A. Lachaux

Improving outcomes of biliary atresia: French national series 1986-2009.

BACKGROUND & AIMS This study analyses the prognosis of biliary atresia (BA) in France since liver transplantation (LT) became widely available. METHODS The charts of all BA patients living in France and born between 1986 and 2009 were reviewed. Patients were divided into 3 cohorts according to their years of birth: 1986-1996, 1997-2002, and 2003-2009. RESULTS 1107 BA children were identified, 990 born in metropolitan France (incidence 1/18,400 live births). Kasai operation was performed in 1044 (94%), leading to complete clearance of jaundice (total serum bilirubin ≤ 20 μmol/L) in 38% of patients. Survival with native liver (SNL) after Kasai operation was 40%, 36%, and 30% at 5, 10, and 20 years, stable in the 3 cohorts. Median age at Kasai operation was 59 days, unchanged over time. Twenty-year SNL was 39%, 32%, 28%, and 19% after Kasai operation performed in the first, second, third months of life or thereafter (p=0.0002). 588 children underwent 692 LTs. Mortality without transplantation decreased over time: 16%, 7%, and 4% in the 3 cohorts (p<0.0001). Survival after transplantation was 83%, 82%, and 77% at 5, 10, and 20 years in the whole series. Five-year post-transplant survival was 75%, 90%, and 89% in the 3 cohorts (p<0.0001). In the whole series, overall BA patient survival was 81%, 80%, and 77% at 5, 10, and 20 years. Five-year BA patient overall survival increased over time: 72%, 88%, and 89% in the 3 cohorts (p<0.0001). CONCLUSIONS BA patients currently have an 89% live expectancy, and a 30% chance to reach adulthood without transplantation. Early Kasai operation, without age threshold, reduces the need for liver transplantation until adulthood.

Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia

BACKGROUND & AIMS Non-alcoholic steatohepatitis leading to fibrosis occurs in patients with abetalipoproteinemia (ABL) and homozygous or compound heterozygous familial hypobetalipoproteinemia (Ho-FHBL). We wanted to establish if liver alterations were more frequent in one of both diseases and were influenced by comorbidities. METHODS We report genetic, clinical, histological and biological characteristics of new cases of ABL (n =7) and Ho-FHBL (n = 7), and compare them with all published ABL (51) and Ho-FHBL (22) probands. RESULTS ABL patients, diagnosed during infancy, presented mainly with diarrhea, neurological and ophthalmological impairments and remained lean, whereas Ho-FHBL were diagnosed later, with milder symptoms often becoming overweight in adulthood. Despite subtle differences in lipid phenotype, liver steatosis was observed in both groups with a high prevalence of severe fibrosis (5/27 for Ho-FHBL vs. 4/58 for ABL (n.s.)). Serum triglycerides concentration was higher in Ho-FHBL whereas total and HDL-cholesterol were similar in both groups. In Ho-FHBL liver alterations were found to be independent from the apoB truncation size and apoB concentrations. CONCLUSIONS Our findings provide evidence for major liver abnormalities in both diseases. While ABL and Ho-FHBL patients have subtle differences in lipid phenotype, carriers of APOB mutations are more frequently obese. These results raise the question of a complex causal link between apoB metabolism and obesity. They suggest that the genetic defect in VLDL assembly is critical for the occurrence of liver steatosis leading to fibrosis and shows that obesity and insulin resistance might contribute by increasing lipogenesis.

Complications of percutaneous liver biopsy in infants and children

AbstractIn this study, 144 consecutive percutaneous liver biopsies performed with a 1.6 mm Menghini needle, during a 2-year period were reviewed. All the children were aged under 15 years, 57 patients less than 1 year and 87 more than 1 year. All biopsies were adequate and the mean number of portal tracts examined was 17.6 per biopsy (14.3 in patients weighing less than 10 kg and 19.1 in the others). There were no deaths and we observed only bleeding complications. In patients with normal coagulation (128 cases), 1 bleeding requiring transfusion occurred; and in patients with abnormal coagulation (16 cases), we observed 2 bleeding cases requiring transfusion.ConclusionPercutaneous liver biopsy can be performed with 1.6 mm needles in children. For increased safety, ultrasound-guided biopsies are recommended.

High thiopurine metabolite concentrations associated with lymphopenia in inflammatory bowel disease (IBD) pediatric patients receiving aminosalicylates combined with azathioprine.

OBJECTIVE Aminosalicylates are widely used with azathioprine in the treatment of IBD. The association results in an increase in 6-TGN levels in adults with IBD with a difference in the occurrence of myelotoxic effects. Scarce data are available in pediatric population. We proposed to investigate the effect of the coadministration of aminosalicylates on thiopurine concentrations in pediatric IBD patients. MATERIALS AND METHODS Data from 71 patients treated for at least 1 y by azathioprine and aminosalicylates were recorded. 6-TGN and 6-MeMPN concentrations, blood cell counts and liver function tests were compared between patients taking and those not taking aminosalicylates. RESULTS Aminosalicylate therapy was associated with a significant increase in mean 6-TGN but also 6-MeMPN concentrations. In patients in remission, 6-TGN level was related to aminosalicylate dosage (r = 0.561, p = 0.010). Lymphopenia rate was higher in patients receiving combined therapy compared to monotherapy whereas a slight rise in leucopenia was found. CONCLUSIONS This observation suggests that the higher frequency of lymphopenia may be associated with the elevated 6-TGN concentrations recovered in patients treated with aminosalicylates. This combination does not improve remission rate but could increase adverse effects especially lymphopenia.

