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Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs mostly in the context of insulin resistance and obesity. It has rapidly evolved into the most common cause of liver disease among children. The incidence is high in obese children and a greater risk of disease progression is associated with severe obesity, highlighting the role of nutrition. To date, there is no consensus on NAFLD management. This is a narrative review of clinical studies on the potential benefit of nutritional interventions, including lifestyle modifications, vitamins, docosahexaenoic acid, and probiotics in children with NAFLD. The Comité de nutrition de la Société Française de Pédiatrie (CN-SFP) emphasizes the effect of limiting added sugar intake, i.e., fructose or sucrose-containing beverages, and promoting physical activity in the care of NAFLD. [ABSTRACT FROM AUTHOR]

Résumé Le prurit est un symptôme invalidant des cholestases chroniques de l’enfant. Dans certains cas, son caractère réfractaire conduit à proposer des thérapeutiques agressives pouvant aller jusqu’à la transplantation hépatique. Sa physiopathologie est mal connue. Elle repose sur une voie neuronale spécifique, proche de celle de la douleur, activée et régulée par différents médiateurs, dont les acides biliaires, les opioïdes, la sérotonine et l’acide lysophosphatidique plus récemment identifié. Alors que la prise en charge thérapeutique du prurit cholestatique est bien codifiée chez les patients adultes, il n’existe pas de consensus chez l’enfant, compte tenu de la difficulté à mener des études cliniques contrôlées. La stratégie de prise en charge actuellement recommandée repose sur plusieurs lignes thérapeutiques spécifiques qui doivent toujours être associées à des soins locaux ainsi qu’à une prise en charge non spécifique de la cholestase, dont la prescription d’acide ursodésoxycholique. Le prurit doit être évalué le plus objectivement possible entre chaque ligne de traitement. La rifampicine, un inducteur enzymatique est le traitement spécifique de première intention du prurit cholestatique. Les traitements de 2 e ligne relèvent d’une prise en charge spécialisée et sont discutés au cas par cas selon la maladie causale, l’expérience du centre et la volonté de la famille. Il peut s’agir de traitements par inhibiteurs de la recapture de sérotonine (sertraline) ou antagonistes opioïdes (naloxone), ou bien de thérapeutiques interventionnelles par dérivation biliaire ou transplantation hépatique dans les cas les plus sévères. Summary Pruritus is a disabling symptom accompanying chronic cholestasis. In some cases, refractory pruritus may require invasive therapies including liver transplantation. The pathogenesis of pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway and several pruritogenic substances such as bile acids, opioids, serotonin, and the more recently identified lysophosphatidic acid. While the therapeutic management of cholestatic pruritus is well established in adult patients, there is no consensus in children, given the difficulty in conducting controlled clinical studies. The currently recommended strategy to manage cholestatic pruritus in children is based on several lines of therapy that should always be associated with local cutaneous care and with nonspecific treatment of cholestasis including ursodeoxycholic acid therapy. Pruritus should be assessed as objectively as possible between each therapeutic step. Rifampicin, an enzyme inducer, is the specific first-line treatment of cholestatic pruritus. The second-line therapies require evaluation of the child in an expert center and are discussed on a case-by-case basis depending on the underlying disease, the experience of the center and the will of the child and his family. It could be inhibitors of serotonin reuptake (sertraline) or an opioid antagonist (naloxone). Invasive therapies such as biliary diversion or liver transplantation can also be proposed in the most severe cases. [ABSTRACT FROM AUTHOR]

Abstract: Every neonatal jaundice lasting more than 2 weeks needs urgent investigations, beginning with examination of stools colour, and blood tests with total and conjugated serum bilirubin. If neonatal cholestasis (NC) is confirmed, vitamin K should be immediately injected, and the child should be referred to a specialised centre for investigations and treatment. Biliary atresia (BA) is the first cause of NC. Its diagnosis is urgent, since the chance of success of the conservative surgical treatment (Kasai operation or variants) decreases rapidly as the age at surgery increases. Normal ultrasound scans cannot rule out BA. After prompt work-up looking for the main other causes of NC, BA can often be strongly suspected before surgery, and is confirmed by operative findings and cholangiogram if needed. In case of failure to restore the biliary drainage, biliary cirrhosis progresses and leads to liver transplantation, generally in the first years of life. Currently, more than 90 % of children with BA can live, with a close to normal quality of life for most of them. Early diagnosis and treatment of BA contribute to decrease the needs for liver transplantation in infancy and childhood. [Copyright &y& Elsevier]

