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Pediatric non-alcoholic fatty liver disease:Preventive and therapeutic value of lifestyle intervention

World Journal of Gastroenterology 2009年第48期15卷 6017-6022页

作者： valerio nobili Anna Alisi Massimiliano Raponi Liver Unit Research InstituteBambino Gesù Children's Hospital Liver Unit Research InstituteBambino Gesù Children’s Hospital Health Planning Department Research Institute Bambino Gesù Children’s Hospital

Nonalcoholic fatty liver disease(NAFLD),ranging from simple steatosis to nonalcoholic steatohepatitis(NASH),and eventually cirrhosis and liver failure,is seen to be increasing amongst Western children.NAFLD rates are rising in parallel with the epidemic of childhood obesity,and in particular,fatty liver evolves more easily in NASH when poor dietary habits and sedentary lifestyle are combined.In fact,its general prevalence in the child population varies between 2.6% and 10%,but increases up to 80% in obese children.Since NASH is expected to become the most common cause of pediatric chronic liver disease in the near future,there is broad interest amongst clinical researchers to move forward,both in diagnosis and treatment.Unfortunately,to date,the expensive and invasive procedure of liver biopsy is seen as the gold standard for NASH diagnosis and few noninvasive diagnostic methods can be applied successfully.Moreover,there are still no approved pharmacological interventions for NAFLD/NASH.Therefore,current management paradigms are based upon the presence of associated risk factors and aims to improve an individual's quality of life,thus reducing NAFLD-associated morbidity and mortality.Today,lifestyle intervention(diet and exercise) is the treatment of choice for NAFLD/ NASH.Thus far,no study has evaluated the potential preventive effect of lifestyle intervention on children at risk of NAFLD/NASH.Future studies will be required in this area with the perspective of developing a national program to promote nutrition education and increase physical activity as means of preventing the disease in individuals at risk.Here,we outline the clinical course,pathogenesis and management of NAFLD in children,highlighting the preventive and therapeutic value of lifestyle intervention.

关键词：生活方式肝疾病酒精性价值治疗预防脂肪小儿

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NGM282: a step forward in the nonalcoholic steatohepatitis treatment landscape?

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Hepatobiliary Surgery and Nutrition 2018年第6期7卷 484-486页

作者： Luca Valenti valerio nobili Internal Medicine and Metabolic Diseases Fondazione IRCCS Ca’Granda Ospedale Policlinico MilanoDepartment of Pathophysiology and TransplantationUniversitàdegli Studi di MilanoMilanItaly Hepatology Gastroenterology and Nutrition UnitIRCCS“Bambino Gesù”Children’s HospitalRomeItaly Department of Pediatric University“La Sapienza”RomeItaly

Nonalcoholic fatty liver disease(NAFLD)is becoming the leading cause of liver disease worldwide,and the prevalence is still increasing,especially during the developmental age(1-3).NAFLD is defined in the presence of increased hepatic fat content not explained by at risk alcohol intake,and is epidemiologically associated with obesity,insulin resistance and metabolic disorders.

关键词： NAFLD intake hepatic

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Pediatric nonalcoholic fatty liver disease,metabolic syndrome and cardiovascular risk

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世界胃肠病学杂志：英文版 2011年第26期17卷 3082-3091页

作者： Lucia Pacifico valerio nobili Caterina Anania Paola Verdecchia Claudio Chiesa Department of Pediatrics Sapienza University of Rome Department of Hepato-gastroenterology and Nutrition Pediatric Hospital "Bambino Gesù" Institute of Translational Pharmacology National Research Council

Nonalcoholic fatty liver disease(NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use.The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes.A more advanced form of NAFLD,nonalcoholic steatohepatitis,includes inflammation and liver cell injury,progressive to cryptogenic cirrhosis.NAFLD has become the most common cause of chronic liver disease in children and adolescents.The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide.NAFLD is strongly associated with abdominal obesity,type 2 diabetes,and dyslipidemia,and most patients have evidence of insulin resistance.Thus,NAFLD shares many features of the metabolic syndrome(MetS),a highly atherogenic condition,and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis.Accumulating evidence suggests thatNAFLD is associated with a significantly greater overall mortality than in the general population,as well as with increased prevalence of cardiovascular disease(CVD),independently of classical atherosclerotic risk factors.Yet,several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS.Therefore,the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes.In children,the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively.Therapeutic goals for NAFLD should address nutrition,physical activity,and avoidance of smoking to prevent not only end-stage liver disease but also CVD.

