Publications by authors named "Valerio Nobili"

339 Publications

Comparison between non-alcoholic fatty liver disease screening guidelines in children and adolescents.

JHEP Rep 2019 Oct 9;1(4):259-264. Epub 2019 Jul 9.

Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA.

Background & Aim: There is currently no agreement on the screening strategy for non-alcoholic fatty liver disease (NAFLD) in children at risk. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) recommends screening for NAFLD using alanine aminotransferase (ALT) in obese/overweight children, while the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommends using both ALT and abdominal ultrasound. The aim of this study was to assess the prevalence of suspected NAFLD in obese children based on the 2 screening strategies.

Method: Consecutive overweight/obese children seen at a weight-management program were included. Each child underwent a liver ultrasound and had ALT level measured at first visit. Two screening strategies were compared: the NASPGHAN strategy using ALT ≫2x the gender specific cut-off and the ESPGHAN strategy using elevated ALT ≫45 IU/L and/or fatty liver on ultrasound. Univariate and multivariate analyses were performed to assess predictors of low ALT in individuals with evidence of suspected NAFLD on ultrasound.

Results: Overweight/obese children were included. NAFLD was suspected as follows: 26% based on the NASPGHAN strategy, and 58% based on the ESPGHAN strategy. Fatty liver was present on ultrasound in 53% of our cohort. ALT was ≫2x the gender specific cut-off in only 26% of children with fatty liver on ultrasound. Univariate and multivariate analyses indicated that children with fatty infiltration on ultrasound and low ALT were less likely to have metabolic syndrome, insulin resistance, or hypertriglyceridemia.

Conclusion: By relying on ALT values alone to screen for NAFLD, suspected NAFLD might be missed in many children who are at risk. Children with fatty infiltration on ultrasound and low ALT may be less likely to have metabolic syndrome, insulin resistance or hypertriglyceridemia.

Lay Summary: Using the combination of elevated alanine aminotransferase and fatty infiltration on ultrasound increases the detection rate of suspected non-alcoholic fatty liver disease in at-risk children. Notably, a significant percentage of children with fatty infiltration on ultrasound have low alanine aminotransferase (≪52/44). Children with fatty infiltration on ultrasound and low alanine aminotransferase may be less likely to have features of the metabolic syndrome.
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http://dx.doi.org/10.1016/j.jhepr.2019.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001548PMC
October 2019

Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease.

Gastroenterology 2020 05 25;158(6):1597-1610.e7. Epub 2020 Jan 25.

Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom.

Background & Aims: Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD.

Methods: We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing.

Results: Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (β = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (β = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis.

Conclusions: In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).
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http://dx.doi.org/10.1053/j.gastro.2020.01.031DOI Listing
May 2020

AISF update on the diagnosis and management of adult-onset lysosomal storage diseases with hepatic involvement.

Dig Liver Dis 2020 04 2;52(4):359-367. Epub 2020 Jan 2.

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.dld.2019.12.005DOI Listing
April 2020

The interferon-gamma pathway is selectively up-regulated in the liver of patients with secondary hemophagocytic lymphohistiocytosis.

PLoS One 2019 17;14(12):e0226043. Epub 2019 Dec 17.

Division of Rheumatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Aim of this study was to investigate the activation of the IFNγ pathway in the affected liver and in the blood of patients with secondary hemophagocytic lymphohistiocytosis (sHLH). To this purpose, the mRNA expression levels of IFNG and IFNγ-inducible genes as well as Tyrosine (701)-phosphorylated signal transducer and activator of transcription 1 (STAT1) protein levels were evaluated in the liver and in peripheral blood mononuclear cells (PBMCs) of three patients with sHLH with predominant liver involvement. The mRNA expression levels of IFNG and IFNγ-inducible genes were markedly higher in patient livers compared to control livers and to one disease control liver. Conversely, slight differences in the expression levels of Type I IFN-inducible genes and other classical inflammatory cytokine genes were found. Further supporting the activation of the IFNγ pathway, higher protein levels of phosphorylated and total STAT1 were detected in patient livers compared to control livers. When the expression of the same genes analysed in liver tissues was evaluated in PBMCs collected from 2 out of 3 patients before the liver biopsy, we found that mRNA levels of IFNγ-inducible genes were markedly increased. Accordingly, high circulating levels of IFNγ-inducible CXCL9 were observed in patients. Altogether, these data demonstrate the selective and marked up-regulation of the IFNγ pathway in the liver tissue and blood of patients with active sHLH. Finally, we show that measurement of circulating CXCL9 levels and evaluation of IFNγ-inducible gene expression levels in PBMCs may represent a new valid tool to better identify patients with suspected HLH with predominant liver involvement.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226043PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917341PMC
April 2020

β-Klotho gene variation is associated with liver damage in children with NAFLD.

J Hepatol 2020 03 23;72(3):411-419. Epub 2019 Oct 23.

Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy. Electronic address:

Background & Aim: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in adults and children. Along with obesity, diabetes and insulin resistance, genetic factors strongly impact on NAFLD development and progression. Dysregulated bile acid metabolism and the fibroblast growth factor 19 (FGF19) pathway play a pivotal role in NAFLD pathogenesis. However, the mechanism through which the FGF19 receptor system is associated with liver damage in NAFLD remains to be defined.

Methods: We evaluated the impact of the rs17618244 G>A β-Klotho (KLB) variant on liver damage in 249 pediatric patients with biopsy-proven NAFLD and the association of this variant with the expression of hepatic and soluble KLB. In vitro models were established to investigate the role of the KLB mutant.

Results: The KLB rs17618244 variant was associated with an increased risk of ballooning and lobular inflammation. KLB plasma levels were lower in carriers of the rs17618244 minor A allele and were associated with lobular inflammation, ballooning and fibrosis. In HepG2 and Huh7 hepatoma cell lines, exposure to free fatty acids caused a severe reduction of intracellular and secreted KLB. Finally, KLB downregulation obtained by the expression of a KLB mutant in HepG2 and Huh7 cells induced intracellular lipid accumulation and upregulation of p62, ACOX1, ACSL1, IL-1β and TNF-α gene expression.

Conclusion: In conclusion, we showed an association between the rs17618244 KLB variant, which leads to reduced KLB expression, and the severity of NAFLD in pediatric patients. We can speculate that the KLB protein may exert a protective role against lipotoxicity and inflammation in hepatocytes.

Lay Summary: Genetic and environmental factors strongly impact on the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD). The FGF19/FGFR4/KLB pathway plays a pivotal role in the pathogenesis of NAFLD. The aim of the study was to investigate the impact of a genetic variant in the KLB gene on the severity of liver disease. Our data suggest that the KLB protein plays a protective role against lipotoxicity and inflammation in hepatocytes.
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http://dx.doi.org/10.1016/j.jhep.2019.10.011DOI Listing
March 2020

Eosinophilic esophagitis in children: current knowledge to open new horizons.

Scand J Gastroenterol 2019 Jul 26;54(7):822-829. Epub 2019 Jul 26.

Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital , Rome , Italy.

Eosinophilic Esophagitis (EoE) is a chronic immune/antigen-mediated condition which is also driven by genetic and environmental factors. It has been deeply investigated over the last years and its incidence is widely increasing in childhood. Although atopic diseases are closely linked with EoE, it does not recognize a classical IgE-mediate immune pathogenesis but it is rather a T helper type 2 inflammatory process. Familial clustering supports genetic predisposition in EoE and recent advances in understanding the genetic basis for EoE may eventually translate into targeted management of the disease. EoE diagnosis is based on clinical symptoms, micro, and macroscopic findings along with exclusion of gastroesophageal reflux disease (GERD) evidence. Management of the disease encompasses both dietary and pharmacological solutions that need to be specifically targeted on patients' history, clinical symptoms, and diagnostic evaluations. New therapies, currently not available in children, may represent the basis for future therapeutic options in the next years.
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http://dx.doi.org/10.1080/00365521.2019.1641214DOI Listing
July 2019

The Contribution of the Adipose Tissue-Liver Axis in Pediatric Patients with Nonalcoholic Fatty Liver Disease after Laparoscopic Sleeve Gastrectomy.

J Pediatr 2020 01 13;216:117-127.e2. Epub 2019 Sep 13.

Hepatology, Gastroenterology and Nutrition Unit - Bambino Gesù Children's Hospital, Rome, Italy; Department of Pediatric - University "La Sapienza", Rome, Italy.

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.
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http://dx.doi.org/10.1016/j.jpeds.2019.07.037DOI Listing
January 2020

Plasma N-terminal propeptide of type III procollagen accurately predicts liver fibrosis severity in children with non-alcoholic fatty liver disease.

Liver Int 2019 12 10;39(12):2317-2329. Epub 2019 Sep 10.

Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.

Background & Aims: We examined the diagnostic performance of plasma N-terminal propeptide of type III procollagen (PIIINP) levels, aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for predicting non-alcoholic steatohepatitis (NASH) and liver fibrosis stage in children/adolescents with non-alcoholic fatty liver disease (NAFLD).

Methods: We enrolled 204 children/adolescents with biopsy-proven NAFLD at the "Bambino Gesù" Children's Hospital. We measured plasma PIIINP levels using a commercially available enzyme-linked immunosorbent assay kit and calculated APRI and FIB-4 scores using standard methods.

