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Pietro Vajro - One of the best experts on this subject based on the ideXlab platform.
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Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation
BMC, 2018Co-Authors: Pietro Vajro, Claudia Mandato, Hudson H. Freeze, Katarzyna Zielinska, Marco Maccarana, Per Bengtson, Marco Poeta, Elisa D’acunto, Erik A. EklundAbstract: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
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Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations
MDPI AG, 2017Co-Authors: Jacopo Troisi, Luca Pierri, Annamaria Landolfi, Francesca Marciano, Antonella Bisogno, Federica Belmonte, Carmen Palladino, Salvatore Guercio Nuzio, Pietro Campiglia, Pietro VajroAbstract:To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index <85th or >95th percentile, respectively) ± ultrasonographic bright liver and Hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations
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Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease
Clinics and Research in Hepatology and Gastroenterology, 2014Co-Authors: Claudio Veropalumbo, Valeria Raia, Fabiola De Gregorio, Angelo Campanozzi, Antonio Correra, Pietro VajroAbstract:Summary Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation.
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Hypertransaminasemia is it always liver disease the case of subclinical myopathies and macroenzymes
Global Journal of Gastroenterology & Hepatology, 2013Co-Authors: Claudio Veropalumbo, Giulia Paolella, Roberta Daniello, Maria Sangermano, Pietro VajroAbstract:Abstract: Aminotransferases increase in serum is generally considered indicative of liver cell injury. However, these enzymes are also present in tissues other than the liver, mainly the muscles. Therefore, after an incidental finding of Hypertransaminasemia, serum creatine kinase check and an accurate physical examination -looking for subtle signs of muscular affection- are necessary to reach a correct diagnosis and avoid missing salient signs of a muscular disorder. In the case of protracted isolated AST elevation, the possibility of macro -AST should be taken into account as well. This is a generally benign condition, whose prompt recognition might avoid expensive, and occasionally invasive liver disease-related diagnostic procedures. Polyethylene glycol testing is considered a valuable screening test.
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pediatric celiac disease cryptogenic Hypertransaminasemia and autoimmune hepatitis
Journal of Pediatric Gastroenterology and Nutrition, 2013Co-Authors: Pietro Vajro, Giulia Paolella, Giuseppe Maggiore, Giuseppe GiordanoAbstract:ABSTRACTObjective:The association between celiac disease (CD) and liver disease in pediatrics is widely recognized, but its prevalence is unknown. This study aims to conduct a systematic review and meta-analysis to evaluate the prevalence of CD in children with cryptogenic persistent hypertransamina
Dario Conte - One of the best experts on this subject based on the ideXlab platform.
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anti tumour necrosis factor agent and liver injury literature review recommendations for management
World Journal of Gastroenterology, 2014Co-Authors: Roberta Elisa Rossi, I Parisi, Edward J Despott, Andrew K Burroughs, J Obeirne, Dario Conte, M Hamilton, Charles MurrayAbstract:Abnormalities in liver function tests, including transient and self-limiting Hypertransaminasemia, cholestatic disease and hepatitis, can develop during treatment with anti-tumour-necrosis-factor (TNF) therapy. The optimal management of liver injury related to anti-TNF therapy is still a matter of debate. Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than 5 times the upper limit of normal, or the occurrence of jaundice, there are no standard guidelines for the management of anti-TNF-related liver injury. Bibliographical searches were performed in PubMed, using the following key words: inflammatory bowel disease (IBD); TNF inhibitors; Hypertransaminasemia; drug-related liver injury; infliximab. According to published data, elevation of transaminases in patients with IBD treated with anti-TNF is a common finding, but resolution appears to be the usual outcome. Anti-TNF agents seem to be safe with a low risk of causing severe drug-related liver injury. According to our centre experience, we found that Hypertransaminasemia was a common, mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses. An algorithm for the management of liver impairment occurring during anti-TNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases. However, hepatic injury is generally self-limiting and drug withdrawal seems to be an exception.