Neonatal jaundice lasting more than two weeks needs urgent investigations, starting with examination of stool colour and blood tests with total and conjugated serum bilirubin. If neonatal cholestasis (NC) is confirmed, vitamin K should be immediately injected, and the child should be referred to a specialised centre for investigations and treatment. Biliary atresia (BA) is the first cause of NC. Its diagnosis is urgent, since the chance of success of the conservative surgical treatment (Kasai operation or variants) decreases rapidly as the age at surgery increases. Normal ultrasound scans cannot rule out BA. The diagnosis can often be suspected before surgery, and is confirmed by operative findings with or without cholangiogram. In case of failure to restore the biliary drainage, biliary cirrhosis progresses and leads to liver transplantation, generally in the first years of life. The other causes of neonatal obstructive jaundice are stones in the main bile duct, choledocal cyst and spontaneous perforation of bile ducts. Correction of biliary obstruction (by surgery or interventional radiology) is also urgent to prevent progression of liver fibrosis, which is very rapid in the first months of life. The most common medical aetiologies of NC are: Alagille syndrome, 1-antitrypsin deficiency, progressive familial intrahepatic cholestasis and cystic fibrosis. Other medical causes of NC are numerous, including infectious, hormonal, nutritional, metabolic or storage diseases. Some of the conditions may require a specific therapy. [ABSTRACT FROM AUTHOR]

Despite the availability of potent immunosuppressive drugs, rejection after organ transplantation in children remains a serious concern, and may lead to significant morbidity, graft loss, and death of the patient. Acute graft rejection in pediatric recipients is first treated with methylprednisolone pulses, followed by progressive taper of corticosteroid doses. After control of the rejection episode, baseline immunosuppression has to be adjusted and closely monitored since rejection (especially late episodes, occurring more than 6 months after transplantation) may be due to a lack of compliance or sub-therapeutic drug concentrations. The management of corticosteroid resistant rejection is not standardized, and depends on the transplanted organ and previous immunosuppressive regimen. In patients experiencing corticosteroid resistant acute rejection while on a cyclosporine-based immunosuppressive regimen, cyclosporine is generally changed to tacrolimus. In case of tacrolimus-based immunosuppression, tacrolimus blood levels may be increased, and/or mycophenolate mofetil (which nowadays tends to replace azathioprine) or sirolimus may be added, although pharmacodynamic data and clinical studies with these agents are still scarce in pediatric recipients. The use of antithymocyte globulins or monoclonal anti-CD3 antibodies, muromonab CD3 (OKT3) is hampered by numerous adverse effects, including a significant risk of over-immunosuppression. These therapies are nowadays indicated in very selected cases. Other treatments such as plasmapheresis and high dose immunoglobulins may be useful in difficult cases. In patients with refractory rejection despite therapeutic escalation, the risks of over-immunosuppression, including opportunistic infections and malignancies (especially the Epstein-Barr virus related post-transplant lymphoproliferative disease) have to be balanced with the consequences of graft loss due to rejection. Detransplantation or retransplantation may, in some instances, be preferable to severe infectious or tumoral complications. [ABSTRACT FROM AUTHOR]

Unlabelled: Most studies on the prevalence of asialoglycoprotein antibodies have involved adults. In this study the prevalence of antibodies to the human asialoglycoprotein receptor (ASGP-R) was determined in 63 children with auto-immune hepatitis. It was shown that 75% of those with auto-immune hepatitis type 1 and 40% of those with auto-immune hepatitis type 2 were positive and the presence of anti-ASGP-R auto-antibodies, at a mean titre of 1:1,600 and 1:1,000 respectively. No statistical significance was found between anti-ASGP-R positive and negative patients with respect to the median age at onset, proportion of females and ALT levels. However, the titre of anti-ASGP-R antibodies correlated significantly with hypergammaglobulinaemia.Conclusion: Anti-asialoglycoprotein receptor antibodies are frequently present in the sera of children with auto-immune hepatitis, particularly type 1, The presence of these antibodies is an indirect marker of inflammatory activity. [ABSTRACT FROM AUTHOR]

