Guidelines of the Czech Society of Hepatology for diagnosis and treatment of primary biliary cholangitis

Česká verze

Authors: T. Fejfar ¹; T. Vaňásek ¹; P. Hůlek ^1,2; L. Vítek ^3,4; S. Fraňková ⁵ ; R. Brůha ⁴
Authors place of work: II. interní gastroenterologická klinika LF UK a FN Hradec Králové ¹; Katedra interních oborů, LF OU a FNsP Ostrava ²; Ústav lékařské biochemie a laboratorní diagnostiky, 1. LF UK a VFN v Praze ³; IV. interní klinika – klinika gastroenterologie a hepatologie 1. LF UK a VFN v Praze ⁴; Klinika hepatogastroenterologie, Transplantcentrum, IKEM, Praha ⁵
Published in the journal: Gastroent Hepatol 2018; 72(2): 109-118
Category: Hepatologie: doporučené postupy
doi: https://doi.org/10.14735/amgh2018109

Primární biliární cholangitida je chronické autoimunní cholestatické onemocnění. Diagnóza je založena na nálezu cholestázy, průkazu specifických antimitochondriálních protilátek nebo typickém histologickém nálezu. Velká část nemocných je v době diagnózy asymptomatická. Pokud jsou symptomy přítomny, nejčastěji se objevuje pruritus a únava. Základní léčbou 1. linie je ursodeoxycholová kyselina. U nemocných, kteří na léčbu ursodeoxycholovou kyselinou neodpoví adekvátním ústupem cholestázy, zůstává prognóza nepříznivá. Pro tyto nemocné lze zvážit podání léčby 2. linie. Léčbu vyžadují i často přidružené symptomy nebo komplikace, jako je pruritus a kostní choroba. V pokročilých stadiích vyžadují léčbu komplikace asociované portální hypertenze. Ve stadiu jaterní cirhózy je nutno zvážit transplantaci jater.

Summary

Primary biliary cholangitis is a chronic cholestatic disease that is diagnosed based on cholestatic laboratory features, antimitochondrial antibody positivity, or a typical histological pattern. Most patients are asymptomatic at the time of diagnosis. Pruritus and fatigue are the most common symptoms in symptomatic patients. Ursodeoxycholic acid is the first-line therapy. If this fails, the prognosis is unfavorable and second-line therapy can be considered. The associated symptoms must be treated. In advanced disease, liver transplantation should be considered and the complication of portal hypertension must be treated.

Key words:
biliary cholangitis – primary – diagnosis – treatment

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

Zdroje

1. AASLD. A name change for PBC: cholangitis replacing cirrhosis. [online]. Dostupné z: http: // www.aasld.org/name-change-pbc-cholangitis-replacing-cirrhosis#sthash.hrd6kN6F.dpuf.

2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: the diag-nosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67 (1): 145–172. doi: 10.1016/j.jhep.2017.03.022.

3. Invernizzi P, Lleo A, Podda M. Interpreting serological tests in diagnosing autoimmune liver diseases. Semin Liver Dis 2007; 27 (2): 161–172.

4. Vergani D, Alvarez F, Bianchi FB et al. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol 2004; 41 (4): 677–683.

5. Ong J, Erdei E, Rubin RL et al. Mercury, autoimmunity, and environmental factors on cheyenne river sioux tribal lands. Autoimmune Dis 2014; 2014: 325461. doi: 10.1155/2014/325461.

6. 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 (1): 152–163. doi: 10.1002/hep.28859.

7. Hirschfield GM, Heathcote EJ. Antimitochondrial antibody-negative primary biliary cirrhosis. Clin Liver Dis 2008; 12 (2): 323–331. doi: 10.1016/j.cld.2008.02.003.

8. Kakuda Y, Harada K, Sawada-Kitamura S et al. Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems. Hum Pathol 2013; 44 (6): 1107–1117. doi: 10.1016/j.humpath.2012.09.017.

9. 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. doi: 10.1053/j.gastro.2012.12.005.

10. Mayo clinic. Mayo PBC model. [online]. Dostupné z: https: //www.mayoclinic.org/medical-professionals/model-end-stage-liver-disease/updated-natural-history-model-for-primary-biliary-cirrhosis.

