Antonietta Giannattasio

Chronic Hepatitis C in Childhood: An 18-Year Experience

BACKGROUND The long-term outcome of chronic hepatitis C (CHC) has not been well studied, both for untreated and interferon-treated children. The aim of this study was to evaluate the long-term outcome of disease in a large series of children with CHC. METHODS Clinical, biochemical, virological, and histological features were evaluated in all children (age, 2-18 years) with CHC who did not have concomitant disease and who attended at our hospitals liver unit during the period of 1986-2004. RESULTS One hundred twenty-five children with CHC were studied. All patients remained free of symptoms throughout the period of observation. On the basis of transaminase levels during the first year of positivity for antibodies to hepatitis C virus (HCV), children were divided into 2 groups: patients with hypertransaminasemia (100 patients, all of whom had detectable HCV RNA), and those with normal transaminases (25 patients; 16 had viremia and 9 did not have viremia). Sustained clearance of viremia was achieved in 38% of the patients treated with interferon, compared with 12% of untreated children (P<.05). A sustained response to therapy was obtained in 64.7% of children infected with an HCV genotype other than genotype 1 and in 24.2% of those infected with HCV genotype 1 (P<.05). Histological lesions were mild in all 64 patients who underwent liver biopsy. No linear correlation was found between duration of disease and progression of fibrosis. Examination of a follow-up liver biopsy specimen revealed cirrhosis only in 1 (4.7%) of 21 children. CONCLUSIONS Children with CHC were symptom free and had a morphologically mild liver disease. Interferon therapy may be effective for patients infected with HCV genotypes other than genotype 1, whereas lower response rates are expected for HCV genotype 1-infected children. The real impact of therapy on long-term outcome remains to be established.

Evaluation of the Quality of Guidelines for Acute Gastroenteritis in Children With the AGREE Instrument

Aim: The aim of the study was to assess the quality of clinical practice guidelines (CPGs) using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument, a validated international tool. Materials and Methods: CPGs were identified by searching MEDLINE (1966–January 2009) and Embase (1988–January 2009), CPG databases, and relevant Web sites of agencies and organizations that produce and/or endorse guidelines. Included in the study were CPGs in English that addressed the management of acute gastroenteritis in children. Retrieved CPGs were evaluated with the AGREE instrument for quality assessment by 6 independent reviewers. AGREE consists of 6 domains for a total of 23 items. Results: Nine CPGs were identified. Four were evidence based (EB) and 2 of these included tables of evidence. Eight CPGs (88%) scored <50% for “applicability,” 7 (77%) for “stakeholder involvement,” and 6 (66%) for “editorial independence.” Compared with non-EB CPGs, EB CPGs had higher quality scores for all AGREE domains, with a better score for “rigor of development” (P < 0.001), “stakeholder involvement” and “clarity of presentation” (P < 0.01), and applicability (P < 0.05). Over time, the quality of guidelines tended to improve. The main recommendations of CPGs were similar. However, there were differences in the treatment of diarrhea, namely based on the settings and circumstances in which CPGs were produced. Conclusions: The overall quality of CPGs on acute gastroenteritis management in children is fair. Aims, target population, synthesis of evidence, formulation of recommendations, and clarity of presentation are points of strength. Weak issues are applicability, including identification of organizational barriers and adherence parameters, and cost/efficacy analysis.

Hypertransaminasemia in childhood as a marker of genetic liver disorders

BackgroundThe widespread use of routine biochemical assays has led to increased incidental findings of hypertransaminasemia. We aimed to evaluate the prevalence of different causes of raised aminotransferase levels in children referred to a university department of pediatrics.MethodsWe investigated 425 consecutive children (age range, 1–18 years) with isolated hypertransaminasemia. All patients had raised aminotransferase levels on at least two occasions in the last month before observation. Cases due to major hepatotropic viruses were excluded.ResultsDuring the first 6 months of observation, 259 children showed normalized liver enzymes. Among the remaining 166 patients with hypertransaminasemia lasting for more than 6 months, 75 had obesity-related liver disease; 51, genetic disorders; 7, autoimmune hepatitis; 5, cholelithiasis; 3, choledochal cyst; and 3, celiac disease. Among the 51 children with genetic disorders, 18 had Wilson disease; 14, muscular dystrophy; 4, alpha-1-antitrypsin deficiency; 4, Alagille syndrome; 4, hereditary fructose intolerance; 3, glycogen storage disease (glycogenosis IX); 2, ornithine transcarbamylase deficiency; and 2, Shwachman’s syndrome. In 22 children, the hypertransaminasemia persisted for more than 6 months in the absence of a known cause.ConclusionsGenetic disease accounted for 12% of cases of isolated hypertransaminasemia observed in a tertiary pediatric department. A high level of suspicion is desirable for an early diagnosis of these disorders, which may present with isolated hypertransaminasemia and absence of typical clinical signs.