Acyclovir-induced neurotoxicity is a rare adverse effect, found especially in adults with pre-existing renal failure. We report a case of neurotoxicity of acyclovir in a six-month-old liver transplant recipient. Case report and review of literature are discussed. [ABSTRACT FROM AUTHOR]

• CFTR-related disorders (RD) are a group of conditions caused by CFTR protein dysfunction, but to a level of dysfuncton not satisfying the diagnostic crtieria for cystic fibrosis (CF). • This paper discusses the individual disorders, including congenital absence of the vas deferens (CAVD), diffuse bronchiectasis, chronic or acute recurrent pancreatitis, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling of the palms. • The CFTR functional and genetic evidence in support of each condition being a CFTR-RD are discussed and guidance for reaching the diagnosis is provided. • Gaps in our knowledge and future areas of research, including the role of CFTR modulators, are highlighted. This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted. [ABSTRACT FROM AUTHOR]

Résumé Environ 5 à 8% des patients atteints de mucoviscidose développent une cirrhose multilobulaire au cours de la première décennie. Le dépistage annuel de signes d'atteinte hépatique par l'examen clinique, les tests biologiques hépatiques, l'échographie et le suivi sont recommandés afin d'instaurer un traitement par acide ursodésoxycholique et d'identifier les complications: hypertension portale et insuffisance hépatocellulaire. La correction de la malnutrition et la prévention de l'hémorragie digestive sont les principaux objectifs de la prise en charge. Différentes atteintes digestives peuvent être rencontrées chez ces enfants. Le reflux gastro-œsophagien, très fréquent mais souvent négligé, doit être recherché par pH-métrie couplée éventuellement à une impédancemétrie. Des épisodes de pancréatite aigüe peuvent survenir chez des patients ayant une activité pancréatique exocrine résiduelle suffisante. Invagination intestinale aigüe, mucocèle appendiculaire (accumulation de mucus épais dans l'appendice), syndrome d'occlusion intestinale distale (impaction de selles et de mucus au niveau iléo-caecal), syndrome de pullulation bactérienne de l'intestin grêle et colite à Clostridium difficile sont à évoquer devant des douleurs abdominales. Sur le plan nutritionnel, la prise en charge préventive et la surveillance attentive de la croissance débutent dès le diagnostic. L'alimentation, tout en restant équilibrée, doit être hyper-énergétique et supplémentée en sel. Les extraits pancréatiques lors des repas sont prescrits dès l'insuffisance pancréatique exocrine confirmée, de même que les vitamines liposolubles. En cas de dénutrition, la prise en charge nutritionnelle curative par assistance nutritionnelle est d'autant plus efficace qu'elle est précoce, chez des patients à l'état respiratoire satisfaisant. Les difficultés d'alimentation sont très fréquentes, liées à la physiopathologie de la maladie mais également à son retentissement psychologique. Le vécu corporel négatif de l'enfant, la pression médicale et parentale parfois excessive peuvent majorer les refus alimentaires. L'équipe multidisciplinaire doit veiller à proscrire toute attitude contre-productive de nourrissage intrusif et valoriser l'instauration d'un climat de plaisir au cours des repas. In cystic fibrosis (CF), approximately 5–8% of the patients develop multilobular cirrhosis during the first decade of life. Annual screening (clinical examination, liver biochemistry, ultrasonography) is recommended in order to identify early signs of liver involvement, initiate ursodeoxycholic acid therapy and detect complications (portal hypertension and liver failure). Management should focus on nutrition and prevention of variceal bleeding. The gut may also be involved in children with CF. Gastroesophageal reflux is frequent, although often neglected and should be investigated by pH monitoring and impedancemetry, if available. Acute pancreatitis occurs in patients with persistent exocrine pancreatic activity. Intussusception, appendicular mucocele, distal intestinal occlusion syndrome, small bowel bacterial overgrowth and Clostridium difficile colitis should be considered in case of abdominal pain. Preventive nutritional support should be started as soon as possible after diagnosis of CF. Attainment of normal growth is one of the main goals and can be achieved with hypercaloric and salt supplemented food. Pancreatic enzyme replacement therapy should be started as soon as exocrine pancreatic insufficiency is confirmed and ingested immediately prior to meals with intake of fat-soluble vitamins. Curative nutritional interventions are more likely to be effective in the early stages of pulmonary disease. Feeding disorders, related to the physiopathology and the psychologic aspects of the disease are frequent. Repeated corporeal aggressions, associated with inappropriate medical and parental pressure, may increase the child's refusal of food. The multidisciplinary team should guide parents in order to avoid all intrusive feeding practices and promote pleasant mealtimes. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to assess the prevalence of de novo malignancy after solid organ transplantation in childhood. A retrospective questionnaire-based survey was sent to 9 referral centers for pediatric organ transplantation in France. Among 1326 children who underwent solid organ transplantation since 1996, 80 (6%) presented with de novo malignancy posttransplantation during childhood: posttransplant lymphoproliferative disease was the most common (5% of pediatric recipients) comprising 80% of all tumors, with a disproportionately high prevalence among combined liver and small bowel recipients (18%). Various solid tumors were observed mainly among kidney recipients. No skin cancer was reported. [Copyright &y& Elsevier]

