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3. Pediatric Acute Liver Failure

Author

Claudia Mandato and Pietro Vajro

Subjects
n/a, Medicine, Pediatrics, RJ1-570
Abstract

Pediatric acute liver failure (PALF) has recently become a subject of great interest when multiple clusters of non-A to non-E severe acute hepatitis in otherwise healthy young children with a median age of 2 years were reported around the world [...]

Published
2023
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4. Drug dosing in children with obesity: a narrative updated review

Author

Francesca Gaeta, Valeria Conti, Angela Pepe, Pietro Vajro, Amelia Filippelli, and Claudia Mandato

Subjects
Children, Obesity, Drugs, Drug dosing, Clinical practice, pharmacodynamics, pharmacokinetics, therapy, pharmacology, Pediatrics, RJ1-570
Abstract

Abstract Childhood obesity and its associated comorbidities are highly prevalent diseases that may add to any other possible health problem commonly affecting the pediatric age. Uncertainties may arise concerning drug dosing when children with obesity need pharmacologic therapies. In general, in pediatric practice, there is a tendency to adapt drug doses to a child’s total body weight. However, this method does not consider the pharmacological impact that a specific drug can have under a two-fold point of view, that is, across various age and size groups as well. Moreover, there is a need for a therapeutic approach, as much as possible tailored considering relevant interacting aspects, such as modification in metabolomic profile, drug pharmacokinetics and pharmacodynamics. Taking into account the peculiar differences between children with overweight/obesity and those who are normal weight, the drug dosage in the case of obesity, cannot be empirically determined solely by the per kg criterion. In this narrative review, we examine the pros and cons of several drug dosing methods used when dealing with children who are affected also by obesity, focusing on specific aspects of some of the drugs most frequently prescribed in real-world practice by general pediatricians and pediatric subspecialists.

Published
2022
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5. Perceptions and Expectations of Youth Regarding the Respect for Their Rights in the Hospital

Author

Roberta De Rosa, Maria Anna Siano, Angelo Colucci, Anna Giulia Elena De Anseris, Paolo Siani, Pietro Vajro, Giulia Savarese, and Claudia Mandato

Subjects
adolescents, children, drawings, healthcare, hospitalization, humanization of care, Pediatrics, RJ1-570
Abstract

Information obtained from children themselves regarding the characteristics of the ideal hospital that ensure well-being during a hospital stay is scarce. Here, we report the opinions, perceptions, and expectations of 700 children and adolescents about their experiences, assessed through a mixed-method research approach with age-appropriate questionnaires, three open-ended questions, and an analysis of optional pictorial and textual narratives. Most children indicated that, while they acknowledged the expertise of hospital staff, they also noted several shortcomings, e.g., insufficiently understandable medical information as well as emotional and cognitive support. The continuity of schooling and the right to suffer as little as possible were also critical issues. Adolescents valued in particular the quality of care and services provided, the hospital’s adherence to equality and non-discrimination rights, and protection systems but negatively perceived several aspects related to play and participation. Significant differences in the co-occurrences of the most frequently used text terms with the keywords “hospital” and “child/adolescent” between age groups highlight variations in the way patients perceive and articulate their experiences within the hospital setting depending on the cognitive processes linked to age. In drawings, prevailing attention was placed on the physical context of the hospital room, with figures expressing mostly negative emotions. Specifically, in this regard, the main emotion in children was sadness, and, in adolescents, it was fear. Overall, these insights are pivotal in the context of our research objectives as they shed light on the nuanced preferences, needs, and perspectives of children and adolescents during their hospital stays. Recognizing the identified shortcomings, we propose recommendations emphasizing the improvement of medical communication clarity, enhancement of emotional and cognitive support, and the improvement of programs to avoid instructional gaps during hospital stays. Addressing these specific needs is critical for a more comprehensive approach to pediatric healthcare provision.

Published
2024
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7. Case Report: Add-on treatment with odevixibat in a new subtype of progressive familial intrahepatic cholestasis broadens the therapeutic horizon of genetic cholestasis

Author

Angela Pepe, Angelo Colucci, Martina Carucci, Lucia Nazzaro, Cristina Bucci, Giusy Ranucci, Angelo Di Giorgio, Pietro Vajro, and Claudia Mandato

Subjects
PFIC, cholestasis, odevixibat, IBAT, itching, Pediatrics, RJ1-570
Abstract

Odevixibat, an ileal bile acid transporter (IBAT) inhibitor, is effective for the treatment of pruritus in children diagnosed with progressive familial intrahepatic cholestasis (PFIC) type 1 and 2. There are no studies showing the efficacy of Odevixibat in children with different subtypes of PFIC. We describe the case of a 6-year-old girl with chronic cholestatic jaundice. In the last 12 months laboratory data showed high serum levels of bilirubin (total bilirubin x 2.5 ULN; direct bilirubin x 1.7 ULN) and bile acids (sBA x 70 ULN), elevated transaminases (x 3–4 ULN), and preserved synthetic liver function. Genetic testing showed homozygous mutation in ZFYVE19 gene, which is not included among the classic causative genes of PFIC and determined a new non-syndromic phenotype recently classified as PFIC9 (OMIM # 619849). Due to the persistent intensity of itching [score of 5 (very severe) at the Caregiver Global Impression of Severity (CaGIS)] and sleep disturbances not responsive to rifampicin and ursodeoxycholic acid (UDCA), Odevixibat treatment was started. After treatment with odevixibat we observed: (i) reduction in sBA from 458 to 71 μmol/L (absolute change from baseline: −387 μmol/L), (ii) reduction in CaGIS from 5 to 1, and (iii) resolution of sleep disturbances. The BMI z-score progressively increased from −0.98 to +0.56 after 3 months of treatment. No adverse drug events were recorded. Treatment with IBAT inhibitor was effective and safe in our patient suggesting that Odevixibat may be potentially considered for the treatment of cholestatic pruritus also in children with rare subtypes of PFIC. Further studies on a larger scale could lead to the increasing of patients eligible for this treatment.

Published
2023
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8. Genetics, epigenetics and transgenerational transmission of obesity in children

Author

Nadia Panera, Claudia Mandato, Annalisa Crudele, Sara Bertrando, Pietro Vajro, and Anna Alisi

Subjects
obesity, pregnancy, gestation, transgenerational transmission, genetics, epigenetics, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Sedentary lifestyle and consumption of high-calorie foods have caused a relentless increase of overweight and obesity prevalence at all ages. Its presently epidemic proportion is disquieting due to the tight relationship of obesity with metabolic syndrome and several other comorbidities which do call for urgent workarounds. The usual ineffectiveness of present therapies and failure of prevention campaigns triggered overtime a number of research studies which have unveiled some relevant aspects of obesity genetic and epigenetic inheritable profiles. These findings are revealing extremely precious mainly to serve as a likely extra arrow to allow the clinician’s bow to achieve still hitherto unmet preventive goals. Evidence now exists that maternal obesity/overnutrition during pregnancy and lactation convincingly appears associated with several disorders in the offspring independently of the transmission of a purely genetic predisposition. Even the pre-conception direct exposure of either father or mother gametes to environmental factors can reprogram the epigenetic architecture of cells. Such phenomena lie behind the transfer of the obesity susceptibility to future generations through a mechanism of epigenetic inheritance. Moreover, a growing number of studies suggests that several environmental factors such as maternal malnutrition, hypoxia, and exposure to excess hormones and endocrine disruptors during pregnancy and the early postnatal period may play critical roles in programming childhood adipose tissue and obesity. A deeper understanding of how inherited genetics and epigenetics may generate an obesogenic environment at pediatric age might strengthen our knowledge about pathogenetic mechanisms and improve the clinical management of patients. Therefore, in this narrative review, we attempt to provide a general overview of the contribution of heritable genetic and epigenetic patterns to the obesity susceptibility in children, placing a particular emphasis on the mother-child dyad.

Published
2022
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10. Multiple Sclerosis—Related Dietary and Nutritional Issues: An Updated Scoping Review with a Focus on Pediatrics

Author

Claudia Mandato, Angelo Colucci, Roberta Lanzillo, Annamaria Staiano, Elena Scarpato, Luigi Schiavo, Francesca Felicia Operto, Maria Rosaria Serra, Cristina Di Monaco, Julia Sara Napoli, Grazia Massa, and Pietro Vajro

Subjects
multiple sclerosis, pediatric-onset multiple sclerosis, nutrition, diet, gut microbiota, gut-brain axis, Pediatrics, RJ1-570
Abstract

Purpose. Lifestyle/dietetic habits play an important role in the development and progression of multiple sclerosis (MS) disease. Here, we examine the basic pathomechanisms underlying intestinal and brain barrier modifications in MS and consider diets and dietary supplementations proposed over time to complement pharmacological therapies for improving disease outcome both in adults and in children. Methods. Scoping literature search about evidence-based findings in MS-related gut-brain axis (GBA) pathophysiology and nutritional issues at all ages. Findings. Data show that (1) no universal best diet exists, (2) healthy/balanced diets are, however, necessary to safeguard the adequate intake of all essential nutrients, (3) diets with high intakes of fruits, vegetables, whole grains, and lean proteins that limit processed foods, sugar, and saturated fat appear beneficial for their antioxidant and anti-inflammatory properties and their ability to shape a gut microbiota that respects the gut and brain barriers, (4) obesity may trigger MS onset and/or its less favorable course, especially in pediatric-onset MS. Vitamin D and polyunsaturated fatty acids are the most studied supplements for reducing MS-associated inflammation. Conclusions. Pending results from other and/or newer approaches targeting the GBA (e.g., pre- and probiotics, engineered probiotics, fecal-microbiota transplantation), accurate counseling in choosing adequate diet and maintaining physical activity remains recommended for MS prevention and management both in adults and children.

