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DOI: 10.1055/a-1922-9264
Autoimmune Lebererkrankungen – ein Update (Teil 2)
Primär biliäre Cholangitis (PBC) und primär sklerosierende Cholangitis (PSC)Im 1. Teil der Reihe „Autoimmune Lebererkrankungen – ein Update (Teil 1)“ wurden die Grundlagen zur Diagnostik und Surveillance autoimmuner Lebererkrankungen und die autoimmune Hepatitis (AIH) behandelt [1]. In diesem 2. Teil werden mit der primär biliären Cholangitis (PBC) und der primär sklerosierenden Cholangitis (PSC) cholestatische autoimmune Lebererkrankungen beleuchtet.
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Zur Therapie der primär biliären Cholangitis (PBC) stehen Ursodesoxycholsäure (UDCA) mit einem guten Wirkungs-/
Nebenwirkungs-Profil, Obeticholsäure (OCA) sowie Bezafibrat (Off-Label-Use) zur Verfügung. -
Besondere Beachtung erfordern PBC-assoziierte Symptome wie Sicca-Symptomatik, Fatigue und Juckreiz. Letzterer lässt sich durch die Gabe von Bezafibrat adressieren.
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Eine effektive medikamentöse Therapie der primär sklerosierenden Cholangitis (PSC) steht nicht zur Verfügung. Das Management konzentriert sich daher
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erstens auf das Erkennen, Abklären und Behandeln hochgradiger und klinisch relevanter Gallengangstrikturen,
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zweitens auf die Durchführung von Vorsorgeuntersuchungen zur frühzeitigen Detektion hepatobiliärer und kolorektaler Tumoren.
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Bei Vorliegen einer relevanten Stenose (bildmorphologische Einengung auf mehr als 75% und Zeichen der Cholestase/Cholangitis) sollte bei der primär sklerosierenden Cholangitis eine endoskopische retrograde Cholangiopankreatikografie (ERCP) erwogen werden. Die Ballondilatation ist der Stenteinlage überlegen, weshalb auf Letztere, wenn möglich, verzichtet werden sollte. Falls eine Stenteinlage notwendig ist, sollte diese zeitlich limitiert bleiben.
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Insbesondere bei Patient*innen mit primär sklerosierender Cholangitis (PSC) sowie Patient*innen mit autoimmuner Hepatitis (AIH) und primär biliärer Cholangitis (PBC) mit unzureichendem Therapieansprechen sollte eine Anbindung an ein erfahrenes Zentrum erfolgen und der Einschluss in klinische Studien geprüft werden.
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Der MELD-Score (Model of End Stage Liver Disease) bildet den Schweregrad der primär sklerosierenden Cholangitis oft nur unzureichend ab. Eine Listung zur Lebertransplantation ist deshalb zusätzlich über Standard-Exception-Kriterien möglich (≥ 2 Cholangioseptitiden, Entwicklung einer dominanten Stenose, Reduktion ≥ 10% des Body-Mass-Indexes in 12 Monaten; 2 von 3 Kriterien müssen erfüllt sein).
Schlüsselwörter
primär biliäre Cholangitis - primär sklerosierende Cholangitis - hepatischer PruritusPublication History
Article published online:
11 October 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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Literatur
- 1 Steinmann S, Schregel I, Schramm C. Autoimmune Lebererkrankungen – ein Update (Teil 1). Autoimmune Hepatitis (AIH) und allgemeines Vorgehen bei immunvermittelten Lebererkrankungen. Gastroenterologie up2date 2022; 18: 225-241 DOI: 10.1055/a-1364-8489.
- 2 Sebode M, Kloppenburg A, Aigner A. et al. Population-based study of autoimmune hepatitis and primary biliary cholangitis in Germany: rising prevalences based on ICD codes, yet deficits in medical treatment. Z Gastroenterol 2020; 58: 431-438 DOI: 10.1055/a-1135-9306.
- 3 Gershwin ME, Selmi C, Worman HJ. et al. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients. Hepatology 2005; 42: 1194-1202 DOI: 10.1002/HEP.20907.