Summary: In cystic fibrosis (CF), approximately 5–10% of the patients develop multilobular cirrhosis during the first decade of life. Most of these will develop signs of portal hypertension with complications, mainly variceal bleeding during the second decade, while liver failure is usually late, after the pediatric age. Annual screening for liver disease is recommended in order to initiate ursodeoxycholic acid, that may halt the progression of liver disease. Liver disease should be considered if at least two of the following variables are present: hepatomegaly and/or splenomegaly; persistent abnormalities of liver enzymes, and pathological ultrasonography of the liver. A liver biopsy is indicated if there is diagnostic doubt. All CF patients with liver disease need annual follow-up in order to evaluate the progression to cirrhosis, and screen for portal hypertension and liver failure. Management should focus on nutrition and prevention of variceal bleeding. The decision for a liver transplant is evaluated with the transplant team, taking into account the liver function and complications of portal hypertension as well as CF related extrahepatic involvement. [Copyright &y& Elsevier]

Background and purpose The severity of Wilson's disease ( WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (Cu EXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity. Methods Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging ( MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. Cu EXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups. Results Extra-hepatic patients had significantly higher Cu EXC values than those with the hepatic form ( P < 0.0001). The overall ability of Cu EXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 μmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, Cu EXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score ( r = 0.45, P = 0.016), the Kayser−Fleischer ring score ( r = 0.46, P = 0.014) and the brain MRI score ( r = 0.38, P = 0.048), but it was not correlated with the hepatic score. Conclusions Exchangeable copper determination is useful when diagnosing WD as a value >2.08 μmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes. [ABSTRACT FROM AUTHOR]

Objectif: Les injections intramusculaires de vitamines sont douloureuses et source de phobie des soins lorsqu’elles sont répétées. La douleur est liée à l’effraction cutanée et au produit injecté. Malgré crème anesthésiante, prise de sucre, inhalation de MEOPA et distraction, la douleur est forte. Nous présentons notre expérience d’une nouvelle technique d’analgésie. Méthodes: Anesthésie locale par injection IM (cuisse) de Xylocaïne® 1 % tamponnée (par du bicarbonate de sodium) (0,25 à 1,5 ml selon le poids de l’enfant). L’injection de la vitamine est faite par la même aiguille laissée en place, 1 à 3 minutes plus tard. L’injection successive de 2 vitamines est possible en modifiant l’orientation de l’aiguille. Plusieurs gestes ont été filmés, évaluation en cours. Population: Tous les enfants suivis pour cholestase chronique bénéficient de cette technique pour l’injection des vitamines A, D, E, K, depuis une année. Résultats: Peu ou aucune manifestation de douleur lors de l’injection. Les parents présents témoignent d’une grande satisfaction. Douleur mesurée pour 5 enfants : score FLACC entre 0 et 2 sur 10. Les taux sanguins de vitamines, suivis régulièrement, sont normaux. Conclusion: Cette technique simple, validée par le CLUD et réalisable en ambulatoire permet l’injection IM sans douleur. [ABSTRACT FROM AUTHOR]

