Publications (14)41.94 Total impact
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Article: Levels of Serum Ceruloplasmin Associate With Pediatric Nonalcoholic Fatty Liver Disease.
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ABSTRACT: OBJECTIVES:: Nonalcoholic fatty liver disease (NAFLD) in adolescents and children is rapidly becoming one of the most common causes of chronic liver disease worldwide. NAFLD varies from simple fatty liver to nonalcoholic steatohepatitis (NASH) with possible fibrosis. Several studies suggest that oxidative stress plays a central role in several metabolic abnormalities and cellular damage that characterize NAFLD. We investigated whether transition metals and their related proteins were related to NAFLD symptoms and their underlying processes. METHODS:: We measured copper, iron, ceruloplasmin (Cp) concentration and activity, transferrin (Tf), ferroxidase activity, and ferritin, and we calculated Tf saturation and ceruloplasmin to transferrin ratio (Cp/Tf) as an index of the activity of the antioxidant Cp-Tf system in 100 children with biopsy-proven NAFLD. Pediatric patients were grouped by NAS score ≥ 5 (30 subjects) and NAS <5 (70). RESULTS:: Cp distinguished children with NAS score ≥5 from those with NAS <5 with an accuracy of 82%. Specifically, a ROC curve showed that a cut-off of 28.6 mg/dL separated NAS score ≥5 from NAS <5 with a specificity of 92% and a sensitivity of 76%. The Cp/Tf ratio, as well as copper concentration and Cp activity, decreased in the NAS≥5 group, pointing out an imbalance in metal regulation. Either copper or Cp concentrations were lower in subjects having ballooning. CONCLUSIONS:: Serum antioxidant capacity via Cp failure is strongly associated with NAFLD-related damage. However, further studies are required to clarify the role of Cp in NAFLD pathogenesis and to evaluate its potential application as diagnostic marker.Journal of pediatric gastroenterology and nutrition 11/2012; · 2.18 Impact Factor -
Article: Transient elastography for assessment of fibrosis in paediatric liver disease.
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ABSTRACT: The prognosis and management of chronic liver diseases in children largely depend on the extent and progression of liver fibrosis, which is often the most important predictor of disease outcome, and thus influences the indication for potential therapy. Unfortunately, liver biopsy continues to be the gold standard for the staging and grading of fibrosis. Liver biopsy is an invasive and painful technique with several limitations. These limitations have led to the development of alternative noninvasive methods for the accurate assessment of fibrosis and for the maintenance of an acceptable risk/benefit ratio. In the last decades, transient elastography (TE) has received increasing consideration as a means of evaluating disease progression in paediatric chronic liver disease. TE is an accurate and reproducible methodology for identifying subjects without fibrosis or significant fibrosis, or with advanced fibrosis. In this review, we provide an outline of liver fibrosis in paediatric liver diseases, including fibrogenesis, and noninvasive techniques for the diagnosis and follow-up of fibrosis, and then focus on the characteristics of TE and on its strength in the assessment of liver fibrosis, paying particular attention to studies conducted in children.Pediatric Radiology 06/2011; 41(10):1232-8. · 1.67 Impact Factor -
Article: Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial.
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ABSTRACT: To investigate whether dietary supplementation with docosahexaenoic acid (DHA) decreases liver fat content in children with non-alcoholic fatty liver disease (NAFLD). We performed a randomised controlled trial of DHA supplementation (250 and 500 mg/day) versus placebo in 60 children with biopsy-proven NAFLD (20 children per group). The main outcome was the change in liver fat content as detected by ultrasonography after 6 months of treatment. Secondary outcomes were the changes in insulin sensitivity index, alanine transaminase, triglycerides and body mass index after 6 months of treatment. Blood DHA increased in children supplemented with DHA (0.65%, 95% CI 0.30% to 1.10% for the DHA 250 mg group and 1.15%, 0.87% to 1.43% for the DHA 500 mg group). The odds of more severe versus less severe liver steatosis after treatment was lower in children treated with DHA 250 mg/day (OR = 0.01, 0.002 to 0.11, p <0.001) and DHA 500 mg/day (OR = 0.04, 0.002 to 0.46, p = 0.01) as compared to placebo but there was no difference between the DHA groups (p = 0.4). Insulin sensitivity index increased and triglycerides decreased to a similar degree in both DHA groups as compared to placebo but there was no effect on alanine transaminase and body mass index. DHA supplementation improves liver steatosis and insulin sensitivity in children with NAFLD.Archives of Disease in Childhood 01/2011; 96(4):350-3. · 2.88 Impact Factor -
Article: Extrahepatic portal vein thrombosis in children and adolescents: Influence of genetic thrombophilic disorders.
