFLD in obese children.
- Author
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Maffeis C, Banzato C, Rigotti F, Nobili V, Valandro S, Manfredi R, and Morandi A
- Subjects
- Adiponectin blood, Alanine Transaminase blood, Biochemical Phenomena, Body Composition, Body Mass Index, Child, Cohort Studies, Fatty Liver blood, Fatty Liver complications, Female, Glucose Tolerance Test, Humans, Insulin Resistance, Logistic Models, Male, Non-alcoholic Fatty Liver Disease, Obesity blood, Obesity complications, Risk Factors, White People, Anthropometry, Fatty Liver physiopathology, Models, Biological, Obesity physiopathology
- Abstract
The aim of the present study was to build a predictive model of nonalcoholic fatty liver disease (NAFLD) in obese children. Fifty-six obese 10-year-old children underwent blood tests for biochemical measures and magnetic resonance imaging for NAFLD diagnosis. A model combining waist-to-height ratio, homeostasis model assessment of insulin resistance, adiponectin, and alanine aminotransferase was accurate in predicting NAFLD (AUROC = 0.94 [95% confidence interval 0.89-0.99], P < 10). When adiponectin was not included in the model, the discrimination accuracy was still good (AUROC = 0.88 [95% confidence interval 0.79-0.97], P < 10). In conclusion, a predictive equation combining routinely available variables may allow physicians to identify obese children at the highest risk of NAFLD.
- Published
- 2011
- Full Text
- View/download PDF
30. Ultrasonographic quantitative estimation of hepatic steatosis in children With NAFLD.
- Author
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Shannon A, Alkhouri N, Carter-Kent C, Monti L, Devito R, Lopez R, Feldstein AE, and Nobili V
- Subjects
- Adolescent, Biopsy, Body Mass Index, Child, Cohort Studies, Fatty Liver pathology, Female, Humans, Liver blood supply, Liver pathology, Liver Cirrhosis diagnostic imaging, Liver Cirrhosis pathology, Male, Prospective Studies, ROC Curve, Severity of Illness Index, Ultrasonography, Fatty Liver diagnostic imaging, Liver diagnostic imaging
- Abstract
Background and Aims: The diagnostic accuracy of hepatic ultrasonography (US) for detection and grading of hepatic steatosis in children with suspected nonalcoholic fatty liver disease (NAFLD) remains poorly characterized. The aim of this study was to prospectively evaluate the clinical utility of ultrasonographic quantification of hepatic steatosis., Patients and Methods: Our cohort consisted of 208 consecutive pediatric patients with biopsy-proven NAFLD. Hepatic US was performed within 1 month of the liver biopsy procedure. Steatosis identified by US was scored using a 0 to 3 scale based on echogenicity and visualization of vasculature, parenchyma, and diaphragm, and compared to histological features based on Brunt's classification., Results: The median age at time of first visit was 10.8 years and 64% were boys. Sixty-nine percent had moderate to severe steatosis on histology. Ultrasonographic steatosis score (USS) had an excellent correlation with histological grade of steatosis (with a Spearman's coefficient of 0.80). The area under the receiver operating characteristic curve for ultrasonographic detection of moderate-to-severe steatosis was 0.87. The USS did not correlate significantly with inflammatory activity or fibrosis stage; however, there was significant correlation with the NAFLD activity score (NAS), albeit this was in large part the result of the strong correlation with the steatosis component of NAS. Serum alanine transaminase and aspartate transaminase were not associated with histological grade of steatosis and showed no correlation with USS., Conclusions: Our results, which represent the largest prospective pediatric study evaluating the role of hepatic US in children with biopsy-proven NAFLD, demonstrate the utility of this technique for noninvasive diagnosis and estimation of hepatic steatosis in children.
- Published
- 2011
- Full Text
- View/download PDF
31. Biomarkers in nonalcoholic fatty liver disease: a new era in diagnosis and staging of disease in children.
- Author
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Feldstein AE and Nobili V
- Subjects
- Biomarkers blood, Child, Humans, Non-alcoholic Fatty Liver Disease, Severity of Illness Index, Fatty Liver blood, Fatty Liver diagnosis
- Published
- 2010
- Full Text
- View/download PDF
32. Intensive treatment and dietary fats in adolescents with nonalcoholic fatty liver disease.
- Author
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Manco M and Nobili V
- Subjects
- Humans, Nutritional Status, Patient Compliance, Patient Selection, Sample Size, Fatty Liver etiology, Fatty Liver therapy, Obesity complications
- Published
- 2008
- Full Text
- View/download PDF
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