Objectifs: Préciser la place du zinc dans le traitement de la maladie de Wilson (MW) chez l’enfant. Matériels et Méthodes: Les données cliniques de la MW, les modalités thérapeutiques, l’évolution clinique et biologique ont été étudiés chez 26 enfants traités par le zinc. Résultats: La découverte de la MW a été fortuite au cours d’un bilan (38 %), lors d’un dépistage dans le cas d’un bilan familial (50 %), devant une atteinte hépatique (88 %), une atteinte neurologique (4 %). La médiane d’âge était de 8 ans (0,8 – 16,1) au diagnostic et de 10,8 ans (2,3 – 19,1) au début du traitement par le zinc. Le zinc était initié dès la découverte de la MW chez 54 % des enfants. Un traitement par D-penicillamine était associé dans 69 % des cas, par trientine dans 15 % des cas, et 11 % des enfants avaient reçu les 3 thérapeutiques. Une posologie du zinc supérieure aux doses recommandées était utilisée chez 5/6 enfants de moins de 5 ans, 10/19 enfants entre 6 et 15 ans, et 1/1 enfant de plus de 16 ans. Une normalisation des transaminases et de la cupriurie était obtenue après 5 mois de traitement. Après ce délai, la cupriurie médiane est restée inférieure à 50 μg/l. Les effets secondaires étaient rares. Conclusion: Le zinc est un traitement efficace et bien toléré dans la MW chez l’enfant. [ABSTRACT FROM AUTHOR]

Summary: Perinatal hemochromatosis (PH) includes neonatal acute liver failure (ALF) with cirrhosis and extrahepatic iron overload sparing the reticuloendothelial system. This is the main cause of neonatal ALF. Prognosis is very poor, usually with neonatal death or neonatal orthotopic liver transplantation occurring in more than 70%. The recurrence rate is more than 90%. Diagnosis is hard to make and is proved after exclusion of other neonatal ALF causes. A recent physiopathological hypothesis proposed HP as a maternofetal alloimmune disease against the fetal liver. A maternal antibody may activate the terminal complement cascade, responsible for the membrane attack complex directed against fetal hepatocytes. Maternal prenatal treatment after a pregnancy complicated by PH modifies the course and the prognosis of this disease. In France, approval of prenatal IVIG treatment is required after analysis of clinical and pathological data by a national multidisciplinary committee. [ABSTRACT FROM AUTHOR]

Context: A subset (approximately 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension.Objective: To assess whether any of 9 polymorphisms in 5 candidate genes (alpha(1)-antitrypsin or alpha(1)-antiprotease [SERPINA1], angiotensin-converting enzyme [ACE], glutathione S-transferase [GSTP1], mannose-binding lectin 2 [MBL2], and transforming growth factor beta1 [TGFB1]) are associated with severe liver disease in patients with CF.Design, Setting, and Participants: Two-stage case-control study enrolling patients with CF and severe liver disease with portal hypertension (CFLD) from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America, with the University of North Carolina at Chapel Hill as the coordinating site. In the initial study, 124 patients with CFLD (enrolled January 1999-December 2004) and 843 control patients without CFLD were studied by genotyping 9 polymorphisms in 5 genes previously studied as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 patients with CFLD (enrolled January 2005-February 2007) and 1088 with no CFLD.Main Outcome Measures: Differences in distribution of genotypes in patients with CFLD vs patients without CFLD.Results: The initial study showed CFLD to be associated with the SERPINA1 Z allele (odds ratio [OR], 4.72; 95% confidence interval [CI], 2.31-9.61; P = 3.3 x 10(-6)) and with TGFB1 codon 10 CC genotype (OR, 1.53; 95% CI, 1.16-2.03; P = 2.8 x 10(-3)). In the replication study, CFLD was associated with the SERPINA1 Z allele (OR, 3.42; 95% CI, 1.54-7.59; P = 1.4 x 10(-3)) but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (OR, 5.04; 95% CI, 2.88-8.83; P = 1.5 x 10(-8)).Conclusions: The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater risk (OR, approximately 5) of developing severe liver disease with portal hypertension. [ABSTRACT FROM AUTHOR]