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chronic unexplained Hypertransaminasemia may be caused by occult celiac disease
Hepatology, 1999Co-Authors: M T Bardella, Dario Conte, Maurizio Vecchi, Ersilio Del Ninno, M Fraquelli, S Pacchetti, E Minola, M Landoni, Bruno Mario Cesana, Roberto De FranchisAbstract:In a subset of patients attending liver units, a chronic increase in serum transaminases may remain of undetermined cause despite thorough investigations. On the other hand, elevated levels of serum transaminases have been reported in about 40% of adult celiac patients. To evaluate the prevalence of subclinical celiac disease in patients with chronic unexplained Hypertransaminasemia in comparison with that in the general population (0.5%), 140 consecutive patients with chronic increases of serum transaminases levels of unknown cause were tested for antigliadin and antiendomysium IgA antibodies. All patients with positive antibody tests were offered upper gastrointestinal endoscopy with distal duodenal biopsy. Thirteen patients (9.3%, 95% confidence interval 5. 0-15.4) had positive antigliadin and antiendomysium antibodies. The prevalence of antibodies was 17% in women and 5.4% in men (8/47 vs. 5/93 respectively; relative risk 3.2, 95% confidence interval 1.1-9. 1). Distal duodenal biopsy performed in all but one of the patients showed mild villous atrophy with increased intraepithelial lymphocytes in three cases, subtotal villous atrophy in six, and total villous atrophy in three. The prevalence of celiac disease in the patient group was significantly higher than that in the general population (P <.001) with a relative risk of 18.6 (95% confidence interval 11.1-31.2). On the basis of the present findings, screening for celiac disease is an important tool in the initial diagnostic work-up of patients with chronic unexplained Hypertransaminasemia.
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prevalence of Hypertransaminasemia in adult celiac patients and effect of gluten free diet
Hepatology, 1995Co-Authors: Maria Teresa Bardella, M Fraquelli, M Quatrini, N Molteni, Paolo Bianchi, Dario ConteAbstract:The prevalence of Hypertransaminasemia and the effect of gluten-free diet (GFD) were evaluated in 158 consecutive adult celiac patients, 127 women and 31 men, aged 18 to 68 years (mean, 32). At diagnosis, 67 patients (42%) had raised aspartate and/or alanine transaminase levels (AST and ALT; mean, 47 IU/L, range, 30 to 190; and 61 IU/L, range, 25 to 470, respectively), whereas 91 patients had normal liver function tests (LFT). Patients with and without Hypertransaminasemia were comparable for epidemiological data, body mass index (18.5 vs. 19.6), and severity of intestinal histological involvement. All patients were given a strict GFD and were followed for 1 to 10 years (median, 4). At 1 year, a highly significant improvement in intestinal histology was observed in both groups (P < .0001). In the 67 patients with raised transaminase levels body mass index (BMI) also increased significantly (from 18.5 to 21.0, P < .001), and transaminase levels normalized in 60 (95%). In the other seven cases liver biopsy showed fatty infiltration in two and chronic active hepatitis (CAH) in the other five, related to chronic infection with hepatitis B virus in three and hepatitis C virus in one, and to autoimmune type in the fifth. We conclude that in adult celiac patients elevated serum transaminases are a frequent finding and normalize in most cases after GFD. When they persist, liver biopsy is mandatory to further investigate hepatic involvement, which is our series was mainly attributable to CAH.
Claudio Veropalumbo - One of the best experts on this subject based on the ideXlab platform.
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Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease
Clinics and Research in Hepatology and Gastroenterology, 2014Co-Authors: Claudio Veropalumbo, Valeria Raia, Fabiola De Gregorio, Angelo Campanozzi, Antonio Correra, Pietro VajroAbstract:Summary Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation.
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Hypertransaminasemia is it always liver disease the case of subclinical myopathies and macroenzymes
Global Journal of Gastroenterology & Hepatology, 2013Co-Authors: Claudio Veropalumbo, Giulia Paolella, Roberta Daniello, Maria Sangermano, Pietro VajroAbstract:Abstract: Aminotransferases increase in serum is generally considered indicative of liver cell injury. However, these enzymes are also present in tissues other than the liver, mainly the muscles. Therefore, after an incidental finding of Hypertransaminasemia, serum creatine kinase check and an accurate physical examination -looking for subtle signs of muscular affection- are necessary to reach a correct diagnosis and avoid missing salient signs of a muscular disorder. In the case of protracted isolated AST elevation, the possibility of macro -AST should be taken into account as well. This is a generally benign condition, whose prompt recognition might avoid expensive, and occasionally invasive liver disease-related diagnostic procedures. Polyethylene glycol testing is considered a valuable screening test.
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persistent Hypertransaminasemia in asymptomatic children a stepwise approach
World Journal of Gastroenterology, 2013Co-Authors: Pietro Vajro, S Maddaluno, Claudio VeropalumboAbstract:We aimed to examine the major causes of isolated chronic Hypertransaminasemia in asymptomatic children and develop a comprehensive diagnostic flow diagram. A MEDLINE search inclusive of publications throughout August 2012 was performed. We found only a small number of publications that had comprehensively investigated this topic. Consequently, it was difficult to construct a diagnostic flowchart similar to those already available for adults. In children, a "retesting panel" prescription, including gamma-glutamyl transpeptidase and creatine kinase in addition to aminotransferases, is considered a reasonable approach for proficiently confirming the persistence of the abnormality, ruling out cholestatic hepatopathies and myopathies, and guiding the subsequent diagnostic steps. If re-evaluation of physical and historical findings suggests specific etiologies, then these should be evaluated in the initial enzyme retesting panel. A simple multi-step diagnostic algorithm incorporating a large number of possible pediatric scenarios, in addition to the few common to adults, is available. Accurately classifying a child with asymptomatic persistent Hypertransaminasemia may be a difficult task, but the results are critical for preventing the progression of an underlying, possibly occult, condition later in childhood or during transition. Given the high benefit/cost ratio of preventing hepatic deterioration, no effort should be spared in diagnosing and properly treating each case of persistent Hypertransaminasemia in pediatric patients.
