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Biomedical subjects

G Maggiore

Publications and source records attributed to G Maggiore.

At least 19 recordsLinked to original sources

Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome.

BACKGROUND AND AIMS: Little is known of hepatitis C virus (HCV) genotypes in HCV infected children. This retrospective, multicentre study investigated genotype distribution and correlation with clinical features and outcome in a large series of Italian children. METHODS: Between 1990 and 2002, 373 HCV RNA positive children, consecutively recruited in 15 centres, were assayed for genotypes by a commercial line probe assay. RESULTS: The following genotype distribution pattern was recorded: genotype 1b = 41%; 1a = 20%; 2 = 17%; 3 = 14.5%; 4 = 5%; other = 2.5%. The prevalence of genotypes 1b and 2 decreased significantly (p<0.001) among children born from 1990 onwards compared with older children (46% v 70%) while the rate of genotypes 3 and 4 increased significantly (from 8% to 30%). Children infected with genotype 3 had the highest alanine aminotransferase levels and the highest rate of spontaneous viraemia clearance within the first three years of life (32% v 3% in children with genotype 1; p<0.001). Of 96 children enrolled in interferon trials during the survey, 22% definitely lost HCV RNA, including 57% of those with genotypes 2 and 3. CONCLUSION: HCV genotypes 1 and 2 are still prevalent among infected adolescents and young adults in Italy but rates of infection with genotypes 3 and 4 are rapidly increasing among children. These changes could modify the clinical pattern of hepatitis C in forthcoming years as children infected with genotype 3 have the best chance of spontaneous viraemia clearance early in life, and respond to interferon in a high proportion of cases.

Adolescent↗

Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents.

BACKGROUND: Conventional treatment for autoimmune hepatitis results in a significant percentage of failures and several, poorly tolerated, side-effects. Therapy for autoimmune cholangitis and giant cell hepatitis associated with autoimmune haemolysis is poorly documented. Ciclosporin is a promising treatment for all of these diseases. METHODS: We reviewed the records of 12 patients treated in our unit between 1987 and 2001. Eight had autoimmune hepatitis, two had autoimmune cholangitis and two had giant cell hepatitis. Indications for ciclosporin were treatment failure (four patients) and contraindications to/refusal of steroids (eight patients). Ciclosporin was administered in five untreated cases and in seven patients during relapse. The mean duration of ciclosporin administration was 35.6 months (8-89 months). The median follow-up was 6.5 years (1.5-15 years). RESULTS: All patients achieved complete remission in a median period of 4.5 weeks (2-12 weeks). No treatment withdrawal due to side-effects occurred. Three patients required a combination of ciclosporin with conventional treatment due to severe liver function impairment. Tolerance to ciclosporin was excellent. A 20% transient elevation of serum creatinine occurred in one case, gingival hypertrophy in two and moderate hypertrichosis in two. CONCLUSIONS: Ciclosporin may be considered as a safe treatment for all autoimmune liver diseases and as an effective alternative for front-line therapy.

Autoimmune Diseases↗

Enterocyte actin autoantibody detection: a new diagnostic tool in celiac disease diagnosis: results of a multicenter study.

OBJECTIVES: This study describes a new method to detect autoantibodies against actin filaments (AAA) as a serological marker of intestinal villous atrophy (IVA) in celiac disease (CD), and reports the results of an Italian double-blind multicenter study. METHODS: IgA-AAA were analyzed by immunofluorescence using a newly developed method based on intestinal epithelial cells cultured in presence of colchicine. IgA-AAA were blindly evaluated prospectively in 223 antiendomysial antibody (AEA) and/or antitransglutaminase antibody (TGA) positive subjects and in 78 AEA and TGA negative subjects. IgA-AAA positive patients underwent an intestinal biopsy to confirm the diagnosis. Moreover, IgA-AAA were retrospectively investigated in 84 biopsy-proven CD patients and in 2,000 new consecutively collected serum samples from AEA and TGA negative nonbiopsied subjects. RESULTS: IgA-AAA were positive in 98.2% of the CD patients with flat mucosa, in 89% with subtotal villous atrophy, and in 30% with partial villous atrophy. IgA-AAA were present in none of the AEA and TGA negative nonbiopsied controls. In AEA and/or TGA positive CD patients IgA-AAA positivity significantly correlated with IVA (p < 0.000 in the prospective study, p = 0.005 in the retrospective study). In the prospective study, the values of sensitivity, specificity, the positive predictive value, the negative predictive value, and the efficiency of the IgA-AAA test to identify patients with IVA were, respectively, 83.9%, 95.1%, 97.8%, 69.2%, and 87.0%. Furthermore, a significant correlation (p < 0.0001) was found between the IgA-AAA serum titre and the degree of IVA (rs 0.56). CONCLUSIONS: The results of this multicenter study show that the new method for IgA-AAA detection could represent a practical diagnostic tool in AEA and/or TGA positive subjects, which would be especially useful when IVA shows a patchy distribution, when the histological picture is difficult to interpret, or when a biopsy could represent a life-threatening risk.

