82 results on '"Nobili, Valerio"'
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2. Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven non-alcoholic fatty liver disease
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Nobili, Valerio, Mantovani, Alessandro, Cianfarani, Stefano, Alisi, Anna, Mosca, Antonella, Sartorelli, Maria Rita, Maffeis, Claudio, Loomba, Rohit, Byrne, Christopher D., and Targher, Giovanni
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- 2019
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3. Statin use and non-alcoholic steatohepatitis in at risk individuals
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Dongiovanni, Paola, Petta, Salvatore, Mannisto, Ville, Mancina, Rosellina Margherita, Pipitone, Rosaria, Karja, Vesa, Maggioni, Marco, Kakela, Pirjo, Wiklund, Olov, Mozzi, Enrico, Grimaudo, Stefania, Kaminska, Dorota, Rametta, Raffaela, Craxi, Antonio, Fargion, Silvia, Nobili, Valerio, Romeo, Stefano, Pihlajamaki, Jussi, and Valenti, Luca
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- 2015
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4. The IRGM rs10065172 variant increases the risk for steatosis but not for liver damage progression in Italian obese children
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Bellini, Giulia, Miraglia del Giudice, Emanuele, Nobili, Valerio, and Rossi, Francesca
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- 2017
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5. AISF update on the diagnosis and management of adult-onset lysosomal storage diseases with hepatic involvement.
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Nascimbeni, Fabio, Dionisi Vici, Carlo, Vespasiani Gentilucci, Umberto, Angelico, Francesco, Nobili, Valerio, Petta, Salvatore, and Valenti, Luca
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Lysosomal storage diseases (LSDs) are a heterogeneous group of inherited disorders caused by loss-of-function mutations in genes encoding for lysosomal enzymes/proteins. The consequence is a progressive accumulation of substrates in these intracellular organelles, resulting in cellular and tissue damage. The overall incidence is about 1/8000 live births, but is likely underestimated. LSDs are chronic progressive multi-systemic disorders, generally presenting with visceromegaly, and involvement of the central nervous system, eyes, the skeleton, and the respiratory and cardiovascular systems. The age at onset and phenotypic expression are highly variable, according to the specific enzymatic defect and tissues involved, the residual activity, and the disease-causing genotype. Enzyme-replacement therapies and substrate-reduction therapies have recently become available, leading to the improvement in symptoms, disease progression and quality of life of affected individuals. Liver involvement and hepatosplenomegaly are frequent features of LSDs and a hallmark of adult-onset forms, frequently leading to medical attention. LSDs should therefore be considered in the differential diagnosis of liver disease with organomegaly. The present document will provide a short overview of adult-onset LSDs with hepatic involvement, highlighting the specificities and systemic manifestations of the ones most frequently encountered in clinical practice, which may hint at the correct diagnosis and the appropriate treatment. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Pancreatic disorders in children: New clues on the horizon.
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Della Corte, Claudia, Faraci, Simona, Majo, Fabio, Lucidi, Vincenzina, Fishman, Douglas S., and Nobili, Valerio
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Abstract Pancreatic disorders in children represent a growing health problem in pediatric patients. In the past two decades, several advances have been made in the knowledge of pediatric pancreatic disorders, with better understanding of different etiologies and clinical manifestations of these disorders. Moreover, many efforts have been made in pancreatology, aiming to define guidelines in the management of pancreatitis in children, initially based on the available information in adults. A multidisciplinary and multicenter approach is necessary to better determine pancreatic disease pathways and treatment options in children. [ABSTRACT FROM AUTHOR]
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- 2018
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7. Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents.
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Mosca, Antonella, Nobili, Valerio, De Vito, Rita, Crudele, Annalisa, Scorletti, Eleonora, Villani, Alberto, Alisi, Anna, and Byrne, Christopher D.
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FATTY liver , *URIC acid , *FRUCTOSE , *OVERWEIGHT children , *HYPERURICEMIA , *PHYSIOLOGY - Abstract
Background & Aims Recent research has suggested that dietary fructose intake may increase serum uric acid (UA) concentrations. Both UA concentration and fructose consumption maybe also increase in NAFLD. It is not known whether dietary fructose consumption and UA concentration are independently associated with non-alcoholic steatohepatitis (NASH). Our aim was to investigate the factors associated with NASH in children and adolescents with proven NAFLD, and to test whether UA concentrations and fructose consumption are independently associated with NASH. Methods Obese children with NAFLD were studied (n = 271). NASH was diagnosed by a NAFLD activity score ~5 and the fatty liver inhibition of progression (FLIP) algorithm. Fructose consumption (g/day) was assessed by food frequency questionnaire, and UA (mg/dl) was measured in serum. Binary logistic regression with adjustment for covariates and potential confounders was undertaken to test factors independently associated with NASH. Results NASH occurred in 37.6% of patients. Hyperuricaemia (UA ~5.9 mg/dl) was present in 47% of patients with NASH compared with 29.7% of non-NASH patients (p = 0.003). Both UA concentration (OR = 2.488, 95% CI: 1.87-2.83, p = 0.004) and fructose consumption (OR = 1.612, 95% CI 1.25-1.86, p = 0.001) were independently associated with NASH, after adjustment for multiple (and all) measured confounders. Fructose consumption was independently associated with hyperuricaemia (OR = 2.021, 95% CI: 1.66-2.78, p = 0.01). These data were confirmed using the FLIP algorithm. Conclusions Both dietary fructose consumption and serum UA concentrations are independently associated with NASH. Fructose consumption was the only factor independently associated with serum UA concentration. Lay summary Currently, it is not known whether dietary fructose consumption and uric acid (UA) concentration are linked with non-alcoholic steatohepatitis (NASH) in children and adolescents. Our aim was to test whether UA concentrations and fructose consumption are independently associated with NASH in children and adolescents with proven non-alcoholic fatty liver disease (NAFLD). We show that both dietary fructose consumption and serum UA concentrations are independently associated with NASH and fructose consumption was independently linked with high serum UA concentrations. [ABSTRACT FROM AUTHOR]
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- 2017
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8. Reduced lysosomal acid lipase activity – A potential role in the pathogenesis of non alcoholic fatty liver disease in pediatric patients.
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Selvakumar, Praveen Kumar Conjeevaram, Kabbany, Mohammad Nasser, Lopez, Rocio, Tozzi, Giulia, Alisi, Anna, Alkhouri, Naim, and Nobili, Valerio
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Background Within the spectrum of nonalcoholic fatty liver disease (NAFLD), recent evidence suggests that adult patients with nonalcoholic steatohepatitis (NASH) have significantly lower blood lysosomal acid lipase (LAL) activity than those with steatosis. This has not been studied in pediatric patients with NAFLD. Aim Investigate blood LAL activity in pediatric patients with NAFLD and assess its correlation with histological severity. Methods We collected data on consecutive children with biopsy-proven NAFLD including demographics, anthropometrics, and routine laboratory tests. The histological features were graded according to the NAFLD activity scoring proposed by Kleiner et al. Blood LAL activity was measured prospectively using Lalistat 2. Results A total of 168 children were included for analysis. Mean age was 12.6 ± 8.5 years, 60.1% were males and 52.4% had NASH. Children with significant fibrosis (stage 2–3, n = 64) had a significantly lower LAL activity compared to those with mild fibrosis (stage 0–1, n = 104). There was no significant difference in LAL activity between children with NASH compared to those without NASH. Conclusion Reduced blood LAL activity correlates with severity of liver fibrosis in children with NAFLD indicating a potential role of reduced LAL activity in the pathogenesis of NAFLD-induced fibrosis. [ABSTRACT FROM AUTHOR]
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- 2016
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9. Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease.
