Skip to main content

Advertisement

SpringerLink
Log in

Cholestase-assoziierte Lebererkrankungen im Neugeborenen- und Säuglingsalter

Cholestasis-associated hepatopathies in neonates and infants

  • Schwerpunkt: Leberpathologie
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Cholestasen im Neugeborenen- und Säuglingsalter stellen Pädiater und Pathologen nicht selten vor diagnostische Probleme. Eine Besonderheit der Neugeborenenleber besteht in ihrer Eigenschaft, auf unterschiedliche kausalgenetische Faktoren mit einem unspezifischen Reaktionsmuster unter dem Bild der so genannten neonatalen Hepatitis in Erscheinung zu treten. Eine differenzialdiagnostische Abgrenzung der verschiedenen Krankheitsbilder ist histologisch bei Beachtung spezieller morphologischer Teilkomponenten durchaus möglich. So manifestieren sich extrahepatische Gallenabflussstörungen wie Atresien oder Stenosen des Ductus hepaticus bzw. Choledochuszysten zudem mit portalen Gallengangsproliferaten einschließlich Gallenretentionszeichen. Bei einem Alagille-Syndrom (Syn.: arteriohepatische Dysplasie) hingegen ist der Nachweis eines interlobulären Gallengangsmangels ein wichtiges, differenzialdiagnostisches Merkmal. Stoffwechseldefekte, wie die Fruktoseintoleranz und die Galaktosämie, sind zusätzlich mit einer Leberzellverfettung vergesellschaftet. Die Kenntnis des klinischen Verlaufs, der laborchemischen und bildgebenden Daten sind in der Zusammenschau mit dem morphologischen Befund für die definitive Diagnosestellung erforderlich und setzen eine enge Kooperation zwischen Pädiater und Pathologen voraus.

Abstract

Cholestasis in neonates and infants frequently confronts pediatricians and pathologists with diagnostic problems. A specific feature of the liver in neonates is the ability to react to different causative factors with a non-specific hepatitis-like picture, the so-called neonatal hepatitis. A diagnostic discrimination of the various diseases is histologically only possible with close attention to typical morphologic features. Thus, extrahepatic biliary obstructions, such as atresia or stenosis of the hepatic duct or choledochal cysts present with portal bile duct proliferation and signs of bile retention in the neoducts. In Alagille syndrome (arteriohepatic dysplasia), however, paucity of intrahepatic bile ducts is an important diagnostic feature. Metabolic disorders, such as fructosemia and galactosemia are additionally associated with steatosis. Knowledge of the clinical course and laboratory and imaging data are necessary to make the definitive diagnosis in synopsis with the morphologic findings and requires a close co-operation between the pediatrician and the pathologist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5

Literatur

  1. Angulo P, Lindor KD (1999) Primary sclerosing cholangitis. Hepatology 30: 325–332

    Article  PubMed  CAS  Google Scholar 

  2. Azar G, Beneck D, Lane B et al. (2002) Atypical morphologic presentation of biliary atresia and value of serial liver biopsies. J Pediatr Gastroenterol Nutr 34: 212–215

    Article  PubMed  Google Scholar 

  3. Bates MD, Bucuvales JC, Alonso W et al. (1998) Biliary atresia: Pathogenesis and treatment. Semin Liver Dis 18: 281–293

    Article  PubMed  CAS  Google Scholar 

  4. Bar Meir M, Hadas-Halperin J, Fisher D et al. (2000) Neonatal sclerosing cholangitis associated with autoimmune phenomena. J Pediatr Gastroenterol Nutr 30: 332–334

    Article  Google Scholar 

  5. Brown HL, Abernathy MP (1998) Cytomegalovirus infection. Semin Perinatol 22: 260–266

    Article  PubMed  CAS  Google Scholar 

  6. Colombo C, Crosignani A, Batezzati PM (1999) Liver involvement in cystic fibrosis. J Hepatol 31: 946–954

    Article  PubMed  CAS  Google Scholar 

  7. Demers SI, Russo P, Lettre F et al. (2003) Frequent mutation reversion in a severe liver disease, hereditary tyrosinemia, inversely correlates with clinical severity. Hum Pathol 34: 1313–1320

