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Primär sklerosierende Cholangitis

Von der Pathogenese zu zukünftigen Therapien

Primary sclerosing cholangitis

From pathogenesis to therapy

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Der Gastroenterologe Aims and scope

Zusammenfassung

Die primär sklerosierende Cholangitis (PSC) ist eine chronisch-progrediente cholestatische Lebererkrankung, die mit multifokalen Strikturen der großen und mittleren Gallenwege und einem hohen Risiko für biliäre und kolorektale Malignome einhergeht. Die Patienten erkranken meist bereits in jungem Alter und leiden in der Mehrzahl auch an einer chronisch-entzündlichen Darmerkrankung (CED). Die komplexe Pathogenese ist nicht vollständig geklärt. Im Zusammenspiel genetischer Prädisposition und bislang nicht identifizierter Umweltfaktoren wird vermutlich eine immunologische Fehlregulation ausgelöst. Hierbei migrieren im Darm aktivierte Lymphozyten mittels spezifischer fehlexprimierter Bindungsproteine über das Endothel der Lebersinusoide in die Leber. Dort kommt es zu einer überschießenden peribiliären Entzündungsreaktion und nachfolgender Fibrose. Veränderungen der Gallensäurehomöostase und/oder Insuffizienz der biliären Schutzmechanismen sind potenzielle pathogenetische Kofaktoren. Ursodesoxycholsäure in mittlerer Dosierung (13–23 mg/kgKG) wird häufig eingesetzt, ist aber bei insgesamt unzureichender Evidenz allenfalls bei Patienten mit biochemischem Ansprechen wirksam. Etablierte nichtkausale Therapien sind die endoskopische Dilatation der Gallengangstrikturen und die Lebertransplantation im Endstadium der Erkrankung. Neue medikamentöse Therapieansätze greifen entweder am primären immunologischen Geschehen an oder an den sekundären Mechanismen der Gallenwegschädigung durch Einfluss auf die Gallehomöostase oder den Fibrosierungsprozess.

Abstract

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease characterized by multi-focal bile duct strictures and a high risk of biliary and colorectal malignancies. Most patients are diagnosed at young age and the majority also suffers from inflammatory bowel disease (IBD). The complex pathogenesis is not completely understood. However, it is hypothesised that due to the interaction of genetic predisposition and so far unidentified environmental factors, an immunological dysregulation is triggered, which leads to the activation of lymphocytes in the bowel. The atypical expression of specific adhesion proteins facilitates these lymphocytes to migrate into the liver via the endothelium of the liver sinusoids. There they induce a peribiliary inflammatory reaction and subsequent fibrosis. Changes in bile acid homeostasis and/or insufficiency of biliary protective mechanisms are potential pathogenetic cofactors. Medium-dose ursodeoxycholic acid is widely used, but is effective probably in patients with biochemical response only. Established non-causal therapies include endoscopic dilation of bile duct strictures and liver transplantation for end-stage disease. New drug therapies focus either on the mentioned immunological mechanisms or on the secondary cascade of bile duct damage by affecting bile homeostasis or the fibrosis process.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland

    Tobias J. Weismüller &  Christian P. Strassburg

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  1. Tobias J. Weismüller
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Correspondence to Tobias J. Weismüller.

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C.P. Strassburg erhielt Vortragshonorare von Falk Pharma, Unterstützung für Fortbildungsveranstaltungen von Falk Pharma und Fujinon. T.J. Weismüller gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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C. Strassburg, Bonn

C. Trautwein, Aachen

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Weismüller, T.J., Strassburg, C.P. Primär sklerosierende Cholangitis. Gastroenterologe 13, 180–188 (2018). https://doi.org/10.1007/s11377-018-0250-0

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  • DOI: https://doi.org/10.1007/s11377-018-0250-0

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