Abstract: We report five paediatric cases of portal vein thrombosis (PVT) occurring during chemotherapy, observed in two institutions over an 8-year time period. These children aged 2.5–15 years were treated for Burkitt’s lymphoma, Ewing’s tumour, small cell bone tumour or medulloblastoma. PVT was diagnosed on colour Doppler ultrasonography (US). In four patients, thrombosis occurred 2–45 days after severe hepatic veno-occlusive disease (HVOD) secondary to intensive chemotherapy containing busulfan. In one case, PVT occurred in the absence of HVOD in a patient with pre-existing periportal lymphomatous infiltration. Four patients experienced persistent portal hypertension, which resulted in death in one. PVT during chemotherapy in children is a rare event and appears to be closely related to intensive chemotherapy containing busulfan and to be associated with HVOD. [Copyright &y& Elsevier]

Abstract: A cross-sectional study was performed to assess quality of life (QoL) after kidney or liver transplantation during childhood. Self-questionnaires explored children, adolescent and parent QoL. Seventy-five transplant children, 36 transplant adolescents, 67 mothers, 34 fathers and 67 caregivers filled out the questionnaires; they were compared with a reference population. Children reported a rather good QoL, but their extra-family involvement appeared not as satisfactory as that of the reference population children. Adolescents reported a very high QoL when completing the structured format scale; however, their responses to open-ended questions showed qualitative differences compared with those of a reference population: they expressed concern about their body or health, less pleasure than ordinary adolescents to manage by themselves, and a poor relationship with peers. Mothers indicated a deep impact of the child's illness on their own QoL, and the need for psychological support. In conclusion, a rather good QoL is a long-lasting feature of kidney and liver transplantation in children. Such an assessment is mandatory to identify remaining impairments in some selected areas, either in the recipient or family. [ABSTRACT FROM AUTHOR]

Idiopathic Reye syndrome is a rare disease revealed by unexplained encephalopathy and microvesicular liver steatosis. Some clinical and epidemiological studies mainly performed in English speaking countries questionned the reality of Reye syndrome because numerous known inherited metabolic diseases, and some of them unrecognized, could mimick this disorder. We focused in our study on severe forms of Reye syndrome admitted to a pediatric intensive care unit.Methods. – Retrospective study over the last eleven years (1991–2001) included all the pediatric patients admitted to our tertiary referral center with the classical American Reye syndrome criteria (e.g CDC). Extensive metabolic screening was performed in all cases, except for the ultimately dead patients.Result. – Fourteen patients (mean age 52 months) were included. Fever always occurred before their admission and aspirin (n=12) or acetaminophen (n=7) was prescribed. Median Glasgow scale was 7 on admission. Mean amoniac plasma level was 320 μmol/L and alanine-aminotransferase peak plasma level 1475 ± 1387 IU/L. Mechanical ventilation was started in ten children and six of them underwent continuous venovenous hemofiltration. Three patients ultimately died and 11 survived with a mean five years follow-up without relapses or neurological impairment. Any of them demonstrated inherited metabolic disease except for one infant with hereditary fructose intolerance.Conclusion. – Unlike widespread opinion, severe Reye syndrome without identified metabolic disorders seems to not disappear in our country. Reye syndrome remains a potentially life threatening disease and raises for aggressive treatment of brain edema. If aspirin and Reye syndrome association are not formally documented in France, cautiousness must be kept in mind and all the aspirin adverse effects notifications should be addressed to the public drugs survey network. [ABSTRACT FROM AUTHOR]

Summary: Langerhans cell histiocytosis (LCH) is a multisystemic disease, which may present with neurological involvement. We report the case of a 20-month-old girl with initial liver and skin involvement. Initial symptoms were recurrent episodes of trunk dystonia, lasting approximately 2 months prior to the diagnosis of LCH. No brain MRI abnormality was demonstrated at initial work-up and over 7 years of follow-up, except for a postpituitary involvement noted after 3 years of follow-up. These episodes of dystonia subsided during the first week of specific LCH chemotherapy (vinblastine and steroid), suggesting that they may have resulted from hepatalgia related to the histiocytic infiltration of the liver. [Copyright &y& Elsevier]