Results: Children with NASH had higher plasma PIIINP levels, APRI and FIB-4 scores compared with those without NASH (all P < .001). However, PIIINP levels had much better diagnostic performance and accuracy than APRI and FIB-4 scores for predicting liver fibrosis stage. PIIINP levels correlated with the total NAFLD activity score (NAS) and its constituent components (P < .0001). The risk of either NASH or F ≥ 2 fibrosis progressively increased with increasing PIIINP levels (P < .0001), independent of age, gender, adiposity measures, insulin resistance, NAS score and the patatin-like phospholipase domain-containing protein-3 rs738409 polymorphism. For every 3.6 ng/mL increase in PIIINP levels, the likelihood of having F ≥ 2 fibrosis increased by ~14-fold (adjusted-odds ratio 14.1, 95% CI 5.50-35.8, P < .0001) after adjustment for the aforementioned risk factors. The area under the receiver operating characteristics curve was 0.921 (95% CI 0.87-0.97) for F ≥ 2 fibrosis, and 0.993 (95% CI 0.98-1.0) for F3 fibrosis respectively.

Conclusions: Unlike APRI and FIB-4 scores, plasma PIIINP levels are a promising, non-invasive biomarker for diagnosing liver fibrosis stage in children/adolescents with biopsy-proven NAFLD.
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http://dx.doi.org/10.1111/liv.14225DOI Listing
December 2019

The Liver in Children With Metabolic Syndrome.

Front Endocrinol (Lausanne) 2019 2;10:514. Epub 2019 Aug 2.

Department of Pediatrics, University "La Sapienza", Rome, Italy.

Non-alcoholic fatty liver disease (NAFLD) is recognized as an emerging health risk in obese children and adolescents. NAFLD represents a wide spectrum of liver conditions, ranging from asymptomatic steatosis to steatohepatitis. The growing prevalence of fatty liver disease in children is associated with an increased risk of metabolic and cardiovascular complications. NAFLD is considered the hepatic manifestation of Metabolic Syndrome (MetS) and several lines of evidence have reported that children with NAFLD present one or more features of MetS. The pathogenetic mechanisms explaining the interrelationships between fatty liver disease and MetS are not clearly understood. Altough central obesity and insulin resistance seem to represent the core of the pathophysiology in both diseases, genetic susceptibility and enviromental triggers are emerging as crucial components promoting the development of NAFLD and MetS in children. In the present review we have identified and summarizied studies discussing current pathogenetic data of the association between NAFLD and MetS in children.
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http://dx.doi.org/10.3389/fendo.2019.00514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687849PMC
August 2019

The Number of Liver Galectin-3 Positive Cells Is Dually Correlated with NAFLD Severity in Children.

Int J Mol Sci 2019 Jul 14;20(14). Epub 2019 Jul 14.

Molecular Genetics of Complex Phenotypes Research Unit, Bambino Gesù Hospital, IRCCS, 00146 Rome, Italy.

Non-alcoholic fatty liver disease (NAFLD) is a complex disease ranging from steatosis to non-alcoholic steatohepatitis (NASH). Galectin-3 (Gal-3), which is a β-galactoside binding protein, has been associated with liver fibrosis, but its role in NAFLD remains elusive. We investigated the expression of Gal-3 in liver resident cells and its potential association with liver damage in 40 children with biopsy-proven NAFLD. We found that several liver cells expressed Gal-3. The number of total Gal-3 positive cells decreased with the severity of disease and the cells were correlated with the presence of steatosis and the diagnosis of NASH. CD68 macrophages expressed Gal-3 but the number CD68/Gal-3 positive cells was significantly reduced in patients diagnosed with steatosis and NASH. Triple CD68/CD206/Gal-3, which represented the subpopulation of M2 macrophages, were mainly present in patients without NASH, and clearly reduced in patients with steatosis and NASH. On the contrary, the number of α-smooth muscle actin (SMA)/Gal-3 positive cells increased with the severity of fibrosis in children with NAFLD. Our data demonstrated that the number of Gal-3 positive cells was associated with tissue damage in different ways, which suggests a dual role of this protein in the pathogenesis of pediatric NAFLD, even if the role of Gal-3 deserves further studies.
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http://dx.doi.org/10.3390/ijms20143460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679049PMC
July 2019

Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven non-alcoholic fatty liver disease.

J Hepatol 2019 10 4;71(4):802-810. Epub 2019 Jul 4.

Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. Electronic address:

Background & Aims: We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity.

Methods: We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD. The diagnosis of prediabetes and diabetes was based on either hemoglobin A1c, fasting plasma glucose or 2 h post-load glucose concentrations.

Results: Children/adolescents with NAFLD had a significantly higher prevalence of abnormal glucose tolerance (prediabetes or diabetes) than those without NAFLD (20.6% vs. 11%, p = 0.02). In particular, 124 (20.6%) children/adolescents with NAFLD had abnormal glucose tolerance, with 19.8% (n = 119) satisfying the diagnostic criteria for prediabetes and 0.8% (n = 5) satisfying the criteria for diabetes. The combined presence of prediabetes and diabetes was associated with a nearly 2.2-fold increased risk of non-alcoholic steatohepatitis (NASH; unadjustedodds ratio 2.19; 95% CI 1.47-3.29; p <0.001). However, this association was attenuated (but remained significant) after adjustment for age, sex, waist circumference (adjustedodds ratio 1.69, 95% CI 1.06-2.69, p = 0.032), and the PNPLA3 rs738409 polymorphism. Both this PNPLA3 polymorphism and waist circumference were strongly associated with NASH.