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Nobili, Valerio, Alisi, Anna, Newton, Kimberly P., and Schwimmer, Jeffrey B.
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Nonalcoholic fatty liver disease (NAFLD) is one of the main chronic noncommunicable diseases in Westernized societies; its worldwide prevalence has doubled during the last 20 years. NAFLD has serious health implications not only for adults, but also for children. However, pediatric NAFLD is not only an important global problem in itself, but it is likely to be associated with increases in comorbidities, such as metabolic syndrome and cardiovascular diseases. There are several differences between NAFLD in children and adults, and it is not clear whether the disease observed in children is the initial phase of a process that progresses with age. The increasing prevalence of pediatric NAFLD has serious implications for the future adult population requiring appropriate action. Studies of NAFLD progression, pathogenesis, and management should evaluate disease phenotypes in children and follow these over the patient’s lifetime. We review the similarities and differences of NAFLD between children and adults. [ABSTRACT FROM AUTHOR]
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- 2016
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10. A non-invasive prediction model for non-alcoholic steatohepatitis in paediatric patients with non-alcoholic fatty liver disease.
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Eng, Katharine, Lopez, Rocio, Liccardo, Daniela, Nobili, Valerio, and Alkhouri, Naim
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Background Non-alcoholic fatty liver disease encompasses a spectrum of diseases that range from simple steatosis to the aggressive form of non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis is currently diagnosed through liver biopsy. Aim To develop a non-invasive predictive model of non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease. Methods Anthropometric, laboratory, and histologic data were obtained in a cohort of children with biopsy-proven non-alcoholic fatty liver disease. Multivariable logistic regression analysis was employed to create a nomogram predicting the risk of non-alcoholic steatohepatitis. Internal validation was performed by bootstrapping. Results Three hundred and two children were included in this analysis with a mean age of 12.3 ± 3.1 years, a mean body mass index percentile of 94.3 ± 6.9, and non-alcoholic steatohepatitis was present in 67%. Following stepwise variable selection, total cholesterol, waist circumference percentile, and total bilirubin were included as variables in the model, with good discrimination with an area under the receiver operating characteristic curve of 0.737. Conclusions A nomogram was constructed with reasonable accuracy that can predict the risk of non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease. If validated externally, this tool could be utilized as a non-invasive method to diagnose non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]
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- 2014
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11. Breastfeeding and NAFLD from the maternal side of the mother-infant dyad
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Nobili, Valerio, Schwimmer, Jeffrey B., and Vajro, Pietro
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- 2019
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12. Fatty liver in adolescents: Mechanisms, clinical features and therapy.
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Nobili, Valerio and Feldstein, Ariel E.
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FATTY liver , *LIVER diseases , *SEDENTARY lifestyles , *SINGLE nucleotide polymorphisms , *LIPID metabolism - Abstract
The article discusses issues associated with Non-Alcoholic Fatty Liver Disease (NAFLD), which is currently the most common cause of chronic liver disease in children. Topics discussed include prevalence of NAFLD due to unhealthy diet and sedentary lifestyle, pathogenesis of NAFLD involving both genetic and environmental factors and single nucleotide polymorphisms (SNPs) in genes involved in lipid metabolism.
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- 2016
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13. Insulin-Like Growth Factor-I and -II Levels Are Associated with the Progression of Nonalcoholic Fatty Liver Disease in Obese Children.
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Cianfarani, Stefano, Inzaghi, Elena, Alisi, Anna, Germani, Daniela, Puglianiello, Antonella, and Nobili, Valerio
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Objective: To correlate circulating levels of insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein (IGFBP)-3 in a population of obese children with biopsy-proven nonalcoholic fatty liver disease (NAFLD) with clinical, biochemical, and histological features. Study design: We conducted a cross-sectional study at the Hepatometabolic Unit of the Bambino Gesù Children's Hospital, Rome, Italy. Obese children (42 girls and 57 boys) underwent liver biopsy, anthropometry, biochemical assessment, and IGF system evaluation. Serum concentrations of IGF-I, IGF-II, and IGFBP-3 were measured. The liver biopsy features of each case were graded according to the NAFLD Activity Scoring system. The degrees of steatosis, inflammation, ballooning, and fibrosis were calculated. Results: Nonalcoholic steatohepatitis was diagnosed in 14/99 obese subjects. Stepwise regression analysis revealed that IGF-I was the major predictor of ballooning (β = −0.463; P < .0001) and NAFLD activity score (β = −0.457; P < .0001), IGF-I/IGFBP-3 ratio was the major predictor of liver inflammation (β = -0.285; P = .005), and IGF-II was the major predictor of liver fibrosis (β = 0.343; P < .005). Conclusion: Circulating levels of IGF-I and IGF-II are associated with the histological stages of NAFLD and may represent novel markers of liver damage progression in obese children. [Copyright &y& Elsevier]
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- 2014
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14. Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with liver disease severity.
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Giorgio, Valentina, Miele, Luca, Principessa, Luigi, Ferretti, Francesca, Villa, Maria Pia, Negro, Valentina, Grieco, Antonio, Alisi, Anna, and Nobili, Valerio
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Abstract: Background: Increased intestinal permeability seems to play a major role in non-alcoholic liver disease development and progression. Aim: To investigate the prevalence of altered intestinal permeability in children with non-alcoholic fatty liver disease, and to study its potential association with the stage of liver disease. Methods: We performed a case–control study examining intestinal permeability in children using the lactulose–mannitol bowel permeability test. Results: Overall, 39 consecutive patients (30 males, median age 12 years) and 21 controls (14 males, median age 11.8 years) were included. The lactulose/mannitol ratio resulted impaired in 12/39 patients (31%) and none of the controls. Intestinal permeability was higher in children with non-alcoholic fatty liver disease (lactulose/mannitol ratios: 0.038±0.037 vs. 0.008±0.007, p <0.05). Within the non-alcoholic fatty liver disease group, intestinal permeability was increased in children with steatohepatitis compared to those with steatosis only (0.05±0.04 vs. 0.03 vs. 0.03, p <0.05). Pathological lactulose/mannitol ratio correlated with portal inflammation (p =0.02), fibrosis (p =0.0002), and ballooning of hepatocytes (p =0.003). Blood lipopolysaccharides levels were higher in children with steatohepatitis (2.27±0.68 vs. 2.80±0.35, p <0.05). Conclusions: Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with the severity of the disease. [Copyright &y& Elsevier]
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- 2014
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15. Non-alcoholic fatty liver disease.
