Skip to main content
SpringerLink
Log in

Primary Biliary Cholangitis

  • Chapter
  • First Online:
Liver Diseases

  • 2901 Accesses

Abstract

Primary Biliary Cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterised by the presence of antimitochondrial antibodies, which are considered disease-specific and progressive destruction of small intrahepatic bile ducts leading to cholestasis and end-stage liver disease in a proportion of patients.

Since its first description, a considerable amount of data has significantly changed our perception of the disease’s pathogenesis, epidemiology, natural history and treatment.

The geoepidemiology of PBC has changed with prevalence and incidence rates rising over time mainly in developed countries. The strong genetic predisposition of PBC has been revealed by genome-wide association studies, while a large number of environmental factors have emerged as disease triggers over time. Immune mechanisms in PBC are better understood, including the role of biliary epithelial cells in stimulation and maintenance of the inflammatory process.

Treatment aims at delaying disease progression and managing patients’ symptoms. Treatment strategies should be individualized based on patient’s stratification risk as assessed by various prognostic factors. Ursodeoxycholic acid, the mainstay of PBC treatment has in general improved significantly the disease’s natural history, however a proportion of patients don’t respond to treatment. These patients should be offered emerging second-line treatments, including obeticholic acid and other drugs under investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Carey EJ, Ali AH, Lindor KD. Primary biliary cirrhosis. Lancet. 2015;386(10003):1565–75.

    Article  CAS  Google Scholar 

  2. Beuers U, Gershwin ME, Gish RG, Invernizzi P, Jones DE, Lindor K, et al. Changing nomenclature for PBC: from ‘cirrhosis’ to ‘cholangitis’. J Hepatol. 2015;63(5):1285–7.

    Article  Google Scholar 

  3. Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol. 2012;56(5):1181–8.

    Article  Google Scholar 

  4. James OF, Bhopal R, Howel D, Gray J, Burt AD, Metcalf JV. Primary biliary cirrhosis once rare, now common in the United Kingdom? Hepatology. 1999;30(2):390–4.

    Article  CAS  Google Scholar 

  5. Kim WR, Lindor KD, Locke GR 3rd, Therneau TM, Homburger HA, Batts KP, et al. Epidemiology and natural history of primary biliary cirrhosis in a US community. Gastroenterology. 2000;119(6):1631–6.

    Article  CAS  Google Scholar 

  6. Gatselis NK, Zachou K, Lygoura V, Azariadis K, Arvaniti P, Spyrou E, et al. Geoepidemiology, clinical manifestations and outcome of primary biliary cholangitis in Greece. Eur J Intern Med. 2017;42:81–8.

    Article  Google Scholar 

  7. Hamlyn AN, Sherlock S. The epidemiology of primary biliary cirrhosis: a survey of mortality in England and Wales. Gut. 1974;15(6):473–9.

    Article  CAS  Google Scholar 

  8. Cheung KS, Seto WK, Fung J, Lai CL, Yuen MF. Epidemiology and natural history of primary biliary cholangitis in the Chinese: a territory-based study in Hong Kong between 2000 and 2015. Clin Transl Gastroenterol. 2017;8(8):e116.

    Article  Google Scholar 

  9. Kim KA, Ki M, Choi HY, Kim BH, Jang ES, Jeong SH. Population-based epidemiology of primary biliary cirrhosis in South Korea. Aliment Pharmacol Ther. 2016;43(1):154–62.

    Article  Google Scholar 

  10. Hirschfield GM, Gershwin ME. The immunobiology and pathophysiology of primary biliary cirrhosis. Annu Rev Pathol. 2013;8:303–30.

    Article  CAS  Google Scholar 

  11. Webb GJ, Siminovitch KA, Hirschfield GM. The immunogenetics of primary biliary cirrhosis: a comprehensive review. J Autoimmun. 2015;64:42–52.

    Article  CAS  Google Scholar 

  12. Lleo A, Maroni L, Glaser S, Alpini G, Marzioni M. Role of cholangiocytes in primary biliary cirrhosis. Semin Liver Dis. 2014;34(3):273–84.

    Article  CAS  Google Scholar 

  13. Selmi C, Mayo MJ, Bach N, Ishibashi H, Invernizzi P, Gish RG, et al. Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment. Gastroenterology. 2004;127(2):485–92.

    Article  Google Scholar 

  14. Tanaka A, Leung PSC, Gershwin ME. The genetics and epigenetics of primary biliary cholangitis. Clin Liver Dis. 2018;22(3):443–55.

    Article  Google Scholar 

  15. Joshita S, Umemura T, Tanaka E, Ota M. Genetics and epigenetics in the pathogenesis of primary biliary cholangitis. Clin J Gastroenterol. 2018;11(1):11–8.

    Article  Google Scholar 

  16. Banales JM, Sáez E, Uriz M, Sarvide S, Urribarri AD, Splinter P, et al. Up-regulation of microRNA 506 leads to decreased Cl−/HCO3 − anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology. 2012;56(2):687–97.