Introduction La sévérité de la maladie de Wilson (MW) dépend étroitement du cuivre libre et par conséquent toxique qui s’accumule dans le foie et le cerveau. Le cuivre échangeable (CuEXC) est un nouveau dosage de ce cuivre libre. Le REC (rapport CuEXC/cuivre total) est d’un grand intérêt dans le diagnostic de la MW ainsi que dans le dépistage familial de la maladie. Objectif Déterminer si le CuEXC est un marqueur de la sévérité de la maladie et en particulier de l’atteinte extra-hépatique. Matériel et méthodes Quarante-huit nouveaux patients atteints de la MW ont été évalués de façon prospective avec des scores hépatique, neurologique (UWDRS : Unified Wilson Disease Rating Score), ophtalmologique et neuro-radiologique (IRM cérébrale). Trois présentations phénotypiques ont été distinguées : pré-symptomatique, hépatique (H) et extra-hépatique (EH). Le CuEXC a été évalué en plus des dosages cupriques habituels (cuprémie, cuprurie/24 h et céruloplasminémie) avant le début du traitement chélateur. Les groupes H et EH ont été comparés et des corrélations entre les paramètres biologiques et les différents scores ont été recherchées. Résultats Les patients du groupe EH ont un CuEXC significativement plus élevé que ceux du groupe H ( p < 0,0001). Un CuEXC > 2,08 μmol/L est associé à une atteinte EH (Se : 85,7 % ; Sp : 94,1 %). Le CuEXC est significativement corrélé à l’importance de l’anneau de Kayser-Fleischer ( p = 0,01), au score neurologique UWDRS ( p = 0,001) et à la diffusion des lésions sur l’IRM cérébrale ( p = 0,04). Il reflète donc la sévérité de l’atteinte extra-hépatique. En revanche, le CuEXC n’est pas corrélé au score hépatique. Conclusion Le dosage du cuivre échangeable CuEXC se révèle être un marqueur important dans la prise en charge de la MW. Une valeur > 2,08 μmol/L doit faire rechercher une atteinte extra-hépatique (cornée, neurologique) même si la présentation clinique de la maladie apparaît purement hépatique. Le suivi de cette cohorte devrait nous permettre de savoir si le CuEXC est un marqueur pronostic de la MW et s’il est prédictif de la réponse au traitement médical. [ABSTRACT FROM AUTHOR]

Contexte Le prurit est un symptôme invalidant des cholestases chroniques de l’enfant. La prise en charge repose classiquement sur l’association d’acide ursodésoxycholique (AUDC) et de rifampicine. En cas d’échec, des thérapeutiques invasives dont la transplantation hépatique peuvent être proposées. Des études cliniques ont montré chez l’adulte que la sertraline, un inhibiteur de la recapture de sérotonine, diminue le prurit cholestatique. Objectif Déterminer l’efficacité et la tolérance d’un traitement par sertraline dans le prurit cholestatique réfractaire de l’enfant. Méthode Dans cette étude prospective et multicentrique, 20 patients présentant une cholestase chronique (PFIC à γGT normales n = 13, syndrome d’Alagille n = 7) accompagnée d’un prurit réfractaire sans insuffisance hépatocellulaire ont été inclus entre 2007 et 2014. La sertraline était introduite à la posologie de 1 mg/kg/j et augmentée selon la réponse clinique jusqu’à 4 mg/kg/j. Les traitements préexistants (AUDC et rifampicine) ont été maintenus à posologie constante. L’efficacité du traitement était évaluée à 3 mois puis tous les 6 mois à l’aide d’un score de prurit (échelle visuelle analogique), du nombre de réveils nocturnes et des lésions cutanées. Les patients présentant une diminution d’au moins 3 points du score de prurit associée à une amélioration de l’état cutané et/ou du sommeil à 3 mois ont été considérés comme répondeurs. La bilirubinémie, les acides biliaires sériques, la sertralinémie résiduelle ont été dosés pendant le suivi et les évènements indésirables rapportés. Résultats La durée médiane de traitement était de 15 mois, à la posologie moyenne de 2,2 mg/kg/j. Le score de prurit diminuait de 2,5 points en moyenne à 3 mois sur l’ensemble des patients traités et de 4,5 points chez les patients répondeurs (10 patients sur 20). Il n’a pas été retrouvé de facteurs prédictifs de réponse au traitement parmi les paramètres clinico-biologiques initiaux, l’évolution de la bilirubinémie, des acides biliaires sériques ou de la sertralinémie. Des évènements indésirables ont été rapportés chez 6 enfants. Sept patients sont toujours traités actuellement dont 5 depuis plus de deux ans avec un contrôle durable du prurit. Les causes d’interruption du traitement ont été : effet indésirable ( n = 4), arrêt du suivi ( n = 3), transplantation hépatique ( n = 3), inefficacité ( n = 2), ou décès ( n = 1). Conclusion La sertraline peut constituer un traitement de troisième ligne du prurit cholestatique de l’enfant réfractaire à l’association d’AUDC et de rifampicine. [ABSTRACT FROM AUTHOR]

