Skip to main content

Les cholestases néonatales

Neonatal cholestasis

Résumé

Tout ictère néonatal persistant au-delà de deux semaines de vie impose un diagnostic étiologique urgent, avec un premier bilan comportant au minimum un examen de la couleur des selles, et un dosage de la bilirubine totale et conjuguée. En cas de cholestase néonatale (CN) confirmée, l’hypovitaminose K doit être systématiquement prévenue par l’injection de vitamine K1, et l’enfant doit être adressé rapidement dans un centre spécialisé. L’atrésie des voies biliaires (AVB) est la première cause de CN. Son diagnostic est urgent, car les chances de succès du traitement conservateur du foie natif (intervention de Kasai ou ses variantes) décroissent rapidement avec l’âge de l’enfant. Une échographie hépatique normale n’exclut pas une AVB. Le diagnostic peut souvent être suspecté avant l’intervention et sera confirmé par les constatations opératoires complétées si nécessaire par une cholangiographie. En cas d’échec de rétablissement du flux biliaire après l’intervention de Kasai, la cirrhose biliaire continue de progresser et conduit à la transplantation hépatique, souvent dans les premières années de vie. Les autres causes de cholestases obstructives sont la lithiase de la voie biliaire principale (VBP), le kyste du cholédoque et la perforation spontanée des voies biliaires. Là encore, la levée de l’obstacle biliaire (par chirurgie ou radiologie interventionnelle) est urgente, afin d’éviter l’évolution vers la fibrose hépatique et la cirrhose, très rapide dans les premiers mois de vie. Les principales étiologies médicales de CN sont: le syndrome d’Alagille, le déficit en alpha-1-antitrypsine, les cholestases familiales fibrogènes et la mucoviscidose. Les autres causes médicales de CN sont multiples, certaines pouvant nécessiter un traitement spécifique: infectieuses, endocriniennes, nutritionnelles, métaboliques ou maladies de surcharge.

Abstract

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.

This is a preview of subscription content, access via your institution.

Références

  1. 1.

    Chardot C (2006) Biliary atresia. Orphanet J Rare Dis 1:28

    Article  PubMed  Google Scholar 

  2. 2.

    Chardot C, Carton M, Spire-Bendelac N, et al (1999) Epidemiology of biliary atresia in France: a national study 1986–1996. J Hepatol 31(6):1006–1013

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Debray D, Bernard O, Gauthier F (2009) Pediatric liver transplantation. Presse Med 38(9):1299–1306

    Article  PubMed  Google Scholar 

  4. 4.

    Jacquemin E, Cresteil D, Raynaud N, Hadchouel M (2002) CFCI gene mutation and biliary atresia with polysplenia syndrome. J Pediatr Gastroenterol Nutr 34(3):326–327

    PubMed  Google Scholar 

  5. 5.

    Hasegawa T, Sasaki T, Kimura T, et al (2002) Prenatal ultrasonographic appearance of type IIId (uncorrectable type with cystic dilatation) biliary atresia. Pediatr Surg Int 18(5–6):425–428

    CAS  PubMed  Google Scholar 

  6. 6.

    Debray D, Pariente D, Urvoas E, et al (1994) Sclerosing cholangitis in children. J Pediatr 124(1):49–56

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Hadj-Rabia S, Baala L, Vabres P, et al (2004) Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology 127(5):1386–1390

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Debray D, Pariente D, Gauthier F, et al (1993) Cholelithiasis in infancy: a study of 40 cases. J Pediatr 122(3):385–391

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Pariente D, Franchi-Abella S (2009) Cystic biliary atresia is different from choledochal cyst. Pediatr Radiol 39(9):1019

    Article  PubMed  Google Scholar 

  10. 10.

    Schroeder D, Smith L, Prain HC (1989) Antenatal diagnosis of choledochal cyst at 15 weeks’ gestation: etiologic implications and management. J Pediatr Surg 24(9):936–938

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Chardot C, Iskandarani F, De Dreuzy O, et al (1996) Spontaneous perforation of the biliary tract in infancy: a series of 11 cases. Eur J Pediatr Surg 6(6):341–346

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Crosnier C, Attié-Bitach T, Encha-Razavi F, et al (2000) Jagged1 gene expression during human embryogenesis elucidates the wide phenotypic spectrum of Alagille syndrome. Hepatology 32(3): 574–581

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Jung C, Driancourt C, Baussan C, et al (2007) Prenatal molecular diagnosis of inherited cholestatic diseases. J Pediatr Gastroenterol Nutr 44(4):453–458

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Fregonese L, Stolk J (2008) Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. Orphanet J Rare Dis 3:16

    Article  PubMed  Google Scholar 

  15. 15.