    Article  CAS  Google Scholar 

  17. Smyk D, Rigopoulou EI, Baum H, Burroughs AK, Vergani D, Bogdanos DP. Autoimmunity and environment: am I at risk? Clin Rev Allergy Immunol. 2012;42(2):199–212.

    Article  CAS  Google Scholar 

  18. Shimoda S, Nakamura M, Ishibashi H, Kawano A, Kamihira T, Sakamoto N, et al. Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis. Gastroenterology. 2003;124(7):1915–25.

    Article  CAS  Google Scholar 

  19. Bogdanos DP, Baum H, Grasso A, Okamoto M, Butler P, Ma Y, et al. Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis. J Hepatol. 2004;40(1):31–9.

    Article  CAS  Google Scholar 

  20. Tanaka T, Zhang W, Sun Y, Shuai Z, Chida AS, Kenny TP, et al. Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics. Hepatology. 2017;66(3):885–95.

    Article  CAS  Google Scholar 

  21. Liaskou E, Patel SR, Webb G, Bagkou Dimakou D, Akiror S, Krishna M, et al. Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN-γ secreting cells. J Autoimmun. 2018;94:143–55.

    Article  CAS  Google Scholar 

  22. Prince MI, Chetwynd A, Craig WL, Metcalf JV, James OF. Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort. Gut. 2004;53(6):865–70.

    Article  CAS  Google Scholar 

  23. Khanna A, Leighton J, Lee Wong L, Jones DE. Symptoms of PBC—pathophysiology and management. Best Pract Res Clin Gastroenterol. 2018;34–35:41–7.

    Article  Google Scholar 

  24. EASL Clinical Practice Guidelines. The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145–72.

    Article  Google Scholar 

  25. Hirschfield GM, Dyson JK, Alexander GJM, Chapman MH, Collier J, Hübscher S, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568–94.

    Article  CAS  Google Scholar 

  26. Rigopoulou EI, Dalekos GN. Molecular diagnostics of primary biliary cirrhosis. Expert Opin Med Diagn. 2008;2(6):621–34.

    Article  CAS  Google Scholar 

  27. Rigopoulou EI, Davies ET, Pares A, Zachou K, Liaskos C, Bogdanos DP, et al. Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis. Gut. 2005;54(4):528–32.

    Article  CAS  Google Scholar 

  28. Corpechot C. Utility of noninvasive markers of fibrosis in cholestatic liver diseases. Clin Liver Dis. 2016;20(1):143–58.

    Article  Google Scholar 

  29. Goel A, Kim WR. Natural history of primary biliary cholangitis in the ursodeoxycholic acid era: role of scoring systems. Clin Liver Dis. 2018;22(3):563–78.

    Article  Google Scholar 

  30. Locke GR 3rd, Therneau TM, Ludwig J, Dickson ER, Lindor KD. Time course of histological progression in primary biliary cirrhosis. Hepatology. 1996;23(1):52–6.

    Article  Google Scholar 

  31. Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(6):318–28.

    Article  CAS  Google Scholar 

  32. Corpechot C, Carrat F, Poupon R, Poupon RE. Primary biliary cirrhosis: incidence and predictive factors of cirrhosis development in ursodiol-treated patients. Gastroenterology. 2002;122(3):652–8.

    Article  CAS  Google Scholar 

  33. Murillo Perez CF, Goet JC, Lammers WJ, Gulamhusein A, van Buuren HR, Ponsioen CY, et al. GLOBAL PBC Study Group. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: a changing natural history. Hepatology. 2018;67(5):1920–30.

    Article  CAS  Google Scholar 

  34. Bossen L, Gerussi A, Lygoura V, Mells GF, Carbone M, Invernizzi P. Support of precision medicine through risk-stratification in autoimmune liver diseases – histology, scoring systems, and non-invasive markers. Autoimmun Rev. 2018;17(9):854–65.

    Article  Google Scholar 

  35. 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):715–20.

    Article  Google Scholar 

  36. Carbone M, Nardi A, Flack S, Carpino G, Varvaropoulou N, Gavrila C, et al. Italian PBC Study Group and the UK–PBC Consortium. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score. Lancet Gastroenterol Hepatol. 2018;3(9):626–34.

    Article  Google Scholar 

  37. Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, et al. POISE Study Group. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 2016;375(7):631–43.

    Article  CAS  Google Scholar 

  38. Corpechot C, Chazouillères O, Rousseau A, Le Gruyer A, Habersetzer F, Mathurin P, et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N Engl J Med. 2018;378(23):2171–81.

    Article  CAS  Google Scholar 

  39. Montano-Loza AJ, Bhanji RA, Wasilenko S, Mason AL. Systematic review: recurrent autoimmune liver diseases after liver transplantation. Aliment Pharmacol Ther. 2017;45(4):485–500.