Conclusions: Abnormal glucose tolerance (especially prediabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. These children also have a higher risk of NASH, though central adiposity is the factor that is most strongly associated with NASH.

Lay Summary: Children with biopsy-proven non-alcoholic fatty liver disease (NAFLD) have a higher prevalence of abnormal glucose tolerance (prediabetes or type 2 diabetes) than children without NAFLD. Children with biopsy-proven NAFLD and abnormal glucose tolerance also have a higher prevalence of the progressive form of disease, non-alcoholic steatohepatitis, than those with normal glucose tolerance, though central adiposity is the factor that is most strongly associated with non-alcoholic steatohepatitis.
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http://dx.doi.org/10.1016/j.jhep.2019.06.023DOI Listing
October 2019

NAFLD in children: new genes, new diagnostic modalities and new drugs.

Nat Rev Gastroenterol Hepatol 2019 09 5;16(9):517-530. Epub 2019 Jul 5.

Texas Liver Institute, UT Health San Antonio, San Antonio, TX, USA.

Nonalcoholic fatty liver disease (NAFLD) has rapidly become the most common form of chronic liver disease in children and adolescents. Over the past 5 years, developments have revolutionized our understanding of the genetic factors, natural history, diagnostic modalities and therapeutic targets for this disease. New polymorphisms, such as those in PNPLA3, TM6SF2, MBOAT7 and GCKR, have been identified and used to predict the development and severity of NAFLD in both adults and children, and their interaction with environmental factors has been elucidated. Studies have demonstrated the true burden of paediatric NAFLD and its progression to end-stage liver disease in adulthood. In particular, nonalcoholic steatohepatitis can progress to advanced fibrosis and cirrhosis, emphasizing the importance of early diagnosis. Non-invasive imaging tests, such as transient elastography, will probably replace liver biopsy for the diagnosis of nonalcoholic steatohepatitis and the assessment of fibrosis severity in the near future. The therapeutic landscape is also expanding rapidly with the development of drugs that can modify liver steatosis, inflammation and fibrosis, indicating that pharmacotherapy for NAFLD will become available in the future. In this Review, we summarize current knowledge and new advances related to the pathogenesis and management of paediatric NAFLD.
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http://dx.doi.org/10.1038/s41575-019-0169-zDOI Listing
September 2019

Wilson Disease in a Child With Mild Neuropsychiatric and Hepatic Involvement: A Challenging Diagnosis for a Heterogeneous Disorder.

J Pediatr Gastroenterol Nutr 2019 10;69(4):e118-e119

Hepatology, Gastroenterology and Nutrition Unit.

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http://dx.doi.org/10.1097/MPG.0000000000002433DOI Listing
October 2019

The Role of Genetic Predisposition, Programing During Fetal Life, Family Conditions, and Post-natal Diet in the Development of Pediatric Fatty Liver Disease.

J Pediatr 2019 08 23;211:72-77.e4. Epub 2019 May 23.

Hepatology, Gastroenterology, and Nutrition Unit, IRCCS Bambino Gesù Children's Hospital, Rome, Italy; Department of Pediatrics - University "La Sapienza", Rome, Italy.

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.
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http://dx.doi.org/10.1016/j.jpeds.2019.04.018DOI Listing
August 2019

Pediatric Intestinal Pseudo-obstruction: Impact of Neonatal and Later Onset on Clinical and Nutritional Outcomes.

J Pediatr Gastroenterol Nutr 2019 08;69(2):212-217

Division of Neurogastroenterology and Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, NHS Foundation Trust, London, United Kingdom.

Objective: The aim of the study was to evaluate long-term nutritional outcomes and clinical characteristics in a cohort of children with pediatric intestinal pseudo-obstruction (PIPO) at neonatal-onset (NO-PIPO) and at later-onset (LO-PIPO).

Methods: All children fulfilling new PIPO criteria over a 30-year period were reviewed. Baseline demographic and clinical features as well as nutritional outcomes were collected. Nutritional outcomes included overall survival, prevalence of enteral autonomy and parenteral nutrition (PN) dependency, rate of major PN complications, and growth course.

Results: Forty-four patients were still alive at the end of the follow-up. Twenty-five patients (57%) achieved enteral autonomy, whilst 18 remained on PN. Among the patients requiring PN at the beginning of the study period, we found that 55% (CI 34-70) has the probability of remaining on PN at the latest follow-up. Prevalence of gastrointestinal obstruction symptoms (P < 0.01), urinary involvement (P < 0.05), stoma placements [gastrostomy (P < 0.01), ileostomy P < 0.05)] and complex gastrointestinal surgery (P < 0.05) were significantly higher in NO-PIPO than in LO-PIPO. The number of patients requiring long-term PN (P < 0.001) and the number of PN days (P < 0.05) were significantly higher in NO-PIPO, whilst the number of patients achieving enteral autonomy was significantly higher in LO-PIPO (P < 0.05).

