Diagnosis and Therapy of Intrahepatic Cholestasis of Pregnancy

Zusammenfassung

Die intrahepatische Schwangerschaftscholestase (ISC) bezeichnet ein Syndrom, das durch Pruritus in der Spätschwangerschaft gekennzeichnet ist. Die Diagnose der ISC erfolgt durch Ausschluss pruritogener Hauterkrankungen und den Nachweis von erhöhten Gesamtgallensäuren-Serumkonzentrationen. Es gibt Hinweise auf eine genetische Prädisposition. Zahlreiche Studien haben den Stellenwert von Mutationen in bekannten Cholestase-Genen wie ABCB4 (auch MDR3 genannt), ABCB11 (BSEP) und ATP8B1 (FIC1) für die Entwicklung einer ISC untersucht. Die bisher vorliegenden Daten weisen auf eine heterogene Ätiologie des Syndroms hin. Die ISC scheint mit einem erhöhten Risiko von Früh- und Totgeburten des Kindes vergesellschaftet zu sein. Weiterhin kann die Symptomatik in Einzelfällen sehr stark sein und eine frühzeitige Entbindung mit den dazugehörigen Risiken für Mutter und Kind erzwingen. Schwangerschaften von Patientinnen mit ISC sind daher als Risikoschwangerschaften einzuschätzen. Therapien zur Verminderung des Pruritus oder der Cholestase durch Antihistaminika, Phenobarbital, Anionenaustauscher, Dexamethason und S-Adenosylmethionin sind nur begrenzt wirksam oder werden wegen ihrer Nebenwirkungen nur selten eingesetzt. Neuere kontrollierte Studien zeigen, dass Ursodeoxycholsäure (UDCA) einen positiven Effekt auf Juckreiz und laborchemische Veränderungen bei ISC hat. Die weitere Aufklärung der molekularen Ursachen der ISC wird in Zukunft eventuell zur gezielteren und wirkungsvolleren Therapie des Krankheitsbildes beitragen.

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is characterized by the occurrence of pruritus mostly in the third trimenon. Diagnosis is based on the presence of pruritus and elevated levels of serum bile acids in the absence of pruritic skin diseases. There is strong evidence of a genetic predisposition for ICP. Numerous studies have investigated the association of known cholestasis genes such as ABCB4 (also designated MDR3), ABCB11 (BSEP) and ATP8B1 (FIC1) with ICP. The results of these studies implicate a heterogeneous etiology of this syndrome. ICP increases the risk of preterm delivery and fetal loss. Furthermore, intense pruritus may necessitate premature induction of labor with its known higher frequency of complications for mother and child. Therefore, ICP pregnancies should be managed as high-risk pregnancies. Pharmaceuticals to alleviate pruritus or improve cholestasis like antihistamines, phenobarbital, anion exchange resins, dexamethasone or S-adenosylmethionine are not widely accepted because of questionable efficacy or side effects. Recent randomized studies have shown beneficial effects of ursodeoxycholic acid (UDCA) on laboratory data and pruritus in patients with ICP. Improved knowledge about the diagnostic classification of different types and pathophysiological mechanisms of ICP may allow for a more targeted treatment of this disease in future.

Intrahepatische Schwangerschaftscholestase - pruritogene Hauterkrankungen - Gallensäuren-Serumkonzentration - progressive familial intrahepatishe Cholestase - low-phospholipid-assoziierte Cholelithiasis - ABCB4 Gen - ABCB11 Gen - ATP8B1 Gen

Intrahepatic cholestasis of pregnancy - pruritus - serum bile acids - progressive familial intrahepatic cholestasis - low phospholipid-associated cholelithiasis - ABCB4 gene - ABCB11 gene - ATP8B1 gene

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