11. Angulo P, Lindor KD, Therneau TM et al. Utilization of the Mayo risk score in patients with primary biliary cirrhosis receiving ursodeoxycholic acid. Liver 1999; 19 (2): 115–121.

12. Parés A, Caballería L, Rodés J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastroenterology 2006; 130 (3): 715–720.

13. Corpechot C, Abenavoli L, Rabahi N et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology 2008; 48 (3): 871–877. doi: 10.1002/hep.22428.

14. Kuiper EM, Hansen BE, de Vries RA et al. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology 2009; 136 (4): 1281–1287. doi: 10.1053/j.gastro.2009.01.003.

15. Kumagi T, Guindi M, Fischer SE et al. Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol 2010; 105 (10): 2186–2194. doi: 10.1038/ajg.2010.216.

16. Lammert C, Juran BD, Schlicht E et al. Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients. J Gastroenterol 2014; 49 (10): 1414–1420. doi: 10.1007/s00535-013-0903-1.

17. Corpechot C, Chazouillères O, Poupon R. Early primary biliary cirrhosis: biochemical response to treatment and prediction of long-term outcome. J Hepatol 2011; 55 (6): 1361–1367. doi: 10.1016/j.jhep.2011.02.031.

18. Azemoto N, Abe M, Murata Y et al. Early biochemical response to ursodeoxycholic acid predicts symptom development in patients with asymptomatic primary biliary cirrhosis. J Gastroenterol 2009; 44 (6): 630–634. doi: 10.1007/s00535-009-0051-9.

19. Azemoto N, Kumagi T, Abe M et al. Biochemical response to ursodeoxycholic acid predicts long-term outcome in Japanese patients with primary biliary cirrhosis. Hepatol Res 2011; 41 (4): 310–317. doi: 10.1111/j.1872-034X.2011.00782.x.

20. Momah N, Silveira MG, Jorgensen R et al. Optimizing biochemical markers as endpoints for clinical trials in primary biliary cirrhosis. Liver Int 2012; 32 (5): 790–795. doi: 10.1111/j.1478-3231.2011.02678.x.

21. Carbone M, Sharp SJ, Flack S et al. The UK-PBC risk scores: derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cirrhosis. Hepatology 2016; 63 (3): 930–950. doi: 10.1002/hep.28017.

22. Lammers WJ, Hirschfield GM, Corpechot C et al. Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy. Gastroenterology 2015; 149 (7): 1804–1812. doi: 10.1053/j.gastro.2015.07.061.

23. Beuers U, Trauner M, Jansen P et al. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J Hepatol 2015; 62 (1 Suppl): S25–S37. doi: 10.1016/j.jhep.2015.02.023.

24. Leuschner U, Fischer H, Kurtz W et al. Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial. Gastroenterology 1989; 97 (5): 1268–1274.

25. Juřica J. Ursodeoxycholová kyselina. Remedia 2016; 26 (6): 529–535.

26. Poupon RE, Lindor KD, Cauch-Dudek K et al. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 1997; 113 (3): 884–890.

27. Lindor KD, Dickson ER, Baldus WP et al. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology 1994; 106 (5): 1284–1290.

28. Corpechot C, Carrat F, Bonnand AM et al. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology 2000; 32 (6): 1196–1199.

29. Shi J, Wu C, Lin Y et al. Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2006; 101 (7): 1529–1538.

30. Lammers WJ, van Buuren HR, Hirschfield GM et al. Levels of alkaline phosphate and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow up study. Gastroenterology 2014; 147 (6): 1338–1349. doi: 10.1053/j.gastro.2014.08.029.

31. Hempfling W, Dilger K, Beuers U. Systematic review: ursodeoxycholic acid-adverse effects and drug interactions. Aliment Pharmacol Ther 2003; 18 (10): 963–972.

32. European Association for Study of Liver, Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63 (1): 237–264. doi: 10.1016/j.jhep.2015.04.006.

33. Poupon RE, Lindor KD, Cauch-Dudek K et al. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 1997; 113 (3): 884–890.

34. Hirschfield GM, Mason A, Luketic V et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology 2015; 148 (4): 751–761. doi: 10.1053/j.gastro.2014.12.005.

