Download PDF
Dtsch Med Wochenschr 2020; 145(05): 296-305
DOI: 10.1055/a-0944-8805
Dossier

Autoimmune cholestatische Lebererkrankungen

Autoimmune mediated cholestatic liver diseases
Lena Sophie Mayer
,
Rafael Käser
,
Tobias Böttler
› Further Information
Also available at
    Permissions and Reprints

Abstract

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are rare, autoimmune mediated cholestatic liver diseases. Other auto-immune diseases are often associated with PBC and PSC, and inflammatory bowel disease is present in the majority of PSC patients. In the course of disease, chronic inflammation in the liver leads to fibrotic restructuring and ultimately cirrhosis. The diagnosis of PBC is confirmed serologically and PSC is diagnosed via cholangiography, whereas MRCP is preferred over ERCP. For PBC, the first line therapy is ursodeoxycholic acid (UDCA). Prognosis is strongly dependent on the response to UDCA. The only approved second line therapy is obeticholic acid (OCA). Alternatively, Budesonide or Fibrates are often used off-label. In the management of PSC, prevention and adequate treatment of bacterial cholangitis play a major role. For both PBC and PSC novel treatments are currently being tested in clinical trials. Disease management should address compromising symptoms like pruritus and sicca as well as complications due to maldigestion and concomitant autoimmune diseases. The only curative treatment available is liver transplantation and should be considered at a MELD score of 15.

Die primär sklerosierende Cholangitis und die primär biliäre Cholangitis sind autoimmun vermittelte cholestatische Lebererkrankungen, die unbehandelt chronisch-progredient verlaufen und über Fibrosestadien zur Leberzirrhose führen. Dieser Beitrag gibt einen Überblick über das diagnostische Vorgehen, die häufigen Begleiterkrankungen, die im Behandlungskonzept zu berücksichtigen sind, und die aktuellen Therapieoptionen.

Schlüsselwörter

primär biliäre Cholangitis - primär sklerosierende Cholangitis - Cholestase - Ursodesoxycholsäure - Obeticholsäure

Key words

primary biliary cholangitis - primary sclerosing cholangitis - cholestasis - ursodeoxycholic acid - obeticholic acid


Publication History

Article published online:
02 March 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • Literatur