关键词：心血管疾病脂肪肝病代谢综合征酒精性肝疾病动脉粥样硬化小儿风险

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Therapeutic strategies for pediatric non-alcoholic fatty liver disease: A challenge for health care providers

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World Journal of Gastroenterology 2007年第18期13卷 2639-2641页

作者： valerio nobili Melania Manco Liver Unit Bambino Gesù Children's Hospital and Research Institute Rome Italy

Non-alcoholic steato-hepatitis (NASH) is related to insulin resistance and, thus, frequently occurs as part of the metabolic changes that accompany obesity, diabetes and hyperlipidemia. In childhood, the overwhelming boost of obesity and its co-morbidities have lead to the extraordinarily increased prevalence of NASH. Establishing effective therapeutic strategies to treat the disease represents the challenge for hepatologists and gastroenterologists in the next decade. Therapeutic approaches have aimed at treating associated conditions (obesity, insulin resistance, hyperlipemia, etc ) or reducing liver oxidative damage (vitamin E).

关键词：儿童非酒精性脂肪肝治疗策略饮食卫生保健

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Extrahepatic portal vein thrombosis in children and adolescents:Influence of genetic thrombophilic disorders

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World Journal of Gastroenterology 2010年第48期16卷 6123-6127页

作者： Andrea Pietrobattista Matteo Luciani Juan G Abraldes Manila Candusso Simona Pancotti Massimo Soldati Lidia Monti Giuliano Torre valerio nobili Liver Unit Research InstituteBambino Gesù Children's Hospital Department of Hematology Bambino Gesù Children's Hospital Hepatic Hemodynamic Laboratory Liver UnitHospital ClínicIDIBAPS and CIBERhedUniversity of Barcelona Department of Laboratory Pediatrics Bambino Gesù Children's Hospital Radiology Department Bambino Gesù Children's Hospital

AIM:To explore the prevalence of local and genetic thrombophilic disorders as risk factors for portal vein thrombosis (PVT) in our series,the largest ever published in pediatric literature. METHODS:We conducted a case-control study enrolling 31 children with PVT and 26 age-matched controls. All were screened for thrombophilia,including genetic disorders,protein C,protein S and homocysteine deficiencies. All coagulation parameters were studied at least 3 mo after the diagnosis of portal vein obstruction.RESULTS:In our study we showed that most pediatric patients with PVT have local prothrombotic risk factors,which are probably the most important factors leading to PVT. However,there is a clear association between the presence of prothrombotic disorders and PVT,suggesting that these increase the risk of thrombosis in patients with local factors such as perinatal umbilical vein catheterization or sepsis. CONCLUSION:Patients with PVT should be screened for inherited prothrombotic disorders regardless of a history of an obvious local risk factor.

关键词： Portal vein thrombosis Children Thrombophilic disorders Protein C Protein S

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Epidemiology of fatty liver: An update

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World Journal of Gastroenterology 2014年第27期20卷 9050-9054页

作者： Giorgio Bedogni valerio nobili Claudio Tiribelli Liver Research Center Fondazione Italiana Fegato-ONLUS 34013 Trieste Italy International Center for the Assessment of Nutritional Status University of Milan 20126 Milan Italy Liver Research Unit Bambino Gesù Children’s Hospital IRCCS 00149 Rome Italy Department of Medical Sciences University of Trieste 34013 Trieste Italy

We provide a concise review of the main epidemiological literature on fatty liver(FL) published between January 2011 and October 2013. The findings from the literature will be considered in light of the already available knowledge. We discuss the limitations inherent in the categorization of FL into non-alcoholic and alcoholic FL, the potential relevance of FL as an independent predictor of cardiometabolic disease, and recent research addressing the role of FL as an independent predictor of mortality. This review is organized as a series of answers to relevant questions about the epidemiology of FL.

关键词： Fatty liver Epidemiology

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Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease

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World Journal of Gastroenterology 2014年第44期20卷 16443-16451页

作者： Sara Ceccarelli valerio nobili Anna Alisi Hepato-Metabolic Disease Unit and Liver Research Unit Bambino Gesù Children’s Hospital IRCCS

Chronic abuse of alcohol leads to various histological abnormalities in the liver. These are conditions collectively known as alcoholic liver disease(ALD). Currently, ALD is considered to be one of the major causes of death worldwide. An impaired intestinal barrier with related endotoxemia is among the various pathogenetic factors. This is mainly characterized by circulating levels of lipopolysaccharide(LPS), considered critical for the onset of intra-hepatic inflammation. This in turn promotes hepatocellular damage and fibrosis in ALD. Elevated levels of LPS exert their effects by binding to Toll-like receptors(TLRs) which are expressed by all liver-resident cells. The activation of TLR signaling triggers an overproduction and release of some cytokines, which promote an autocatalytic cascade of other proinflammatory signals. In this review, we provide an overview of the mechanisms that sustain LPS-mediated activation of TLR signaling, reporting current experimental and clinical evidence of its role during inflammation in ALD.