35. Nevens F, Andreone P, Mazzella G et al. POISE Study Group. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med 2016; 375 (7): 631–643. doi: 10.1056/NEJMoa1509840.

36. Kowdley KV, Luketic V, Chapman R et al. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis. Hepatology 2017. In press.

37. Samur S, Klebanoff M, Banken R et al. Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis. Hepatology 2017; 65 (3): 920–928. doi: 10.1002/hep.28932.

38. Arenas F, Hervias I, Uriz M et al. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest 2008; 118 (2): 695–709. doi: 10.1172/JCI33156.

39. Leuschner M, Maier KP, Schlichting J et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial. Gastroenterology 1999; 117 (4): 918–925.

40. Rautiainen H, Kärkkäinen P, Karvonen AL et al. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology 2005; 41 (4): 747–752.

41. Kanda T, Yokosuka O, Imazeki F et al. Bezafibrate treatment: a new medical approach for PBC patients? J Gastroenterol 2003; 38 (6): 573–578.

42. Hosonuma K, Sato K, Yamazaki Y et al. A prospective randomized controlled study of long-term combination therapy using ursodeoxycholic acid and bezafibrate in patients with primary biliary cirrhosis and dyslipidemia. Am J Gastroenterol 2015; 110 (3): 423–431. doi: 10.1038/ajg.2015.20.

43. Lens S, Leoz M, Nazal L et al. Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid. Liver Int 2014; 34 (2): 197–203. doi: 10.1111/liv.12290.

44. Grigorian AY, Mardini HE, Corpechot C et al. Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: a meta-analysis. Clin Res Hepatol Gastroenterol 2015; 39 (3): 296–306. doi: 10.1016/j.clinre.2015.02.011.

45. Matsuzaki Y, Tanaka N, Osuga T et al. Improvement of biliary enzyme levels and itching as a result of long-term administration of ursodeoxycholic acid in primary biliary cirrhosis. Am J Gastroenterol 1990; 85 (1): 15–23.

46. Bachs LP, Parés A, Elena M et al. Effects of long-term rifampicinadministration in primary biliary cirrhosis. Gastroenterology1992; 102 (6): 2077–2080.

47. Tandon P, Rowe BH, Vandermeer B et al. The efficacy and safety ofbile acid binding agents, opioid antagonists or rifampin in the treatment of cholestasis-associated pruritus. Am J Gastroenterol 2007; 102 (7): 1528–1536.

48. Khurana S, Singh P. Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials. Liver Int 2006; 26 (8): 943–948.

49. Wolfhagen FH, van Buuren HR, den Ouden JW et al. Cyclical etidronate in the prevention of bone loss in corticosteroid-treated primary biliary cirrhosis. A prospective, controlled pilot study. J Hepatol 1997; 26 (2): 325–330.

50. Zein CO, Jorgensen RA, Clarke B et al. Alendronate improves bone mineral density in primary biliary cirrhosis: a randomized placebo-controlled trial. Hepatology 2005; 42 (4): 762–771.

51. Bodingbauer M, Wekerle T, Pakrah B et al. Prophylactic bisphosphonates treatment prevents bone fractures after liver transplantation. Am J Transplant 2007; 7 (7): 1763–1769.

52. Misof BM, Bodingbauer M, Roschger P et al. Short-term effects of highdose zoledronic acid treatment on bone minera-lization density distribution after orthotopic liver transplantation. Calcif Tissue Int 2008; 83 (3): 167–175. doi: 10.1007/s00223-008-9161-2.

53. Trivedi PJ, Kumagi T, Al-Harthy N et al. Good maternal and fetal outcomes for pregnant women with primary biliary cirrhosis. Clin Gastroenterol Hepatol 2014; 12 (7): 1179–1185. doi: 10.1016/j.cgh.2013.11.030.

54. Kondrackiene J, Beuers U, Kupcinskas L. Efficacy and safety of ursodeoxycholicacid versus cholestyramine in intrahepatic cholestasis of pregnancy. Gastroenterology 2005; 129 (3): 894–901.

55. Geenes V, Chambers J, Khurana R et al. Rifampicin in the treatment of severe intrahepatic cholestasis of pregnancy. Eur J Obstet Gynecol Reprod Biol 2015; 189: 59–63. doi: 10.1016/j.ejogrb.2015.03.020.