  • 1 Samant H, Manatsathit W, Dies D. et al Cholestatic liver diseases: An era of emerging therapies. World J Clin Cases 2019; 7: 1571-1581 . doi:10.12998/wjcc.v7.i13.1571
    PubMedGoogle Scholar
  • 2 Heathcote EJ. Diagnosis and management of cholestatic liver disease. Clin Gastroenterol Hepatol 2007; 5: 776-782 . doi:10.1016/j.cgh.2007.05.008
    CrossrefPubMedGoogle Scholar
  • 3 EASL Clinical Practice Guidelines. The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67: 145-172 . doi:10.1016/j.jhep.2017.03.022
    CrossrefPubMedGoogle Scholar
  • 4 Karlsen TH, Folseraas T, Thorburn D. et al Primary sclerosing cholangitis – a comprehensive review. J Hepatol 2017; 67: 1298-1323 . doi:10.1016/j.jhep.2017.07.022
    CrossrefPubMedGoogle Scholar
  • 5 Invernizzi P, Floreani A, Carbone M. et al Primary Biliary Cholangitis: advances in management and treatment of the disease. Dig Liver Dis 2017; 49: 841-846 . doi:10.1016/j.dld.2017.05.001
    CrossrefPubMedGoogle Scholar
  • 6 Marchioni Beery RM, Vaziri H, Forouhar F. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective. J Clin Transl Hepatol 2014; 2: 266-284 . doi:10.14218/JCTH.2014.00024
    PubMedGoogle Scholar
  • 7 Floreani A, Franceschet I, Cazzagon N. et al Extrahepatic autoimmune conditions associated with primary biliary cirrhosis. Clin Rev Allergy Immunol 2015; 48: 192-197 . doi:10.1007/s12016-014-8427-x
    CrossrefPubMedGoogle Scholar
  • 8 Hirschfield GM, Karlsen TH, Lindor KD. et al Primary sclerosing cholangitis. The Lancet 2013; 382: 1587-1599 . doi:10.1016/S0140-6736(13)60096-3
    CrossrefPubMedGoogle Scholar
  • 9 Agarwal K, Jones DE, Bassendine MF. Genetic susceptibility to primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999; 11: 603-606
    CrossrefPubMedGoogle Scholar
  • 10 Bowlus CL, Li C-S, Karlsen TH. et al Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: unique clinical and human leukocyte antigen associations. Liver Transpl 2010; 16: 1324-1330 . doi:10.1002/lt.22161
    CrossrefPubMedGoogle Scholar
  • 11 Giordano DM, Pinto C, Maroni L. et al Inflammation and the Gut-Liver Axis in the Pathophysiology of Cholangiopathies. Int J Mol Sci 2018; 19 DOI: 10.3390/ijms19103003.
    CrossrefPubMedGoogle Scholar
  • 12 Tomizawa M, Shinozaki F, Fugo K. et al Anti-mitochondrial M2 antibody-positive autoimmune hepatitis. Exp Ther Med 2015; 10: 1419-1422 . doi:10.3892/etm.2015.2694
    CrossrefPubMedGoogle Scholar
  • 13 EASL Clinical Practice Guidelines. management of cholestatic liver diseases. J Hepatol 2009; 51: 237-267 . doi:10.1016/j.jhep.2009.04.009
    CrossrefPubMedGoogle Scholar
  • 14 Lindor KD, Bowlus CL, Boyer J. et al Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology 2019; 69: 394-419 . doi:10.1002/hep.30145
    PubMedGoogle Scholar
  • 15 Selvaraj EA, Culver EL, Bungay H. et al Evolving role of magnetic resonance techniques in primary sclerosing cholangitis. World J Gastroenterol 2019; 25: 644-658 . doi:10.3748/wjg.v25.i6.644
    CrossrefPubMedGoogle Scholar
  • 16 Gidwaney NG, Pawa S, Das KM. Pathogenesis and clinical spectrum of primary sclerosing cholangitis. World J Gastroenterol 2017; 23: 2459-2469 . doi:10.3748/wjg.v23.i14.2459
    CrossrefPubMedGoogle Scholar
  • 17 Bonato G, Cristoferi L, Strazzabosco M. et al Malignancies in Primary Sclerosing Cholangitis--A Continuing Threat. Dig Dis 2015; 33: 140-148 . doi:10.1159/000440826
    CrossrefPubMedGoogle Scholar
  • 18 Ricciuto A, Kamath BM, Griffiths AM. The IBD and PSC Phenotypes of PSC-IBD. Curr Gastroenterol Rep 2018; 20: 16 . doi:10.1007/s11894-018-0620-2
    CrossrefPubMedGoogle Scholar
  • 19 Strassburg CP, Beckebaum S, Geier A. et al S2k-Leitlinie Autoimmune Lebererkrankungen. Z Gastroenterol 2017; 55: 1135-1226 . doi:10.1055/s-0043-120199
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology 2011; 54: 1842-1852 . doi:10.1002/hep.24570
    CrossrefPubMedGoogle Scholar
  • 21 Hirschfield GM, Dyson JK, Alexander GJM. et al The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut 2018; 67: 1568-1594 . doi:10.1136/gutjnl-2017-315259
    CrossrefPubMedGoogle Scholar
  • 22 Nevens F. PBC-transplantation and disease recurrence. Best Practice & Research Clinical Gastroenterology 2018; 34–35: 107-111 . doi:10.1016/j.bpg.2018.09.001
    PubMedGoogle Scholar
  • 23 Bahar R, Wong KA, Liu CH. et al Update on New Drugs and Those in Development for the Treatment of Primary Biliary Cholangitis. Gastroenterol Hepatol 2018; 14: 154-163
    PubMedGoogle Scholar
  • 24 Corpechot C. Primary Biliary Cirrhosis Beyond Ursodeoxycholic Acid. Semin Liver Dis 2016; 36: 15-26 . doi:10.1055/s-0035-1571273
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Corpechot C, Poupon R, Chazouillères O. New treatments/targets for primary biliary cholangitis. JHEP Reports 2019; 1: 203-213 . doi:10.1016/j.jhepr.2019.05.005
    CrossrefPubMedGoogle Scholar
  • 26 Rupp C, Hippchen T, Bruckner T. et al Effect of scheduled endoscopic dilatation of dominant strictures on outcome in patients with primary sclerosing cholangitis. Gut 2019; DOI: 10.1136/gutjnl-2018-316801.
    CrossrefPubMedGoogle Scholar
  • 27 Weismüller TJ, Trivedi PJ, Bergquist A. et al Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis. Gastroenterology 2017; 152: 1975-1984.e8 . doi:10.1053/j.gastro.2017.02.038
    CrossrefPubMedGoogle Scholar