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Della Corte, Claudia, Liccardo, Daniela, Mosca, Antonella, Vania, Andrea, and Nobili, Valerio
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THERAPEUTICS ,OBESITY complications ,FATTY liver ,METABOLIC syndrome ,SEDENTARY lifestyles ,DISEASE complications ,CHILDREN - Abstract
Abstract: Non-alcoholic fatty liver disease is rapidly becoming one of most common liver diseases in the paediatric population in industrialized countries due to the growing prevalence of obesity and overweight. Paediatric NAFLD is typically of primary origin and it is strongly associated with several features of the metabolic syndrome. The mainstay of NAFLD therapy is represented by lifestyle interventions on obesogenic environment and sedentary lifestyle, which aim to improve obesity, hepatic changes and quality of life as well. Unfortunately, this goal is very difficult to be achieved and pharmacological approaches have become necessary. Although in fairly recent years, many pharmacological agents, on the basis of pathogenetic mechanism of the disease, have been attempted, to date guidelines for the management of fatty liver are still lacking. Establishing effective therapeutic strategies to treat the disease represents the challenge for paediatric hepatologists in the near future. In this article, we briefly review the current knowledge and ideas concerning paediatric non-alcoholic fatty liver disease. [Copyright &y& Elsevier]
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- 2013
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16. Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: An input for novel therapies.
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Frasinariu, Otilia E., Ceccarelli, Sara, Alisi, Anna, Moraru, Evelina, and Nobili, Valerio
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Abstract: Non-alcoholic fatty liver disease is a multifactorial condition, ranging from simple steatosis to non-alcoholic steatohepatitis with or without fibrosis. In non-alcoholic fatty liver disease, alteration of gut microbiota and increased intestinal permeability increase exposure of the liver to gut-derived bacterial products: lipopolysaccharides and unmethylated CpG DNA. These products stimulate innate immune receptors, namely Toll-like receptors, which activate signalling pathways involved in liver inflammation and fibrogenesis. Currently, there are several studies on the involvement of lipopolysaccharide-activated Toll-like receptor 4 signalling in non-alcoholic fatty liver disease pathogenesis. There has been widespread interest in the study of the involvement of resident hepatic stellate cells and Kupffer cells activation in liver fibrogenesis upon TLR4 stimulation. Although the best evidence to support a role for gut microbiota in non-alcoholic fatty liver disease-induced fibrosis comes largely from animal models, data from human studies are accumulating and could lead to new therapeutic approaches. Therapeutic modulation of gut microflora may be an alternative strategy to develop an anti-fibrotic therapy. In this review, we discuss the relevant role of gut-liver axis in non-alcoholic liver disease-associated liver fibrosis and discuss the evidence on novel anti-fibrotic therapeutic approaches. [Copyright &y& Elsevier]
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- 2013
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17. A 360-degree overview of paediatric NAFLD: Recent insights
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Nobili, Valerio, Svegliati-Baroni, Gianluca, Alisi, Anna, Miele, Luca, Valenti, Luca, and Vajro, Pietro
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FATTY degeneration , *PEDIATRICS , *FIBROSIS , *JUVENILE diseases , *FATTY liver , *OBESITY , *DIAGNOSIS - Abstract
Summary: Non-alcoholic fatty liver disease (NAFLD) is a multi-faceted disorder, which ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) with/without fibrosis. The effects of specific risk factors, such as obesity and sedentary lifestyle, on predisposing genetic settings eventually lead to the development of NAFLD in children. The complex interplay between genes and environment in NAFLD pathogenesis is sustained by multiple mechanisms that involve liver crosstalk with other organs and tissues, especially gut and adipose tissue. Unfortunately, natural history of paediatric NAFLD is lacking, and the etiopathogenesis is still in the process of being defined. Potential early predictors and suitable non-invasive diagnostic tools can be discovered based on the pathogenetic mechanisms and histological patterns. This will also help design novel treatments and a comprehensive and successful management strategy for patients. In this review, we discuss the recent advances made in genetics, etiopathogenesis, diagnosis, and therapeutic management of NAFLD, focusing especially on the obesity-related steatotic liver condition. [ABSTRACT FROM AUTHOR]
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- 2013
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18. Nonalcoholic Fatty Liver in Children and Adolescents: An Overview.
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Della Corte, Claudia, Alisi, Anna, Saccari, Alessia, De Vito, Rita, Vania, Andrea, and Nobili, Valerio
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Abstract: Nonalcoholic fatty liver disease is rapidly becoming one of the most common liver diseases in the pediatric population in industrialized countries because of the growing prevalence of obesity and overweight. For this reason, there is a keen and broad interest among researchers to identify new diagnostic noninvasive tools and novel treatment modalities for this condition. Unfortunately, to date, liver biopsy remains the imperfect gold standard for diagnosis. In addition, available noninvasive markers are not fully satisfactory for the diagnosis of fatty liver. Although in recent years many pharmacological agents, on the basis of pathogenetic mechanism of the disease, have been attempted, to date, the guidelines for the management of fatty liver are still lacking. Establishing effective therapeutic strategies to treat the disease represents the challenge for pediatric hepatologists in the near future. In this article, we briefly review the current knowledge and ideas concerning pediatric nonalcoholic fatty liver disease, and discuss the new perspective therapies. [Copyright &y& Elsevier]
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- 2012
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19. Non-alcoholic fatty liver disease in children now: Lifestyle changes and pharmacologic treatments
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Alisi, Anna and Nobili, Valerio
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INSULIN resistance , *THERAPEUTIC use of vitamin E , *DOCOSAHEXAENOIC acid , *THIAZOLIDINEDIONES , *BEHAVIOR modification , *DIABETES , *DIETARY supplements , *FATTY liver , *HEALTH behavior , *METABOLIC regulation , *WEIGHT loss , *OXIDATIVE stress , *METABOLIC syndrome , *PHYSICAL activity , *CHILDREN , *PREVENTION , *THERAPEUTICS , *DISEASE risk factors - Abstract
Abstract: Over the past decade, non-alcoholic fatty liver disease (NAFLD) has become one of most common chronic liver diseases in children. A greater understanding about the risk factors and molecular pathogenesis of NAFLD suggests that lifestyle interventions aiming to decrease obesity/body mass index and metabolic derangement are the first line of treatments adopted in children affected by this disease. However, because these therapeutic options are often at the beginning misjudged by the patients and their parents, the use of pharmacologic agents may help to protect the liver and other organs from further irreversible tissue damage. Pharmacologic therapies against one or more specific factors and/or molecules involved in the development of NAFLD (i.e., insulin resistance, free fatty acid lipid toxicity, and oxidative stress) also might slow the progression of this increasingly prevalent pediatric disorder. On this basis, insulin sensitizers, antioxidants, cytoprotective agents, and dietary supplementations have been evaluated in pediatric clinical trials. In this review, we discuss the efficacy of the dietary approaches, possibly coupled with regular exercise, on decreasing the metabolic and histologic damage in pediatric NAFLD. We also emphasize several advantages of the pharmacologic treatments adopted or adoptable in combination with lifestyle interventions in children with NAFLD. [Copyright &y& Elsevier]
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- 2012
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20. The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver
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Valenti, Luca, Nobili, Valerio, Al-Serri, Ahmad, Rametta, Raffaela, Leathart, Julian B.S., Zappa, Marco A., Dongiovanni, Paola, Fracanzani, Anna L., Alterio, Arianna, Roviaro, Giancarlo, Daly, Ann K., Fargion, Silvia, and Day, Christopher P.