Published
2023
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11. Atypically Protracted Course of Liver Involvement in Kawasaki Disease. Case Report and Literature Review

Author

Pamela Paglia, Lucia Nazzaro, Anna Giulia Elena De Anseris, Milena Lettieri, Rossella Colantuono, Maria Chiara Rocco, Maria Anna Siano, Nicola Biffaro, and Pietro VAJRO

Subjects
Kawasaki disease, persistent hypertransaminasemia, case report, literature review, Medicine, Pediatrics, RJ1-570
Abstract

Hypertransaminasemia in patients with Kawasaki disease (KD) is reported to be transient. Here, we describe a child with an atypically protracted course of liver tests abnormalities and review the inherent literature. The patient was hospitalized at age 7-months for isolated hypertransaminasemia detected during a classical KD diagnosed 3 months before, and persistent since then. KD clinical evolution had been favorable, with rapid response to acetylsalicylic acid and intravenous immunoglobulins. Liver enzymes however remained persistently elevated with a fluctuating pattern (ALT > AST levels; peak of AST 186 IU/L and ALT 240 IU/L). During follow-up, the main causes of liver dysfunction had to be excluded through appropriate and extensive laboratory investigations. Transaminases values become steadily normal only 7 months after the acute presentation of KD. Conclusions: Our report shows that an atypically protracted courses of KD-related hypertransaminasemia above the previously reported temporal limits should be taken into account during the stepwise diagnostic approach to the patient’s liver dysfunction. Insidious acetylsalycilic acid-hepatotoxicity warrants consideration in the differential diagnosis.

Published
2021
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13. Case report: Unusual and extremely severe lipoprotein X-mediated hypercholesterolemia in extrahepatic pediatric cholestasis

Author

Rossella Colantuono, Chiara Pavanello, Andrea Pietrobattista, Marta Turri, Paola Francalanci, Marco Spada, Pietro Vajro, Laura Calabresi, and Claudia Mandato

Subjects
cholestasis, hypercholesterolemia, lipoprotein X, spontaneous biliary perforation, extra-hepatic, Pediatrics, RJ1-570
Abstract

BackgroundLipoprotein X (LpX) - mediated extremely severe hyperlipidemia is a possible feature detectable in children with syndromic paucity of intralobular bile ducts (Alagille syndrome) but rarely in other types of intra- and/or extrahepatic infantile cholestasis.Case presentationHere we report on a previously well 18-month child admitted for cholestatic jaundice and moderate hepatomegaly. Laboratory tests at entry showed conjugated hyperbilirubinemia, elevated values of serum aminotransferases, gamma-glutamyl transpeptidase (GGT) and bile acids (100 folds upper normal values). Extremely severe and ever-increasing hypercholesterolemia (total cholesterol up to 1,730 mg/dl) prompted an extensive search for causes of high GGT and/or hyperlipidemic cholestasis, including an extensive genetic liver panel (negative) and a liver biopsy showing a picture of obstructive cholangitis, biliary fibrosis, and bile duct proliferation with normal MDR3 protein expression. Results of a lipid study showed elevated values of unesterified cholesterol, phospholipids, and borderline/low apolipoprotein B, and low high-density lipoprotein-cholesterol. Chromatographic analysis of plasma lipoproteins fractions isolated by analytical ultracentrifugation revealed the presence of the anomalous lipoprotein (LpX). Magnetic resonance cholangiopancreatography and percutaneous transhepatic cholangiography showed stenosis of the confluence of the bile ducts with dilation of the intrahepatic biliary tract and failure to visualize the extrahepatic biliary tract. Surgery revealed focal fibroinflammatory stenosis of the left and right bile ducts confluence, treated with resection and bilioenteric anastomosis, followed by the rapid disappearance of LpX, paralleling the normalization of serum lipids, bilirubin, and bile acids, with a progressive reduction of hepatobiliary enzymes.ConclusionWe have described a unique case of focal non-neoplastic extrahepatic biliary stenosis of uncertain etiology, presenting with unusual extremely high levels of LpX-mediated hypercholesterolemia, a condition which is frequently mistaken for LDL on routine clinical tests.

Published
2022
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14. A ZFYVE19 gene mutation associated with neonatal cholestasis and cilia dysfunction: case report with a novel pathogenic variant

Author

Claudia Mandato, Maria Anna Siano, Lucia Nazzaro, Monica Gelzo, Paola Francalanci, Francesca Rizzo, Ylenia D’Agostino, Manuela Morleo, Simona Brillante, Alessandro Weisz, Brunella Franco, and Pietro Vajro

Subjects
Cholestasis, Ciliopathy, ZFYVE19, Children, Medicine
Abstract

Abstract Background ZFYVE19 (Zinc Finger FYVE-Type Containing 19) mutations have most recently been associated to a novel type of high gamma-glutamyl transpeptidase (GGT), non-syndromic, neonatal-onset intrahepatic chronic cholestasis possibly associated to cilia dysfunction. Herein, we report a new case with further studies of whole exome sequencing (WES) and immunofluorescence in primary cilia of her cultured fibroblasts which confirm the observation. Results A now 5-year-old girl born to clinically healthy consanguineous Moroccan parents was assessed at 59 days of life due to severe cholestatic jaundice with increased serum bile acids and GGT, and preserved hepatocellular synthetic function. Despite fibrosis/cirrhosis and biliary ducts proliferation on liver biopsy suggested an extrahepatic biliary obstacle, normal intra-operatory cholangiography excluded biliary atresia. Under choleretic treatment, she maintained a clinically stable anicteric cholestasis but developped hyperlipidemia. After exclusion of the main causes of cholestasis by multiple tests, abnormal concentrations of sterols and WES led to a diagnosis of hereditary sitosterolemia (OMIM #618666), likely unrelated to her cholestasis. Further sequencing investigation revealed a homozygous non-sense mutation (p.Arg223Ter) in ZFYVE19 leading to a 222 aa truncated protein and present in both heterozygous parents. Immunofluorescence analysis of primary cilia on cultured skin fibroblasts showed a ciliary phenotype mainly defined by fragmented cilia and centrioles abnormalities. Conclusions Our findings are consistent with and expands the recent evidence linking ZFYVE19 to a novel, likely non-syndromic, high GGT-PFIC phenotype with neonatal onset. Due to the possible role of ZFYVE19 in cilia function and the unprecedented coexistence of a coincidental hereditary sterol disorder in our case, continuous monitoring will be necessary to substantiate type of liver disease progression and/or possible emergence of a multisystemic involvement. What mentioned above confirms that the application of WES in children with undiagnosed cholestasis may lead to the identification of new causative genes, widening the knowledge on the pathophysiology.

Published
2021
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17. Humanization of care in pediatric wards: differences between perceptions of users and staff according to department type

Author

C. Mandato, M. A. Siano, A. G. E. De Anseris, M. Tripodi, G. Massa, R. De Rosa, M. Buffoli, A. Lamanna, P. Siani, and P. Vajro

Subjects
Humanization of care, Pediatric wards, Facilities, Perception, Users and staff, Pediatrics, RJ1-570
Abstract

Abstract Background As the quality and quantity of patient-centered care may be perceived differently by recipients and independent observers, assessment of humanization of pediatric care remains an elusive issue. Herein we aim to analyze differences between the degrees of verified existing vs. perceived humanization issues of a pediatric ward. Furthermore, we examine whether there is concurrence between the degrees of humanization perceived by users (parents/visitors) vs. staff members. Methods The study was conducted in the pediatric wards of seven medical centers of the Campania region (Italy) categorized as general (n = 4), children’s (n = 1), and university (n = 2) hospitals. The degree of existing humanization was assessed by a multidisciplinary focus group for each hospital through a pediatric care-oriented checklist specifically developed to individuate the most critical areas (i.e., those with scores

Published
2020
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19. Monkeypox Infection 2022: An Updated Narrative Review Focusing on the Neonatal and Pediatric Population

Author

Francesca Gaeta, Francesco De Caro, Gianluigi Franci, Pasquale Pagliano, Pietro Vajro, and Claudia Mandato

Subjects
antivirals, breastfeeding, children, monkeypox, newborn, outbreak, Pediatrics, RJ1-570
Abstract

Monkeypox disease has been endemic in sub-Saharan Africa for decades, attracting remarkable attention only i23n 2022 through the occurrence of a multi-country outbreak. The latter has raised serious public health concerns and is considered a public health emergency by the World Health Organization. Although the disease is usually self-limiting, it can cause severe illness in individuals with compromised immune systems, in children, and/or the pregnant woman–fetus dyad. Patients generally present with fever, lymphadenopathy, and a vesicular rash suggestive of mild smallpox. Serious eye, lung and brain complications, and sepsis can occur. However, cases with subtler clinical presentations have been reported in the recent outbreak. A supportive care system is usually sufficient; otherwise, treatment options are needed in patients who are immunocompromised or with comorbidities. A replication-deficient modified and a live infectious vaccinia virus vaccine can be used both before and after exposure. Due to the persistent spread of monkeypox, it is necessary to focus on the pediatric population, pregnant women, and newborns, who represent fragile contagion groups. Here we assess and summarize the available up-to-date information, focusing on available therapeutic options, with insights into social and school management, breastfeeding, and prevention that will be useful for the scientific community and in particular neonatal and pediatric health professionals.