Conclusions: In our study, we have reported the nutritional outcome of a cohort of children with PIPO over a 30-year period showing that about 20% of patients develop irreversible intestinal failure requiring life-long PN. Nutritional and clinical outcomes seem to be influenced by the time of onset of the disease.
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http://dx.doi.org/10.1097/MPG.0000000000002373DOI Listing
August 2019

gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients.

J Lipid Res 2019 06 27;60(6):1144-1153. Epub 2019 Mar 27.

Departments of Pathophysiology and Transplantation Università degli Studi di Milano, Milan, Italy

Dyslipidemia and altered iron metabolism are typical features of nonalcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 () gene variation has been associated with circulating lipids and liver damage during iron overload. The aim of this study was to examine the impact of the rs236918 variant on NAFLD-related traits in 1,801 individuals from the Liver Biopsy Cohort (LBC), 500,000 from the UK Biobank Cohort (UKBBC), and 4,580 from the Dallas Heart Study (DHS). The minor rs236918 C allele was associated with higher triglycerides, aminotransferases, and hepatic inflammation in the LBC ( < 0.05) and with hypercholesterolemia and liver disease in the UKBBC. In the DHS, missense variants were associated with circulating lipids. was expressed in hepatocytes and its hepatic expression correlated with that of lipogenic genes ( < 0.05). The rs236918 C allele was associated with upregulation of a new "intra-PCSK7" long noncoding RNA predicted to interact with the protein, higher hepatic and circulating PCSK7 protein ( < 0.01), which correlated with triglycerides ( = 0.04). In HepG2 cells, deletion reduced lipogenesis, fat accumulation, inflammation, transforming growth factor β pathway activation, and fibrogenesis. In conclusion, gene variation is associated with dyslipidemia and more severe liver disease in high risk individuals, likely by modulating expression/activity.
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http://dx.doi.org/10.1194/jlr.P090449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547640PMC
June 2019

Relationship Between PNPLA3 rs738409 Polymorphism and Decreased Kidney Function in Children With NAFLD.

Hepatology 2019 07 17;70(1):142-153. Epub 2019 May 17.

Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.

Emerging evidence suggests that patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 genotype (the major genetic variant associated with susceptibility to nonalcoholic fatty liver disease [NAFLD]) is associated with decreased kidney function in adults. Currently, it is uncertain whether this association also occurs in children/adolescents and whether any association is independent of liver disease severity. We enrolled a sample of 142 Caucasian children and adolescents with biopsy-proven NAFLD, presenting to the Liver Unit of the "Bambino Gesù" Children's Hospital. The glomerular filtration rate (e-GFR) was estimated using the Bedside Schwartz equation, whereas 24-hour proteinuria was measured using a radioimmunoassay method. Genotyping for the PNPLA3 rs738409 genotype was undertaken using the single-nucleotide polymorphism genotyping allelic discrimination method. Overall, 45 children had G/G, 56 had G/C, and 41 had C/C PNPLA3 rs738409 genotype, respectively. Children with G/G genotype had significantly lower e-GFR (107.5 ± 20 versus 112.8 ± 18 versus 125.3 ± 23 mL/min/1.73 m , P = 0.002) and higher 24-hour proteinuria (58.5 ± 21 versus 53.9 ± 22 versus 42.9 ± 20 mg/day, P = 0.012) compared with those with either G/C or C/C genotypes. After adjustment for age, sex, systolic blood pressure, measures of adiposity, homeostasis model assessment-estimated insulin resistance and biopsy-confirmed nonalcoholic steatohepatitis and stage of liver fibrosis, the presence of rs738409 G/G genotype was independently associated with both lower e-GFR (β coefficient: -23.6; 95% confidence interval [CI]: -36.3 to -10.8; P < 0.001) and higher 24-hour proteinuria (β coefficient: 15.3; 95% CI: 1.12 to 30.5; P = 0.046). Conclusion: Regardless of established renal risk factors and the histological severity of NAFLD, the PNPLA3 G/G genotype was strongly associated with decreasing kidney function and increasing 24-hour proteinuria in children/adolescents with histologically confirmed NAFLD.
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http://dx.doi.org/10.1002/hep.30625DOI Listing
July 2019

Post-transplant metabolic syndrome in children: Know better to cure better.

Pediatr Transplant 2019 05 21;23(3):e13367. Epub 2019 Feb 21.

Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy.

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http://dx.doi.org/10.1111/petr.13367DOI Listing
May 2019

Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH.

Sci Rep 2019 02 14;9(1):2045. Epub 2019 Feb 14.

Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.