    Article  PubMed  CAS  Google Scholar 

  8. Deutsch GH, Sokol RJ, Stathos TH et al. (2001) Proliferation to paucity: evolution of bile duct abnormalities in a case of Alagille syndrome. Pediatr Dev Pathol 4: 559–563

    Article  PubMed  CAS  Google Scholar 

  9. Dimmick JE, Applegarth DA (1993) Pathology of peroxisomal disorders. Perspect Pediatr Pathol 17: 45–98

    PubMed  CAS  Google Scholar 

  10. Drut R, Drut RM, Gomez MA et al. (1998) Presence of human papilloma virus in EBA. J Pediatr Gastroenterol Nutr 27: 530–535

    Article  PubMed  CAS  Google Scholar 

  11. Dufour JF, Pratt DS (2001) Alagille syndrome with colonic polyposis. Am J Gastorenterol 96: 2727–2777

    Google Scholar 

  12. Emmerick KM, Rand EB, Goldmuntz E et al. (1999) Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology 29: 431–437

    Article  Google Scholar 

  13. Flynn DM, Nijjar S, Hubscher SG et al. (2004) The role of Notch receptor expression in bile duct development and disease. J Pathol 204: 55–64

    Article  PubMed  CAS  Google Scholar 

  14. Guarner J, Greer PW, Barlett J et al. (1999) Congenital syphilis in a newborn: an immunopathologic study. Mod Pathol 12: 82–87

    PubMed  CAS  Google Scholar 

  15. Ishak KG (2002) Inherited metabolic diseases of the liver. Clin Liver Dis 6: 455–479

    Article  PubMed  Google Scholar 

  16. Ishak K, Sharp H, Schwarzenberg S (2002) Metabolic errors and liver disease. In: MacSween RNM, Burt AD, Portmann BC et al. (eds) Pathology of the liver. Churchill-Livingstone, London, p 194

  17. Jacquemin E (2000) Progressive familial intrahepatic Cholestasis: genetic basis and treatment. Clin Liver Dis 4: 753–763

    Article  PubMed  CAS  Google Scholar 

  18. Jansen PL, Muller M (2000) The molecular genetics of familial intrahepatic cholestasis. Gut 47: 1–5

    Article  PubMed  CAS  Google Scholar 

  19. Karrev FM, Hall RJ, Lilly JR (1991) Biliary atresia and the polysplenia syndrome. J Pediatr Surg 26: 524–527

    Article  Google Scholar 

  20. Kelly AL, Lunt PW, Rodrigues F et al. (2001) Classification and genetic features of neonatal hemochromatosis: a study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism. J Med Genet 38: 599–610

    Article  PubMed  CAS  Google Scholar 

  21. Kelley RJ, Raymond GV, Watkins PA (2004) Zellweger syndrome and other disorders of peroxisomal metabolism. In: Walker AM, Goulet OJ, Kleinman RE et al. (eds) Pediatric gastrointestinal disease. Decker BC, Hamilton, pp 1401–1428

  22. Libbrecht L, Spinner NB, Moore EC et al. (2005) Peripheral bile duct paucity and cholestasis in the liver of a patient with Alagille syndrome: further evidence supporting a lack of postnatal bile duct branching and elongation. Am J Surg Pathol 29: 820−826

    Article  PubMed  Google Scholar 

  23. Liu C, Chiu JH, Chin T et al. (2000) Expression of fas Ligand on bile ductule epithelium in biliary atresia – a poor prognostic factor. J Pediatr Surg 35: 1591–1596