Published
2022
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20. Pediatric vs. adult NAFLD to MAFLD transition: a welcome but tangled path

Author

Angelo Colucci, Maria Chiara Rocco, Anna Giulia Elena De Anseris, Lucia Nazzaro, Pietro Vajro, and Claudia Mandato

Subjects
nonalcoholic fatty liver disease, metabolic (dysfunction)-associated fatty liver disease, children, inborn errors of metabolism, pediatric fatty liver disease, Other systems of medicine, RZ201-999
Abstract

The term non-alcoholic fatty liver disease (NAFLD) appears unfitting both in adults and in children. As obesity and metabolic syndrome play a relevant pathogenic role, an international group of adults’ liver disease experts has proposed to rename this condition metabolic (dysfunction)-associated fatty liver disease (MAFLD). While this new more appropriate and useful definition has mostly been met with good reactions in adults, it may present a tangled path in pediatrics. Here we further stress the recommendations of the North American and the European Societies for Pediatric Gastroenterology, Hepatology and Nutrition that a hyperechogenic liver in a child affected by obesity or overweight with chronically elevated liver enzymes should not be assumed to have NAFLD only. Especially in those patients who are not in the classic age range or who have particularly severe laboratory anomalies, other genetic, metabolic (inborn errors of metabolism, IEM), endocrine, intestinal and hepatic pediatric-onset conditions, should in fact be excluded, particularly when response to a weight loss trial is not available. The term pediatric fatty liver disease (PeFLD) with three subtypes [1. contextual diagnosis of an IEM; 2. metabolic (dysfunction)-associated fatty liver; 3. unknown cause of fatty liver] has recently been proposed aiming to separate true MAFLD from IEM and/or the other above mentioned conditions, which may be rare when considered individually but represent a large group when considered collectively. Although the cost-effectiveness ratio of this attitude is still indeterminate, it is likely that the advantage of the early identification of a specifically treatable pediatric-onset liver disease associated to/mimicking MAFLD would be rewarding.

Published
2021
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21. Use and Misuse of Emergency Room for Children: Features of Walk-In Consultations and Parental Motivations in a Hospital in Southern Italy

Author

Maria Calicchio, Francesco Valitutti, Antonio Della Vecchia, Anna Giulia Elena De Anseris, Lucia Nazzaro, Sara Bertrando, Dario Bruzzese, and Pietro Vajro

Subjects
pediatric emergency department, non-urgent visits, parental perception of urgency, primary care, ED overcrowding, Pediatrics, RJ1-570
Abstract

Objective: Inappropriate use of the emergency department (ED) represents a major worldwide issue both in pediatric and adult age. Herein, we aim to describe features of pediatric visits to the ED of Salerno University Hospital and to evaluate parental reasons behind the decision to walk in.Materials and Methods: We performed a retrospective observational study evaluating ED encounters for children from January 2014 to December 2019. The appropriateness of visits was measured with a national tool assessing every ED encounter, namely, “the Mattoni method,” which consists of the combination of the triage code assigned, the diagnostic resources adopted, and the consultation outcomes. Moreover, 64 questionnaires were collected from a sample of parents in the waiting rooms in January 2020.Results: A total number of 42,507 visits were recorded during the study period (19,126 females; mean age ± SD: 4.3 ± 3.8 years), the majority of whom were inappropriate (75.8% over the considered period; 73.6% in 2014; 74.6% in 2015; 76.3% in 2016; 76.7% in 2017; 77.9% in 2018; 75.5% in 2019). Most of the inappropriate consultations arrived at the ED by their own vehicle (94.4%), following an independent decision of the parents (97.2%), especially in the evening and at night on Saturdays/Sundays/holidays (69.7%). A multivariate analysis revealed the following: patients of younger age (OR: 1.11, 95% C.I. 1.06–1.16; p < 0.0019), night visits (OR 1.39; 95% C.I.: 1.32–1.47; p < 0.001), patients living in the municipality of Salerno (OR 1.28; 95% C.I.: 1.22–1.34; p < 0.001), weekend day visits (OR 1.48; 95% C.I.: 1.41–1.56; p < 0.001), and independent parental decision without previous contact with primary care pediatrician (OR 3.01; 95% C.I.: 2.64–3.44; p < 0.001) were all significant independent predictors of inappropriate consultation. The most frequent trigger of ED encounters was fever (51.4%). Hospital admission made up 17.6% of all consultations. The questionnaire showed that most parents were aware of the lack of urgency (20.3%) or minor urgency (53.1%) of the visit. The reasons for walking in were the impossibility to receive a home consultation (70%), the difficulty of contacting their family pediatrician during weekends and holidays (54.4%), as well as the search for a quick, effective, diagnosis and therapy (48.4%).Conclusions: The study suggests a highly inappropriate use of ED for children in our region. This issue deserves considerable attention by health care system leaders in order to optimally integrate hospitals and primary care.

Published
2021
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22. Cholestatic jaundice in infancy: struggling with many old and new phenotypes

Author

Claudia Mandato, Giada Zollo, and Pietro Vajro

Subjects
Alagille syndrome, ARC syndrome, Cholestasis, Hepatocyte nuclear factor-1-beta, Neonatal cholestasis, Paucity of intralobular bile ducts, Pediatrics, RJ1-570
Abstract

Abstract Background Clinical diagnosis of neonatal cholestasis is considered to be an extremely challenging process. Here we highlight the importance not only of the prompt distinction between extrahepatic and intrahepatic cholestasis forms, but also of the precise identification of the latter ones amongst the hotchpotch of recently discovered metabolic/genetic causes. Biliary atresia is considered a surgical emergency in a newborn infant. The rate of success in establishing the bile drainage is in fact a function of the early age when the hepato-portoenterostomy intervention is performed. Intrahepatic cholestasis is due to a broad and more and more puzzling variety of infectious, endocrine, genetic, metabolic and toxic disorders where Gamma-glutamyl transpeptidase serum levels may help for differential diagnosis. Recently established laboratory diagnostic techniques have allowed to discover new causes of neonatal cholestasis. Aim of the Commentary is to go through some of them and bring the focus particularly on the information deriving from the paper by Pinon et al. in this issue of the Journal, which paves the way to the inclusion of the hepatocyte nuclear factor-1-beta deficiency as a new condition to consider in the diagnostic process of the syndromic forms with paucity of intralobular bile ducts. Conclusion Neonatal cholestasis poses diagnostic challenges in practice. Recent advances in the pathophysiology and in molecular genetics together with clinical features, histopathologic findings and careful reasoning remains paramount to put together the pieces of the jigsaw.

Published
2019
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23. Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review

Author

Maria Anna Siano, Claudia Mandato, Lucia Nazzaro, Gennaro Iannicelli, Gian Paolo Ciccarelli, Ferdinando Barretta, Cristina Mazzaccara, Margherita Ruoppolo, Giulia Frisso, Carlo Baldi, Salvatore Tartaglione, Francesco Di Salle, Daniela Melis, and Pietro Vajro

Subjects
steatohepatitis, hypertransaminasemia, fatty liver, MADD, case report, Pediatrics, RJ1-570
Abstract

Diagnosis of pediatric steatohepatitis is a challenging issue due to a vast number of established and novel causes. Here, we report a child with Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) presenting with an underrated muscle weakness, exercise intolerance and an atypically severe steatotic liver involvement. A systematic literature review of liver involvement in MADD was performed as well. Our patient is a 11-year-old otherwise healthy, non-obese, male child admitted for some weakness/asthenia, vomiting and recurrent severe hypertransaminasemia (aspartate and alanine aminotransferases up to ×20 times upper limit of normal). Hepatic ultrasound showed a bright liver. MRI detected mild lipid storage of thighs muscles. A liver biopsy showed a micro-macrovacuolar steatohepatitis with minimal fibrosis. Main causes of hypertransaminasemia were ruled out. Serum aminoacids (increased proline), acylcarnitines (increased C4-C18) and a large excretion of urinary glutaric acid, ethylmalonic, butyric, isobutyric, 2-methyl-butyric and isovaleric acids suggested a diagnosis of MADD. Serum acylcarnitines and urinary organic acids fluctuated overtime paralleling serum transaminases during periods of illness/catabolic stress, confirming their recurrent nature. Genetic testing confirmed the diagnosis [homozygous c.1658A > G (p.Tyr553Cys) in exon 12 of the ETFDH gene]. Lipid-restricted diet and riboflavin treatment rapidly ameliorated symptoms, hepatic ultrasonography/enzymes, and metabolic profiles. Literature review (37 retrieved eligible studies, 283 patients) showed that liver is an extramuscular organ rarely involved in late-onset MADD (70 patients), and that amongst 45 patients who had fatty liver only nine had severe presentation.Conclusion: MADD is a disorder with a clinically heterogeneous phenotype. Our study suggests that MADD warrants consideration in the work-up of obesity-unrelated severe steatohepatitis.