Two recent randomized controlled trials demonstrated improved radiographic, histological and hepatometabolic cues of non-alcoholic steatohepatitis (NASH) in pediatric patients treated with the ω-3 fatty acid docosahexaenoic acid (DHA) in combination with vitamin D (VD) or with choline (CHO) and vitamin E (VE), the DHA-VD and DHA-CHO-VE trials, respectively). In the present study we verified the nutritional compliance to these DHA-based multivitamin treatments; lipidomics biomarkers of the reported outcome on NASH indicators were also investigated. Samples were obtained from 30 biopsy-proven pediatric NASH patients of the DHA-CHO-VE trial randomized in multivitamin treatment group and placebo group (n = 15 each), and from 12 patients of the treatment group of the DHA-VD trial. All patients underwent 6-month therapy plus 6 months of follow-up. Plasma samples and clinical data were obtained at baseline and at the end of the study (12 months). Selected biomarkers included the free form of DHA and other ω-3 fatty acid arachidonic acid (AA), indices of the vitamin E status, and some hepatic metabolites of these lipids. Radiographic and histological improvements of treated patients were associated with increased concentrations of DHA, α-linolenic acid and α-tocopherol (i.e. VE), and with decreased AA that was also investigated in complex lipids by untargetd lipidomics. As a result a significantly lowered AA/DHA ratio was observed to represent the main indicator of the response to the DHA-based therapy. Furthermore, baseline levels of AA/DHA showed strong association with NAS and US improvement. A stable correction of DHA AA metabolism interaction is associated with the curative effect of this therapy and may represent a key nutritional endpoint in the clinical management of pediatric NASH.
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http://dx.doi.org/10.1038/s41598-018-37209-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375912PMC
February 2019

Lesson from epidemiology of paediatric Crohn's disease.

Dig Liver Dis 2019 04 17;51(4):503-504. Epub 2019 Jan 17.

Women's and Children's Department, Sapienza University of Rome, Italy.

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http://dx.doi.org/10.1016/j.dld.2018.12.020DOI Listing
April 2019

Prevalence and Risk Factors of Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Without Steatohepatitis.

Clin Gastroenterol Hepatol 2019 10 29;17(11):2310-2319.e6. Epub 2019 Jan 29.

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Transfusion Medicine and Hematology, Translational Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

Background & Aims: In patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is a risk factor for the development of fibrosis. However, fibrosis has been observed in livers of patients without NASH. We aimed to estimate the prevalence of fibrosis in patients without NASH and risk factors for fibrosis.

Methods: We analyzed data from 1738 subjects (44.9% with severe obesity) in a cross-sectional liver biopsy cohort enrolled at referral centers in Italy and Finland. Biopsy specimens were analyzed histologically by a blinded pathologist at each center, and a diagnosis of NASH was made based on steatosis (≥5% of hepatocytes), hepatocellular ballooning, and lobular inflammation. We also collected data on demographic features, metabolic comorbidities, and genetic factors, and performed logistic regression analyses. Findings were validated using data from 118 consecutive patients with NAFLD who underwent sequential liver biopsies at tertiary referral centers in Italy.

Results: In the cross-sectional cohort, 132 of 389 patients (33.9%) with significant fibrosis had no NASH and 39 patients (10.0%) had no inflammation. The dissociation between NASH and fibrosis was significantly greater in patients with severe obesity (P < .005). Steatosis, ballooning, and lobular inflammation each were associated independently with significant fibrosis (P < .001); age, adiposity, fasting hyperglycemia, and the PNPLA3 I148M variant also were associated with fibrosis. In patients without, but not in those with NASH, significant fibrosis was associated with steatosis grade and the PNPLA3 I148M variant. In patients without NASH, age, fasting hyperglycemia, ballooning, and inflammation were associated with fibrosis. In the validation cohort, 16 of 47 patients (34.0%) with clinically significant fibrosis did not have NASH at baseline. In patients with fibrosis without baseline NASH, worsening of fibrosis (based on later biopsies) was associated with fasting hyperglycemia and more severe steatosis (P = .016).

Conclusions: In an analysis of biopsy specimens collected from patients with NAFLD at a single time point, one third of patients with significant fibrosis did not have NASH. We validated this finding in a separate cohort. In patients without NASH, fasting hyperglycemia, severe steatosis, mild inflammation or ballooning, and the PNPLA3 I148M variant identified those at risk of significant fibrosis.
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http://dx.doi.org/10.1016/j.cgh.2019.01.027DOI Listing
October 2019

Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children: A Meta-Analysis.

Hepatology 2019 09 18;70(3):812-823. Epub 2019 Mar 18.

Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.