New molecular approaches in the diagnosis of acute diarrhea: advantages for clinicians and researchers.

Purpose of review To provide an update of the advantages of new-generation molecular diagnostics as regards acute diarrhea, and to evaluate how they can help clinicians and researchers diagnose this condition. Recent findings Thanks to real-time polymerase chain reaction techniques, many enteropathogens can now be identified simultaneously within hours. Most techniques are based on amplification of specific nucleotide sequences. With high-resolution melting analyses, microarrays, and metagenomic analyses, multiple genomic sequences can be evaluated in a single sample; thus, a wide range of enteropathogens can be evaluated in one run. Molecular techniques have elucidated the role of major enteropathogens such as norovirus and bocavirus and their evolving epidemiology. They have revealed novel transmission routes, also in food-borne diarrhea outbreaks, and have opened the way to new therapies and preventive measures, as well as to surveillance of emerging rotavirus strains after vaccine introduction. Summary Molecular approaches are best suited for epidemiologic purposes and for selected clinical conditions such as early identification of treatable agents in at-risk patients, rather than for cases requiring only oral rehydration. In the field of acute diarrhea, the major application of molecular techniques is the identification of novel agents of gastroenteritis and their epidemiology.

Pneumococcal and influenza vaccination rates and their determinants in children with chronic medical conditions

BackgroundTo investigate the rates of pneumococcal and influenza vaccinations and their determinants in children with chronic medical conditions.Patients and MethodsChildren with HIV infection, cystic fibrosis, liver transplantation and diabetes mellitus were enrolled. Physicians of regional Reference Centres for each condition, primary care paediatricians and caregivers of children provided information through specific questionnaires. For diabetes, 3 Reference Centres were included.ResultsLess than 25% of children in each group received pneumococcal vaccination. Vaccination rates against influenza were 73% in patients with HIV-infection, 90% in patients with cystic fibrosis, 76% in patients with liver transplantation, and ranged from 21% to 61% in patients with diabetes mellitus. Reference Centres rather than primary care paediatricians had a major role in promoting vaccinations. Lack of information was the main reason for missing vaccination. Awareness of the severity of pneumococcus infection by key informants of at-risk children was associated with higher vaccination rate.ConclusionsVaccination rates in children with chronic conditions were poor for pneumococcus and slightly better for influenza. Barriers to vaccination include lack of awareness, health care and organization problems.

Steroid Therapy for a Case of Severe Drug-Induced Cholestasis

Objective: To report a Severe case of cholestatic liver disease successfully treated with corticosteroids following combined therapy with clarithromycin and nimesulide. Case Summary: A 15-year-old girl was admitted with cholestasis probably related to treatment with clarithromycin and nimesulide for an upper respiratory tract infection. Other causes of liver disease (infections, metabolic liver disorders, genetic cholestatic syndromes, autoimmune diseases, primary biliary tract disorders) were excluded. Liver biopsy showed a severe canalicular cholestasis with bile plugs in dilated bile canaliculi, giant cell transformation, and portal and lobular infiltrate. An objective causality assessment suggested that cholestasis was probably related to clarithromycin and/or nimesulide use. No benefit was derived from a course of ursodeoxycholic acid therapy. Since the patient experienced a progressive worsening in cholestasis, prednisone was started after 20 days. This therapy was promptly followed by improvement in clinical and laboratory test results. After 2 months of prednisone treatment, the patient became symptom-free with normal liver function tests. Discussion: The manifestations of drug-induced hepatotoxicity are highly variable, ranging from asymptomatic hypertransaminemia to fulminant hepatic failure. No specific treatment for drug-induced hepatotoxicity exists. Early recognition and drug withdrawal are the keys to management of hepatotoxicity, but in some cases, liver disease may persist despite discontinuation of the drug. Possible advantages of corticosteroid therapy have not been well demonstrated. Conclusions: Application of the Naranjo probability scale indicates a probable relationship between cholestasis and nimesulide plus clarithromycin use. This case draws attention to a possible therapeutic option for some cases of drug-induced hepatotoxicity that show a severe course without any sign of improvement.

The effect of physician’s recommendation on seasonal influenza immunization in children with chronic diseases