- 4 Lazaridis KN, Juran BD, Boe GM. et al. Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis. Hepatology 2007; 46: 785-792 DOI: 10.1002/HEP.21749.
- 5 Corpechot C, Chrétien Y, Chazouillères O. et al. Demographic, lifestyle, medical and familial factors associated with primary biliary cirrhosis. J Hepatol 2010; 53: 162-169 DOI: 10.1016/J.JHEP.2010.02.019.
- 6 Lindor KD, Gershwin ME, Poupon R. et al. Primary biliary cirrhosis. Hepatology 2009; 50: 291-308 DOI: 10.1002/HEP.22906.
- 7 Mattalia A, Quaranta S, Leung PS. et al. Characterization of antimitochondrial antibodies in health adults. Hepatology 1998; 27: 656-661 DOI: 10.1002/HEP.510270303.
- 8 Nakamura M, Kondo H, Mori T. et al. Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology 2007; 45: 118-127 DOI: 10.1002/HEP.21472.
- 9 Baldo DC, Dellavance A, Ferraz MLG. et al. Evolving liver inflammation in biochemically normal individuals with anti-mitochondria antibodies. Auto Immun Highlights 2019; 10: 10 DOI: 10.1186/S13317-019-0120-X.
- 10 Dahlqvist G, Gaouar F, Carrat F. et al. Large-scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis. Hepatology 2017; 65: 152-163 DOI: 10.1002/HEP.28859.
- 11 European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009; 51: 237-267 DOI: 10.1016/j.jhep.2009.04.009.
- 12 Kaps L, Grambihler A, Yemane B. et al. Symptom burden and treatment response in patients with primary biliary cholangitis (PBC). Dig Dis Sci 2020; 65: 3006-3013 DOI: 10.1007/s10620-019-06009-3.
- 13 Harms MH, De Veer RC, Lammers WJ. et al. Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis. Gut 2020; 69: 1502-1509 DOI: 10.1136/gutjnl-2019-319057.
- 14 Perez CFM, Harms MH, Lindor KD. et al. Goals of treatment for improved survival in primary biliary cholangitis: treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase. Off J Am Coll Gastroenterol ACG 2020; 115: 1066-1074 DOI: 10.14309/ajg.0000000000000557.
- 15 Carbone M, Mells GF, Pells G. et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology 2013; 144: 560-569.e7 DOI: 10.1053/J.GASTRO.2012.12.005.
- 16 Nevens F, Andreone P, Mazzella G. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med 2016; 375: 631-643 DOI: 10.1056/NEJMoa1509840.
- 17 Rote-Hand-Brief zu Ocaliva, 09.06.2022. Im Internet (Stand: 16.09.2022): https://www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/DE/RHB/2022/rhb-ocaliva.html
- 18 Corpechot C, Chazouillères O, Rousseau A. et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N Engl J Med 2018; 378: 2171-2181 DOI: 10.1056/NEJMoa1714519.
- 19 de Vries E, Bolier R, Goet J. et al. Fibrates for itch (FITCH) in fibrosing cholangiopathies: a double-blind, randomized, placebo-controlled trial. Gastroenterology 2021; 160: 734-743 DOI: 10.1053/j.gastro.2020.10.001.
- 20 European Association for the Study of the Liver. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77: 761-806 DOI: 10.1016/J.JHEP.2022.05.011.
- 21 Soret P-A, Lam L, Carrat F. et al. Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis. Aliment Pharmacol Ther 2021; 53: 1138-1146 DOI: 10.1111/apt.16336.
- 22 Strassburg CP, Beckebaum S, Geier A. et al. S2k Leitlinie Autoimmune Lebererkrankungen. AWMF-Reg. Nr. 021–27. Z Gastroenterol 2017; 55: 1135-1226 DOI: 10.1055/S-0043-120199.
- 23 European Association for the Study of the Liver. 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.