Actins↗

Guidelines for the screening and follow-up of infants born to anti-HCV positive mothers.

Hepatitis C virus infection in infancy largely depends on vertical transmission. The transfer of hepatitis C virus from mother to child is almost invariably restricted to children whose mother is viremic, and the rate of transmission seems to be influenced by maternal virus load, although, in the single patient, the levels of viremia cannot be used as predictors of pediatric infection. In fact, the flow-chart for screening children at risk for vertically transmitted hepatitis C virus infection takes into account maternal viremia. In children born to anti-hepatitis C virus antibody positive, hepatitis C virus-RNA negative mothers, alanine aminotransferase and anti-hepatitis C virus should be investigated at 18-24 months of life. If alanine aminotransferase values are normal and anti-hepatitis C virus is undetectable, follow-up should be interrupted. In children born to hepatitis C virus-RNA positive mothers, alanine aminotransferase and hepatitis C virus RNA should be investigated at 3 months of age: (1) hepatitis C virus-RNA positive children should be considered infected if viremia is confirmed by a second assay performed within the 12th month; (2) hepatitis C virus-RNA negative children with abnormal alanine aminotransferase should be tested again for viremia at 6-12 months, and for anti-hepatitis C virus at 18 months; (3) hepatitis C virus-RNA negative children with normal alanine aminotransferase should be tested for anti-hepatitis C virus and alanine aminotransferase at 18-24 months, and should be considered non-infected if alanine aminotransferase is normal and anti-hepatitis C virus undetectable; (4) anti-hepatitis C virus seropositivity beyond the 18th month in a never-viremic child with normal alanine aminotransferase is likely consistent with past hepatitis C virus infection.

Breast Feeding↗

Antigranulocyte monoclonal antibody immunoscintigraphy in inflammatory bowel disease in children and young adolescents.

AIM: Diagnostic delay for inflammatory bowel disease (IBD) is frequent, especially in paediatric patients. Scintigraphy with labelled leucocytes has been proposed as a very sensitive diagnostic tool for detecting bowel inflammation. The aim of this study was to evaluate the sensitivity and specificity of immunoscintigraphy in the diagnosis and follow-up of children with IBD and to compare this technique with other diagnostic techniques. METHODS: Sixty-six children with histologically confirmed IBD were enrolled in the study. Twenty-one children in whom IBD was suspected but subsequently not confirmed were used as controls. A total of 138 immunoscintigraphies were performed using 99mTechnetium-labelled monoclonal anti-granulocyte antibodies. Immunoscintigraphy was also compared with other diagnostic techniques. RESULTS: Overall sensitivity of monoclonal antibody immunoscintigraphy (MoAb-IS) in patients with clinically active disease was 94% for Crohn's disease (CD) and 85% for ulcerative colitis (UC). Ultrasonography, endoscopy and radiology were carried out at the same time in 29 patients with CD and in 6 patients with UC: sensitivity of IS was 90% compared with 76% of colonoscopy, 75% for enemas, and 55% for sonography. IS was negative (specificity) in 24% of patients with CD and in 67% of patients with UC during remission, and in 64% of controls with other causes of intestinal inflammation. Diagnostic delay was significantly shorter when compared with a historical cohort of patients. CONCLUSION: Immunoscintigraphy is a highly sensitive detector of intestinal inflammation in young patients with IBD and can be useful for reducing diagnostic delay. However, its specificity is low and all positive cases must be confirmed histologically.

Adolescent↗

An epidemiological survey of hepatitis C virus infection in Italian children in the decade 1990-1999.

BACKGROUND: A retrospective-prospective survey of Italian children with hepatitis C virus (HCV) infection was planned in 1998 to explore the epidemiologic features of infection during the past decade. METHODS: Anti-HCV-positive patients (or HCV RNA-positive infants) aged 1 month to 16 years, consecutively observed in 20 pediatric Institutions, were considered. An anonymous epidemiologic questionnaire based on clinical records was used. RESULTS: From 1990 through March 1999, 606 patients were observed (296 boys, average age 5.8 years). Maternal infection (46% of cases) and blood transfusions (34%) were the most frequent risk factors. Of 279 infected mothers, 61% did not recall a putative source of infection (by history, many could possibly have had exposure through routes such as therapeutic injections with nondisposable material), whereas 94 (34%) admitted drug abuse, including 49 (17%) coinfected with human immunodeficiency virus (HIV). Only 157 (26%) children were born after 1991: 90% of their mothers were infected (11% were HIV coinfected vs. 25% mothers of older children, P < 0.01). CONCLUSIONS: Maternal infection is a prominent source of pediatric HCV infection in Italy. The fact that most mothers had a history of covert exposure to HCV, probably through percutaneous routes that are no longer operating, and that the number of those with HIV coinfection has decreased suggests that the frequency of pediatric infection could decrease in the future.