BackgroundDespite recommendations by Health Authorities, influenza immunization coverage remains low in children with chronic diseases. Different medical providers involved in the management of children with chronic conditions may affect the pattern of influenza vaccine recommendations and coverage. The likelihood of vaccination by type of provider in children with chronic conditions is poorly understood. Therefore, the objectives of this study were to analyze the pattern and the effect of recommendations for seasonal influenza immunization provided by different physician profiles to families of children with chronic diseases and to measure the frequency of immunization in the study population.MethodsWe recruited children with chronic diseases aged 6 months–18 years who subsequently presented to specialty clinics for routine follow-up visits, during spring 2009, in three Italian Regions Families of children with chronic diseases were interviewed during routine visits at reference centers through a face-to-face interview. We analyzed the following immunization predictors: having received a recommendation toward influenza immunization by a health provider; child’s sex and age; mothers and fathers’ age; parental education and employment; underlying child’s disease; number of contacts with health providers in the previous year. Influenza immunization coverage was calculated as the proportion of children who received at least one dose of seasonal influenza vaccine in the previous season. We calculated prevalence ratios and we used a generalized linear model with Poisson family, log link and robust error variance to assess the effect of socio-demographic variables, underlying diseases, and recommendations provided by physicians on influenza immunization.ResultsWe enrolled 275 families of children with chronic diseases. Overall influenza coverage was 57.5%, with a low of 25% in children with neurological diseases and a high of 91.2% in those with cystic fibrosis. While 10.6% of children who did not receive any recommendation toward influenza immunization were immunized, among those who received a recommendation 87.5-94.7% did, depending on the health professional providing the recommendation. Receiving a recommendation by any provider is a strong predictor of immunization (PR = 8.5 95% CI 4.6;15.6) Most children received an immunization recommendation by a specialty (25.8%) or a family pediatrician (23.3%) and were immunized by a family pediatrician (58.7%) or a community vaccinator (55.2%).ConclusionsReceiving a specific recommendation by a physician is a strong determinant of being immunized against seasonal influenza in children with chronic diseases independently of other factors. Heterogeneity exists among children with different chronic diseases regarding influenza recommendation despite international guidelines. Increasing the frequency of appropriate recommendations toward influenza immunization by physicians is a single powerful intervention that may increase coverage in children with chronic conditions.

Pandemic flu: a comparative evaluation of clinical, laboratory, and radiographic findings in HIV-positive and negative children.

Eleven HIV-infected and 30 otherwise healthy children hospitalized for H1N1 influenza were studied. Leukopenia was recorded in 64% of HIV-infected and in 20% of healthy children (P = 0.01). Chest radiograph was abnormal in 18 (46%) children. Interstitial pneumonia was more frequent in HIV-positive children and consolidation was more frequent in HIV-negative children. Although the duration of symptoms and hospital stay was significantly longer in HIV-negative than in HIV-positive children, only 37% of HIV-negative children and 91% of HIV-positive received oseltamivir. The H1N1 influenza attack rate was very high (20%) in HIV-infected children, but it consistently ran a mild course.

Psychosocial Issues in Children and Adolescents with HIV Infection Evaluated with a World Health Organization Age-Specific Descriptor System

Objectives: After active antiretroviral therapy, children with HIV are clinically well, whereas psychosocial issues continue to influence their quality of life. The International Classification of Functioning, Disability and Health (ICF) of the World Health Organization evaluates health status and environmental and social factors associated with health. We investigated the efficacy of the ICF to describe the health status and needs of a cohort of children and adolescents with HIV seen at a reference center for pediatric AIDS in Europe. Methods: A quantitative analysis of structured interviews was performed. Caregivers of children and adolescents with HIV infection in follow-up at 2 reference centers for pediatric AIDS were enrolled. Four major areas included in the ICF instrument were investigated: impairments of body structures; impairments of body functions; environmental factors; and activity limitations and restrictions to social life. Results: Forty-one families of children with HIV were enrolled. Body structures and functions were marginally impaired, whereas environmental factors and psychosocial issues had a relevant impact on quality of life. Most families considered environmental factors to be “barriers”; these were poverty, unemployment, and single-parent family structure. Activity limitations and social restrictions were also reported in a few cases. Almost all parents reported problems in disclosing their childs HIV status because of the fear of social stigma. Conclusion: Psychosocial issues are part of the well-being of children with HIV. The ICF is a standard tool to evaluate the clinical and psychosocial status of children and adolescents with HIV infection and to measure the impact of therapeutic interventions and strategies on psychosocial functioning.

The functional effects of nutrients on enterocyte proliferation and intestinal ion transport in early infancy.

Nutrition has a key role in the modulation of the developing intestine in early infancy, and nutrients are able to modulate several intestinal functions including nutrient absorption, ion transport, cell growth and differentiation, motility and immunomodulation. Such modulation is exerted in part through a direct interaction between a single nutrient and the enterocyte. Two functions--ion transport and cell growth--are closely connected and appear to be modulated by nutrients. This is supported by the finding that a single nutrient (e.g. zinc) stimulates ion absorption and also promotes enterocyte growth. Interestingly, intracellular signalling for either effect is similar and involves mitogen-activated protein kinase. Other nutrients also modulate enterocyte function and there is evidence that their effect may depend on their side of action (apical or basolateral) and concentration. Knowledge of the interaction between nutrients and enterocytes may be exploited to obtain clinical effects using nutrition as a long-term treatment for intestinal and non-intestinal conditions.