Mohammad Reza Zali - One of the best experts on this subject based on the ideXlab platform.
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the effects of gluten free diet on Hypertransaminasemia in patients with celiac disease
International Journal of Preventive Medicine, 2013Co-Authors: Mostafa Alavi Moghaddam, Mohammad Rostami Nejad, Hamid Mohaghegh Shalmani, Kamran Rostami, Ehsan Nazemalhosseini Mojarad, David Aldulaimi, Mohammad Reza ZaliAbstract:Background: Celiac disease (CD) is an immune mediated condition that leads to small bowel atrophy that resolves with a gluten free diet (GFD). Extra-intestinal manifestations of CD include Hypertransaminasemia. In this study, the effects of a GFD on Hypertransaminasemia in patients with newly diagnosed CD were studied. Methods: Ninety eight new diagnosed consecutive patients with CD 40 males and 58 females) with mean age of 32 ± 17.1 were studied. All patients with CD were treated with a GFD. Patients with Hypertransaminasemia, at diagnosis, had a cirrhosis screen performed. Patients with a negative cirrhosis screen were reviewed, 6 months after the introduction of a GFD, and serum levels of liver transaminases were measured again. Results: Nine patients had Hypertransaminasemia. One patient was Hepatitis B surface antigen positive and was excluded from this study. The 8 remaining patients had no obvious cause for the Hypertransaminasemia. Mean (± SD) of baseline aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were 42.6 ± 16.5 IU/L (range: 16-66 IU/L) and 69.3 ± 9.3 IU/L (range: 52-81 IU/L). Six months after treatment with a GFD, mean AST and ALT levels decreased to 24.5 ± 5.1 IU/L (range: 18-31 IU/L) ( P : 0.04) and 24.6 ± 6 IU/L (range: 17-32 IU/L) ( P : 0.01), respectively. In 7 patients the Hypertransaminasemia, at diagnosis had resolved. Conclusions: This study provides further evidence that some patients with CD have a reversible Hypertransaminasemia that resolves with a GFD. Keywords: Celiac disease, gluten-free diet, Hypertransaminasemia, liver
Giuseppe Montalto - One of the best experts on this subject based on the ideXlab platform.
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screening for autoantibodies to tissue transglutaminase reveals a low prevalence of celiac disease in blood donors with cryptogenic Hypertransaminasemia
Digestion, 2001Co-Authors: Maurizio Soresi, M Amplo, Rosalia Agliastro, Roberta Sesti, G Di Giovanni, C Magliarisi, M Belvedere, Antonio Carroccio, Giuseppe MontaltoAbstract:Patients with chronic cryptogenic Hypertransaminasemia are at high risk of developing celiac disease (CD). In fact, among the various serological disorders, CD patients at onset frequently present Hypertransaminasemia. In this study, we evaluated usefulness and reliability of the new test for antitissue transglutaminase (tTG) in screening for CD as well as in estimating the prevalence of CD in a population of blood donors presenting unexplained Hypertransaminasemia at donation. Controls were 180 consecutive healthy donors without Hypertransaminasemia and 20 CD patients with known antiendomysial antibody (EmA) positivity. Out of 22,204 blood donors over a period of 2 years, we found 258 subjects (1.2%) with cryptogenic Hypertransaminasemia. Four of these subjects (1.5%) were positive for anti-tTG, but only 3 of them were positive for EmA. EmA were negative in all the remaining Hypertransaminasemia subjects. In the control groups, anti-tTG antibodies were negative in all the 180 healthy donors without Hypertransaminasemia, but positive in all the CD patients known to be EmA positive. 3 of the 4 subjects positive for anti-tTG, including 2 who were also EmA positive, underwent biopsy of the distal duodenal mucosa which showed a picture compatible with CD only in the 2 patients with concomitant EmA positivity. After 3 months of gluten-free diet, the serum transaminase values normalized in these 2 patients. In conclusion, the prevalence of CD in our blood bank population was lower than that reported in other similar studies, but the new test for anti-tTG showed a good sensitivity and reliability, and, therefore, it can be proposed as a first-level test in screening for CD in selected populations such as subjects with Hypertransaminasemia.