- 24 Mells GF, Pells G, Newton JL. et al. Impact of primary biliary cirrhosis on perceived quality of life: the UK-PBC national study. Hepatology 2013; 58: 273-283 DOI: 10.1002/HEP.26365.
- 25 White PD, Goldsmith KA, Johnson AL. et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823-836 DOI: 10.1016/S0140-6736(11)60096-2.
- 26 Boonstra K, Van Erpecum KJ, Van Nieuwkerk KMJ. et al. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis 2012; 18: 2270-2276 DOI: 10.1002/ibd.22938.
- 27 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.
- 28 Chapman MH, Thorburn D, Hirschfield GM. et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019; 68: 1356-1378 DOI: 10.1136/gutjnl-2018-317993.
- 29 Barberio B, Massimi D, Cazzagon N. et al. Prevalence of primary sclerosing cholangitis in patients with inflammatory bowel disease: a systematic review and meta-analysis. Gastroenterology 2021; 161: 1865-1877 DOI: 10.1053/J.GASTRO.2021.08.032.
- 30 Angulo P, Pearce DH, Johnson CD. et al. Magnetic resonance cholangiography in patients with biliary disease: its role in primary sclerosing cholangitis. J Hepatol 2000; 33: 520-527 DOI: 10.1034/J.1600-0641.2000.033004520.X.
- 31 European Association for the Study of the Liver. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol 2022; 76: 1151-1184 DOI: 10.1016/j.jhep.2021.09.003.
- 32 Sebode M, Weiler-Normann C, Liwinski T. et al. Autoantibodies in autoimmune liver disease-clinical and diagnostic relevance. Front Immunol 2018; 9: 609 DOI: 10.3389/FIMMU.2018.00609.
- 33 Hov JR, Boberg KM, Karlsen TH. Autoantibodies in primary sclerosing cholangitis. World J Gastroenterol 2008; 14: 3781-3791 DOI: 10.3748/WJG.14.3781.
- 34 Wunsch E, Norman GL, Milkiewicz M. et al. Anti-glycoprotein 2 (anti-GP2) IgA and anti-neutrophil cytoplasmic antibodies to serine proteinase 3 (PR3-ANCA): antibodies to predict severe disease, poor survival and cholangiocarcinoma in primary sclerosing cholangitis. Aliment Pharmacol Ther 2021; 53: 302 DOI: 10.1111/APT.16153.
- 35 Chapman R, Fevery J, Kalloo A. et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010; 51: 660-678 DOI: 10.1002/HEP.23294.
- 36 Björnsson E, Olsson R, Bergquist A. et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology 2008; 134: 975-980 DOI: 10.1053/J.GASTRO.2008.01.042.
- 37 Weismüller TJ, Strassburg CP, Trivedi PJ. 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.
- 38 Lynch KD, Chapman RW, Keshav S. et al. Effects of vedolizumab in patients with primary sclerosing cholangitis and inflammatory bowel diseases. Clin Gastroenterol Hepatol 2020; 18: 179 DOI: 10.1016/J.CGH.2019.05.013.
- 39 Lindor KD, Kowdley KV, Luketic VAC. et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009; 50: 808-814 DOI: 10.1002/HEP.23082.
- 40 Venkatesh SK, Welle CL, Miller FH. et al. Reporting standards for primary sclerosing cholangitis using MRI and MR cholangiopancreatography: guidelines from MR Working Group of the International Primary Sclerosing Cholangitis Study Group. Eur Radiol 2022; 32: 923-937 DOI: 10.1007/s00330-021-08147-7.
- 41 Schramm C, Eaton J, Ringe KI. et al. Recommendations on the use of magnetic resonance imaging in PSC-A position statement from the International PSC Study Group. Hepatology 2017; 66: 1675-1688 DOI: 10.1002/hep.29293.
- 42 Trivedi PJ, Crothers H, Mytton J. et al. Effects of primary sclerosing cholangitis on risks of cancer and death in people with inflammatory bowel disease, based on sex, race, and age. Gastroenterology 2020; 159: 915-928 DOI: 10.1053/j.gastro.2020.05.049.