    Article  PubMed  CAS  Google Scholar 

  24. Lynfield R, Guerina NG (1997) Toxoplasmosis. Pediatr Rev 18: 75–83

    Article  PubMed  CAS  Google Scholar 

  25. McKiernan PJ, Baker AJ, Kelly DA (2000) The frequency and outcome of biliary atresia in the UK and Ireland. Lancet 355: 25–29

    Article  PubMed  CAS  Google Scholar 

  26. Piccoli DA, Spinner NB (2001) Alagille sindrome and the Jagged 1 gene. Semin Liver Dis 21: 525–534

    Article  PubMed  CAS  Google Scholar 

  27. Raweily EA, Gibson AA, Burt AD (1990) Abnormalities of intrahepatic bile ducts in extrahepatic biliary atresia. Histopathology 17: 521–527

    Article  PubMed  CAS  Google Scholar 

  28. Riepenhoff-Talty M, Gouvea V, Evans MJ et al. (1996) Detection of group C rotavirus in infants with extrahepatic atresia. J Infect Dis 174: 8–15

    PubMed  CAS  Google Scholar 

  29. Russo PA, Mitchel GA, Tanguay RM (2001) Tyrosinemia: a review. Pediatr Dev Pathol 4: 212–221

    Article  PubMed  CAS  Google Scholar 

  30. Russo P, Rand E, Haber BA (2004) Diseases of the biliary tree in infancy and childhood. In: Russo P, Ruchelli E, Piccoli D (eds) Pathology of pediatric and liver disease. Springer, New York, pp 203–236

  31. Russo P, Loomes KM (2004) Diseases of the biliary tree in infancy and childhood. Part B: Disease of the intrahepatic biliary tree-paucity of intrahepatic bile ducts. In: Russo P, Ruchelli E, Piccoli D (eds) Pathology of pediatric gastrointestinal and liver disease. Springer, New York, pp 220–228

  32. Schreiber RA, Kleinman RE (2002) Biliary atresia. J Pediatr Gastroenterol Nutr (Suppl 1) 35: S11–S16

    Article  Google Scholar 

  33. Silver MM, Valberg LS, Cutz E et al. (1993) Hepatic morphology and iron quantitation in perinatal hemochromatosis. Comparison with a large perinatal control population, including cases with chronic liver disease. Am J Pathol 143: 1312–1325

    PubMed  CAS  Google Scholar 

  34. Tatekawa Y, Asonuma K, Remoto S et al. (2001) Liver transplantation for biliary atresia associated with malignant hepatic tumors. J Pediatr Surg 36: 436–439

    Article  PubMed  CAS  Google Scholar 

  35. Trauner M, Fickert P, Wagner M (2007) MDR 3 (ABCB4) defects: a paradigm for the genetics of adult cholestastic syndromes. Semin Liver Dis 27: 77–98

    Article  PubMed  CAS  Google Scholar 

  36. Tyler KL, Sokol RY, Oberhaus SM et al. (1998) Detection of reovirus RNA in choledochal cysts. Hepatology 27: 1475–1482

    Article  PubMed  CAS  Google Scholar 

Download references

Danksagung

Für die Herstellung der Schnittpräparate und Färbungen danken wir Frau Susanne Steiner, für die Hilfe bei der Bildbearbeitung danken wir Herrn Gerrit Klemm und seinen Mitarbeiterinnen und Mitarbeitern.

Interessenkonflikt

Die korrespondierende Autorin gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Institut für Pathologie der Universität Bonn , Sigmund-Freud-Straße 25, 53127, Bonn, Deutschland

    G. Knöpfle, A. Adam & H.-P. Fischer

Authors
  1. G. Knöpfle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Adam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H.-P. Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Knöpfle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knöpfle, G., Adam, A. & Fischer, HP. Cholestase-assoziierte Lebererkrankungen im Neugeborenen- und Säuglingsalter. Pathologe 29, 61–72 (2008). https://doi.org/10.1007/s00292-007-0955-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-007-0955-1

Schlüsselwörter

Keywords

Search

Navigation