Adolescent↗

Bartonella henselae and inflammatory bowel disease.

Sustained fever and increased thickness of the distal ileum on ultrasound suggested Crohn's disease in an adolescent boy. Bartonella henselae infection was diagnosed by specific serology and the patient recovered. Ileitis could be related to B. henselae infection.

Adolescent↗

Widening of the clinical spectrum of Bartonella henselae infection as recognized through serodiagnostics.

UNLABELLED: The recently improved diagnostics have widened, in children, the spectrum of clinical manifestations recognisable as Bartonella henselae infection. We report here the clinical features of 20 (14 males) consecutive children with serologically proved B. henselae infection observed within 12 months in the Paediatric Department of the University of Pisa. The patients had a mean age of 7 years 4 months (range 1.1-14.1 years). All children but one had a history of contact with kittens. Clinical manifestations included regional lymphadenopathy in 14 patients, representing in five the only clinical manifestation at onset, infectious mononucleosis-like syndrome in six, erythema nodosum in three, and Parinaud oculoglandular syndrome in one. In five patients a severe disorder was first suspected: fever of unknown origin in two with multiple hepatosplenic granulomatosis in one; osteolytic lesion suggesting bone neoplasm, marked inguinal lymph-node enlargement, suggesting Burkitt lymphoma, and an acute encephalopathy in one each. Bartonella henselae IgG antibody was positive in all patients with a titre ranging from 1:128 to 1:8590. IgM antibody was present in all except one child with an IgG titre of 1:2048. All patients recovered, some spontaneously. CONCLUSION: Bartonella henselae infection is frequent in Tuscany and probably underdiagnosed due to the high frequency of atypical onset of the clinical manifestations. An accurate clinical history and a reasonably wide use of the serological test may allow a rapid and accurate diagnosis, reassuring the family of the patient and avoiding invasive and expensive diagnostic procedures.

Adolescent↗

Pseudoinfectious mononucleosis: a presentation of Bartonella henselae infection.

Six children presented during one year with clinical features of infectious mononucleosis, but with laboratory findings of leucocytosis with neutrophilia, increased erythrocyte sedimentation rate, and hypergammaglobulinaemia. Serology for Epstein-Barr virus, cytomegalovirus, adenovirus, and Toxoplasma gondii was negative, while anti-Bartonella henselae IgM with high IgG titre (>/=1/1024) was present in all. All children had contact with kittens. No specific treatment was administered and all recovered.

Bartonella henselae↗

MR imaging of CNS involvement in children affected by chronic liver disease.

BACKGROUND AND PURPOSE: MR imaging sheds new light on CNS involvement in the course of acquired chronic liver disease; however, the exact pathogenetic mechanisms of hepatic encephalopathy and associated MR abnormalities remain unclear. Our purpose was to relate MR signal intensity abnormalities of the CNS to clinical, biochemical, and pathologic features of childhood-onset chronic liver disease. METHODS: Twenty-one patients (12 male and nine female patients) were included in the study; two had Crigler-Najjar disease type 2, 17 had chronic liver disease of different causes, and two had idiopathic copper toxicosis. Twelve patients had histologically proved liver cirrhosis, with a median disease duration of 175 months at the time of MR study. None had clinical symptoms of hepatic encephalopathy. MR imaging was performed using spin-echo T1- and T2-weighted sequences. RESULTS: Eleven patients had abnormal MR imaging findings of the brain revealed by T1-weighted MR sequences; two of the 11 had idiopathic copper toxicosis. The affected sites were the hypothalamus and globus pallidus, presenting symmetrical and bilateral high signal intensities, or the pituitary gland, which appeared homogeneously hyperintense, or both findings. Eight of the 12 patients with cirrhosis had abnormal MR signals of the brain. In these, the median cirrhosis duration was shorter (169 months) than in the remaining four patients with normal MR signals (177 months). A significant correlation was found between abnormal MR signals of the brain and cirrhosis (P = .008) and factor V activity (P = .008). CONCLUSION: MR imaging confirms the presence of abnormal brain signals in the globus pallidus, hypothalamus, and pituitary gland in patients with childhood-onset liver disease in the absence of clinical symptoms of encephalopathy. Signal intensity abnormalities are likely caused by an as yet unidentified metabolic process partially correlated with the severity of liver disease.

Adolescent↗

Efficacy of cyclosporin A in children with type 2 autoimmune hepatitis.

The conventional treatment of autoimmune hepatitis (AIH) with prednisone and azathioprine induces remission in most cases but is often associated with poorly tolerated side effects. We carried out a retrospective study to evaluate the efficacy of and the tolerance to cyclosporin treatment in 15 children and adolescents with type 2 AIH. Eight children received cyclosporin as primary immunosuppression because of risk factors for poor tolerance of steroids. Five other patients with relapsing AIH refused to resume treatment with steroids and were treated with cyclosporin. In both groups alanine aminotransferase activity returned to normal within 6 months. Side effects were minimal and well tolerated. No relapse occurred in 10 patients after 1 to 6 years. Cyclosporin was withdrawn in 3 patients after 1, 2, and 3 years and replaced by low doses of prednisone in combination with azathioprine. In 2 other children with acute liver failure, which progressed despite treatment with steroids and azathioprine, the addition of cyclosporin was followed by normalization of prothrombin time.

Adolescent↗

Systemic Bartonella henselae infection with hepatosplenic involvement.

BACKGROUND: Systemic manifestations of Bartonella henselae infection are rare in the immunocompetent host. The infection generally has initial symptoms of prolonged fever and multiple granulomatous lesions in liver and spleen. METHODS: Retrospective analysis of the records of all patients with hypoechogenic lesions in the liver and/or spleen diagnosed from 1990 through 1996 in three pediatric clinics in northern Italy. RESULTS: Among the 13 patients reviewed, 9 had evidence of B. henselae infection and hepatosplenic involvement: five had prolonged and unexplained fever lasting from 3 to 16 weeks, and four had typical cat-scratch disease and peripheral lymphadenitis. All patients had increased sedimentation rate and normal aminotransferase serum activity. Five children had a liver biopsy, by laparotomy in three and by needle in two. In all, the predominant liver lesion was a necrotizing granuloma. All patients were treated with broad-spectrum antibiotics. Fever lasted from 3 to 16 weeks, and hepatic and splenic lesions resolved in all with residual splenic calcification in one. CONCLUSIONS: Systemic B. henselae infection represents an important cause of inflammatory hypoechogenic hepatosplenic lesions in children. Serology provides rapid diagnosis, avoiding multiple and invasive investigations. Hepatosplenic involvement can be found even in children with typical cat-scratch disease without apparent systemic manifestations. The frequency of liver and/or splenic involvement in cat-scratch disease is probably underestimated.

Adolescent↗

Sera of children with hepatitis C infection and anti-liver-kidney microsome-1 antibodies recognize different CYP2D6 epitopes than adults with LKM+/HCV+ sera.

BACKGROUND: Liver-kidney microsome type 1 (LKM1) antibodies are specific markers of autoimmune hepatitis (AIH) type 2. Antibodies to LKM1 have been found in 2% to 3% of adults infected with hepatitis C virus (HCV) without AIH. Thirty percent of these antibodies are directed against linear sequences of CYP2D6 protein. LKM1 antibodies in HCV+/LKM1+ sera and in sera of AIH patients do not recognize the same CYP2D6 epitopes. The current study was conducted to determine whether LKM1 antibodies in HCV+/LKM1+ children's sera are the result of the same immune response as the antibodies described in AIH type 2 and in HCV+/LKM1+ adult patients. METHODS: Sera from 10 HCV+/LKM1+ children were tested against human liver microsomal and cytosolic proteins by Western blot analysis and against synthetic peptides of the CYP2D6 sequence between amino acids 200 and 429 by dot blot. The same sera were tested against radiolabeled CYP2D6 by immunoprecipitation. RESULTS: Four of 10 sera tested by Western blot analysis showed immunoglobulin (Ig) G-type antibodies against CYP2D6, and 2 had antibodies against proteins of 58, 66, and 84 kDa. One of the sera also contained IgM-type anti-66-kDa and 84-kDa proteins. The radioligand test detected anti-CYP2D6 antibodies in 9 of 10 patients. Five of the anti-CYP2D6-positive sera recognized a peptide between amino acids 200 and 429 including amino acids 254-271. CONCLUSIONS: Most HCV+/LKM1+ sera from children recognize conformational epitopes of the CYP2D6 antigen, and half recognize linear epitopes. Some HCV+/LKM1+ sera demonstrated antibodies against the AIH type 2 main antigenic site of the CYP2D6. Screening of HCV RNA should be performed before starting treatment of presumed autoimmune hepatitis associated with LKM1.

Adolescent↗