Recent cross-sectional studies have examined the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) in children or adolescents, but these have produced conflicting results. We performed a systematic review and meta-analysis of these published studies to quantify the magnitude of the association, if any, between NAFLD and BMD. We searched publication databases from January 2000 to September 2018, using predefined keywords to identify relevant observational studies conducted in children or adolescents in whom NAFLD was diagnosed either by imaging or by histology and BMD Z score was measured by dual-energy X-ray absorptiometry. Data from selected studies were extracted, and a meta-analysis was performed using random-effects modeling. A total of eight observational cross-sectional or case-control studies enrolling 632 children and adolescents (mean age 12.8 years), 357 of whom had NAFLD, were included in the final analysis. Meta-analysis showed significant differences in whole-body or lumbar BMD Z scores between children/adolescents with and without NAFLD (n = 6 studies; pooled weighted mean difference [WMD], -0.48; 95% confidence interval [CI], -0.74 to -0.21; I = 55.5%), as well as between those with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and those with no-NASH (n = 4 studies; pooled WMD, -0.27; 95% CI, -0.40 to -0.13; I = 0%). The aforementioned WMDs in BMD Z scores were independent of common clinical risk factors, such as age, sex, race/ethnicity, and body mass index. Sensitivity analyses did not modify these findings. Funnel plot and Egger test did not reveal significant publication bias. Conclusion: This meta-analysis shows that the presence and severity of NAFLD are significantly associated with reduced whole-body BMD Z scores in children and adolescents; however, the observational design of the studies included does not allow for proving causality.
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http://dx.doi.org/10.1002/hep.30538DOI Listing
September 2019

Similarities and Differences in Allocation Policies for Pediatric Liver Transplantation Across the World.

J Pediatr Gastroenterol Nutr 2019 05;68(5):700-705

Department of Pediatrics, Recanati/Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Objectives: We aimed to investigate national allocation policies for pediatric liver transplantation (LT).

Method: A survey was prepared by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Hepatology Committee in collaboration with the North American Studies of Pediatric Liver Transplantation consortium. The survey was sent to pediatric hepatologists and transplant surgeons worldwide. National data were obtained from centrally based registries.

Results: Replies were obtained from 15 countries from 5 of the world continents. Overall donation rate varied between 9 and 35 per million inhabitants. The number of pediatric LTs was 4 to 9 per million inhabitants younger than 18 years for 13 of the 15 respondents. In children younger than 2 years mortality on the waiting list (WL) varied between 0 and 20%. In the same age group, there were large differences in the ratio of living donor LT to deceased donor LT and in the ratio of split liver segments to whole liver. These differences were associated with possible discrepancies in WL mortality.

Conclusions: Similarities but also differences between countries were detected. The described data may be of importance when trying to reduce WL mortality in the youngest children.
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http://dx.doi.org/10.1097/MPG.0000000000002283DOI Listing
May 2019

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

Hepatobiliary Surg Nutr 2018 Dec;7(6):484-486

Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.

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http://dx.doi.org/10.21037/hbsn.2018.10.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295393PMC
December 2018

Association of Bright Liver With the PNPLA3 I148M Gene Variant in 1-Year-Old Toddlers.

J Clin Endocrinol Metab 2019 06;104(6):2163-2170

Research Area for Multifactorial Disease, Children's Hospital Bambino Gesù, Rome, Italy.

Context: Nonalcoholic fatty liver disease (NAFLD) is being increasingly diagnosed at younger ages, pointing toward an early-life origin.

Objective: To evaluate the frequency and risk factors for bright liver (BL) in 1-year-old toddlers.

Design: Secondary analysis of the 1-year follow-up of the Feeding Study. Exposures were child PNPLA3 and TM6SF2 gene variants; child anthropometry at birth and at 1 year of follow-up; child subcutaneous, visceral, and epicardial adipose tissue at 1 year of follow-up; maternal anthropometry at the start and at the end of pregnancy; and maternal red blood cell fatty-acid composition at the third trimester of pregnancy.

Setting: General population.

Participants: Among 505 mother-toddler pairs, 391 children (77%) underwent liver and abdominal ultrasonography at the 1-year follow-up.

Main Outcome: BL as diagnosed by ultrasonography.

Results: Seventeen (4%) of 391 toddlers had BL. Compared with the toddlers with the PNPLA 3 CC genotype, the odds (95% CI) of BL were 3.01 (1.05 to 8.64, P < 0.05) times higher in those with the PNAPLA3 CG genotype and 5.37 (1.12 to 25.77, P < 0.05) higher in those with the PNPLA3 CC genotype. We found no association between BL status and TM6SF2. Body weight, body mass index, and maternal weight gain during pregnancy were higher in BL+ than in BL- children. Visceral adipose tissue was higher but subcutaneous adipose tissue and epicardial adipose tissue were similar in BL+ and BL- children.

Conclusions: Four percent of the Feeding Study children had BL at 1 year of age. In line with expectations, PNAPLA3 was already a predictor of BL at this early age.
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http://dx.doi.org/10.1210/jc.2018-01998DOI Listing
June 2019

The Antioxidant Effects of Hydroxytyrosol and Vitamin E on Pediatric Nonalcoholic Fatty Liver Disease, in a Clinical Trial: A New Treatment?

Antioxid Redox Signal 2019 07 11;31(2):127-133. Epub 2019 Feb 11.