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FATTY liver , *DYSLIPIDEMIA , *INSULIN resistance , *SINGLE nucleotide polymorphisms , *GENETIC mutation , *LIPIDS - Abstract
Background & Aims: The T-455C and C-482T APOC3 promoter region polymorphisms (SNPs) have recently been reported to predispose to dyslipidemia, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) in Indian subjects, but the association with liver damage has not been evaluated so far. The aim was to assess the association between APOC3 SNPs and liver damage in Caucasian patients. Methods: We considered 437 Italian patients with histological diagnosis of NAFLD (including 137 children, 120 morbid obese) and 316 healthy controls, 71 Italian family trios, and 321 patients from the UK. APOC3 SNPs were determined by sequencing, allele-specific oligonucleotide probes and PCR–restriction fragment length polymorphism analysis, hepatic APOC3 mRNA levels by real-time PCR. Results: APOC3 SNPs were not associated with NAFLD in Italian subjects, although a borderline significance for the transmission of the −455T allele was observed in the family study. Homozygosity for the APOC3 wild-type genotype (APOC3 WT) was associated with a more favorable lipid profile in control subjects, and consistently with lower hepatic APOC3 mRNA levels in obese patients without diabetes. However, APOC3 SNPs, alone or in combination, were not associated with insulin resistance, altered lipid levels, liver enzymes, and with liver damage (severity of steatosis, nonalcoholic steatohepatitis, and moderate/severe fibrosis) in Italian as well as in UK patients, and in the whole cohort. Stratification for the I148M PNPLA3 mutation, associated with the susceptibility to NASH, did not alter the results. Conclusions: APOC3 genotype is not associated with progressive liver damage in Caucasian patients with NAFLD. [ABSTRACT FROM AUTHOR]
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- 2011
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21. Liver fibrosis in paediatric liver diseases.
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Alisi, Anna, de Vito, Rita, Monti, Lidia, and Nobili, Valerio
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FIBROSIS ,PEDIATRICS ,LIVER biopsy ,CIRRHOSIS of the liver ,DISEASE progression ,HISTOPATHOLOGY - Abstract
Numerous paediatric liver diseases from different origins may be complicated by development of liver fibrosis and progression to cirrhosis. Although fibrogenesis, which represents a major driving force for the development of liver fibrosis, has common tracts whatever the aetiology, liver fibrosis has different histopathological patterns in paediatric liver disease. In these diseases management choices may depend upon the stage of liver fibrosis. Thus, the accurate estimation of histological pattern of liver fibrosis is important for the prevention of the subsequent complications. Liver biopsy has long been considered as a gold standard diagnostic method for assessing liver fibrosis. However, due to its several disadvantages, in the last decades alternative and accurate non-invasive means to estimate fibrosis are developed. In this review, we characterised the most frequent histological patterns of liver fibrosis in paediatric liver diseases. Furthermore, we describe use of liver biopsy in diagnosis and staging of liver fibrosis, list the alternative non-invasive techniques that have an emerging role in the assessment of liver fibrosis, and propose a management algorithm. [ABSTRACT FROM AUTHOR]
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- 2011
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22. Relationship between portal chronic inflammation and disease severity in paediatric non-alcoholic fatty liver disease.
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Alisi, Anna, Bedogni, Giorgio, De Vito, Rita, Comparcola, Donatella, Manco, Melania, and Nobili, Valerio
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FATTY liver ,INFLAMMATION ,CHRONIC diseases ,JUVENILE diseases ,FIBROSIS ,BIOPSY ,DISEASES in teenagers - Abstract
Abstract: Background: The non-alcoholic steato-hepatitis Clinical Research Network has recently shown that portal chronic inflammation is associated with liver fibrosis in American children with non-alcoholic fatty liver disease. Aim: We tested whether the portal chronic inflammation-fibrosis association was present in a series of Italian children with non-alcoholic fatty liver disease. Methods: We re-assessed the liver biopsies of 144 consecutive Italian children with non-alcoholic fatty liver disease aged 3–18 years and followed at the “Bambino Gesù” Paediatric Hospital. Non-alcoholic fatty liver disease and portal chronic inflammation were diagnosed using the non-alcoholic steato-hepatitis Clinical Research Network criteria. Anthropometry, body composition, liver enzymes, metabolic parameters and blood pressure were measured in all children. Results: Two children had no portal chronic inflammation, 84 had mild and 58 more than mild portal chronic inflammation according to the non-alcoholic steato-hepatitis Clinical Research Network criteria. Children with no or mild portal chronic inflammation had the same clinical features of those with more than mild portal chronic inflammation except for insulin resistance, which was greater. There was no association between steatosis, lobular inflammation, ballooning, fibrosis and portal chronic inflammation. Conclusion: We were not able to confirm the existence of a clinico-pathological association between portal chronic inflammation and disease severity in a series of Italian children with non-alcoholic fatty liver disease. Some clinico-pathological correlates of paediatric non-alcoholic fatty liver disease may be population-specific. [ABSTRACT FROM AUTHOR]
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- 2011
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23. Hyaluronic acid predicts hepatic fibrosis in children with nonalcoholic fatty liver disease.
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Nobili, Valerio, Alisi, Anna, Torre, Giuliano, De Vito, Rita, Pietrobattista, Andrea, Morino, Giuseppe, De ville De Goyet, Jean, Bedogni, Giorgio, and Pinzani, Massimo
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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents, and it may progress to liver fibrosis and cirrhosis. Liver biopsy, which is the recognized gold standard for the diagnosis of hepatic fibrosis, is invasive. Thus, there has been increasing interest in the development of noninvasive markers. Hyaluronic acid (HA) has been shown to be a good marker of liver fibrosis in adults. In the current study, we evaluated the association of HA with liver fibrosis in 100 consecutive children with biopsy-proven NAFLD. In all, 65% of the children had liver fibrosis. Using proportional-odds ordinal logistic regression, we found that values of HA ≥ 1200 ng/mL made the absence of fibrosis (F0) unlikely (7%, 95% confidence interval [CI]: 1% to 14%), whereas values of HA ≥ 2100 ng/mL made F2, F3, or F4 fibrosis likely (89%, 95% CI: 75% to 100%). Our study shows that HA is a predictor of fibrosis in children with NAFLD followed at a tertiary care center. Additional studies are needed to test whether HA can be employed to predict liver fibrosis in pediatric populations with similar and lower prevalence of liver fibrosis. [ABSTRACT FROM AUTHOR]
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- 2010
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24. Pediatric Nonalcoholic Fatty Liver Disease in 2009.
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Alisi, Anna, Manco, Melania, Vania, Andrea, and Nobili, Valerio
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- 2009
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25. Retinol-Binding Protein 4: A Promising Circulating Marker of Liver Damage in Pediatric Nonalcoholic Fatty Liver Disease.
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Nobili, Valerio, Alkhouri, Naim, Alisi, Anna, Ottino, Simonetta, Lopez, Rocio, Manco, Melania, and Feldstein, Ariel E.