- 43 Ali AH, Tabibian JH, Nasser-Ghodsi N. et al. Surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis. Hepatology 2018; 67: 2338-2351 DOI: 10.1002/hep.29730.
- 44 Bergquist A, Weismüller TJ, Levy C. et al. Impact on follow-up strategies in patients with primary sclerosing cholangitis. Liver Int 2022; DOI: 10.1111/liv.15286.
- 45 Villard C, Friis-Liby I, Nilsson E. et al. Population-based prospective surveillance of patients with primary sclerosing cholangitis (PSC) for early detection of cholangiocarcinoma. Hepatology 2021; 74 (Suppl.) 91A-92A DOI: 10.1002/hep.32187.
- 46 van Erp LW, Cunningham M, Narasimman M. et al. Risk of gallbladder cancer in patients with primary sclerosing cholangitis and radiographically detected gallbladder polyps. Liver Int 2020; 40: 382-392 DOI: 10.1111/liv.14326.
- 47 Said K, Glaumann H, Bergquist A. Gallbladder disease in patients with primary sclerosing cholangitis. J Hepatol 2008; 48: 598-605 DOI: 10.1016/j.jhep.2007.11.019.
- 48 Foley KG, Lahaye MJ, Thoeni RF. et al. Management and follow-up of gallbladder polyps: updated joint guidelines between the ESGAR, EAES, EFISDS and ESGE. Eur Radiol 2022; 32: 3358-3368 DOI: 10.1007/s00330-021-08384-w.
- 49 Rupp C, Bode KA, Chahoud F. et al. Risk factors and outcome in patients with primary sclerosing cholangitis with persistent biliary candidiasis. BMC Infect Dis 2014; 14: 562 DOI: 10.1186/S12879-014-0562-8.
- 50 Ponsioen CY, Arnelo U, Bergquist A. et al. No superiority of stents vs. balloon dilatation for dominant strictures in patients with primary sclerosing cholangitis. Gastroenterology 2018; 155: 752-759.e5 DOI: 10.1053/J.GASTRO.2018.05.034.
- 51 Peiseler M, Reiners D, Pinnschmidt HO. et al. Risk of endoscopic biliary interventions in primary sclerosing cholangitis is similar between patients with and without cirrhosis. PLoS One 2018; 13: e0202686 DOI: 10.1371/journal.pone.0202686.
- 52 Buescher G, Villard C, Bergquist A. et al. Percutaneous transhepatic cholangiodrainage in patients with PSC: a multicentre, retrospective analysis. Z Gastroenterol 2021; 59: e15 DOI: 10.1055/s-0040-1721982.
- 53 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; 68: 2170-2178 DOI: 10.1136/gutjnl-2018-316801.
- 54 Loftus EV, Harewood GC, Loftus CG. et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005; 54: 91-96 DOI: 10.1136/GUT.2004.046615.
- 55 Boonstra K, Weersma RK, van Erpecum KJ. et al. Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis. Hepatology 2013; 58: 2045-2055 DOI: 10.1002/HEP.26565.
- 56 Vesterhus M, Karlsen TH. Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities. J Gastroenterol 2020; 55: 588-614 DOI: 10.1007/s00535-020-01681-z.
- 57 Visseren T, Erler NS, Polak WG. et al. Recurrence of primary sclerosing cholangitis after liver transplantation – analysing the European Liver Transplant Registry and beyond. Transpl Int 2021; 34: 1455-1467 DOI: 10.1111/tri.13925.
- 58 Adam R, Karam V, Cailliez V. et al. 2018 Annual Report of the European Liver Transplant Registry (ELTR) – 50-year evolution of liver transplantation. Transpl Int 2018; 31: 1293-1317 DOI: 10.1111/tri.13358.
- 59 Weismuller 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.
- 60 Bundesärztekammer. Richtlinien zur Organtransplantation gem. § 16 TPG. Dtsch Arztebl Ausg A 2019; 116A: 1-19 DOI: 10.3238/arztebl.2019.rili_baek_OrgaWlOvLeberTx20190924.