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ABSTRACT: to explore the prevalence of local and genetic thrombophilic disorders as risk factors for portal vein thrombosis (PVT) in our series, the largest ever published in pediatric literature. we conducted a case-control study enrolling 31 children with PVT and 26 age-matched controls. All were screened for thrombophilia, including genetic disorders, protein C, protein S and homocysteine deficiencies. All coagulation parameters were studied at least 3 mo after the diagnosis of portal vein obstruction. in our study we showed that most pediatric patients with PVT have local prothrombotic risk factors, which are probably the most important factors leading to PVT. However, there is a clear association between the presence of prothrombotic disorders and PVT, suggesting that these increase the risk of thrombosis in patients with local factors such as perinatal umbilical vein catheterization or sepsis. patients with PVT should be screened for inherited prothrombotic disorders regardless of a history of an obvious local risk factor.World Journal of Gastroenterology 12/2010; 16(48):6123-7. · 2.47 Impact Factor -
Article: Hyaluronic acid predicts hepatic fibrosis in children with nonalcoholic fatty liver disease.
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ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents, and it may progress to liver fibrosis and cirrhosis. Liver biopsy, which is the recognized gold standard for the diagnosis of hepatic fibrosis, is invasive. Thus, there has been increasing interest in the development of noninvasive markers. Hyaluronic acid (HA) has been shown to be a good marker of liver fibrosis in adults. In the current study, we evaluated the association of HA with liver fibrosis in 100 consecutive children with biopsy-proven NAFLD. In all, 65% of the children had liver fibrosis. Using proportional-odds ordinal logistic regression, we found that values of HA ≥ 1200 ng/mL made the absence of fibrosis (F0) unlikely (7%, 95% confidence interval [CI]: 1% to 14%), whereas values of HA ≥ 2100 ng/mL made F2, F3, or F4 fibrosis likely (89%, 95% CI: 75% to 100%). Our study shows that HA is a predictor of fibrosis in children with NAFLD followed at a tertiary care center. Additional studies are needed to test whether HA can be employed to predict liver fibrosis in pediatric populations with similar and lower prevalence of liver fibrosis.Translational research : the journal of laboratory and clinical medicine. 10/2010; 156(4):229-34. -
Article: Glutathionylation of p65NF-kappaB correlates with proliferating/apoptotic hepatoma cells exposed to pro- and anti-oxidants.
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ABSTRACT: Oxidative stress influences a variety of regulatory proteins, including nuclear factor-kappaB (NF-kappaB). NF-kappaB is critical for maintaining the proliferation/apoptosis balance in hepatocytes. In this study we investigated the causal links between glutathione, NF-kappaB and hepatocyte damage. HepG2 and 3B cells were exposed to different doses of H2O2 or N-acetylcysteine (NAC) and the proliferation/apoptosis rate, glutathione forms, and p65NF-kappaB glutathionylation and activity were analysed. Our results demonstrate that H2O2 stopped proliferative response at low doses, but induced apoptosis only at high doses. In contrast, NAC exerted, proportionally to its concentration, a dual role simultaneously increasing both proliferation and apoptosis. Interestingly, the levels of protein-bound glutathione were increased by H2O2 and decreased by NAC. Moreover, the antibody recognizing the glutathionylated proteins co-precipitated and -localized with the cytoplasmic inactive form of p65NF-kappaB in H2O2- and NAC-treated cells, even when, in 1 mM NAC-treated cells, a part of p65 was glutathione-free and localized into the nucleus. Apoptotic cells were characterised principally by a cytoskeletal staining of glutathionylation and retention of NF-kappaB in the cytoplasmic region; whereas in proliferating cells, glutathionylated proteins were concentrated into the perinuclear region and p65NF-kappaB was traslocated into the nucleus. While cytoplasmic NF-kappaB retention correlated well with an increased apoptotic rate, a greater expression of this protein was observed in association with the NAC-dependent. In conclusion, our findings suggest that glutathionylation inhibits NF-kappaB activity causing reduced hepatocyte survival, which is common in several liver diseases.International Journal of Molecular Medicine 10/2009; 24(3):319-26. · 1.98 Impact Factor -
Article: Oral gancyclovir therapy for immunocompetent infants with cytomegalovirus-associated hemorrhagic or intractable enterocolitis.
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ABSTRACT: Three infants, who had prenatal or immediately postnatal cytomegalovirus (CMV) infection associated with persistently severe enterocolitis requiring total parenteral or nasal gastric feeding, were treated with gancyclovir. The intestinal CMV involvement was shown by the detection of CMV-DNA in the stools of all 3 infants and in the enteral sample from 1 of 2 biopsied infants. Gancyclovir, when given intravenously to the infants, was not followed by CMV clearance or stable clinical improvement. On the contrary, oral gancyclovir that was given for 1- to 2-month courses at the dosage of 70 mg/kg, was associated with clinical improvement or recovery and reintroduction of oral feeding. Cytomegalovirus-DNA detection became persistently negative in the stools of the infants within 17 months after starting oral gancyclovir. Each child showed normal growth and sensorial, mental, and motor development at the age of 4.7 to 6 years. Oral gancyclovir may be suggested for treatment of CMV-associated chronic hemorrhagic or intractable enterocolitis.Journal of pediatric gastroenterology and nutrition 09/2009; 50(1):111-3. · 2.18 Impact Factor -
Article: A protective effect of breastfeeding on the progression of non-alcoholic fatty liver disease.
