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Primary Biliary Cholangitis: Updates in Management and Goals of Treatment

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Abstract

Purpose of Review

Primary biliary cholangitis (PBC) is a chronic autoimmune disease of the liver characterized by cholestasis and destruction of bile ducts. Goals of treatment include normalization of liver enzymes and prevention of progression to cirrhosis as well as symptom control. The purpose of this review is to summarize the current state of treatment of primary biliary cholangitis.

Recent Findings

In 2021, AASLD released a statement recommending fibrates as an off-label alternative for PBC patients with inadequate response or contraindications to approved therapies. Caution should be used when considering OCA in advanced liver disease. Multiple other therapies for PBC are in phase III trials including PPAR agonists and IBAT inhibitors.

Summary

There are two FDA-approved treatments for primary biliary cholangitis, ursodeoxycholic acid (UDCA) and obeticholic acid (OCA). Obeticholic acid is used when there is inadequate response to UDCA, and fibrates can also be considered as off-label alternatives in the setting of inadequate response to first-line therapy. Several other classes of drugs are in development for primary biliary cholangitis including multiple in phase III trials.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance 

  1. Trivella J, John BV, Levy C. Primary biliary cholangitis: epidemiology, prognosis, and treatment. Hepatol Commun. 2023;7(6):e0179. https://doi.org/10.1097/HC9.0000000000000179.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Current Medical Diagnosis & Treatment 2023 | AccessMedicine | McGraw Hill Medical. Accessed June 14, 2023. https://accessmedicine.mhmedical.com/book.aspx?bookID=3212

  3. Younossi ZM, Bernstein D, Shiffman ML, et al. Diagnosis and management of primary biliary cholangitis. Am J Gastroenterol. 2019;114(1):48–63. https://doi.org/10.1038/s41395-018-0390-3.

    Article  PubMed  Google Scholar 

  4. Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2018 practice guidance from the american association for the study of liver diseases. Hepatology. 2019;69(1):394. https://doi.org/10.1002/hep.30145.

    Article  PubMed  Google Scholar 

  5. Lu M, Zhou Y, Haller IV, et al. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment. Clin Gastroenterol Hepatol. 2018;16(8):1342–1350.e1. https://doi.org/10.1016/j.cgh.2017.12.033.

    Article  PubMed  Google Scholar 

  6. Danford CJ, Trivedi HD, Papamichael K, Tapper EB, Bonder A. Osteoporosis in primary biliary cholangitis. World J Gastroenterol. 2018;24(31):3513–20. https://doi.org/10.3748/wjg.v24.i31.3513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Seki A, Ikeda F, Miyatake H, et al. Risk of secondary osteoporosis due to lobular cholestasis in non-cirrhotic primary biliary cholangitis. J Gastroenterol Hepatol. 2017;32(9):1611–6. https://doi.org/10.1111/jgh.13746.

    Article  CAS  PubMed  Google Scholar 

  8. Chalifoux SL, Konyn PG, Choi G, Saab S. Extrahepatic manifestations of primary biliary cholangitis. Gut Liver. 2017;11(6):771–80. https://doi.org/10.5009/gnl16365.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Floreani A, Mangini C, Reig A, et al. Thyroid dysfunction in primary biliary cholangitis: a comparative study at two european centers. Am J Gastroenterol. 2017;112(1):114–9. https://doi.org/10.1038/ajg.2016.479.

    Article  PubMed  Google Scholar 

  10. Werner M, Prytz H, Ohlsson B, et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol. 2008;43(10):1232–40. https://doi.org/10.1080/00365520802130183.

    Article  PubMed  Google Scholar 

  11. Czaja AJ. Diagnosis and management of the overlap syndromes of autoimmune hepatitis. Can J Gastroenterol. 2013;27(7):417–23. https://doi.org/10.1155/2013/198070.

    Article  PubMed  PubMed Central  Google Scholar 

  12. • Poupon RE, Poupon R, Balkau B. Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group. N Engl J Med. 1994;330(19):1342–7. https://doi.org/10.1056/NEJM199405123301903. Landmark randomized-controlled trial showing decreased progression and need for transplant in PBC patients treated with UDCA.

    Article  CAS  PubMed  Google Scholar 

  13. Lee J, Belanger A, Doucette JT, Stanca C, Friedman S, Bach N. Transplantation trends in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007;5(11):1313–5. https://doi.org/10.1016/j.cgh.2007.07.015.

