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Z Gastroenterol 2016; 54(12): 1327-1333
DOI: 10.1055/s-0042-118388
Kasuistik
© Georg Thieme Verlag KG Stuttgart · New York

Intrahepatic cholestasis of pregnancy (ICP): case report and review of the literature

Intrahepatische Schwangerschaftscholestase (ICP): Kasuistik und Übersicht über die Literatur
V. Keitel
1   Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstr. 5, Düsseldorf, Germany
,
C. Dröge
1   Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstr. 5, Düsseldorf, Germany
,
S. Stepanow
2   Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-University, Universitätstr. 1, Düsseldorf, Germany
,
T. Fehm
3   Department of Obstetrics and Gynecology, Heinrich-Heine-University, Moorenstr. 5, Düsseldorf, Germany
,
E. Mayatepek
4   Department of General Pediatrics, Neonatalogy and Pediatric Cardiology, Heinrich-Heine-University, Moorenstr. 5, Düsseldorf, Germany
,
K. Köhrer
2   Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-University, Universitätstr. 1, Düsseldorf, Germany
,
D. Häussinger
1   Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstr. 5, Düsseldorf, Germany
› Author Affiliations
Further Information

Publication History

21 July 2016



Publication Date:
09 December 2016 (online)

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Abstract

Intrahepatic cholestasis of pregnancy (ICP) represents the most common pregnancy-related liver disease in women. Women frequently present in the third trimester with pruritus and elevated serum bile acid and/or alanine transaminase levels. Clinical symptoms quickly resolve after delivery; however, recurrence in subsequent pregnancies has to be expected. Intrahepatic cholestasis of pregnancy is associated with increased perinatal complications, such as premature delivery, meconium staining of the amniotic fluid, respiratory distress, low Apgar scores, and even stillbirth. The risk for the fetus is significantly increased with maternal serum bile acid levels above 40 µmol/L, which characterize severe ICP. An important factor for ICP development is a rise of gestational hormones leading to cholestasis in genetically predisposed women. Variants in the bile salt export pump (BSEP) and the multidrug resistance protein 3 (MDR3) are most often identified in ICP. Here, we give an overview of the current literature on ICP and present the case of a woman with recurrent severe ICP. A common BSEP polymorphism as well as a rare MDR3 mutation may underlie the development of ICP in our patient. She had a premature delivery with meconium staining of the amniotic fluid. The neonate showed signs of respiratory distress with a low Apgar score. This case emphasizes that women with severe ICP have an increased risk for perinatal complications. Furthermore, severe ICP was associated with a MDR3 mutation, which has already been described in adult patients with liver cirrhosis. Thus, ICP may unmask an underlying MDR3 defect, which may predispose to development of hepatobiliary diseases such as gallstone disease, liver fibrosis/cirrhosis, as well as hepatobiliary malignancies. Therefore, genetic testing should be considered in women with severe as well as early onset ICP. Furthermore, regular follow-up should be discussed for women with genetic variants.

Zusammenfassung

Die intrahepatische Schwangerschaftscholestase (ICP) ist die häufigste schwangerschaftsspezifische Lebererkrankung bei Frauen. ICP tritt üblicherweise im dritten Trimenon mit Pruritus und erhöhten Serumspiegeln für Gallensäuren und/oder Alanin-Aminotransferase auf. Die Symptome klingen zeitnah nach der Entbindung ab, ein Rezidiv in nachfolgenden Schwangerschaften ist jedoch zu erwarten. Die ICP ist mit einer erhöhten Wahrscheinlichkeit für perinatale Komplikationen, wie Frühgeburt, Mekonium im Fruchtwasser, Atemnot, niedrigem Apgar-Score bis hin zur Totgeburt assoziiert. Das Risiko für den Fetus steigt bei Serum-Gallensäurespiegeln der Mutter oberhalb von 40 µmol/L, welche eine schwere ICP ausmachen, signifikant an. Die Erhöhung der Schwangerschaftshormone hat einen erheblichen Einfluss auf die Entwicklung einer ICP, insbesondere bei Frauen mit genetischer Prädisposition. Besonders häufig sind Varianten in der Gallensalzexportpumpe BSEP und der Phospholipidfloppase MDR3. Mit der vorliegenden Arbeit geben wir einen Überblick über die aktuelle ICP-Literatur und berichten über eine Patientin mit wiederkehrender schwerer ICP. Der frühen Manifestation und der Schwere der ICP liegen bei dieser Patientin ein häufiger BSEP-Polymorphismus und eine seltene MDR3-Mutation zugrunde. Die Patientin hatte eine Frühgeburt sowie Mekonium im Fruchtwasser. Das Neugeborene zeigte Zeichen von Atemnot und einen niedrigen Apgar-Score. Dieser Fall verdeutlicht, dass bei Frauen mit schwerer ICP ein erhöhtes Risiko für perinatale Komplikationen besteht. Außerdem ist die vorliegende schwere ICP mit einer MDR3-Mutation assoziiert, die bereits bei erwachsenen Patienten mit Leberzirrhose nachgewiesen wurde. So kann durch das Auftreten einer ICP ein zugrundeliegender MDR3-Defekt identifiziert werden, welcher für die Entwicklung hepatobiliärer Erkrankungen wie Gallensteinleiden, Leberfibrose und -zirrhose oder hepatobiliären Tumoren prädisponieren kann. Daher sollte eine Genanalyse bei Frauen mit schwergradiger, frühmanifester ICP in Betracht gezogen werden. Zudem sollte für Frauen mit nachgewiesenen genetischen Varianten Verlaufsuntersuchungen zur Früherkennung ICP assoziierter Erkrankungen angeboten werden.

Schlüsselwörter

Cholestase - Schwangerschaft - Gallensäuren - MDR3 - BSEP - Polymorphismen

Key words

cholestasis - pregnancy - bile acids - MDR3 - BSEP - polymorphisms
 

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