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ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease characterised by accumulation of large-droplet fat in hepatocytes with possible progression to inflammation and fibrosis. Breastfeeding has benefits for child health, both during infancy and later in life, reducing the risk of manifestations of the metabolic syndrome. Here we investigated the association between early type of feeding (breastfed versus formula-fed and duration of breastfeeding) and later NAFLD development. We investigated 191 young Caucasian children (3-18 years old) with NAFLD consecutively enrolled between January 2003 and September 2007 in our centre. 48% of these children (n = 91) had been breastfed for a median (interquartile range) time of 8 (7) months. After correction for age, waist circumference, gestational age and neonatal weight, the odds of non-alcoholic steatohepatitis (NASH) (OR 0.04, 95% CI 0.01 to 0.10) and fibrosis (OR 0.32, 95% CI 0.16 to 0.65) were lower in breastfed versus not breastfed infants. Moreover, the odds of NASH (OR 0.70, exact 95% CI 0.001 to 0.87) and fibrosis (OR 0.86, exact 95% CI 0.75 to 0.98) decreased for every month of breastfeeding. This observational study suggests that earlier feeding habits might affect the clinical expression of NASH from 3 to 18 years later, with an apparent drug-like preventive effect of breastfeeding.Archives of Disease in Childhood 07/2009; 94(10):801-5. · 2.88 Impact Factor -
Article: Is juvenile liver biopsy unsafe? Putting an end to a common misapprehension.
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ABSTRACT: Percutaneous needle biopsy of the liver is the most common procedure used in clinical hepatology for histopathological examination and assessment of liver disease, and remains the cornerstone in the evaluation and management of parenchymal liver diseases. Liver biopsy is generally regarded as a safe procedure, but mortality rates up to 1:10,000 have been reported. In 2003, our group showed that routine use of US as a guide to liver biopsy reduces the rate of complications and provides a higher diagnostic yield. To report our experience of US-guided liver biopsy in children. We retrospectively reviewed all 421 liver biopsies performed in our department from October 2003 to December 2008. All samples had been obtained by the US-guided technique. All patients had a liver US examination performed prior to the procedure by the same radiologist performing the biopsy. US guidance allowed constant visualization of the needle leading to appropriate tissue sampling in all 421 children (including 221 obese children), and in 79% of children with only one pass. Pain in the right upper quadrant after liver biopsy was experienced by 36% of patients. US-guided percutaneous biopsy of the liver in children, performed in a specialized tertiary care paediatric centre by experienced and skilled physicians, can be considered safe and effective.Pediatric Radiology 07/2009; 39(9):959-61. · 1.67 Impact Factor -
Article: The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease.
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ABSTRACT: Liver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD) which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center. The study included 136 male and 67 female children with NAFLD aged 3.3 to 18.0 years; 141 (69%) of them had fibrosis at liver biopsy. On the basis of biological plausibility, readily availability and evidence from adult studies, we evaluated the following potential predictors of liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin, triglycerides and cholesterol. A final model was developed using bootstrapped logistic regression with bias-correction. We used this model to develop the 'pediatric NAFLD fibrosis index' (PNFI), which varies between 0 and 10. The final model was based on age, waist circumference and triglycerides and had a area under the receiver operating characteristic curve of 0.85 (95% bootstrapped confidence interval (CI) with bias correction 0.80 to 0.90) for the prediction of liver fibrosis. A PNFI >or= 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to 201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0) could be used to rule in liver fibrosis without performing liver biopsy. PNFI may help clinicians to predict liver fibrosis in children with NAFLD, but external validation is needed before it can be employed for this purpose.BMC Medicine 01/2009; 7:21. · 6.03 Impact Factor -
Article: Human herpesvirus type 6 hepatitis or familiar intrahepatic cholestasis: the importance of follow-up.
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ABSTRACT: A 1-month-old child presented to our unit with jaundice and raised aminotransferases, γ-glutamyltranspeptidase and bilirubin. Metabolic diseases were ruled out and ultrasound found no alterations. Human herpesvirus type 6 (HHV-6) DNA was found in blood and saliva and IgG anti-HHV-6 in serum, and a diagnosis of HHV-6 hepatitis was made. In the following weeks, aminotransferase values remained raised while γ-glutamyltranspeptidase levels returned to normal in 45 days. At the age of 5 months symptoms and elevated aminotransferases persisted and immunohistochemistry performed on liver tissue allowed a diagnosis of progressive familiar intrahepatic cholestasis type 2 to be made. The patient is now 7 months old, and cholestatic jaundice and pruritus continue to be present.Case Reports 01/2009; 2009. -
Article: Irreversible intestinal failure: prevalence and prognostic factors.
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ABSTRACT: Parenteral nutrition (PN) is the primary treatment for intestinal failure, which is considered irreversible in patients who remain partially or fully dependent on PN. Causes of irreversible intestinal failure are short bowel syndrome (SBS), motility disorders (MD), and severe protracted diarrhea (SPD). The aim of this study was to report the clinical outcome in these patients in relation to the underlying disease. From January 1, 1989 to December 31, 2006, 218 intestinal failure patients were observed in our center, but only 96 (48 SBS, 39 SPD, and 9 MD) were included because they required at least 50% of their total calories as PN for not less than 3 months. In these patients, survival and complication rates were evaluated. The survival rate was significantly higher in SBS patients than in the other groups (P < 0.01). SBS patients showed a higher rate of major complications, although only intestinal failure-associated liver disease was significantly higher (P < 0.001). In our series, MD was the main cause of irreversible intestinal failure. The potential for bowel adaptation is higher in surgical than in medical causes of intestinal failure and does not seem to be influenced by complications of intestinal failure. SBS, although worsened by the major number of complications, was not the main category contributing to intestinal failure.Journal of pediatric gastroenterology and nutrition 10/2008; 47(4):450-7. · 2.18 Impact Factor -
Article: Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis.
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ABSTRACT: Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in chronic liver disease patients. In this study, we assessed the value of TE for the prediction of fibrosis stage in a cohort of pediatric patients with nonalcoholic steatohepatitis. Furthermore, TE interobserver agreement was evaluated. TE was performed in 52 consecutive biopsy-proven nonalcoholic steatohepatitis patients (32 males, 20 females, age 13.6 +/- 2.44 years). The area under the receiver operating characteristic curves for the prediction of "any" (>or=1), significant (>or=2), or advanced fibrosis (>or=3) were 0.977, 0.992, and 1, respectively. Calculation of multilevel likelihood ratios showed that TE values <5, <7, and <9 kPa, suggest the presence of "any" fibrosis, significant fibrosis, and advanced fibrosis, respectively. TE values between 5 and 7 kPa predict a fibrosis stage of 1, but with some degree of uncertainty. TE values between 7 and 9 kPa predict fibrosis stages 1 or 2, but cannot discriminate between these two stages. TE values of at least 9 kPa are associated with the presence of advanced fibrosis. The intraclass correlation coefficient for absolute agreement was 0.961. Conclusion: TE is an accurate and reproducible methodology to identify pediatric subjects without fibrosis or significant fibrosis, or with advanced fibrosis. In patients in which likelihood ratios are not optimal to provide a reliable indication of the disease stage, liver biopsy should be considered when clinically indicated.Hepatology 04/2008; 48(2):442-8. · 11.66 Impact Factor -
Article: S1906 Lifestyle Intervention and Antioxidants in Children with Nonalcoholic Fatty Liver Disease: A Randomized, Controlled Trial
Gastroenterology 01/2008; 134(4). · 11.68 Impact Factor -
Article: Duodenal stenosis, a new finding on congenital rubella syndrome: case description and literature review.
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ABSTRACT: Congenital rubella syndrome (CRS) continues to represent a public healthcare problem although an effective vaccination program. Gastrointestinal involvement is rather infrequent and the association of CRS with duodenal stenosis has been never reported. In this study a case of CRS with duodenal diaphragm is reported and the gastrointestinal diseases described in association with CRS are reviewed. A 10-month-old child affected by CRS with congenital hearth disease, perceptive deafness and microcephaly, was admitted because of vomiting and failure to thrive. An upper endoscopy demonstrated dilated proximal duodenum and a perforated diaphragm in the second segment of the duodenum. Endoscopic membranectomy was therefore performed. Two months later the patient was submitted to a further endoscopic evaluation that showed a partial diaphragm persistence and a second excision was performed. Follow-up one year after the first treatment showed good clinical conditions, reasonable physical growth and disappearance of vomiting. In conclusion we report the first case of CRS in association with duodenal stenosis. Duodenal stenosis in the absence of other intestinal localizations may be due to rubella capacity of infecting only small numbers of fetal cells but we cannot exclude that the duodenal stenosis in our patient be only a casual association.The Journal of infection 12/2006; 53(5):e207-10. · 4.13 Impact Factor
Top co-authors
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Institutions
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2009
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Ospedale Pediatrico Bambino Gesù
Roma, Latium, Italy -
Università degli Studi dell'Aquila
- SS in Pediatrics
L’Aquila, Abruzzo, Italy
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