Published
2021
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24. Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review

Author

Anna Pia Delli Bovi, Francesca Marciano, Claudia Mandato, Maria Anna Siano, Marcella Savoia, and Pietro Vajro

Subjects
non-alcoholic fatty liver disease, oxidative stress, antioxidants, obstructive sleep apnea syndrome, gut microbiota, obesity, Medicine (General), R5-920
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut–liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.

Published
2021
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26. Effect of Population Lockdown on Pediatric Emergency Room Demands in the Era of COVID-19

Author

Francesco Valitutti, Letizia Zenzeri, Angela Mauro, Rosario Pacifico, Micaela Borrelli, Stefania Muzzica, Giovanni Boccia, Vincenzo Tipo, and Pietro Vajro

Subjects
COVID-19, lockdown, emergency department, overcrowding, appropriateness, children, Pediatrics, RJ1-570
Abstract

Objectives: The aim of this study was to assess the impact of the COVID-19 pandemic and population lockdown on pediatric ED consultations.Methods: A cross-sectional study on pediatric emergency department consultations before and during the current COVID-19 pandemic (March–May 2019 vs. March–May 2020) was performed in two hospitals in the Campania region (Southern Italy) [i.e., Salerno University Hospital (Salerno) and Pediatric Regional Referral Emergency Hub “AORN Santobono-Pausillipon” (Naples)].Results: 29,368 consecutive ED pediatric patients (13,430 females; mean age ± SD = 5.4 ± 4.7 years) were seen in March–May 2019 and 9,133 (4,494 females; mean age ± SD = 5.9 ± 4.2 years) in March–May 2020. Resuscitation/emergency and urgent care pediatric ED consultations were 1,388 (4.7%, 95% CI 4.5–4.9) in the 2019 trimester, while they were 648 (7.1%, 95% CI 6.6–7.6) in the 2020 trimester (p < 0.01). Mean pediatric ED daily consultations were 326.3 (95% CI 299.9–352.7) in the considered period of 2019 and 101.4 (95%CI 77.9–124.9) in the same period of 2020 (p < 0.001). COVID-19 nasal swabs were performed for 385 children; of those, six resulted positive and four of them were hospitalized.Conclusions: This work provides a unique snapshot of the pediatric EDs demands in the era of COVID-19. We witnessed a significant reduction of non-urgent health care demands during the pandemic but an increase of more severe urgent cases. The COVID-19 pandemic and the following lockdown unveiled the inappropriateness of the majority of pediatric ED consultations. Nevertheless, the current scenario highlighted the need for appropriate and timely clinical evaluations in the pediatric primary care to tackle late and more severe diagnoses in EDs.

Published
2020
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27. Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation

Author

Pietro Vajro, Katarzyna Zielinska, Bobby G. Ng, Marco Maccarana, Per Bengtson, Marco Poeta, Claudia Mandato, Elisa D’Acunto, Hudson H. Freeze, and Erik A. Eklund

Subjects
CDG, Glycosylation, Ceruloplasmin, Transferrin, Liver disease, Transaminase, Medicine
Abstract

Abstract Background TMEM199 deficiency was recently shown in four patients to cause liver disease with steatosis, elevated serum transaminases, cholesterol and alkaline phosphatase and abnormal protein glycosylation. There is no information on the long-term outcome in this disorder. Results We here present three novel patients with TMEM199-CDG. All three patients carried the same set of mutations (c.13-14delTT (p.Ser4Serfs*30) and c.92G > C (p.Arg31Pro), despite only two were related (siblings). One mutation (c.92G > C) was described previously whereas the other was deemed pathogenic due to its early frameshift. Western Blot analysis confirmed a reduced level of TMEM199 protein in patient fibroblasts and all patients showed a similar glycosylation defect. The patients presented with a very similar clinical and biochemical phenotype to the initial publication, confirming that TMEM199-CDG is a non-encephalopathic liver disorder. Two of the patients were clinically assessed over two decades without deterioration. Conclusion A rising number of disorders affecting Golgi homeostasis have been published over the last few years. A hallmark finding is deficiency in protein glycosylation, both in N- and O-linked types. Most of these disorders have signs of both liver and brain involvement. However, the present and the four previously reported patients do not show encephalopathy but a chronic, non-progressive (over decades) liver disease with hypertransaminasemia and steatosis. This information is crucial for the patient/families and clinician at diagnosis, as it distinguishes it from other Golgi homeostasis disorders, in having a much more favorable course.

Published
2018
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28. Paediatric steatotic liver disease has unique characteristics: A multisociety statement endorsing the new nomenclature

Author

Baumann, Ulrich, Koot, Bart G. P., Fitzpatrick, Emer, Mann, Jake, Vajro, Pietro, Krag, Aleksander, Newsome, Philip N., Shawcross, Debbie, Francque, Sven, Böttler, Tobias, Gold, Benjamin D., Lightdale, Jenifer R., Mouzaki, Marialena, Rodriguez‐Baez, Norberto, Kohli, Rohit, Ng, Vicky L., D'Agostino, Daniel, Porta, Gilda, Spolidoro, José, Klünder‐Klünder, Miguel, Vázquez‐Frias, Rodrigo, Sibal, Anupam, Ko, Jae Sung, Kim, Kyung Mo, Treepongkaruna, Suporn, Ni, Yen‐Hsuan, El‐Guindi, Mohamed, Mohan, Neelam, Verduci, Elvira, Memon, Iqbal, Bozo, Mahmoud, Godoy, Marcela, Orsi, Marina, Aw, Marion, Bandsma, Robert, Ibrahim, Samar, Xanthakos, Stavra, Treepongkaruna, Suporn, and Mitsinikos, Tania

Abstract

Nonalcoholic fatty liver disease (NAFLD) has been a commonly used term and diagnosis in paediatric hepatology, gastroenterology, and endocrinology clinics for over 30 years. A multisociety Delphi process has determined a new name “Steatotic Liver Disease” (SLD) as the overarching term for disorders associated with hepatic lipid accumulation. Our Societies give our support to steatotic liver disease as the best overarching term for use in our communities. Metabolic dysfunction‐associated steatotic liver disease (MASLD) overcomes many of the shortcomings of the name NAFLD. Here, we highlight several points of the new nomenclature that are of particular importance for our community and their consequences for implementation including: diagnostic criteria, considering alternate diagnoses, practical implementation, research, advocacy, and education for paediatricians. As with all nomenclature changes, it will take a concerted effort from our paediatric societies to help integrate the optimal use of this into practice. “Metabolic dysfunction associated steatotic liver disease” (MASLD) is the new name for “Nonalcoholic fatty liver disease.”Other liver diseases may masquerade as paediatric MASLD. “Metabolic dysfunction associated steatotic liver disease” (MASLD) is the new name for “Nonalcoholic fatty liver disease.” Other liver diseases may masquerade as paediatric MASLD. Globally, paediatric societies endorse the use of MASLD.The diagnostic pathway for paediatric MASLD differs to that of adult MASLD.Ongoing education & training is need for all stakeholders to implement the use of MASLD. Globally, paediatric societies endorse the use of MASLD. The diagnostic pathway for paediatric MASLD differs to that of adult MASLD. Ongoing education & training is need for all stakeholders to implement the use of MASLD.

Published
2024
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32. Global multi-stakeholder endorsement of the MAFLD definition