    Article  CAS  Google Scholar 

  40. EASL Clinical Practice Guidelines. Autoimmune hepatitis. J Hepatol. 2015;63(4):971–1004.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

    Eirini I. Rigopoulou

Authors
  1. Eirini I. Rigopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eirini I. Rigopoulou .

Editor information

Editors and Affiliations

  1. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Florentina Radu-Ionita

  2. New Jersey Medical School, Rutgers University New Jersey Medical School, Newark, NJ, USA

    Nikolaos T. Pyrsopoulos

  3. Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Mariana Jinga

  4. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Ion C. Tintoiu

  5. Medical Radiation Sciences, Curtin University, Perth, WA, Australia

    Zhonghua Sun

  6. “Prof. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania

    Ecaterina Bontas

Self Study

Self Study

1.1 Questions

  1. 1.

    A 55-year old woman presents to the clinic with a 6-month history of progressively deteriorating pruritus and fatigue. Liver biochemistry shows an increase in ALP (×2.5 ULN) and slight increase of gGT and ALT. She denies alcohol drinking and systematic use of any drugs. On clinical examination she has palmar erythema and enlarged liver. Liver and bile duct ultrasound show hepatomegaly, with no liver lesions or bile duct dilatation. What is the test that you are going to order next for this patient?

    1. (a)

      Antinuclear antibodies

    2. (b)

      Antimitochondrial antibodies

    3. (c)

      Serum IgM

    4. (d)

      Liver biopsy

  2. 2.

    What is not true about PBC?

    1. (a)

      PBC affects predominantly men

    2. (b)

      PBC patients often have increased cholesterol levels

    3. (c)

      Hashimoto’s thyroiditis co-exist in a significant proportion of patients

    4. (d)

      Antinuclear antibodies displaying a multiple nuclear dot and a perinuclear/rim-like pattern in indirect immunofluorescence are considered specific for PBC

  3. 3.

    What is the initial recommended treatment of choice in PBC?

    1. (a)

      Budenofalk

    2. (b)

      Ursodeoxycholic acid

    3. (c)

      Azathioprine

    4. (d)

      Fibrates

1.2 Answers

  1. 1.

    A 55-year old woman presents to the clinic with a 6-month history of progressively deteriorating pruritus and fatigue. Liver biochemistry shows an increase in ALP (×2.5 ULN) and slight increase of gGT and ALT. She denies alcohol drinking and systematic use of any drugs. On clinical examination she has palmar erythema and enlarged liver. Liver and bile duct ultrasound show hepatomegaly, with no liver lesions or bile duct dilatation. What is the test that you are going to order next for this patient?

    1. (a)

      Antinuclear antibodies can be positive in PBC and some of them are regarded as disease-specific. However, this is not the first test to be ordered in cases of high suspicion of PBC

    2. (b)

      CORRECT ANSWER. In patients with cholestasis and other clinical features suggestive of the PBC, the diagnosis can be established based on the detection of antimitochondrial antibodies (titre > 1/40), which are present in over 90% of patients and are considered disease specific.

    3. (c)

      Serum IgM is often elevated in PBC patients and can aid in establishing the diagnosis in atypical cases. Though serum IgM is not a criterion for PBC diagnosis.

    4. (d)

      Liver biopsy is not necessary in typical PBC cases with presence of cholestasis and antimitochondrial antibodies.

  2. 2.

    What is not true about PBC?

    1. (a)

      CORRECT ANSWER. PBC affects predominantly women. Average reported female to male ratio are 10:1

    2. (b)

      Hypercholesterolemia is a frequent feature in PBC patients

    3. (c)

      Hashimoto’s thyroiditis is one of the most frequent autoimmune diseases that co-exist in PBC patients

    4. (d)

      Antinuclear antibodies displaying a multiple nuclear dot and a perinuclear/rim-like pattern in indirect immunofluorescence are considered specific for PBC and are present in up to 50% of PBC patients depending from the method used.

  3. 3.

    What is the initial recommended treatment of choice in PBC?

    1. (a)

      Budenofalk is not a licensed drug for PBC and cannot be recommended

    2. (b)

      CORRECT ANSWER. Ursodeoxycholic acid is recommended by scientific societies as first-line treatment for all patients with PBC that usually continues for life.

    3. (c)

      Azathioprine doesn’t belong to the armamentarium of PBC. It can be administered in conjunction with steroids in variant PBC-AIH cases.

    4. (d)

      Fibrates are being studied in PBC as add-on treatment to UDCA in non-responders to UDCA. Up to the present they are non-licensed for PBC treatment.

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rigopoulou, E.I. (2020). Primary Biliary Cholangitis. In: Radu-Ionita, F., Pyrsopoulos, N., Jinga, M., Tintoiu, I., Sun, Z., Bontas, E. (eds) Liver Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-24432-3_24

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-24432-3_24

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-24431-6

  • Online ISBN: 978-3-030-24432-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation