Giuseppe Maggiore | Università di Pisa (original) (raw)
Papers by Giuseppe Maggiore
Diagnostics
Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the ... more Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance. Recent evidence however suggests that treatment discontinuation is possible after a prolonged period of normal aminotransferase activity without the need for liver biopsy prior to withdrawal.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, Jan 7, 2017
Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic mar... more Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings. We collected data from 2 multi-center trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileo-colonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50% from baseline, respectively, for patients with CD, and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, for patients with UC. Pa...
European journal of obstetrics, gynecology, and reproductive biology, Jan 7, 2017
American Journal of Gastroenterology, 2004
This study describes a new method to detect autoantibodies against actin filaments (AAA) as a ser... more 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. 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. 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). 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.
Clinical Rheumatology, 1996
In a patient suffering from histologically-documented immuno-mediated chronic active hepatitis, i... more In a patient suffering from histologically-documented immuno-mediated chronic active hepatitis, intravenous immunoglobulin (IVIG) treatment was initiated as an obligatory alternative therapy because of femur head aseptic necrosis which had followed long-term therapy with steroids. The first cycle of IVIG was followed by remission of most symptoms, normalization of liver enzymes, disappearance of circulating immunecomplexes (CIC), and a negative lupus band test. Improvement in the patient's condition was demonstrated, in liver histology, by the disappearance of peri-portal mononuclear cells infiltrates, while immunohistochemistry showed the disappearance of the intracellular IgG deposits.
Journal of thrombosis and haemostasis : JTH, Jan 3, 2015
Quantitative fibrinogen deficiencies (hypofibrinogenemia, afibrinogenemia) are rare congenital di... more Quantitative fibrinogen deficiencies (hypofibrinogenemia, afibrinogenemia) are rare congenital disorders characterized by low/unmeasurable plasma fibrinogen antigen levels. Their genetic basis is invariantly represented by mutations within the fibrinogen genes (FGA, FGB, and FGG coding for the Aα, Bβ, and γ chains). Currently, only four mutations (p.Gly284Arg, p.Arg375Trp, delGVYYQ 346-350, p.Thr314Pro), all affecting the fibrinogen γ chain, have been reported to cause fibrinogen storage disease (FSD), a disorder characterized by protein aggregation, endoplasmic reticulum retention, and hypofibrinogenemia. To investigate the genetic basis of FSD in two hypobrinogenemic patients. The mutational screening of the fibrinogen genes was performed by direct DNA sequencing. The impact of identified mutations on fibrinogen structure was investigated by in-silico molecular modeling. Liver histology was evaluated by light microscopy, electron microscopy, and immunocytochemistry. Here, we descr...
Archives françaises de pédiatrie, 1985
In order to evaluate the intrafamilial spread of hepatitis B virus (HBV) infection we studied the... more In order to evaluate the intrafamilial spread of hepatitis B virus (HBV) infection we studied the serological markers of HBV in 101 relatives of 35 children with chronic hepatitis B. Sixty per cent of relatives had markers of infection and 25% showed persistent HBs antigenemia. The high prevalence of HBeAg versus anti-HBe in chronically infected relatives suggests a close temporal relationship of the infection between adults and children. These results support the hypothesis that the child is the main carrier of HBV infection in his family.
Journal of pediatric gastroenterology and nutrition
Barrett's esophagus is a gastrointestinal metaplasia of the esophageal epithelium occurring f... more Barrett's esophagus is a gastrointestinal metaplasia of the esophageal epithelium occurring frequently in adults with long-standing peptic esophagitis. Recent reports of Barrett's esophagus in children with gastroesophageal reflux (GER) showed that also at the pediatric age intestinal metaplasia of the esophagus may occur in association with peptic esophagitis. Recently a close association between Campylobacter-like organisms (CLOs) and gastritis has been found in the stomach of both adults and children with a variety of peptic diseases, but evidence of such infection in specimens of Barrett's epithelium has never been described in children. We report here a child with Barrett's esophagus and GER, treated with H2 blockers, who showed a Barrett's ulcer in association with CLO infection. The addition of amoxicillin to antireflux treatment was accompanied by healing of the ulcer, suggesting that bacterial infection of Barrett's epithelium may have an important r...
Indian journal of pediatrics, 2006
Celiac disease may present as a cryptogenic liver disorder being found in 5-10 % of patients with... more Celiac disease may present as a cryptogenic liver disorder being found in 5-10 % of patients with a persistent and cryptogenetic elevation of serum aminotransferase activity. In fact, a wide spectrum of liver injuries in children and adults may be related to CD and in particular: (1) a mild parenchymal damage characterised by absence of any clinical sign or symptom suggesting a chronic liver disease and by non-specific histological changes reversible on a gluten-free diet; (2) a chronic inflammatory liver injury of autoimmune mechanism, including autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis, that may lead to fibrosis and cirrhosis, generally unaffected by gluten withdrawal and necessitating an immunosuppressive treatment; (3) a severe liver failure potentially treatable by a gluten-free diet. Such different types of liver injuries may represent a spectrum of a same disorder where individual factors, such as genetic predisposition, precocity and ...
Blood, 1994
Recombinant interferon-a (rIFN-a) iscurrently used in the treatment of chronic viral hepatitis in... more Recombinant interferon-a (rIFN-a) iscurrently used in the treatment of chronic viral hepatitis in adults'.* and in~ hildren.~ This treatment has never been associated with an increased risk of carcinogenesis. We report two children who developed acute B-lineagelymphoid ...
Helvetica paediatrica acta, 1982
Immunological functions were studied in two 22-month-old dizygotic twins with the characteristic ... more Immunological functions were studied in two 22-month-old dizygotic twins with the characteristic features of Shwachman syndrome. A severe defect of neutrophil motility was found in both children, but not in their parents. An impairment of the activity of the alternative pathway of complement was present in the sera of both patients. This defect, in association with the neutropenia and the chemotactic defect, might be related to the recurrent infections displayed by the twins.
Clinical pediatrics, 1982
Journal of clinical & laboratory immunology, 1982
In 8 children with selective IgA deficiency (serum IgA less than 5 mg/dl, secretory IgA less than... more In 8 children with selective IgA deficiency (serum IgA less than 5 mg/dl, secretory IgA less than 0.5 mg/dl in unstimulated saliva) immunofluorescent staining of intestinal biopsy specimens revealed the presence of IgA-containing plasma cells. This finding supports the hypothesis that in the intestinal mucosa of patients with IgA deficiency B lymphocytes undergo "sterile" differentiation into IgA-containing plasma cells probably incapable of secreting the IgA synthesized.
Archives françaises de pédiatrie, 1983
La semaine des hôpitaux : organe fondé par l'Association d'enseignement médical des hôpitaux de Paris, Jan 3, 1984
Clinical, biochemical and histological features of chronic hepatitis type B were studied in 29 ch... more Clinical, biochemical and histological features of chronic hepatitis type B were studied in 29 children aged 8 months to 13 years. On entry into the study, all were known to have had hepatitis B surface antigen (HBsAg) with elevated serum transaminase levels for at least six months. A possible source of infection was found in 15 children. When they entered the study, all patients were anicteric and all but one asymptomatic. Hepatomegaly was detected in 15 patients and was associated with splenomegaly in two. Hypergammaglobulinemia was present in 4 children. Serological evaluation of hepatitis B virus markers showed evidence of complete viral replication (HBeAg positivity) in 24 cases and incomplete replication (anti-HBeAg positivity) in 5. Liver histology showed chronic persistent hepatitis (CPH) in 18 children, and chronic aggressive hepatitis (CAH) in 10 (3 moderately active and 7 with major signs of aggressivity ) associated with cirrhosis in 5. One patient had only minimal histo...
Clinical and experimental immunology, 1985
Diagnostics
Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the ... more Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance. Recent evidence however suggests that treatment discontinuation is possible after a prolonged period of normal aminotransferase activity without the need for liver biopsy prior to withdrawal.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, Jan 7, 2017
Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic mar... more Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings. We collected data from 2 multi-center trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileo-colonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50% from baseline, respectively, for patients with CD, and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, for patients with UC. Pa...
European journal of obstetrics, gynecology, and reproductive biology, Jan 7, 2017
American Journal of Gastroenterology, 2004
This study describes a new method to detect autoantibodies against actin filaments (AAA) as a ser... more 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. 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. 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). 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.
Clinical Rheumatology, 1996
In a patient suffering from histologically-documented immuno-mediated chronic active hepatitis, i... more In a patient suffering from histologically-documented immuno-mediated chronic active hepatitis, intravenous immunoglobulin (IVIG) treatment was initiated as an obligatory alternative therapy because of femur head aseptic necrosis which had followed long-term therapy with steroids. The first cycle of IVIG was followed by remission of most symptoms, normalization of liver enzymes, disappearance of circulating immunecomplexes (CIC), and a negative lupus band test. Improvement in the patient's condition was demonstrated, in liver histology, by the disappearance of peri-portal mononuclear cells infiltrates, while immunohistochemistry showed the disappearance of the intracellular IgG deposits.
Journal of thrombosis and haemostasis : JTH, Jan 3, 2015
Quantitative fibrinogen deficiencies (hypofibrinogenemia, afibrinogenemia) are rare congenital di... more Quantitative fibrinogen deficiencies (hypofibrinogenemia, afibrinogenemia) are rare congenital disorders characterized by low/unmeasurable plasma fibrinogen antigen levels. Their genetic basis is invariantly represented by mutations within the fibrinogen genes (FGA, FGB, and FGG coding for the Aα, Bβ, and γ chains). Currently, only four mutations (p.Gly284Arg, p.Arg375Trp, delGVYYQ 346-350, p.Thr314Pro), all affecting the fibrinogen γ chain, have been reported to cause fibrinogen storage disease (FSD), a disorder characterized by protein aggregation, endoplasmic reticulum retention, and hypofibrinogenemia. To investigate the genetic basis of FSD in two hypobrinogenemic patients. The mutational screening of the fibrinogen genes was performed by direct DNA sequencing. The impact of identified mutations on fibrinogen structure was investigated by in-silico molecular modeling. Liver histology was evaluated by light microscopy, electron microscopy, and immunocytochemistry. Here, we descr...
Archives françaises de pédiatrie, 1985
In order to evaluate the intrafamilial spread of hepatitis B virus (HBV) infection we studied the... more In order to evaluate the intrafamilial spread of hepatitis B virus (HBV) infection we studied the serological markers of HBV in 101 relatives of 35 children with chronic hepatitis B. Sixty per cent of relatives had markers of infection and 25% showed persistent HBs antigenemia. The high prevalence of HBeAg versus anti-HBe in chronically infected relatives suggests a close temporal relationship of the infection between adults and children. These results support the hypothesis that the child is the main carrier of HBV infection in his family.
Journal of pediatric gastroenterology and nutrition
Barrett's esophagus is a gastrointestinal metaplasia of the esophageal epithelium occurring f... more Barrett's esophagus is a gastrointestinal metaplasia of the esophageal epithelium occurring frequently in adults with long-standing peptic esophagitis. Recent reports of Barrett's esophagus in children with gastroesophageal reflux (GER) showed that also at the pediatric age intestinal metaplasia of the esophagus may occur in association with peptic esophagitis. Recently a close association between Campylobacter-like organisms (CLOs) and gastritis has been found in the stomach of both adults and children with a variety of peptic diseases, but evidence of such infection in specimens of Barrett's epithelium has never been described in children. We report here a child with Barrett's esophagus and GER, treated with H2 blockers, who showed a Barrett's ulcer in association with CLO infection. The addition of amoxicillin to antireflux treatment was accompanied by healing of the ulcer, suggesting that bacterial infection of Barrett's epithelium may have an important r...
Indian journal of pediatrics, 2006
Celiac disease may present as a cryptogenic liver disorder being found in 5-10 % of patients with... more Celiac disease may present as a cryptogenic liver disorder being found in 5-10 % of patients with a persistent and cryptogenetic elevation of serum aminotransferase activity. In fact, a wide spectrum of liver injuries in children and adults may be related to CD and in particular: (1) a mild parenchymal damage characterised by absence of any clinical sign or symptom suggesting a chronic liver disease and by non-specific histological changes reversible on a gluten-free diet; (2) a chronic inflammatory liver injury of autoimmune mechanism, including autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis, that may lead to fibrosis and cirrhosis, generally unaffected by gluten withdrawal and necessitating an immunosuppressive treatment; (3) a severe liver failure potentially treatable by a gluten-free diet. Such different types of liver injuries may represent a spectrum of a same disorder where individual factors, such as genetic predisposition, precocity and ...
Blood, 1994
Recombinant interferon-a (rIFN-a) iscurrently used in the treatment of chronic viral hepatitis in... more Recombinant interferon-a (rIFN-a) iscurrently used in the treatment of chronic viral hepatitis in adults'.* and in~ hildren.~ This treatment has never been associated with an increased risk of carcinogenesis. We report two children who developed acute B-lineagelymphoid ...
Helvetica paediatrica acta, 1982
Immunological functions were studied in two 22-month-old dizygotic twins with the characteristic ... more Immunological functions were studied in two 22-month-old dizygotic twins with the characteristic features of Shwachman syndrome. A severe defect of neutrophil motility was found in both children, but not in their parents. An impairment of the activity of the alternative pathway of complement was present in the sera of both patients. This defect, in association with the neutropenia and the chemotactic defect, might be related to the recurrent infections displayed by the twins.
Clinical pediatrics, 1982
Journal of clinical & laboratory immunology, 1982
In 8 children with selective IgA deficiency (serum IgA less than 5 mg/dl, secretory IgA less than... more In 8 children with selective IgA deficiency (serum IgA less than 5 mg/dl, secretory IgA less than 0.5 mg/dl in unstimulated saliva) immunofluorescent staining of intestinal biopsy specimens revealed the presence of IgA-containing plasma cells. This finding supports the hypothesis that in the intestinal mucosa of patients with IgA deficiency B lymphocytes undergo "sterile" differentiation into IgA-containing plasma cells probably incapable of secreting the IgA synthesized.
Archives françaises de pédiatrie, 1983
La semaine des hôpitaux : organe fondé par l'Association d'enseignement médical des hôpitaux de Paris, Jan 3, 1984
Clinical, biochemical and histological features of chronic hepatitis type B were studied in 29 ch... more Clinical, biochemical and histological features of chronic hepatitis type B were studied in 29 children aged 8 months to 13 years. On entry into the study, all were known to have had hepatitis B surface antigen (HBsAg) with elevated serum transaminase levels for at least six months. A possible source of infection was found in 15 children. When they entered the study, all patients were anicteric and all but one asymptomatic. Hepatomegaly was detected in 15 patients and was associated with splenomegaly in two. Hypergammaglobulinemia was present in 4 children. Serological evaluation of hepatitis B virus markers showed evidence of complete viral replication (HBeAg positivity) in 24 cases and incomplete replication (anti-HBeAg positivity) in 5. Liver histology showed chronic persistent hepatitis (CPH) in 18 children, and chronic aggressive hepatitis (CAH) in 10 (3 moderately active and 7 with major signs of aggressivity ) associated with cirrhosis in 5. One patient had only minimal histo...
Clinical and experimental immunology, 1985