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Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease

World Journal of Gastroenterology 2014年第45期20卷 17107-17114页

作者： Lucia Pacifico Enea Bonci Lidia Marandola sara romaggioli Stefano Bascetta Claudio Chiesa Department of Pediatrics and Child Neuropsychiatry Sapienza University of Rome Department of Experimental Medicine Sapienza University of Rome Institute of Translational Pharmacology National Research Council

AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was performed.Cases were 40 obese children with NAFLD.The diagnosis of NAFLD was based on magnetic resonance imaging(MRI)with high hepatic fat fraction(HFF≥5%),and confirmed by liver biopsy with≥5%of hepatocytes containing macrovesicular fat.Controls were selected from obese children with normal levels of aminotransferases,and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases.Controls were matched(1-to 1)with the cases on age,gender,pubertal stage and as closely as possible on body mass index-standard deviation score.All participants underwent clinical examination,laboratory testsincluding zonulin,inflammatory and metabolic parameters,and MRI for measurement of HFF and visceral adipose tissue.RESULTS:Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD[median(interquartile range),4.23(3.18-5.89)vs 3.31(2.05-4.63),P<0.01].In patients with NAFLD,zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis(r=0.372,P<0.05);however,we did not find a significant correlation between zonulin and lobular inflammation(P=0.23),ballooning(P=0.10),fibrosis score(P=0.18),or presence of nonalcoholic steatohepatitis(P=0.17).Within the entire study population,zonulin levels were positively associated with gamma-glutamyl transferase,2-h insulin,HFF,and negatively associated with whole-body insulin sensitivity index(WBISI),after adjustment for age,gender and pubertal status.When the associations were restricted to the group of NAFLD patients,2-h insulin,hepatic fat,and WBISI retained statistical significance.CONCLUSION:Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of ste

关键词： Zonulin Intestinal permeability Nonalco-holic fatt

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Probiotics for the treatment of Helicobacter pylori infection in children

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World Journal of Gastroenterology 2014年第3期20卷 673-683页

作者： Lucia Pacifico John Frederick Osborn Enea Bonci sara romaggioli Rossella Baldini Claudio Chiesa Department of Pediatrics and Child Neuropsychiatry Sapienza University of Rome Department of Health Sciences and Infectious Diseases Sapienza University of Rome Department of Experimental Medicine Sapienza University of Rome Department of Human Anatomy Sapienza University of Rome Institute of Translational Pharmacology National Research Council

The combination of a proton pump inhibitor and two antibiotics(clarithromycin plus amoxicillin or metronidazole)has been the recommended first-line therapy since the first guidelines for Helicobacter pylori(H.pylori)infection in children were published.In recent years,the success of eradication therapies has declined,in part due to the development of H.pylori resistant strains.Alternative anti-H.pylori treatments are currently becoming more popular than the traditional eradication methods.Components that may be used either as a monotherapy or,in combination with antimicrobials,resulting in a more effective anti-H.pylori therapy have been investigated in depth by several researchers.One of the potential therapies is probiotic cultures;promising results have been observed in initial studies with numerous probiotic strains.Nevertheless,many questions remain unanswered.In this article,we comprehensively review the possible mechanisms of action of probiotics on H.pylori infection,and present the results of published studies using probiotics as possible agents to control H.pylori infection in children.The effect of the addition of probiotics to the standard H.pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed.

关键词： Helicobacter pylori Children Probiotics Eradicatio

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Helicobacter pylori infection and extragastric disorders in children: A critical update

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World Journal of Gastroenterology 2014年第6期20卷 1379-1401页

作者： Lucia Pacifico John F Osborn Valeria Tromba sara romaggioli Stefano Bascetta Claudio Chiesa Department of Pediatrics Sapienza University of Rome Department of Health Sciences and Infectious Diseases Sapienza University of Rome Institute of Translational Pharmacology National Research Council

Helicobacter pylori(H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in thelast decades, abetted by modern clinical practices, may have other health consequences.

关键词： Helicobacter pylori Children Iron defi-ciency anem

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Adipokines and C-reactive protein in relation to bone mineralization in pediatric nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2013年第25期19卷 4007-4014页

作者： Lucia Pacifico Mario Bezzi Concetta Valentina Lombardo sara romaggioli Flavia Ferraro Stefano Bascetta Claudio Chiesa Department of Pediatrics Sapienza University of Rome Department of Radiological Sciences Sapienza University of Rome Department of Radiological Sciences Sapienza University of Rome 00161 Rome Italy Institute of Translational Pharmacology National Research Council

AIM: To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein (HSCRP). METHODS: A case-control study was performed. Cases were 44 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (≥ 5%). Other causes of chronic liver disease were ruled out. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1-basis) with thecases on age, gender, pubertal stage and as closely as possible on body mass index-SD score. All participants underwent clinical examination, laboratory tests, and whole body (WB) and lumbar spine (LS) BMD by dual energy X-ray absorptiometry. BMDZ-scores were calcu- lated using race and gender specific LMS curves. RESULTS: Obese children with NAFLD had a significantly lower LS BMDZ-score than those without NAFLD [mean, 0.55 (95%CI: 0.23-0.86) vs 1.29 (95%CI: 0.95-1.63); P < 0.01]. WB BMD Z-score was also decreased in obese children with NAFLD compared to obese children with no NAFLD, though borderline significance was observed [1.55 (95%CI: 1.23-1.87) vs 1.95 (95%CI: 1.67-2.10); P = 0.06]. Children with NAFLD had significantly higher HSCRP, lower adiponectin, but similar leptin levels. Thirty five of the 44 children with MRI-diagnosed NAFLD underwent liver biopsy. Among the children with biopsy-proven NAFLD, 20 (57%) had nonalcoholic steatohepatitis (NASH), while 15 (43%) no NASH. Compared to children without NASH, those with NASH had a significantly lower LS BMD Z-score [mean, 0.27 (95%CI: -0.17-0.71) vs 0.75 (95%CI: 0.13-1.39); P < 0.05] as well as a significantly lower WB BMD Z-score [1.38 (95%CI: 0.89-1.17) vs 1.93 (95%CI: 1.32-2.36); P < 0.05]. In multiple regression analysis, NASH (standardized β coefficient, -0.272; P < 0

关键词： Bone mineralization Dual energy X-ray absorptiometry Adipokines C-reactive protein Nonalcoholic fatty liver disease Children

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Nonalcoholic fatty liver disease and the heart in children and adolescents

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World Journal of Gastroenterology 2014年第27期20卷 9055-9071页

作者： Lucia Pacifico Claudio Chiesa Caterina Anania Antonio De Merulis John Frederick Osborn sara romaggioli Eugenio Gaudio Department of Pediatrics and Child Neuropsychiatry Sapienza University of Rome Institute of Translational Pharmacology National Research Council Department of Public Health and Infectious Diseases Sapienza University of Rome Department of Human Anatomy HistologyForensic Medicine and Orthopedics Sciences Sapienza University of Rome

Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome(MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.

关键词： Nonalcoholic fatty liver disease Children Atherosc

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