La gastrite collagène, une cause rare d’anémie chez l’enfant. À propos de deux cas

When a child presents a severe anemia or resistant to iron supplementation, an upper gastrointestinal endoscopy has to be realized to find special causes. Case reports. – We report observations of two patients, respectively 11 and 12 years old, who were admitted to hospital for a severe microcytic, hypochromic, aregenerative anemia (hemoglobin less than 50 g/L) due to an iron deficiency. The two children’s history did not reveal a deficient diet, gastrointestinal tract disorder, ingested toxic or gastrotoxic drugs, or exteriorized hemorrhage. Upper gastrointestinal endoscopy showed a macroscopic pattern of gastritis. The stomach biopsies revealed subepithelial collagenous deposits. Conclusion. – The collagenous gastritis involves lesions similar to those described in the small intestine (collagenous sprue) and colon (collagenous colitis). The pathogenic factors of the three entities are presently unknown, but they are often associated with autoimmune pathology. These two observations are the third and the fourth pediatric cases described.

Wilson disease in offspring of affected patients: Report of four French families

BACKGROUND Wilson disease (WD) is an autosomal recessive genetic disorder caused by mutations in the ATP7B gene resulting in toxic accumulation of copper mainly in the liver and brain. Early treatment may prevent irreversible tissue damage. AIM We report on four families with an occurrence of WD in two consecutive generations in order to highlight the need for screening offspring of affected parents. RESULTS In all families, one parent was known to be affected with WD. Screening for the disease was not performed in children from two families until occurrence of liver disease in one and of neurological symptoms in the other. In two other families, screening of children as soon as diagnosis was performed in the affected parent allowed a timely rescue of advanced liver disease in one while two affected children were asymptomatic. In three children, diagnosis required direct sequencing of the ATP7B gene. Two novel disease-causing mutations are reported. CONCLUSION Patients with WD should be offered genetic counselling when considering pregnancy and offspring should always be screened for the disease. Diagnostic difficulties based on copper disturbances in asymptomatic children that are obligate carriers of the Wilson gene and the usefulness of molecular diagnosis are discussed.

Les corps étrangers ingérés

l’estomac car,en 1 heure,des degâts muqueux peuventapparaitre;en 2 a 4 heures,des degâts musculaires;en8 a 12 heures,une perforation. Leur extraction est simi-laire a celle des objets ronds mais peut,plus rarement,etre realisee de facon electromagnetique. Une fois dansl’estomac,les piles s’eliminent le plus souvent spontane-ment [4-6].

Prise en charge des enfants après ingestion de substances acides ou alcalines

In children, caustic ingestion is due to accidents at home and inadequate storage of caustic agents. In emergency, it is useful to remove the soiled clothes, rinse the affected area, and prevent vomiting and feeding. Caustic ingestion (pH<2 or>12) induces burns of the upper gastrointestinal tract requiring esophagogastro-duodenoscopy between H12 and H24. Strong alkalis cause necrosis with liquefaction of the esophagus, penetrating deeply with a high-risk of perforation. Management of these children requires a specialized care center with an intensive care unit, endoscopic equipment, and a surgical team. Esophageal stricture is the main complication; no prophylactic treatment (steroids) is effective. Strictures occur after the 3rd week, and barium swallow should be performed by the end of the 1st month. Stricture are often multiple, long, and tortuous; endoscopic dilatation is difficult with a high-rate of perforation and a low-rate of success. In situ application of mitomycin C or injection of triamcinolone could reduce the recurrence rate of stricture. In recalcitrant or recurrent strictures, it is recommended to perform an esophageal replacement using a colonic interposition or a gastric tube. Endoscopy should also be performed 15-20years after caustic ingestion to screen for early neoplastic lesions. Prevention is very important for avoiding caustic ingestions. Information and education should be given specifically to the parents of toddlers; caustic products should be stored out of reach of children and they should not be kept with food.

Mosaic 18q21.2 deletions including the TCF4 gene: a clinical report.

Pitt–Hopkins syndrome (PTHS) is characterized by distinctive facial dysmorphism, profound intellectual disability, and the possible occurrence of epilepsy and breathing anomalies. It is caused by haploinsufficiency of the TCF4 gene. No significant difference in clinical severity has been reported to date between PTHS patients carrying 18q21 deletions including the TCF4 gene, and those harboring TCF4 point mutations, suggesting a lack of genotype/phenotype correlation. Moreover, the size of 18q21 deletions including the TCF4 gene does not appear to have a significant effect on the phenotypic severity, suggesting that TCF4 haploinsufficiency is the most important prognostic factor in 18q deletions. We describe two unrelated patients presenting with clinical features reminiscent of PTHS and carrying mosaic interstitial 18q21 deletions characterized by array comparative genomic hybridization. One of the patients presented the lowest level of mosaic 18q21 deletion reported to date (5–10%). Our report and a review of the literature show that the mosaic status does not appear to have a significant effect on the clinical severity of 18q21 deletions, which are associated with a poor neurological outcome, whereas a mosaic TCF4 point mutation can result in a significantly milder phenotype. Malformations of internal organs are currently considered to be rare in PTHS. The patients described here had visceral anomalies, suggesting that a full morphological assessment, including heart and abdominal ultrasound scans, should be performed systematically in PTHS patients.

Transient Hyperphosphatasemia after Liver Transplantation in Infancy

Marked increase of alkaline phosphatase (AP) value in an infant after liver transplantation (LT) can suggest liver or bone disease. Lake of recognition of transient hyperphosphatasemia in infancy (THI) can be followed by intensive and unnecessary investigation.