Author

Mendez-Sanchez, N, Bugianesi, E, Gish, R, Lammert, F, Tilg, H, Nguyen, M, Sarin, S, Fabrellas, N, Zelber-Sagi, S, Fan, J, Shiha, G, Targher, G, Zheng, M, Chan, W, Vinker, S, Kawaguchi, T, Castera, L, Yilmaz, Y, Korenjak, M, Spearman, C, Ungan, M, Palmer, M, El-Shabrawi, M, Gruss, H, Dufour, J, Dhawan, A, Wedemeyer, H, George, J, Valenti, L, Fouad, Y, Romero-Gomez, M, Eslam, M, Abate, M, Abbas, B, Abbassy, A, Abd El Ghany, W, Abd Elkhalek, A, Abd ElMajeed, E, Abdalgaber, M, Abdallah, M, Abdallah, N, Abdelaleem, S, Abdelghani, Y, Abdelghany, W, Abdelhalim, S, Abdelhamid, W, Abdelhamid, N, Abdelkader, N, Abdelkreem, E, Abdelmohsen, A, Abdelrahman, A, Abd-elsalam, S, Abdeltawab, D, Abduh, A, Abdulhakam, N, Abdulla, M, Abedpoor, N, Abenavoli, L, Aberg, F, Ablack, O, Abo elftouh, M, Abo-Amer, Y, Aboubkr, A, Aboud, A, Abouelnaga, A, Aboufarrag, G, Aboutaleb, A, Abundis, L, Adali, G, Adames, E, Adams, L, Adda, D, Adel, N, Adel Sayed, M, Afaa, T, Afredj, N, Aghayeva, G, Aghemo, A, Aguilar-Salinas, C, Ahlenstiel, G, Ahmady, W, Ahmed, W, Ahmed, A, Ahmed, S, Ahmed, H, Ahmed, R, Aigner, E, Akarsu, M, Akroush, M, Akyuz, U, Al Mahtab, M, Al Qadiri, T, Al Rawahi, Y, AL rubaee, R, Al Saffar, M, Alam, S, Al-Ani, Z, Albillos, A, Alboraie, M, Al-Busafi, S, Al-Emam, M, Alharthi, J, Ali, K, Ali, B, Ali, M, Ali, R, Alisi, A, AL-Khafaji, A, Alkhatry, M, Aller, R, Almansoury, Y, Al-Naamani, K, Alnakeeb, A, Alonso, A, Alqahtani, S, Alrabadi, L, Alswat, K, Altaher, M, Altamimi, T, Altamirano, J, Alvares-da-Silva, M, Aly, E, Alzahaby, A, Alzamzamy, A, Amano, K, Amer, M, Amin, M, Amin, S, Amir, A, Ampuero, J, Anas, N, Andreone, P, Andriamandimby, S, Anees, M, Angela, P, Antonios, M, Arafat, W, Araya, J, Armendariz-Borunda, J, Armstrong, M, Ashktorab, H, Aspichueta, P, Assal, F, Atef, M, Attia, D, Atwa, H, Awad, R, Awad, M, Awny, S, Awolowo, O, Awuku, Y, Ayada, I, Aye, T, Ayman, S, Ayman, H, Ayoub, H, Azmy, H, Babaran, R, Badreldin, O, Badry, A, Bahcecioglu, I, Bahour, A, Bai, J, Balaban, Y, Balasubramanyam, M, Bamakhrama, K, Banales, J, Bangaru, B, Bao, J, Barahona, J, Barakat, S, Barbalho, S, Barbra, B, Barranco, B, Barrera, F, Baumann, U, Bazeed, S, Bech, E, Benayad, A, Benesic, A, Bernstein, D, Bessone, F, Birney, S, Bisseye, C, Blake, M, Bobat, B, Bonfrate, L, Bordin, D, Bosques-Padilla, F, Boursier, J, Boushab, B, Bowen, D, Bravo, P, Brennan, P, Bright, B, Broekaert, I, Buque, X, Burgos-Santamaria, D, Burman, J, Busetto, L, Byrne, C, Cabral-Prodigalidad, P, Cabrera-Alvarez, G, Cai, W, Cainelli, F, Caliskan, A, Canbay, A, Cano-Contreras, A, Cao, H, Cao, Z, Carrion, A, Carubbi, F, Casanovas, T, Castellanos Fernandez, M, Chai, J, Chan, S, Charatcharoenwitthaya, P, Chavez-Tapia, N, Chayama, K, Chen, J, Chen, L, Chen, Z, Chen, H, Chen, S, Chen, Q, Chen, Y, Chen, G, Chen, E, Chen, F, Chen, P, Cheng, R, Cheng, W, Chieh, J, Chokr, I, Cholongitas, E, Choudhury, A, Chowdhury, A, Chukwudike, E, Ciardullo, S, Clayton, M, Clement, K, Cloa, M, Coccia, C, Collazos, C, 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J., Afredj N., Aghayeva G., Aghemo A., Aguilar-Salinas C. A., Ahlenstiel G., Ahmady W., Ahmed W., Ahmed A., Ahmed S. N., Ahmed H. M., Ahmed R., Aigner E., Akarsu M., Akroush M., Akyuz U., Al Mahtab M., Al Qadiri T., Al Rawahi Y., AL rubaee R., Al Saffar M., Alam S., Al-Ani Z., Albillos A., Alboraie M., Al-Busafi S., Al-Emam M., Alharthi J., Ali K., Ali B. A., Ali M., Ali R. A. R., Alisi A., AL-Khafaji A. R., Alkhatry M., Aller R., Almansoury Y., Al-Naamani K., Alnakeeb A., Alonso A., Alqahtani S. A., Alrabadi L., Alswat K., Altaher M., Altamimi T., Altamirano J., Alvares-da-Silva M. R., Aly E. A. M., Alzahaby A., Alzamzamy A., Amano K., Amer M. A., Amin M. A., Amin S. A., Amir A. A., Ampuero J., Anas N., Andreone P., Andriamandimby S. F., Anees M., Angela P., Antonios M., Arafat W., Araya J. M., Armendariz-Borunda J., Armstrong M. J., Ashktorab H., Aspichueta P., Assal F., Atef M., Attia D., Atwa H., Awad R., Awad M. A. E., Awny S., Awolowo O., Awuku Y. A., Ayada I., Aye T. T., Ayman S., Ayman H., Ayoub H., Azmy H. M., Babaran R. P., Badreldin O., Badry A., Bahcecioglu I. H., Bahour A., Bai J., Balaban Y., Balasubramanyam M., Bamakhrama K., Banales J. M., Bangaru B., Bao J., Barahona J. S., Barakat S., Barbalho S. M., Barbra B., Barranco B., Barrera F., Baumann U., Bazeed S., Bech E., Benayad A., Benesic A., Bernstein D., Bessone F., Birney S., Bisseye C., Blake M., Bobat B., Bonfrate L., Bordin D. S., Bosques-Padilla F., Boursier J., Boushab B. M., Bowen D., Bravo P. M., Brennan P. N., Bright B., Broekaert I., Buque X., Burgos-Santamaria D., Burman J., Busetto L., Byrne C. D., Cabral-Prodigalidad P. A. I., Cabrera-Alvarez G., Cai W., Cainelli F., Caliskan A. R., Canbay A., Cano-Contreras A., Cao H. -X., Cao Z., Carrion A., Carubbi F., Casanovas T., Castellanos Fernandez M. I., Chai J., Chan S. P., Charatcharoenwitthaya P., Chavez-Tapia N., Chayama K., Chen J., Chen L., Chen Z. -W., Chen H., Chen S. -D., Chen Q., Chen Y., Chen G., Chen E. -Q., Chen F., Chen P. -J., Cheng R., Cheng W., Chieh J. T. W., Chokr I., Cholongitas E., Choudhury A., Chowdhury A., Chukwudike E. S., Ciardullo S., Clayton M., Clement K., Cloa M. M., Coccia C., Collazos C., Colombo M., Cosar A. M., Cotrim H. P., Couillerot J., Coulibaly A., Crespo G., Crespo J., Cruells M., Cua I. H. Y., Dabbous H. K., Dalekos G. N., D'Alia P., Dan L., Dao V. H., Darwish M., Datz C., Davalos-Moscol M. B., Dawoud H., de Careaga B. O., de Knegt R., de Ledinghen V., de Silva J., Debzi N., Decraecker M., Del Pozo E., Delgado T. C., Delgado-Blanco M., Dembinski L., Depina A., Derbala M., Desalegn H., Desbois-Mouthon C., Desoky M., Dev A., Di Ciaula A., Diago M., Diallo I., Diaz L. A., Dirchwolf M., Dongiovanni P., Dorofeyev A., Dou X., Douglas M. W., Doulberis M., Dovia C. K., Doyle A., Dragojevic I., Drenth J. P., Duan X., Dulskas A., Dumitrascu D. L., Duncan O., Dusabejambo V., Dwawhi R. S. N. A., Eiketsu S., El Amrousy D., El Deeb A., El Deriny G., El Din H. S., El Kamshishy S., El Kassas M., El Raziky M., Elagamy O. A., Elakel W., Elalfy D., Elaraby H., ElAwady H., Elbadawy R., Eldash H. H., Eldefrawy M. S., Elecharri C. L., Elfaramawy A., Elfatih M., Elfiky M., Elgamsy M., Elgendy M., El-Guindi M. A., Elhussieny N., Eliwa A. M., Elkabbany Z., El-Khayat H., El-Koofy N. M., Elmetwalli A., Elrabat A., El-Raey F., Elrashdy F., Elsahhar M., Elsaid E. M., Elsayed S., Elsayed H., Elsayed A., Elsayed A. M., El-Serafy M., Elsharkawy A. M., Elsheemy R. Y., Elshemy E. E., Elsherbini S., Eltoukhy N., Elwakil R., Emad O., Emad S., Embabi M., Ergenc I., Ermolova T., Esmat G., Esmat D. M., Estupinan E. C., Ettair S., Eugen T., Ezz-Eldin M., Falcon L. P. V., Fan Y. -C., Fandari S., Farag M., Farahat T. M., Fares E. M., Fares M., Fassio E., Fathy H., Fathy D., Fathy W., Fayed S., Feng D., Feng G., Fernandez-Bermejo M., Ferreira C. T., Ferrer J. D., Forbes A., Fouad R., Fouad H. M., Frisch T., Fujii H., Fukunaga S., Fukunishi S., Fulya H., Furuhashi M., Gaber Y., Galang A. J. G., Gallardo J. C., Galloso R., Gamal M., Gamal R., Gamal H., Gan J., Ganbold A., Gao X., Garas G., Garba T., Garcia-Cortes M., Garcia-Monzon C., Garcia-Samaniego J., Gastaldelli A., Gatica M., Gatley E., Gegeshidze T., Geng B., Ghazinyan H., Ghoneem S., Giacomelli L., Giannelli G., Giannini E. G., Giefer M., Gines P., Girala M., Giraudi P. J., Goh G. B. -B., Gomaa A. A., Gong B., Gonzales D. H. C., Gonzalez H. C., Gonzalez-Huezo M. S., Graupera I., Grgurevic