关键词： Alcoholic liver disease Toll-like receptors Inflam

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Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2006年第48期12卷 7821-7825页

作者： Angelo Iacobellis Matilde Marcellini Angelo Andriulli Francesco Perri Gioacchino Leandro Rita Devito valerio nobili Division of Gastroenterology Hospital "Casa Sollievo della Sofferenza" IRCCS San Giovanni Rotondo Italy Liver Unit Bambino Gesu' Children's Hospital Rome Italy Division of Gastroenterology "De Bellis" Hospital IRCCS Castellana Grotte Italy Pathology Department Bambino Gesu' Children's Hospital Rome Italy

AIM: To identify the independent predictors of hepatic fibrosis in 69 children with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease (NAFLD). METHODS: All patients with clinically suspected NASH underwent liver biopsy as a confirmatory test. The following clinical and biochemical variables at baseline were examined as likely predictors of fibrosis at histology: age, body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT), platelet count, prothrombin time (PT). RESULTS: At histology 28 (40.6%) patients had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85, 95% CI = 1.6-21). CONCLUSION: BMI helps identify children with NASH who might have fibrotic deposition in the liver.

关键词：肝纤维儿科非酒精依赖病理

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MicroRNAs as controlled systems and controllers in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第41期20卷 15079-15086页

作者： Nadia Panera Daniela Gnani Annalisa Crudele Sara Ceccarelli valerio nobili Anna Alisi Hepato-Metabolic Disease Unit "Bambino Gesù" Children’s HospitalIRCCS Liver Research Unit "Bambino Gesù" Children’s HospitalIRCCS

Non-alcoholic fatty liver disease(NAFLD) is a multi-faceted condition including simple steatosis alone or associated with inflammation and ballooning(non-alcoholic steatohepatitis) and eventually fibrosis.The NAFLD incidence has increased over the last twenty years becoming the most frequent chronic liver disease in industrialized countries.Obesity,visceral adiposity,insulin resistance,and many other disorders that characterize metabolic syndrome are the major predisposing risk factors for NAFLD.Furthermore,different factors,including genetic background,epigenetic mechanisms and environmental factors,such as diet and physical exercise,contribute to NAFLD development and progression.Several lines of evidence demonstrate that specific microRNAs expression profiles are strongly associated with several pathological conditions including NAFLD.In NAFLD,microRNA deregulation in response to intrinsic genetic or epigenetic factors or environmental factors contributes to metabolic dysfunction.In this review we focused on microRNAs role both as controlled and controllers molecules in NAFLD development and/or their eventual value as non-invasive biomarkers of disease.

关键词： Liver steatosis Fibrosis Non-alcoholic fatty liver

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Ulcerative Colitis and Acute Thrombocytopenia in a Pediatric Patient: A Case Report and Review of the Literature

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Health 2014年第12期6卷 1497-1502页

作者： Bronislava Papadatou Fiammetta Bracci Daniela Knafelz Antonella Diamanti Maria Sole Basso Fabio Panetta Filippo Torroni valerio nobili Giuliano Torre Gastroenterology Digestive Surgery and Endoscopy Unit “Bambino Gesù” Children’s Hospital Rome Italy Gastroenterology Hepathology and Nutrition Unit “Bambino Gesù” Children’s Hospital Rome Italy Gastroenterology Hepato-metabolic Diseases Unit “Bambino Gesù” Children’s Hospital Rome Italy

We report the case of a 14-year-old boy affected by ulcerative colitis (UC) and acute thrombocytopenic purpura (ITP) with simultaneous onset. UC diagnosis was based on symptoms, endoscopy and histology findings. ITP diagnosis was based on the normal bone marrow megakaryocyte count, the presence of platelet associated IgG and the absence of splenomegaly. Medical treatments including high doses of steroids, intravenous immunoglobulins were ineffective on ITP course, while UC course was mild for several months after the onset. When colonic inflammation became untractable not responsive at steroids and immunosuppressive agents, colectomy resolved both pathologies.

关键词： Ulcerative Colitis Thrombocytopenia Children

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