Abstract: Therapeutic drug monitoring is critical to avoid overimmunosuppression or underimmunosuppression in young pediatric transplant recipients. The objective of this study was to examine cyclosporine (CsA) trough (C0) and 2-hour post-dose (C2) concentrations in the early period after liver transplantation (OLT) to determine whether CsA C2 monitoring is justified. Seventeen infants younger than 2 years treated with CsA (Neoral) were monitored at C0. The biopsy-proved acute rejection rate was 65% at 3 months post-OLT. No correlation was observed between values at C0 and C2. Poor absorption of CsA was observed in most infants during the first 2 weeks post-OLT, as well as interindividual variability in CsA clearance. Exposure to CsA could not be estimated using either C0 or C2 determinations in the early post-OLT period. As a marker of poor absorption, C2 is useful but does not indicate delayed or rapid clearance of drug without simultaneous measurement of concentration at C0. We suggest the use of both C0 and C2 monitoring, or AUC monitoring on an individual basis during at least the first 2 weeks post-OLT. [Copyright &y& Elsevier]

Abstract: To our knowledge, the development of renal cystic disease that may contribute to kidney dysfunction has never been reported after liver transplantation. Herein we have reported on the fortuitous finding of renal cystic lesions upon computed tomographic scans (CT) in 33 (30%) of 108 pediatric liver transplant recipients who were the subjects of a prospective study evaluating long-term kidney dysfunction at 10 years after liver transplantation. The renal lesions had 2 different appearances: that of simple renal cysts and that of round lesions that were spontaneously hyperdense before contrast injection. These high-density lesions had a low signal on T2 weighted sequences, but 70% of them had been missed at ultrasonography. Their aspect upon CT and magnetic resonance favored cystic lesions filled with hemorrhagic or milk calcium content. Both types of cystic lesions were associated in 14 children. The renal lesions were significantly associated with moderate renal dysfunction, biopsy-proven chronic liver graft rejection, and thrombosis of the retrohepatic vena cava. The physiopathology of these lesions is undetermined. Two important questions need to be clarified with respect to the risk of progression of renal dysfunction associated with individual volume changes and/or increased number of renal cysts, as well as the risk of renal cancer as has been reported in dialyzed patients with acquired cystic kidney disease. [Copyright &y& Elsevier]

Objectifs: Nous présentons 4 observations d’insuffisance hépatocellulaire aiguë du nourrisson qui ont révélé un déficit du cycle de l’urée. Résultats: L’âge moyen est de 15 mois. Les 4 enfants présentent une symptomatologie digestive. Ils sont admis pour vomissements et troubles du comportement et /ou somnolence. La biologie montre une élévation moyenne des ASAT à 2946UI/L, et ALAT 3870UI/L, sans cholestase, une insuffisance hépatocellulaire (TP 23 %, facteur V 27 %). Les valeurs d’ammoniémie sont très variables. Le diagnostic a été évoqué sur une chromatographie plasmatique des acides aminés et le dosage de l’acide orotique. Ils révèlent un déficit en Ornithine transcarbamylase (3 cas) et une citrullinémie type 1. Un régime contrôlé en protéines et un traitement médical ont permis une normalisation rapide de la fonction hépatique sans transplantation hépatique. Conclusion: Une forme infantile de déficit du cycle de l’urée peut se révéler par une insuffisance hépatocellulaire aiguë qui peut faire discuter une transplantation hépatique. Bien qu’une hyperammoniémie soit difficile à interpréter en raison de l’atteinte hépatique, il est indispensable d’évoquer le diagnostic de déficit primitif du cycle de l’urée et de mener l’exploration diagnostique à son terme [ABSTRACT FROM AUTHOR]