I., Gronbaek H., Gu X., Guan L., Gueye I., Guingane A. N., Gul O. O., Gul C. B., Guo Q., Gupta P. P., Gurakar A., Gutierrez J. C. R., Habib G., Hafez A., Hagman E., Halawa E., Hamdy O., Hamed A. E., Hamed D. H., Hamid S., Hamoudi W., Han Y., Haridy J., Haridy H., Harris D. C. H. H., Hart M., Hasan F., Hashim A., Hassan I., Hassan A., Hassan E. A., Hassan A. A., Hassan M. S., Hassanin F., Hassnine A., Haukeland J. W., Hawal A. I. M., He J., He Q., He Y., He F. -P., Hegazy M., Hegazy A., Henegil O., Hernandez N., Hernandez-Guerra M., Higuera-de-la-Tijera F., Hindy I., Hirota K., Ho L. C., Hodge A., Hosny M., Hou X., Huang J. -F., Huang Y., Huang Z., Huang A., Huang X. -P., Hui-ping S., Hunyady B., Hussein M. A., Hussein O., Hussien S. M., Ibanez-Samaniego L., Ibdah J., Ibrahim L., Ibrahim M., Ibrahim I., Icaza-Chavez M. E., Idelbi S., Idilman R. I., Ikeda M., Indolfi G., Invernizzi F., Irshad I., Isa H. M. A., Iskandar N. J., Ismaiel A., Ismail M., Ismail Z., Ismail F., Iwamoto H., Jack K., Jacob R., Jafarov F., Jafri W., Jahshan H., Jalal P. K., Jancoriene L., Janicko M., Jayasena H., Jefferies M., Jha V., Ji F., Ji Y., Jia J., Jiang C., Jiang N., Jiang Z. -Z., Jin X., Jin Y., Jing X., Jingyu Q., Jinjolava M., Jong F. H. H., Jucov A., Julius I., Kaddah M., Kamada Y., kamal A., Kamal E. M., Kamel A. S., Kao J. -H., Karin M., Karlas T., Kashwaa M., Katsidzira L., Kaya E., Kayasseh M. A., Keenan B., Keklikkiran C., Keml W., Khalaf D. K., Khalefa R., Khamis S., Khater D., khattab H., Khavkin A., Khlynova O., Khmis N., Kobyliak N., Koffas A., Koike K., Kok K. Y. Y., Koller T., Komas N. P., Korochanskaya N. V., Koulla Y., Koya S., Kraft C., Kraja B., Krawczyk M., Kuchay M. S., Kulkarni A. V., Kumar A., Kumar M., Lakoh S., Lam P., Lan L., Lange N. F., Lankarani K. B., Lanthier N., Lapshyna K., Lashen S. A., Laure K. N. J., Lazebnik L., Lebrec D., Lee S. S., Lee W. S., Lee Y. Y., Leeming D. J., Leite N. C., Leon R., Lesmana C. R. A., Li J., Li Q., Li Y. -Y., Li Y., Li L., Li M., li Y., Liang H., Lijuan T., Lim S. 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G., Lim L. -L., Lin S., Lin H. -C., Lin R., Lithy R., Liu Y., Liu X., Liu W. -Y., Liu S., Liu K., Liu T., Lonardo A., Lopez M. B., Lopez-Benages E., Lopez-Jaramillo P., Lu H., Lu L. G., Lu Y., Lubel J., Lui R., Lupasco I., Luzina E., Lv X. -H., Lynch K., Ma H. -L., Machado M. V., Maduka N., Madzharova K., Magdaong R., Mahadeva S., Mahfouz A., Mahmood N. R. K. N., Mahmoud E., Mahrous M., Maiwall R., Majeed A., Majumdar A., Mak L., Maklouf M. M., Malekzadeh R., Mandato C., Mangia A., Mann J., Mansour H. H., Mansouri A., Mantovani A., Mao J. Q., Maramag F., Marchesini G., Marcus C., Marinho R. A. R. T., Martinez-Chantar M. L., Martins A. A. S., Marwan R., Mason K. F., Masoud G., Massoud M. N., Matamoros M. A., Mateos R. M., Mawed A., Mbanya J. C., Mbendi C., McColaugh L., McLeod D., Medina J. F. R., Megahed A., Mehrez M., Memon I., Merat S., Mercado R., Mesbah A., Meskini T., Metwally M., Metwaly R., Miao L., Micah E., Miele L., Milivojevic V., Milovanovic T., Mina Y. L., Mishkovik M., Mishriki A., Mitchell T., Mohamed A., Mohamed M., Mohamed S., Mohammed S., Mohammed A., Mohan V., Mohie S., Mokhtar A., Moniem R., Montilla M. S., Morales J. A. O., Morata M. M. S., Moreno-Planas J. M., Morise S., Mosaad S., Moselhy M., Mostafa A. M., Mostafa E., Mouane N., Mousa N., Moustafa H. M., Msherif A., Muller K., Munoz C., Munoz-Urribarri A. B., Murillo O. A., Mustapha F. I., Muzurovic E., Nabil Y., Nafady S., Nagamatsu A., Nakajima A., Nakano D., Nan Y., Nascimbeni F., Naseef M. S., Nashat N., Natalia T., Negro F., Nersesov A. V., Neuman M., Ng'wanasayi M., Ni Y., Nicoll A., Niizeki T., Nikolova D., Ningning W., Niriella M., Nogoibaeva K. A., Nordien R., O Sullivan C., O'Beirne J., Obekpa S., Ocama P., Ochwoto M., Ogolodom M. P., Ojo O., Okrostsvaridze N., Oliveira C. P., Omana R. C., Omar O. M., Omar H., Omar M., Omran S., Omran R., Osman M. M., Owise N., Owusu-Ansah T., Padilla- Machaca P. M., Palle S., Pan Z., Pan X. -Y., Pan Q., Papaefthymiou A., Paquissi F. C., Par G., Parkash A., Payawal D., Peltekian K. M., Peng X., Peng L., Peng Y., Pengoria R., Perez M., Perez J. L., Perez N. M., Persico M., Pessoa M. G., Petta S., Philip M., Plaz Torres M. C., Polavarapu N., Poniachik J., Portincasa P., Pu C., Purnak T., Purwanto E., Qi X., Qian Z., Qiang Z., Qiao Z., Qiao L., Queiroz A., Rabiee A., Radwan M., Rahetilahy A. M., Ramadan Y., Ramadan D., Ramli A. S., Ramm G. A., Ran A., Rankovic I., RAO H., Raouf S., Ray S., Reau N., Refaat A., Reiberger T., Remes-Troche J. M., Reyes E. C., Richardson B., Ridruejo E., Riestra Jimenez S., Rizk I., Roberts S., Roblero J. P., Robles J. A. P., Rockey D., Rodriguez M., Rodriguez Hernandez H., Roman E., Romeiro F. G., Romeo S., Rosales-Zabal J. M., Roshdi G. R., Rosso N., Ruf A., Ruiz P. C., Runes N. R., Ruzzenente A., Ryan M., Saad A., Sabbagh E. B., Sabbah M., Saber S., Sabrey R., Sabry R., Saeed M. A., Said D., Said E. M., Sakr M. A., Salah Y., Salama R. M., Salama A., Saleh H., Saleh A., Salem A., Salem A. T., Salifou A., Salih A. F., Salman A., Samouda H., Sanai F., Sanchez-Avila J. F., Sanker L., Sano T., Sanz M., Saparbu T., Sawhney R., Sayed F., Sayed S. A., Sayed A. O., Sayed M., Sebastiani G., Secadas L., Sediqi K. Q., Seif S., Semida N., Senates E., Serban E. D., Serfaty L., Seto W. -K., Sghaier I., Sha M., Shabaan H. M., Shalaby L., Shaltout I., Sharara A. I., Sharma V., Shawa I. T., Shawkat A., Shawky N., Shehata O., Sheils S., Shewaye A. B., Shi G., Shi J., Shimose S., Shirono T., Shou L., Shrestha A., Shui G., Sievert W., Sigurdardottir S., Sira M. M., Siradj R., Sison C., Smyth L., Soliman R., Sollano J. D., Sombie R., Sonderup M., Sood S., Soriano G., Stedman C. A. M., Stefanyuk O., Stimac D., Strasser S., Strnad P., Stuart K., Su W., Su M., Sumida Y., Sumie S., Sun D. -Q., Sun J., Suzuki H., Svegliati-Baroni G., Swar M. O., TAHARBOUCHT S., Taher Z., Takamura S., Tan L., Tan S. -S., Tanwandee T., Tarek S., Tatiana G., Tavaglione F., Tecson G. Y., Tee H. -P., Teschke R., Tharwat M., Thong V. D., Thursz M., Tine T., Tiribelli C., Tolmane I., Tong J., Tongo M., Torkie M., Torre A., Torres E. A., Trajkovska M., Treeprasertsuk S., Tsutsumi T., Tu T., Tur J. A., Turan D., Turcan S., Turkina S., Tutar E., Tzeuton C., Ugiagbe R., Uygun A., Vacca M., Vajro P., Van der Poorten D., Van Kleef L. A., Vashakidze E., Velazquez C. M., Velazquez M. I., Vento S., Verhoeven V., Vespasiani-Gentilucci U., Vethakkan S. R., Vilaseca J., Vitek L., Volkanovska A., Wallace M., Wan W., Wang Y., Wang X., Wang C., Wang M., Wangchuk P., Weltman M., White M., Wiegand J., Wifi M. -N., Wigg A., Wilhelmi M., William R., Wittenburg H., Wu S., Wubeneh A. M., Xia H., Xiao J., Xiao X., Xiaofeng W., Xiong W., Xu L., Xu J., Xu W., Xu J. -H., Xu K., Xu Y., Xu S. -H., Xu M., Xu A., Xu C., Yan H., Yang J., Yang R. -X., Yang Y., Yang Q., Yang N., Yao J., Yara J., Yaras S., Yilmaz N., Younes R., younes H., Young S., Youssef F., Yu Y., Yu M. -L., Yuan J., Yue Z., Yuen M. -F., Yun W., Yurukova N., Zakaria S., Zaky S., Zaldastanishvili M., Zapata R., Zare N., Zerem E., Zeriban N., Zeshuai X., Zhang H., Zhang X., Zhang Y., Zhang W. -H., Zhang Y. -P., Zhang Z. -Q., Zhao J., Zhao R. -R., Zhao H., Zheng C., Zheng Y., Zheng R., Zheng T. -L., Zheng K., Zhou X. Q., Zhou Y., Zhou Y. -J., Zhou H., Zhou L., Zhu L. D., Zhu Y. F., Zhu Y., Zhu P. -W., Ziada E., Ziring D., Ziyi L., Zou S., Zou Z., Zou H., and Zuart Ruiz R.