    Hadzic N, Francavilla R, Chambers SM, et al (2005) Outcome of PiSS and PiSZ alpha-1-antitrypsin deficiency presenting with liver involvement. Eur J Pediatr 164(4):250–252

    Article  PubMed  Google Scholar 

  16. 16.

    Lykavieris P, Ducot B, Lachaux A, et al (2008) Liver disease associated with ZZ alpha1-antitrypsin deficiency and ursodeoxycholic acid therapy in children. J Pediatr Gastroenterol Nutr 47(5):623–629

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Lykavieris P, Bernard O, Hadchouel M (1996) Neonatal cholestasis as the presenting feature in cystic fibrosis. Arch Dis Child 75(1):67–70

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Shapira R, Hadzic N, Francavilla R, et al (1999) Retrospective review of cystic fibrosis presenting as infantile liver disease. Arch Dis Child 81(2):125–128

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    van Mil SW, Houwen RH, Klomp LW (2005) Genetics of familial intrahepatic cholestasis syndromes. J Med Genet 42(6):449–463

    Article  PubMed  Google Scholar 

  20. 20.

    Heubi JE, Setchell KD, Bove KE (2007) Inborn errors of bile acid metabolism. Semin Liver Dis 27(3):282–294

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Lee WS, Sokol RJ (2007) Mitochondrial hepatopathies: advances in genetics and pathogenesis. Hepatology 45(6):1555–1565

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Fellman V, Lemmela S, Sajantila A, et al (2008) Screening of BCS1L mutations in severe neonatal disorders suspicious for mitochondrial cause. J Hum Genet 53(6):554–558

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Slama A, Giurgea I, Debrey D, et al (2005) Deoxyguanosine kinase mutations and combined deficiencies of the mitochondrial respiratory chain in patients with hepatic involvement. Mol Genet Metab 86(4):462–465

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Karnsakul W, Sawathiparnich P, Nimkarn S, et al (2007) Anterior pituitary hormone effects on hepatic functions in infants with congenital hypopituitarism. Ann Hepatol 6(2):97–103

    CAS  PubMed  Google Scholar 

  25. 25.

    Jacquemin E, Lykavieris P, Chaoui N, et al (1998) Transient neonatal cholestasis: origin and outcome. J Pediatr 133(4):563–567

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Hermeziu B, Sanlaville D, Girard M, et al (2006) Heterozygous bile salt export pump deficiency: a possible genetic predisposition to transient neonatal cholestasis. J Pediatr Gastroenterol Nutr 42(1):114–116

    Article  PubMed  Google Scholar 

  27. 27.

    Serinet MO, Wildhaber BE, Broue P, et al (2009) Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics 123(5):1280–1286

    Article  PubMed  Google Scholar 

  28. 28.

    Moyer V, Freese DK, Whitington PF, et al (2004) Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 39(2):115–128

    Article  PubMed  Google Scholar 

  29. 29.

    Bernard O (1995) Plaidoyer pour un diagnostic précoce de l’atrésie des voies biliaires. Douze erreurs à éviter. Arch Pediatr 2(10):937–939

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Jacquemin E (2007) Screening for biliary atresia and stool colour: method of colorimetric scale. Arch Pediatr 14(3):303–305

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Lee MS, Kim MJ, Lee MJ, et al (2009) Biliary atresia: color doppler US findings in neonates and infants. Radiology 252(1): 282–289

    Article  PubMed  Google Scholar 

  32. 32.

    Meyers RL, Book LS, O’Gorman MA, et al (2004) Percutaneous cholecysto-cholangiography in the diagnosis of obstructive jaundice in infants. J Pediatr Surg 39(1):16–18

    Article  PubMed  Google Scholar 

  33. 33.

    Shanmugam NP, Harrison PM, Devlin J, et al (2009) Selective use of endoscopic retrograde cholangiopancreatography in the diagnosis of biliary atresia in infants younger than 100 days. J Pediatr Gastroenterol Nutr 49(4):435–441

    Article  PubMed  Google Scholar 

  34. 34.

    Vegting IL, Tabbers MM, Taminiau JA, et al (2009) Is endoscopic retrograde cholangiopancreatography valuable and safe in children of all ages? J Pediatr Gastroenterol Nutr 48(1):66–71

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Chardot C (2009) Endoscopic retrograde cholangiopancreatography in patients with neonatal cholestasis: an additional diagnostic tool for selected indications. J Pediatr Gastroenterol Nutr 49(4): 380–381

    Article  PubMed  Google Scholar 

  36. 36.