5 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Several studies suggest that the improvement of oxidative stress is suggested as a possible therapeutic strategy for pediatric nonalcoholic steatohepatitis. We performed a randomized, double-blind placebo-controlled trial to test the potential efficacy, assessed by improvement of oxidative stress parameters and liver ultrasound, and tolerability of a mixture of vitamin E and hydroxytyrosol (HXT) in adolescents with biopsy-proven NAFLD. Four hundred forty consecutive patients were screened, 80 of these with biopsy-proven NAFLD were enrolled. Forty patients received an oral dose of HXT and vitamin E and 40 children received the capsules of placebo for 4 months. Seventy patients completed the study. Patients in the treatment arm showed a decrease of insulin resistance (IR), triglyceride levels, oxidative stress parameters, and steatosis grade. Noteworthy, the steatosis improvement correlates with the levels of advanced glycation end products and carbonylated proteins. The HXT and vitamin E treatment improved the main oxidative stress parameters, IR, and steatosis in children with NAFLD. The use of two natural molecules that may have antioxidant effects seems a promising strategy that could be easily diet integrated to improve NAFLD-related liver damage in children.
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http://dx.doi.org/10.1089/ars.2018.7704DOI Listing
July 2019

Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT).

Adv Exp Med Biol 2019 ;1125:85-100

Unit of Parasitology, Children's Hospital and Research Institute Bambino Gesú, Rome, Italy.

Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease (NAFLD) to shift into one of the most frequent causes of chronic liver illness in childhood. Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used; overall it ranges between 3% and 10% of pediatric population, increasing up to 70% in patients with metabolic comorbidities (Manco M, Bottazzo G, DeVito R et al, J Am Coll Nutr 27:667-676, 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes (T2D), obesity, and nonalcoholic steatohepatitis (NASH). One of the emerging areas of the study is the link between liver diseases and gut microbiome, which has added new information to the understanding of the so-called gut-liver axis.In order to address the role of gut microbiome in NAFLD onset and progression, it is necessary to "decipher" operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and, hence, to address the function of the intestinal microbiome within the gut microbiota-liver axis.Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of obesity and NAFLD in adults and children. Several randomized clinical trials (RCTs) have been already published on fecal microbiota transplantation (FMT), T2D, NASH, and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions, probiotics, symbiotics, and FMT.
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http://dx.doi.org/10.1007/5584_2018_318DOI Listing
August 2019

Breastfeeding and NAFLD from the maternal side of the mother-infant dyad.

J Hepatol 2019 01 7;70(1):13-14. Epub 2018 Nov 7.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana" Pediatric Section, University of Salerno, Baronissi, SA, Italy.

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http://dx.doi.org/10.1016/j.jhep.2018.10.030DOI Listing
January 2019

European paediatric non-alcoholic fatty liver disease registry (EU-PNAFLD): Design and rationale.

Contemp Clin Trials 2018 12 5;75:67-71. Epub 2018 Nov 5.

Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in children and has the potential to progress to advanced fibrosis/cirrhosis, end-stage liver disease and hepatocellular carcinoma. However, the natural history of the condition is poorly understood and there are no approved treatments. The European Paediatric Non-Alcoholic Fatty Liver Disease Registry (EU-PNAFLD) is a multi-centre registry of paediatric NAFLD that will serve as a prospective, observational, natural history study and provide a tractable back-bone to support recruitment into subsequent interventional trials. Collection of samples into a bio-repository will facilitate translational studies, including genome sequencing and metabolomics. EU-PNAFLD will work closely alongside the existing adult European NAFLD Registry to obtain data on clinical outcomes after 20-30 years. Through an international, well-characterised large-scale cohort, EU-PNAFLD will address the key questions in paediatric NAFLD and benefit patients with the condition.
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http://dx.doi.org/10.1016/j.cct.2018.11.003DOI Listing
December 2018

Growth failure in Crohn's disease children: may the first treatment have a role?

Expert Rev Clin Immunol 2019 01 15;15(1):97-104. Epub 2018 Nov 15.

a Artificial Nutrition Unit , "Bambino Gesù" Children Hospital , Rome , Italy.

: Growth failure in children is a frequent feature of childhood-onset Crohn's disease (CD), and stunting can persist into adulthood. Growth is an important outcome by which to judge the effectiveness of therapies in children; currently available studies in CD children have focused on the short-term impact of treatments on growth, and there are limited data regarding the long-term effects of treatments upon growth. : We designed the present article to review whether the first treatment performed in newly diagnosed CD children may have a role on the future growth course. We conducted a systematic literature search to identify relevant studies published on the PubMed database from January 2002 up to now. We found only six surveys that documented mid-term growth course in newly diagnosed CD patients. : In the last years there have been relevant advances in the clinical management of CD children; however, there is a lack of knowledge about the best strategy to reverse growth failure. Children treated with enteral nutrition have appropriate height and weight gain but do not reverse the growth course. Further surveys are required to better explore not only clinical outcomes but also long-term growth course following each therapeutic strategy.
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http://dx.doi.org/10.1080/1744666X.2019.1543590DOI Listing
January 2019