    Article  PubMed  Google Scholar 

  14. Murillo Perez CF, Harms MH, Lindor KD, van Buuren HR, Hirschfield GM, Corpechot C, 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. Am J Gastroenterol. 2020 Jul;115(7):1066–74. https://doi.org/10.14309/ajg.0000000000000557.

    Article  PubMed  Google Scholar 

  15. • Lammers WJ, van Buuren HR, Hirschfield GM, et al. Levels of alkaline phosphatase 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.e5; quiz e15. https://doi.org/10.1053/j.gastro.2014.08.029. Meta-analysis showing that ALP and bilirubin are surrogate disease markers and can be used to predict outcomes.

    Article  CAS  PubMed  Google Scholar 

  16. • Nevens F, Andreone P, Mazzella G, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 2016;375(7):631–43. https://doi.org/10.1056/NEJMoa1509840. Phase III trial showing benefit of OCA for inadequate responders to UDCA and those who cannot tolerate UDCA.

    Article  CAS  PubMed  Google Scholar 

  17. Jang H, Han N, Staatz CE, Kwak JH, Baek IH. Effect on lipid profile and clinical outcomes of obeticholic acid for the treatment of primary biliary cholangitis and metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2023;47(10):102227. https://doi.org/10.1016/j.clinre.2023.102227.

    Article  CAS  PubMed  Google Scholar 

  18. Eaton JE, Vuppalanchi R, Reddy R, Sathapathy S, Ali B, Kamath PS. Liver injury in patients with cholestatic liver disease treated with obeticholic acid. Hepatology. 2020;71(4):1511–4. https://doi.org/10.1002/hep.31017.

    Article  PubMed  Google Scholar 

  19. • Corpechot C, Chazouillères O, Rousseau A, et al. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis. N Engl J Med. 2018;378(23):2171–81. https://doi.org/10.1056/NEJMoa1714519. The BEZURSO trial; a landmark trial showing improved liver tests in poor-responders to UDCA with bezafibrate + UDCA versus placebo + UDCA.

    Article  CAS  PubMed  Google Scholar 

  20. • Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Hepatology. 2022;75(4):1012. https://doi.org/10.1002/hep.32117. AASLD Practice Guidance Update recommending fibrates as off-label therapy for non-responders to UDCA and includes warning against OCA use in advanced liver cirrhosis.

  21. Singh A, Fritze D, Mansouri M, et al. Characteristics and outcomes of liver transplantation for primary biliary cholangitis in young patients: analysis of the united network for organ sharing database. Transplantation. 2019;103(6):1191. https://doi.org/10.1097/TP.0000000000002501.

    Article  PubMed  Google Scholar 

  22. Corpechot C, Chazouillères O, Belnou P, et al. Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis. J Hepatol. 2020;73(3):559–65. https://doi.org/10.1016/j.jhep.2020.03.043.

    Article  CAS  PubMed  Google Scholar 

  23. Santiago P, Scheinberg AR, Levy C. Cholestatic liver diseases: new targets, new therapies. Therap Adv Gastroenterol. 2018;11:1756284818787400. https://doi.org/10.1177/1756284818787400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. • ENHANCE: safety and efficacy of seladelpar in patients with primary biliary cholangitis—a phase 3, international, randomized, placebo-controlled study. Gastroenterol Hepatol (N Y). 2021;17(2 Suppl 3):5–6. Ongoing phase III trial investigating PPAR agonist seladelpar for PBC.

  25. Bowlus CL, Galambos MR, Aspinall RJ, et al. A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis. J Hepatol. 2022;77(2):353–64. https://doi.org/10.1016/j.jhep.2022.02.033.

    Article  CAS  PubMed  Google Scholar 

  26. • Schattenberg JM, Pares A, Kowdley KV, et al. A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA. J Hepatol. 2021;74(6):1344–54. https://doi.org/10.1016/j.jhep.2021.01.013. Phase II trial for elafibrinor showing improvement in ALP and other secondary endpoints.

    Article  CAS  PubMed  Google Scholar 

  27. • Kowdley KV, Bowlus CL, Levy C, Akarca US, Alvares-da-Silva MR, Andreone P, et al. Efficacy and safety of elafibranor in primary biliary cholangitis. N Engl J Med. 2023; https://doi.org/10.1056/NEJMoa2306185. Phase 3 trial for elafibrinor showing improvement in ALP and other biochemical indicators.