Published
2022

33. Diagnostic approach to neonatal and infantile cholestasis: A position paper by the SIGENP liver disease working group

Author

Ranucci, G, Della Corte, C, Alberti, D, Bondioni, M, Boroni, G, Calvo, P, Cananzi, M, Candusso, M, Clemente, M, D'Antiga, L, Degrassi, I, De Ville De Goyet, J, Di Dato, F, Di Giorgio, A, Vici, C, Ferrari, F, Francalanci, P, Fuoti, M, Fusaro, F, Gaio, P, Grimaldi, C, Iascone, M, Indolfi, G, Iorio, R, Maggiore, G, Mandato, C, Matarazzo, L, Monti, L, Mosca, F, Nebbia, G, Nuti, F, Paolella, G, Pinon, M, Roggero, P, Sciveres, M, Serranti, D, Spada, M, Vajro, P, Nicastro, E, Ranucci G., Della Corte C., Alberti D., Bondioni M. P., Boroni G., Calvo P. L., Cananzi M., Candusso M., Clemente M. G., D'Antiga L., Degrassi I., De Ville De Goyet J., Di Dato F., Di Giorgio A., Vici C. D., Ferrari F., Francalanci P., Fuoti M., Fusaro F., Gaio P., Grimaldi C., Iascone M., Indolfi G., Iorio R., Maggiore G., Mandato C., Matarazzo L., Monti L., Mosca F., Nebbia G., Nuti F., Paolella G., Pinon M., Roggero P., Sciveres M., Serranti D., Spada M., Vajro P., Nicastro E., Ranucci, G, Della Corte, C, Alberti, D, Bondioni, M, Boroni, G, Calvo, P, Cananzi, M, Candusso, M, Clemente, M, D'Antiga, L, Degrassi, I, De Ville De Goyet, J, Di Dato, F, Di Giorgio, A, Vici, C, Ferrari, F, Francalanci, P, Fuoti, M, Fusaro, F, Gaio, P, Grimaldi, C, Iascone, M, Indolfi, G, Iorio, R, Maggiore, G, Mandato, C, Matarazzo, L, Monti, L, Mosca, F, Nebbia, G, Nuti, F, Paolella, G, Pinon, M, Roggero, P, Sciveres, M, Serranti, D, Spada, M, Vajro, P, Nicastro, E, Ranucci G., Della Corte C., Alberti D., Bondioni M. P., Boroni G., Calvo P. L., Cananzi M., Candusso M., Clemente M. G., D'Antiga L., Degrassi I., De Ville De Goyet J., Di Dato F., Di Giorgio A., Vici C. D., Ferrari F., Francalanci P., Fuoti M., Fusaro F., Gaio P., Grimaldi C., Iascone M., Indolfi G., Iorio R., Maggiore G., Mandato C., Matarazzo L., Monti L., Mosca F., Nebbia G., Nuti F., Paolella G., Pinon M., Roggero P., Sciveres M., Serranti D., Spada M., Vajro P., and Nicastro E.

Abstract

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Published
2022

34. Humanization of pediatric care in the world: focus and review of existing models and measurement tools

Author

Marina Tripodi, Maria Anna Siano, Claudia Mandato, Anna Giulia Elena De Anseris, Paolo Quitadamo, Salvatore Guercio Nuzio, Claudia Viggiano, Francesco Fasolino, Annalisa Bellopede, Maria Annunziata, Grazia Massa, Francesco Maria Pepe, Maria De Chiara, Paolo Siani, and Pietro Vajro

Subjects
Humanization, Pediatric care, Family centered care, Child-friendly healthcare, Pediatrics, RJ1-570
Abstract

Abstract Background The term “humanization” indicates the process by which people try to make something more human and civilized, more in line with what is believed to be the human nature. The humanization of care is an important and not yet a well-defined issue which includes a wide range of aspects related to the approach to the patient and care modalities. In pediatrics, the humanization concept is even vaguer due to the dual involvement of both the child and his/her family and by the existence of multiple proposed models. Objective The present study aims to analyze the main existing humanization models regarding pediatric care, and the tools for assessing its grade. Results The main Humanization care programs have been elaborated and developed both in America (Brazil, USA) and Europe. The North American and European models specifically concern pediatric care, while the model developed in Brazil is part of a broader program aimed at all age groups. The first emphasis is on the importance of the family in child care, the second emphasis is on the child’s right to be a leader, to be heard and to be able to express its opinion on the program’s own care. Several tools have been created and used to evaluate humanization of care programs and related aspects. None, however, had been mutually compared. Conclusions The major models of humanization care and the related assessment tools here reviewed highlight the urgent need for a more unifying approach, which may help in realizing health care programs closer to the young patient’s and his/her family needs.

Published
2017
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35. Corrigendum to 'Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)' Nutrition, Metabolism and Cardiovascular diseases volume 32 issue 1 (2022) 1-16

Author

Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., and Miele L. (ORCID:0000-0003-3464-0068)

Abstract

N/A

Published
2023

36. Corrigendum to 'Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)' [Dig Liver Dis 54 (2022) 170-182]

Author

Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., and Miele L. (ORCID:0000-0003-3464-0068)

Abstract

N/A

Published
2023

38. Efficacy of Sofosbuvir/Ledipasvir in Adolescents with Chronic Hepatitis C Genotypes 1, 3, and 4: A Real-world Study

Author

Serranti, D, Nebbia, G, Cananzi, M, Nicastro, E, Dato, F, Nuti, F, Garazzino, S, Silvestro, E, Giacomet, V, Forlanini, F, Pinon, M, Calvo, P, Riva, S, Dodi, I, Cangelosi, A, Antonucci, R, Ricci, S, Bartolini, E, Mastrangelo, G, Trapani, S, Lenge, M, Gaio, P, Vajro, P, Iorio, R, D'Antiga, L, Indolfi, G, Serranti D., Nebbia G., Cananzi M., Nicastro E., Dato F. D., Nuti F., Garazzino S., Silvestro E., Giacomet V., Forlanini F., Pinon M., Calvo P. L., Riva S., Dodi I., Cangelosi A. M., Antonucci R., Ricci S., Bartolini E., Mastrangelo G., Trapani S., Lenge M., Gaio P., Vajro P., Iorio R., D'Antiga L., Indolfi G., Serranti, D, Nebbia, G, Cananzi, M, Nicastro, E, Dato, F, Nuti, F, Garazzino, S, Silvestro, E, Giacomet, V, Forlanini, F, Pinon, M, Calvo, P, Riva, S, Dodi, I, Cangelosi, A, Antonucci, R, Ricci, S, Bartolini, E, Mastrangelo, G, Trapani, S, Lenge, M, Gaio, P, Vajro, P, Iorio, R, D'Antiga, L, Indolfi, G, Serranti D., Nebbia G., Cananzi M., Nicastro E., Dato F. D., Nuti F., Garazzino S., Silvestro E., Giacomet V., Forlanini F., Pinon M., Calvo P. L., Riva S., Dodi I., Cangelosi A. M., Antonucci R., Ricci S., Bartolini E., Mastrangelo G., Trapani S., Lenge M., Gaio P., Vajro P., Iorio R., D'Antiga L., and Indolfi G.