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CARRIER proteins ,VITAMIN A in the body ,BIOMARKERS ,LIVER injuries ,FATTY liver ,JUVENILE diseases ,BODY mass index ,GLUCOSE tolerance tests - Abstract
Background & Aims: Noninvasive methods are needed to identify pediatric nonalcoholic fatty liver disease (NAFLD), the most frequent chronic liver disease in children and adolescents in industrialized countries. Retinol-binding protein 4 (RBP4) is an adipocytokine that has been associated with the pathogenesis of insulin resistance. We tested the serum levels of RBP4 to assess their associations with the metabolic profile and histologic features in a large well-characterized group of children with NAFLD. Methods: The study included 59 children with biopsy-proven NAFLD. Histologic analyses were performed by an experienced hepatopathologist; the NAFLD activity score and fibrosis score were calculated for each patient. RBP4 levels in serum samples were measured by an enzyme-linked immunosorbent assay analysis. Anthropometric, blood pressure, and metabolic profile analyses (including glucose tolerance, fasting glucose, insulin, and lipid panel tests) were performed on samples from all patients. Results: Decreasing levels of RBP4 were associated significantly with increasing levels of serum triglyceride. High levels of RBP4 were associated significantly with low necroinflammatory activity, a low NAFLD activity score, and a low fibrosis score. Furthermore, serum RBP4 levels decreased significantly as disease severity increased; there was a stepwise decrease in RBP4 from children with steatosis (3.8 mg/dL) to borderline nonalcoholic steatohepatitis (2.9 mg/dL) to definitive nonalcoholic steatohepatitis (1.9 mg/dL) (P < .0001). This association remained significant after adjusting for other relevant clinical variables. Conclusions: Our study shows an inverse relationship between RBP4 levels and degree of liver damage. RBP4 therefore might be a potential novel noninvasive marker of severity of pediatric NAFLD. [Copyright &y& Elsevier]
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- 2009
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26. Performance of ELF Serum Markers in Predicting Fibrosis Stage in Pediatric Non-Alcoholic Fatty Liver Disease.
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Nobili, Valerio, Parkes, Julie, Bottazzo, Gianfranco, Marcellini, Matilde, Cross, Richard, Newman, Daniel, Vizzutti, Francesco, Pinzani, Massimo, and Rosenberg, William M.
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BIOMARKERS ,FATTY liver ,FIBROSIS ,LIVER biopsy ,MONOCLONAL antibodies ,BODY mass index ,JUVENILE diseases ,DEVELOPED countries - Abstract
Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease in children and adolescents in industrialized countries. It is important to accurately determine the stage of fibrosis in these patients. The enhanced liver fibrosis (ELF) test has been validated for staging liver fibrosis in adult patients with chronic liver diseases, including NAFLD. We investigated the performance of this test in assessing liver fibrosis in children and adolescents with NAFLD, identified by biopsy. Methods: The ELF test was performed on a panel of serum samples collected from 112 consecutive subjects that were likely to have NAFLD (64 male, mean age of 13.8 ± 3.3). A previously described and validated algorithm was used to analyze the data on hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels. Results: In pediatric patients with NAFLD, the ELF test predicted liver fibrosis stage with a high degree of sensitivity and specificity; results were superior to those reported for adults. The area under receiver operating characteristic curves/best possible ELF test cut-off values for the prediction of “any” (≥stage 1), moderate-perisinusoidal (≥stage 1b), moderate-portal/periportal (≥stage 1c), significant (≥stage 2), or advanced (≥stage 3) fibrosis were 0.92/9.28, 0.92/9.33, 0.90/9.54, 0.98/10.18 and 0.99/10.51, respectively. Conclusions: The ELF test can be used to accurately assess the level of liver fibrosis in pediatric patients with NAFLD. This information is important for identifying patients with progressive fibrosis that require further histopathological analysis or therapeutic follow-up. [Copyright &y& Elsevier]
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- 2009
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27. The Kruppel-Like Factor 6 Genotype Is Associated With Fibrosis in Nonalcoholic Fatty Liver Disease.
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Miele, Luca, Beale, Gary, Patman, Gillian, Nobili, Valerio, Leathart, Julian, Grieco, Antonio, Abate, Marilena, Friedman, Scott L., Narla, Goutham, Bugianesi, Elisabetta, Day, Christopher P., and Reeves, Helen L.
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LIVER diseases ,BODY mass index ,POLYMERASE chain reaction ,GENETIC polymorphisms - Abstract
Background & Aims: Although nonalcoholic fatty liver disease (NAFLD) is increasingly common, only a minority of affected individuals develop fibrotic liver disease. Based on its role in liver growth and repair, we explored whether Kruppel-like factor 6 (KLF6) plays a role in NAFLD progression. Methods: KLF6 expression in 31 fibrosis scored NAFLD liver biopsy specimens was assessed by real-time polymerase chain reaction. Transfected minigene constructs were used to study the effect of a polymorphism, KLF6-IVS1-27G>A, that promotes KLF6 alternative splicing in vitro. We genotyped KLF6-IVS1-27G>A in 3 groups of patients (UK group 1, n = 306; Italian group 2, n = 109; trio group 3, n = 61 children and parents). Results: KLF6 expression was increased in association with increased steatosis, inflammation, and fibrosis in NAFLD livers. KLF6-IVS1-27G>A promoted alternative splicing of KLF6 and abrogated the up-regulation of both α-smooth muscle actin and collagen 1 in LX-2 cells. Group 1 genotyping identified KLF6-IVS1-27G>A in 44 of 306 (14.4%) patients. Notably, KLF6-IVS1-27G>A was associated significantly with milder NAFLD, with only 25% having more advanced fibrosis compared with 45% of wild-type (wt) individuals. This trend was confirmed in group 2. A linear regression analysis including all 415 patients, adjusted for age, sex, body mass index, and blood glucose level, confirmed that presence of the wt KLF6 allele was an independent predictor of fibrotic NAFLD. Furthermore, we have shown preferential transmission of the wt allele to children with fibrotic NAFLD. Conclusions: We report a functional polymorphism in the KLF6 gene associated with advanced NAFLD and believe further study of KLF6 may enhance our understanding of this disease process. [Copyright &y& Elsevier]
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- 2008
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28. Metformin use in children with nonalcoholic fatty liver disease: An open-label, 24-month, observational pilot study
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Nobili, Valerio, Manco, Melania, Ciampalini, Paolo, Alisi, Anna, Devito, Rita, Bugianesi, Elisabetta, Marcellini, Matilde, and Marchesini, Giulio
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MEDICAL research , *METFORMIN , *GUANIDINES , *HYPOGLYCEMIC agents - Abstract