  28. Kowdley KV, Minuk GY, Pagadala MR, Gulamhusein A, Swain MG, Neff GW, et al. The nonsteroidal farnesoid x receptor (FXR) agonist cilofexor improves liver biochemistry in patients with primary biliary cholangitis (PBC): A phase 2, randomized, placebo-controlled trial. Hepatology. 2019;70:31A–2A.

    Google Scholar 

  29. Galoosian A, Hanlon C, Zhang J, Holt EW, Yimam KK. Clinical updates in primary biliary cholangitis: trends, epidemiology, diagnostics, and new therapeutic approaches. J Clin Transl Hepatol. 2020;8(1):49–60. https://doi.org/10.14218/JCTH.2019.00049.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Invernizzi P, Carbone M, Jones D, et al. Setanaxib, a first-in-class selective NADPH oxidase 1/4 inhibitor for primary biliary cholangitis: A randomized, placebo-controlled, phase 2 trial. Liver Int. 2023;15. https://doi.org/10.1111/liv.15596.

  31. • Jones D, Carbone M, Invernizzi P, et al. Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial. Hepatol Commun. 2023;7(3):e0057. https://doi.org/10.1097/HC9.0000000000000057. In this post-hoc analysis, patients receiving setanaxib 400 twice a day compared to daily or placebo had improvements in all domains of the PBC-40 except itch.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Maralixibat: First Approval | SpringerLink. Accessed June 7, 2023. https://link.springer.com/article/10.1007/s40265-021-01649-0

  33. Odevixibat: First Approval | SpringerLink. Accessed June 7, 2023. https://link.springer.com/article/10.1007/s40265-021-01594-y

  34. Mayo MJ, Pockros PJ, Jones D, et al. A randomized, controlled, phase 2 study of maralixibat in the treatment of itching associated with primary biliary cholangitis. Hepatol Commun. 2019;3(3):365–81. https://doi.org/10.1002/hep4.1305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mirum Pharmaceuticals, Inc. A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Volixibat in the Treatment of Cholestatic Pruritus in Patients With Primary Biliary Cholangitis. clinicaltrials.gov; 2023. Accessed June 6, 2023. https://clinicaltrials.gov/ct2/show/NCT05050136

  36. • Levy C, Kendrick S, Bowlus CL, et al. GLIMMER: A randomized phase 2b dose-ranging trial of linerixibat in primary biliary cholangitis patients with pruritus. Clin Gastroenterol Hepatol. 2022; https://doi.org/10.1016/j.cgh.2022.10.032. In this phase two trial, linerixibat was associated with improvement in PBC-related itch.

  37. Hirschfield GM, Beuers U, Kupcinskas L, et al. A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA. J Hepatol. 2021;74(2):321–9. https://doi.org/10.1016/j.jhep.2020.09.011.

    Article  CAS  PubMed  Google Scholar 

  38. Myers RP, Swain MG, Lee SS, Shaheen AAM, Burak KW. B-cell depletion with rituximab in patients with primary biliary cirrhosis refractory to ursodeoxycholic acid. Am J Gastroenterol. 2013;108(6):933–41. https://doi.org/10.1038/ajg.2013.51.

    Article  CAS  PubMed  Google Scholar 

  39. Khanna A, Jopson L, Howel D, et al. Rituximab is ineffective for treatment of fatigue in primary biliary cholangitis: a phase 2 randomized controlled trial. Hepatology. 2019;70(5):1646–57. https://doi.org/10.1002/hep.30099.

    Article  CAS  PubMed  Google Scholar 

  40. Bowlus CL, Yang GX, Liu CH, et al. Therapeutic trials of biologics in primary biliary cholangitis: An open label study of abatacept and review of the literature. J Autoimmun. 2019;101:26–34. https://doi.org/10.1016/j.jaut.2019.04.005.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    Kaitlyn Carlson, Madeleine Hines Salge & George Cholankeril

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K. C. wrote the main text and prepared the figures, compiled, reviewed and edited the manuscript

M. H. S. wrote portions of the main text, reviewed and edited the manuscript

G. C. provided project oversight, reviewed and edited the manuscript.

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Correspondence to Kaitlyn Carlson.

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Kaitlyn Carlson, Madeleine Hines Salge, and George Cholankeril declare no conflicts of interest.

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Carlson, K., Salge, M.H. & Cholankeril, G. Primary Biliary Cholangitis: Updates in Management and Goals of Treatment. Curr Hepatology Rep (2024). https://doi.org/10.1007/s11901-024-00667-2

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