    Chavhan GB, Babyn PS, Manson D, et al (2008) Pediatric MR cholangiopancreatography: principles, technique, and clinical applications. Radiographics 28(7):1951–1962

    Article  PubMed  Google Scholar 

  37. 37.

    Kremer AE, Beuers U, Oude-Elferink RP, et al (2008) Pathogenesis and treatment of pruritus in cholestasis. Drugs 68(15):2163–2182

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Mayo MJ, Handem I, Saldana S, et al (2007) Sertraline as a firstline treatment for cholestatic pruritus. Hepatology 45(3):666–674

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Jacquemin E, Hermans D, Myara A, et al (1997) Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology 25(3):519–523

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Colombo C, Battezzati PM, Podda M, et al (1996) Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis. Hepatology 23(6): 1484–1490

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Serinet MO, Broue P, Jacquemin E, et al (2006) Management of patients with biliary atresia in France: results of a decentralized policy 1986–2002. Hepatology 44(1):75–84

    Article  PubMed  Google Scholar 

  42. 42.

    Chardot C, Serinet MO (2006) Prognosis of biliary atresia: what can be further improved? J Pediatr 148(4):432–435

    Article  PubMed  Google Scholar 

  43. 43.

    Lykavieris P, Chardot C, Sokhn M, et al (2005) Outcome in adulthood of biliary atresia: a study of 63 patients who survived for over 20 years with their native liver. Hepatology 41(2):366–371

    Article  PubMed  Google Scholar 

  44. 44.

    Tsai MS, Lin WH, Hsu WM, et al (2008) Clinicopathological feature and surgical outcome of choledochal cyst in different age groups: the implication of surgical timing. J Gastrointest Surg 12(12):2191–2195

    Article  PubMed  Google Scholar 

  45. 45.

    Bourdeaux C, Darwish A, Jamart J, et al (2007) Living-related versus deceased donor pediatric liver transplantation: a multivariate analysis of technical and immunological complications in 235 recipients. Am J Transplant 7(2):440–447

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Vanier MT, Millat G (2003) Niemann-Pick disease type C. Clin Genet 64(4):269–281

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Wanders RJ (1999) Peroxisomal disorders: clinical, biochemical, and molecular aspects. Neurochem Res 24(4):565–580

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Barbier C, Devisme L, Dobbelaere D, et al (2002) Neonatal cholestasis and infantile Gaucher disease: a case report. Acta Paediatr 91(12):1399–1401

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Dubern B, Broue P, Dubuisson C, et al (2001) Orthotopic liver transplantation for mitochondrial respiratory chain disorders: a study of five children. Transplantation 71(5):633–637

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Nguyen TH, Ferry N (2007) Gene therapy for liver enzyme deficiencies: what have we learned from models for Crigler-Najjar and tyrosinemia? Expert Rev Gastroenterol Hepatol 1(1):155–171

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Smets F, Najimi M, Sokal EM (2008) Cell transplantation in the treatment of liver diseases. Pediatr Transplant 12(1):6–13

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Hsiao CH, Chang MH, Chen HL, et al (2008) Universal screening for biliary atresia using an infant stool color card in Taiwan. Hepatology 47(4):1233–1240

    Article  PubMed  Google Scholar 

  53. 53.

    Robinson DT, Ehrenkranz RA (2008) Parenteral nutritionassociated cholestasis in small for gestational age infants. J Pediatr 152(1):59–62

    Article  PubMed  Google Scholar 

  54. 54.

    Ohura T, Kobayashi K, Tazawa Y, et al (2007) Clinical pictures of 75 patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). J Inherit Metab Dis 30(2):139–144

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Gissen P, Tee L, Johnson CA, et al (2006) Clinical and molecular genetic features of ARC syndrome. Hum Genet 120(3):396–409

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Rossi M, Vajro P, Iorio R, et al (2005) Characterization of liver involvement in defects of cholesterol biosynthesis: long-term follow-up and review. Am J Med Genet A 132A(2):144–151

    Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding authors

Correspondence to D. Debray or C. Chardot.

About this article

Cite this article

Debray, D., Chardot, C. Les cholestases néonatales. Rev. med. perinat. 2, 188–196 (2010). https://doi.org/10.1007/s12611-010-0081-9

Download citation

Mots clés

  • Cholestase néonatale
  • Diagnostic
  • Traitement
  • Chirurgie
  • Pronostic

Keywords

  • Neonatal cholestasis
  • Diagnosis
  • Treatment
  • Surgery
  • Prognosis