Abstract

Objectives: Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA)for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to <18 years old) with CHC in the real-world setting. Methods: Prospective, open-label, multicentre study involving 12 Italian centres. Patients received the fixed-dose combination of SOF/LDV (400/90 mg) once daily-ribavirin as per EMA approval and recommendations. The key efficacy endpoint was sustained virological response 12 weeks after the end of treatment (SVR12) as per intention-to-treat analysis. Safety was assessed by adverse events and clinical/laboratory data. Results: Seventy-eight consecutive adolescents (median age 15.2 years, range 12-17.9; girls 53.8%) were enrolled and treated between June 2018 and December 2019. Genotype distribution was as follows: Genotype 1 (82.1%), 3 (2.5%), and 4 (15.4%). Seventy-six (97.4%) patients completed treatment and follow-up. Overall, SVR12 was 98.7%. One patient was lost to follow-up after 4 weeks of treatment; 1 patient completed treatment and missed the follow-up visit. No virological breakthrough or relapse were observed. No patient experienced grade 3 to 4 adverse event or serious adverse event. Conclusions: The results of this real-world study confirmed the high efficacy and the optimal safety profile of SOF/LDV for treatment of CHC in adolescents.

Published
2021

39. Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group

Author

Di Giorgio, A, Bartolini, E, Calvo, P, Cananzi, M, Cirillo, F, Della Corte, C, Dionisi-Vici, C, Indolfi, G, Iorio, R, Maggiore, G, Mandato, C, Nebbia, G, Nicastro, E, Pinon, M, Ranucci, G, Sciveres, M, Vajro, P, D'Antiga, L, Di Giorgio A., Bartolini E., Calvo P. L., Cananzi M., Cirillo F., Della Corte C., Dionisi-Vici C., Indolfi G., Iorio R., Maggiore G., Mandato C., Nebbia G., Nicastro E., Pinon M., Ranucci G., Sciveres M., Vajro P., D'Antiga L., Di Giorgio, A, Bartolini, E, Calvo, P, Cananzi, M, Cirillo, F, Della Corte, C, Dionisi-Vici, C, Indolfi, G, Iorio, R, Maggiore, G, Mandato, C, Nebbia, G, Nicastro, E, Pinon, M, Ranucci, G, Sciveres, M, Vajro, P, D'Antiga, L, Di Giorgio A., Bartolini E., Calvo P. L., Cananzi M., Cirillo F., Della Corte C., Dionisi-Vici C., Indolfi G., Iorio R., Maggiore G., Mandato C., Nebbia G., Nicastro E., Pinon M., Ranucci G., Sciveres M., Vajro P., and D'Antiga L.

Abstract

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Published
2021

41. Pediatric Fatty Liver and Obesity: Not Always Just a Matter of Non-Alcoholic Fatty Liver Disease

Author

Renata Alfani, Edoardo Vassallo, Anna Giulia De Anseris, Lucia Nazzaro, Ida d'Acunzo, Carolina Porfito, Claudia Mandato, and Pietro Vajro

Subjects
fatty liver, obesity, NAFLD, differential diagnosis, systemic disorders, genetic and metabolic disorders, Pediatrics, RJ1-570
Abstract

Obesity-related non-alcoholic fatty liver disease (NAFLD) represents the most common cause of pediatric liver disease due to overweight/obesity large-scale epidemics. In clinical practice, diagnosis is usually based on clinical features, blood tests, and liver imaging. Here, we underline the need to make a correct differential diagnosis for a number of genetic, metabolic, gastrointestinal, nutritional, endocrine, muscular, and systemic disorders, and for iatrogenic/viral/autoimmune hepatitis as well. This is all the more important for patients who are not in the NAFLD classical age range and for those for whom a satisfactory response of liver test abnormalities to weight loss after dietary counseling and physical activity measures cannot be obtained or verified due to poor compliance. A correct diagnosis may be life-saving, as some of these conditions which appear similar to NAFLD have a specific therapy. In this study, the characteristics of the main conditions which require consideration are summarized, and a practical diagnostic algorithm is discussed.

Published
2018
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42. Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)

Author

Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, Marco, Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), Federici M., Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, Luca, Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, Marco, Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., Colli, A., Miele L. (ORCID:0000-0003-3464-0068), and Federici M.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.

Published
2022

46. Etiology, presenting features and outcome of children with non-cirrhotic portal vein thrombosis: A multicentre national study

Author

Di Giorgio, A, De Angelis, P, Cheli, M, Vajro, P, Iorio, R, Cananzi, M, Riva, S, Maggiore, G, Indolfi, G, Calvo, P, Nicastro, E, D'Antiga, L, Di Giorgio A., De Angelis P., Cheli M., Vajro P., Iorio R., Cananzi M., Riva S., Maggiore G., Indolfi G., Calvo P. L., Nicastro E., D'Antiga L., Di Giorgio, A, De Angelis, P, Cheli, M, Vajro, P, Iorio, R, Cananzi, M, Riva, S, Maggiore, G, Indolfi, G, Calvo, P, Nicastro, E, D'Antiga, L, Di Giorgio A., De Angelis P., Cheli M., Vajro P., Iorio R., Cananzi M., Riva S., Maggiore G., Indolfi G., Calvo P. L., Nicastro E., and D'Antiga L.

Abstract

Objectives: Non-cirrhotic portal vein thrombosis (PVT) is a main cause of portal hypertension in children. We describe the characteristics at presentation and outcome of a cohort of patients with PVT to determine clinical features and predictors of outcome. Methods: We recorded: (1) Associated factors: prematurity, congenital malformations, neonatal illnesses, umbilical vein catheterization (UVC), deep infections, surgery; (2) congenital and acquired prothrombotic disorders; (3) features at last follow up including survival rate and need for surgery. Results: 187 patients, mean age at diagnosis 4 ± 3.7 years, had a history of prematurity (61%); UVC (65%); neonatal illnesses (79%). The diagnosis followed the detection of splenomegaly (40%), gastrointestinal bleeding (36%), hypersplenism (6%), or was incidental (18%). Of 71 patients who had endoscopy at presentation 62 (87%) had oesophageal varices. After 11.3 years’ follow up 63 (34%) required surgery or TIPS. Ten-year survival rate was 98%, with 90% shunt patency. Spleen size, variceal bleeding and hypersplenism at presentation were predictors of surgery or TIPS (p < 0.05). Conclusion: PVT is associated with congenital and acquired co-morbidities. History of prematurity, neonatal illnesses and UVC should lead to rule out PVT. Large spleen, variceal bleeding and hypersplenism at presentation predict the need for eventual surgery in a third of cases.

Published
2019

47. Shortened 8-Week Course of Sofosbuvir/Ledipasvir Therapy in Adolescents With Chronic Hepatitis C Infection

Author

Serranti, D, Dodi, I, Nicastro, E, Cangelosi, A, Riva, S, Ricci, S, Bartolini, E, Trapani, S, Mastrangelo, G, Vajro, P, D'Antiga, L, Resti, M, Indolfi, G, Serranti D., Dodi I., Nicastro E., Cangelosi A. M., Riva S., Ricci S., Bartolini E., Trapani S., Mastrangelo G., Vajro P., D'Antiga L., Resti M., Indolfi G., Serranti, D, Dodi, I, Nicastro, E, Cangelosi, A, Riva, S, Ricci, S, Bartolini, E, Trapani, S, Mastrangelo, G, Vajro, P, D'Antiga, L, Resti, M, Indolfi, G, Serranti D., Dodi I., Nicastro E., Cangelosi A. M., Riva S., Ricci S., Bartolini E., Trapani S., Mastrangelo G., Vajro P., D'Antiga L., Resti M., and Indolfi G.

Abstract

Treatment-naïve, noncirrhotic adults with chronic hepatitis C virus genotype 1 infection and with viremia levels <6 million IU/mL could be effectively treated with sofosbuvir/ledipasvir for 8 weeks. The aim of this pilot, prospective, open-label, multicenter study was to evaluate the efficacy and safety of this shortened treatment course in adolescents (≥12 years). The efficacy endpoint was sustained virological response 12 weeks after the end of treatment. Safety was assessed by adverse events and clinical/laboratory data. Fourteen consecutive adolescents (median age 16.5 years, Q1 14.1-Q3 17.4; female 57.1%), vertically infected, were enrolled and treated (June 2018-January 2019). Overall, the end of treatment response and sustained virological response 12 weeks after the end of treatment were 100%. No grade 3 to 4 adverse event or a serious adverse event was observed. Further studies are needed to confirm the optimal efficacy of the shortened 8-week treatment with sofosbuvir/ledipasvir for treatment-naïve, noncirrhotic adolescents with chronic hepatitis C virus genotype 1 infection and pretreatment viremia level < 6 million IU/mL.

Published
2019

49. Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

Author

Marco Poeta, Luca Pierri, and Pietro Vajro

Subjects
children, endotoxin, gut–liver axis, GLA, intestinal permeability, microbiota, non-alcoholic fatty liver disease, NAFLD, non-alcoholic steato-hepatitis, NASH, pediatrics, probiotics, Pediatrics, RJ1-570
Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A “multiple-hit” hypothesis has been invoked to explain its pathogenesis. The “first hit” is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as “second hits” implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut–liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

Published
2017
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