Abstract: Background: There is no consensus on the treatment of pediatric nonalcoholic fatty liver disease (NAFLD). However, in a small pilot study conducted in 10 children, metformin has been proposed to be effective. Objective: We aimed to determine the effect of metformin in addition to lifestyle intervention/modification in children with NAFLD. Methods: Overweight or obese children aged 9 to 18 years with biopsy-proven NAFLD or nonalcoholic steatohepatitis were enrolled in an observational pilot study, initially planned for 12 months, which aimed to estimate the effect of metformin on liver enzymes. The study was extended to 24 months to estimate outcomes on liver histology. All subjects received lifestyle intervention (nutritional counseling and a physical exercise regimen) and metformin 1.5 g/d (MET group). To serve as the control in this study, we selected a control group from a separate but parallel study (N = 30) that had identical inclusion criteria on the use of antioxidants in NAFLD. End points were changes in liver enzymes and histology. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment of IR (HOMA-IR) and liver biopsy was determined by the NAFLD activity score (NAS). Results: Sixty patients were assessed for inclusion in this study. However, 2 patients in the MET group dropped out of the study during the first year because they relocated abroad, and 1 patient in the control group refused follow-up after 12 months. Thus, study data is based on the findings in the 57 remaining patients. Alanine aminotransferase significantly improved from baseline with decreasing body weight in both groups (MET: 35 [range, 21–43] to 32 [20–46] U/L; control: 66 [28–121] to 33 [14–45] U/L; P ≤ 0.01). HOMA-IR significantly improved in both groups from baseline with decreasing body weight as well (MET: 1.4 [range, 0.5–5.11] to 1.3 [0.13–4.21]; control: 2.29 [0.86–5.76] to 1.5 [0.70–4.23]; P ≤ 0.01). Steatosis was reduced in both the MET (P = 0.02) and control (P = 0.02) groups as well as ballooning (both, P = 0.008). Lobular inflammation improved from baseline in the MET group (P = 0.003). The NAS score decreased from baseline (both, P = 0.001), but no significant changes in fibrosis were detected. Conclusion: In this small, 24-month observational study, metformin did not appear more effective than lifestyle intervention in ameliorating levels of aminotransferases, steatosis, and liver histology in these children with NAFLD. [Copyright &y& Elsevier]
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- 2008
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29. Glutathione metabolism and antioxidant enzymes in patients affected by nonalcoholic steatohepatitis
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Nobili, Valerio, Pastore, Anna, Gaeta, Laura Maria, Tozzi, Giulia, Comparcola, Daniela, Sartorelli, Maria Rita, Marcellini, Matilde, Bertini, Enrico, and Piemonte, Fiorella
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OXIDATIVE stress , *GLUTATHIONE , *BLOOD , *PATIENTS - Abstract
Abstract: Background: Oxidative stress and accumulation of excessive fat in the liver may underlie the pathophysiology of nonalcoholic steatohepatitis (NASH). Given that glutathione blood metabolism may represent an indicator of tissue oxidative status, we analysed the blood profile of various forms of glutathione in children with NASH, and we evaluated the presence of systemic oxidative stress by calculating the oxidised/reduced glutathione ratio (GSSG/GSH). Furthermore, we analysed the catalytic activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione transferase (GST), and glutathione reductase (GR) in blood of patients. Methods: Blood samples were obtained from 21 children with NASH and 28 controls. Total, reduced, oxidised, and protein-bound glutathione concentrations were determined by reversed-phase liquid chromatography with fluorescence detection. Antioxidant enzymes were spectrophotometrically assayed by using specific substrates. Results: Our findings showed a 1.5-fold increase of GSSG in patients, resulting in a significant rise of the GSSG/GSH ratio. SOD, GPx, and GR activities were not significantly different in NASH respect to controls, whereas GST, which provides the second defence line against oxidative stress, was 17.8% increased. Conclusions: Our data demonstrate an impairment of glutathione metabolism and antioxidant enzyme activities in blood of patients with NASH, supporting a consistent role of free radical cytotoxicity in the pathophysiology of the disease. [Copyright &y& Elsevier]
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- 2005
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30. Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease.
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Alisi, Anna, Da Sacco, Letizia, Bruscalupi, Giovannella, Piemonte, Fiorella, Panera, Nadia, De Vito, Rita, Leoni, Silvia, Bottazzo, Gian Franco, Masotti, Andrea, and Nobili, Valerio
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- 2011
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31. Lesson from epidemiology of paediatric Crohn's disease.
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Cucchiara, Salvatore, Isoldi, Sara, and Nobili, Valerio
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- 2019
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32. Programming, metabolic syndrome, and NAFLD: The challenge of transforming a vicious cycle into a virtuous cycle
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Nobili, Valerio, Cianfarani, Stefano, and Agostoni, Carlo
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- 2010
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33. Clinical observation paper: Fatty liver and metabolic syndrome: is it a burden for the future generations?
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Nobili, Valerio and Agostoni, Carlo
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- 2010
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34. The Contribution of the Adipose Tissue-Liver Axis in Pediatric Patients with Nonalcoholic Fatty Liver Disease after Laparoscopic Sleeve Gastrectomy.
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Franchitto, Antonio, Carpino, Guido, Alisi, Anna, De Peppo, Francesco, Overi, Diletta, De Stefanis, Cristiano, Romito, Ilaria, De Vito, Rita, Caccamo, Romina, Sonia, Battaglia, Alessandra, Salvatori, Mosca, Antonella, Alterio, Arianna, Onori, Paolo, Gaudio, Eugenio, and Nobili, Valerio
- Abstract
Objective: To evaluate the histopathologic modifications in liver and visceral adipose tissue (VAT), and to correlate these changes with clinical measures, adipokine production, and proinflammatory cytokines in a population of adolescents with obesity with nonalcoholic fatty liver disease (NAFLD) who underwent laparoscopic sleeve gastrectomy (LSG).Study Design: Twenty adolescents with obesity who underwent LSG and with biopsy-proven NAFLD were included. Patients underwent clinical evaluation and blood tests at baseline and 1 year after the surgical procedure. Liver and VAT specimens were processed for routine histology, immunohistochemistry, and immunofluorescence.Results: In adolescents with obesity and NAFLD, hepatic histologic alterations were uncorrelated with VAT inflammation. LSG induced in both liver and VAT tissue histopathology amelioration and macrophage profile modification that were correlated with body mass index and improvement in insulin resistance. The adipokine profile in liver and VAT was associated with weight loss and histologic improvement after LSG. Serum proinflammatory cytokines were correlated with liver and VAT histopathology and IL-1β and IL-6 levels were independently predicted by liver necroinflammatory grade.Conclusions: This study suggests a unique adipose tissue/fatty liver crosstalk in pediatric patients. LSG induces a similar pattern of histologic improvement in the liver and in VAT. Besides VAT, our results strengthen the role of the liver in adipocytokine production and its contribution to systemic inflammation in pediatric patients with NAFLD. [ABSTRACT FROM AUTHOR]- Published
- 2020
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35. Reply to: “Energy drinks and adolescents – A hepatic health hazard?”.
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Nobili, Valerio, Mosca, A., Scorletti, E., and Byrne, Christopher D.
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ENERGY drinks , *HEPATITIS - Published
- 2018
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36. HCV and steatosis in children
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Comparcola, Donatella, Nobili, Valerio, and Marcellini, Matilde
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- 2006
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37. The Role of Genetic Predisposition, Programing During Fetal Life, Family Conditions, and Post-natal Diet in the Development of Pediatric Fatty Liver Disease.
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Mosca, Antonella, De Cosmi, Valentina, Parazzini, Fabio, Raponi, Massimiliano, Alisi, Anna, Agostoni, Carlo, and Nobili, Valerio
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Objective: To evaluate, in patients with nonalcoholic fatty liver disease (NAFLD), the role of lifetime exposures associated with genetic predisposition, family history (parental obesity, economic income), programming during fetal life (gestational age, birthweight), being breastfed or not, and later biomarkers of dietary habits and lifestyle in the development of fibrosis.Study Design: In total, 182 children with overweight/obesity diagnosed with NAFLD proven by biopsy results were enrolled in our study and evaluated for liver fibrosis. We estimated prevalence ORs of fibrosis according to genetics, parental obesity, occupational socioeconomic status (SES), birth weight, breastfeeding, fructose intake (indicator of junk food consumption), and vitamin D status (inflammatory indicator) using logistic regression models, adjusted for age and children's body mass.Results: One hundred thirty-seven patients (75.3%) had liver fibrosis, and 45 patients (24.7%) did not have liver fibrosis. The ORs of fibrosis were significant (P < .05) for patatin like phospholipase domain-containing 3-GG genotype (OR 2.1), parental obesity (OR 2.9), not being breastfed (OR 3.1), vitamin D status (<20 mg/dL) (OR 1.24), and fructose consumption (OR 1.6 per 1 g/day increase), whereas a high SES maternal occupation was inversely associated with fibrosis (OR 0.30).Conclusions: Our results show independent roles of the patatin like phospholipase domain-containing 3 gene, parental obesity, maternal SES, and postnatal diet and lifestyle in the development of progressive liver disease secondary to NAFLD. [ABSTRACT FROM AUTHOR]- Published
- 2019
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38. Evaluations of Lifestyle, Dietary, and Pharmacologic Treatments for Pediatric Nonalcoholic Fatty Liver Disease: A Systematic Review.
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Mann, Jake Peter, Tang, George Yizhou, Nobili, Valerio, and Armstrong, Matthew James
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There are no approved treatments for pediatric nonalcoholic fatty liver disease (NAFLD) and there is a lack of consensus on the best outcome measure for randomized controlled trials. We performed a systematic review of treatments tested for pediatric NAFLD, the degree of heterogeneity in trial design, and endpoints analyzed in these studies. We searched publication databases and clinical trial registries through January 7, 2018 for randomized controlled trials (published and underway) of children (<18 years) with NAFLD. We assessed improvements in histologic features, radiologic and biochemical markers of reduced fibrosis, metabolic syndrome parameters, and adverse events. The quality of the trials was assessed using a modified version of the Cochrane risk of bias tool. Our final analysis included 21 randomized controlled trials, comprising 1307 participants (mean age, 12.6 years; 63% male; mean duration of intervention, 8 months). Most studies evaluated weight loss with lifestyle intervention (n=8), oral polyunsaturated fatty acid treatment (PUFAs, n=6), or oral antioxidant treatment (n=7). Biomarkers of NAFLD decreased with weight loss, but most studies did not include histologic data. Trials of antioxidants were heterogeneous; some reported reduced histologic features of steatohepatitis with no effect on triglycerides or insulin resistance. PUFAs and probiotics reduced radiologic markers of steatosis, insulin resistance, and levels of triglycerides. Only 38% of the trials had biopsy-proven NAFLD as an inclusion criterion. There was heterogeneity in trial primary endpoints; 10 studies (48%) used levels of aminotransferases or ultrasonography findings as a primary endpoint and only 3 trials (14%) used histologic features as the primary endpoint. We identified 13 randomized controlled trials that are underway in children with NAFLD. None of the protocols include collection of liver biopsies; 9 trials (69%) will use magnetic resonance imaging quantification of steatosis as a primary outcome. In a systematic review of published and active randomized controlled trials of children with NAFLD, we found a large amount of heterogeneity in study endpoints and inclusion criteria. Few trials included histologic analyses. Antioxidants appear to reduce some features of steatohepatitis. Effects of treatment with lifestyle modification, PUFAs, or probiotics have not been validated with histologic analysis. Trials that are underway quantify steatosis magnetic resonance imaging—outcomes are anticipated. [ABSTRACT FROM AUTHOR]
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- 2019
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39. Laparoscopic Sleeve Gastrectomy Improves Nonalcoholic Fatty Liver Disease-Related Liver Damage in Adolescents by Reshaping Cellular Interactions and Hepatic Adipocytokine Production.
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Nobili, Valerio, Carpino, Guido, De Peppo, Francesco, Caccamo, Romina, Mosca, Antonella, Romito, Ilaria, Overi, Diletta, Franchitto, Antonio, Onori, Paolo, Alisi, Anna, and Gaudio, Eugenio
- Abstract
Objectives: To investigate whether the modulation of local cellular cross-talks and the modification of hepatic adipocytokine expression could mechanistically explain the improvement of liver histopathology after laparoscopic sleeve gastrectomy (LSG) in adolescents with nonalcoholic fatty liver disease (NAFLD).Study Design: Twenty obese (body mass index of ≥35 kg/m2) adolescents who underwent LSG and with biopsy-proven NAFLD were included. At baseline (T0) and 1 year after treatment, patients underwent clinical evaluation, blood tests, and liver biopsy. Hepatic progenitor cells, hepatic stellate cells (HSCs), macrophages, and adipocytokines were evaluated by immunohistochemistry and immunofluorescence.Results: Liver biopsy samples after LSG demonstrated a significant improvement of NAFLD Activity Score and fibrosis. Immunohistochemistry indicated a significant reduction of hepatocyte cell cycle arrest, ductular reaction, activated HSC, and macrophage number after LSG compared with T0. The activation state of HSC was accompanied by modification in the expression of the autophagy marker LC3. Hepatocyte expression of adiponectin was significant higher after LSG than into T0. Moreover, LSG caused decreased resistin expression in Sox9+ hepatic progenitor cells compared with T0. The number of S100A9+ macrophages was also reduced by LSG correlating with resistin expression. Finally, serum levels of proinflammatory cytokines significantly correlated with macrophages and activated HSC numbers.Conclusions: The histologic improvement induced by LSG is associated with the reduced activation of local cellular compartments (hepatic progenitor cells, HSCs, and macrophages), thus, strengthening the role of cellular interactions and hepatic adipocytokine production in the pathogenesis of NAFLD. [ABSTRACT FROM AUTHOR]- Published
- 2018
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40. Nonalcoholic Fatty Liver Disease in Italian Children with Down Syndrome: Prevalence and Correlation with Obesity-Related Features.
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Valentini, Diletta, Alisi, Anna, di Camillo, Chiara, Sartorelli, Maria Rita, Crudele, Annalisa, Bartuli, Andrea, Nobili, Valerio, and Villani, Alberto
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Objective: To assess the prevalence of overweight/obesity in a cohort of Italian children with Down syndrome (DS) and to investigate the correlation of both obesity and DS with nonalcoholic fatty liver disease (NAFLD).Study Design: We enrolled 280 children with DS (age range 5-18 years), who were referred to the DS outpatient clinic of the Bambino Gesù Children's Hospital in Rome. For all children, we collected the clinical history and measured anthropometric variables. Eighty-four of 280 children with DS were selected to undergo liver ultrasound scanning to evaluate the presence of NAFLD.Results: Italian children with DS exhibited a prevalence of 19.64% for overweight and 12.14% for obesity. The prevalence of NAFLD in nonobese (45%) and overweight/obese (82%) children with DS is greater than in the European pediatric nonobese (5.7%) or obese population (33%). Moreover, the severity of liver brightness on ultrasound scan correlated positively with body mass index, triglycerides, low-density lipoprotein-cholesterol, and leptin levels and negatively with adiponectin.Conclusions: We demonstrated that, independently from the obese phenotype, children with DS display a greater risk to develop NAFLD than the general pediatric population. [ABSTRACT FROM AUTHOR]- Published
- 2017
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41. The Benefit of Sleeve Gastrectomy in Obese Adolescents on Nonalcoholic Steatohepatitis and Hepatic Fibrosis.
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Manco, Melania, Mosca, Antonella, De Peppo, Francesco, Caccamo, Romina, Cutrera, Renato, Giordano, Ugo, De Stefanis, Cristiano, Alisi, Anna, Baumann, Ulrich, Silecchia, Gianfranco, and Nobili, Valerio
- Abstract
Objective: To determine whether bariatric surgery is effective for the treatment of nonalcoholic steatohepatitis (NASH) in adolescence, we compared the efficacy of laparoscopic sleeve gastrectomy (LSG) with that of lifestyle intervention (nonsurgical weight loss [NSWL]) for NASH reversal in obese adolescents.Study Design: Obese (body mass index ≥ 35 kg/m2) adolescents (13-17 years of age) with biopsy-proven NAFLD underwent LSG, lifestyle intervention plus intragastric weight loss devices (IGWLD), or only NSWL. At baseline and 1 year after treatment, patients underwent clinical and psychosocial evaluation, blood tests, liver biopsy, polysomnography, and 24-hour ambulatory blood pressure estimation.Results: Twenty patients (21%) underwent LSG, 20 (21%) underwent IGWLD, and 53 (58%) received lifestyle intervention alone (NSWL). One year after treatment, patients who underwent LSG lost 21.5% of their baseline body weight, whereas patients who underwent IGWLD lost 3.4%, and patients who underwent NSWL increase 1.7%. In patients who underwent LSG, NASH reverted completely in all patients and hepatic fibrosis stage 2 disappeared in 18 patients (90%). After IGWLD, NASH reverted in 6 patients (24%) and fibrosis in 7 (37%). Patients who received the NSWL intervention did not improve significantly. Hypertension resolved in all patients who underwent LSG with preoperative hypertension (12/12) versus 50% (4/8) of the patients who underwent IGWLD (P = .02). The cohort-specific changes in impaired glucose metabolism were similar: 100% (9/9) of affected patients who underwent LSG versus 50% (1/2) of patients who underwent IGWLD (P = .02). LSG was also more affective in resolving dyslipidemia (55% [7/12] vs 26% [10/19]; P = .05) and sleep apnea (78% [2/9] vs 30% [11/20]; P = .001).Conclusion: LSG was more effective than lifestyle intervention, even when combined with intragastric devices, for reducing NASH and liver fibrosis in obese adolescents after 1 year of treatment. [ABSTRACT FROM AUTHOR]- Published
- 2017
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42. Effect of treatment with polyunsaturated fatty acids on HCV- or diet-induced fatty liver
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Comparcola, Donatella, Nobili, Valerio, Alisi, Anna, and Balsano, Clara
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- 2011
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43. The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent.
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Mancina, Rosellina Margherita, Dongiovanni, Paola, Petta, Salvatore, Pingitore, Piero, Meroni, Marica, Rametta, Raffaela, Borén, Jan, Montalcini, Tiziana, Pujia, Arturo, Wiklund, Olov, Hindy, George, Spagnuolo, Rocco, Motta, Benedetta Maria, Pipitone, Rosaria Maria, Craxì, Antonio, Fargion, Silvia, Nobili, Valerio, Käkelä, Pirjo, Kärjä, Vesa, and Männistö, Ville
- Abstract
Background & Aims Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene ( MBOAT7 , also called LPIAT1 ) and transmembrane channel-like 4 gene ( TMC4 ) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7−TMC4 is a susceptibility locus for the development and progression of NAFLD. Methods We genotyped rs641738 in DNA collected from 3854 participants from the Dallas Heart Study (a multi-ethnic population-based probability sample of Dallas County residents) and 1149 European individuals from the Liver Biopsy Cross-Sectional Cohort. Clinical and anthropometric data were collected, and biochemical and lipidomics were measured in plasma samples from participants. A total of 2736 participants from the Dallas Heart Study also underwent proton magnetic resonance spectroscopy to measure hepatic triglyceride content. In the Liver Biopsy Cross-Sectional Cohort, a total of 1149 individuals underwent liver biopsy to diagnose liver disease and disease severity. Results The genotype rs641738 at the MBOAT7−TMC4 locus associated with increased hepatic fat content in the 2 cohorts, and with more severe liver damage and increased risk of fibrosis compared with subjects without the variant. MBOAT7 , but not TMC4 , was found to be highly expressed in the liver. The MBOAT7 rs641738 T allele was associated with lower protein expression in the liver and changes in plasma phosphatidylinositol species consistent with decreased MBOAT7 function. Conclusions We provide evidence for an association between the MBOAT7 rs641738 variant and the development and severity of NAFLD in individuals of European descent. This association seems to be mediated by changes in the hepatic phosphatidylinositol acyl-chain remodeling. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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44. Tu1723 Extrahepatic Complications Are Extremely Common in Children With Nonalcoholic Fatty Liver Disease (NAFLD) and Their Frequency Correlates With NAFLD Histologic Severity.
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Alkhouri, Naim, Selvakumar, Praveen Kumar Conjeevaram, Kabbany, Mohammad Nasser, Lopez, Rocio, Mosca, Antonella, Corte, Claudia Della, and Nobili, Valerio
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- 2016
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45. Tu1721 Reduced Lysosomal Acid Lipase Activity - A Potential Role in the Pathogenesis of Non Alcoholic Fatty Liver Disease in Pediatric Patients?
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Selvakumar, Praveen Kumar Conjeevaram, Kabbany, Mohammad Nasser, Lopez, Rocio, Tozzi, Giulia, Alkhouri, Naim, and Nobili, Valerio
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- 2016
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46. Molecular genetics of NASH: The role of polymorphisms
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Alisi, Anna and Nobili, Valerio
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- 2007
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47. Mo1196 Lysosomal Acid Lipase Activity in Dried Blood Spots Correlates With the Severity of Hepatic Steatosis and Features of the Metabolic Syndrome in Children.
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Alkhouri, Naim, Ferrari, Federica, Tozzi, Giulia, and Nobili, Valerio
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- 2015
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48. Non-alcoholic fatty liver disease and non-alcoholic fatty pancreas disease: A new intriguing association?
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Della Corte, Claudia, Mosca, Antonella, Sartorelli, Maria Rita, Comparcola, Donatella, Liccardo, Daniela, Alterio, Arianna, Lucidi, Vincenzina, and Nobili, Valerio
- Published
- 2014
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49. Safety of ultrasound-guided-percutaneous core needle liver biopsies of pediatric patients: A single center experience.
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Pietrobattista, Andrea, Giorgio, Valentina, Rollo, Massimo, Fruhwirth, Rodolfo, Alterio, Arianna, Candusso, Manila, Nobili, Valerio, and Torre, Giuliano
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- 2014
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50. A single-centre, tertiary-care, Italian registry of celiac disease: Incidence and clinical presentation.
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Giorgio, Valentina, Sartorelli, Maria Rita, Della Corte, Claudia, Comparcola, Donatella, Liccardo, Daniela, Alterio, Arianna, Nobili, Valerio, and Ferretti, Francesca
- Published
- 2014
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