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====PBCers====
====PBCers====
This is a US-based patient support group which also has a strong on-line presence.<ref>{{cite web|last1=PBCers.org|title=Home page|url=http://pbcers.org/|accessdate=4 August 2015}}</ref> It was founded in 1996 and advocates for greater awareness of the disease and new treatments.<ref>{{cite web|last1=Kim|first1=Margot|title=New hope for PBC liver disease|url=http://abc30.com/health/new-hope-for-pbc-liver-disease/479448/|website=ABC30 Action news|accessdate=4 August 2015}}</ref> It has been a major force behind the initiative for a change in name.<ref name="pbcers.org"/>
This is a US-based patient support group.<ref>{{cite web|last1=PBCers.org|title=Home page|url=http://pbcers.org/|accessdate=4 August 2015}}</ref> It was founded in 1996 and advocates for greater awareness of the disease and new treatments.<ref>{{cite web|last1=Kim|first1=Margot|title=New hope for PBC liver disease|url=http://abc30.com/health/new-hope-for-pbc-liver-disease/479448/|website=ABC30 Action news|accessdate=4 August 2015}}</ref> It has been a major force behind the initiative for a change in name.<ref name="pbcers.org"/>


== References ==
== References ==

Revision as of 12:55, 4 August 2015

Primary biliary cholangitis
SpecialtyGastroenterology Edit this on Wikidata

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver.[1][2] It is marked by slow progressive destruction of the small bile ducts of the liver, with the intralobular ducts (Canals of Hering) affected early in the disease.[3] When these ducts are damaged, bile and other toxins build up in the liver (cholestasis) and over time damages the liver tissue in combination with ongoing immune related damage. This can lead to scarring, fibrosis and cirrhosis.

PBC was previously thought to be a rare disease, but more recent studies have shown that it may affect up to 1 in 3–4,000 people; the sex ratio is at least 9:1 female to male.[4]

As cirrhosis is only a feature of advanced disease, a change of name to "primary biliary cholangitis" was proposed by patient advocacy groups in 2014.[5][6] It has not as of April 2015 been adopted in scientific publications but has been accepted by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.[7]

Signs and symptoms

Individuals with PBC with disease may present with the following:

Causes

The cause of the disease is attributed to an immunological basis for the disease, making it an autoimmune disorder. Most of the patients (>90%) have anti-mitochondrial antibodies (AMAs) against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in the mitochondria.

Many PBC patients have a concomitant autoimmune disease, including rheumatological, endocrinological, gastrointestinal, pulmonary, or dermatological conditions, which suggests shared genetic and immune abnormalities.[8] Common associations include Sjögren's syndrome, systemic sclerosis, rheumatoid arthritis, SLE, hypothyroidism and gluten sensitive enteropathy.[8][9][10][11] In some cases of disease, protein expression may cause an immune tolerance failure, as might be the case with gp210 and p62, nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients.[12] Both proteins appear to be prognostic of liver failure relative to anti-mitochondrial antibodies.

A genetic predisposition to disease has been thought important for some time, as evident by cases of PBC in family members, concordance in identical twins, and clustering of autoimmune diseases. In 2009, a Canadian-led group of investigators reported in the New England Journal of Medicine results from the first PBC genome-wide association study.[13][14] This research revealed parts of the IL12 signaling cascade, particularly IL12A and IL12RB2 polymorphisms, to be important in the etiology of the disease in addition to the HLA region. In 2012, two independent PBC association studies increased the total number of genomic regions associated to 26, implicating many genes involved in cytokine regulation such as TYK2, SH2B3 and TNFSF11.[15][16]

In 2003 it was reported that an environmental Gram negative alphabacterium — Novosphingobium aromaticivorans[17] was strongly associated with this disease. Subsequent reports appear to have confirmed this finding suggesting an aetiological role for this organism.[18][19][20] The mechanism appears to be a cross reaction between the proteins of the bacterium and the mitochondrial proteins of the liver cells.[21] The gene encoding CD101 may also play a role in host susceptibility to this disease.[22]

Diagnosis

Intermediate magnification micrograph of PBC showing bile duct inflammation and periductal granulomas. Liver biopsy. H&E stain.
Immunofluorescence staining pattern of sp100 antibodies (nuclear dots) and AMA.

To diagnose PBC, distinctions should be established from other conditions with similar symptoms, such as autoimmune hepatitis or primary sclerosing cholangitis (PSC).

Diagnostic blood tests include:

Abdominal ultrasound, MR scanning (MRCP) or a CT scan is usually performed to rule out blockage to the bile ducts. Most suspected cases have a liver biopsy performed, and if uncertainty remains an is some patients, endoscopic retrograde cholangiopancreatography or ERCP, where an endoscopic investigation of the bile duct is performed. Most patients are diagnosed without invasive investigation, as the combination of anti-mitochondrial antibodies (see below) and typical (cholestatic) liver enzyme tests are considered diagnostic. However, a liver biopsy is necessary to determine the stage of disease.

Anti-nuclear antibodies appear to be prognostic agents in PBC. Anti-glycoprotein-210 antibodies, and to a lesser degree anti-p62 antibodies, correlate with the disease's progression toward end stage liver failure. Anti-centromere antibodies often correlate with developing portal hypertension.[23] Anti-np62[24] and anti-sp100 are also found in association with PBC.

Biopsy

PBC is characterized by interlobular bile duct destruction. Histopathologic findings of primary biliary cholangitis include the following:[25]

Summary of stages

  • Stage 1 — Portal Stage: Normal sized triads; portal inflammation, subtle bile duct damage. Granulomas are often detected in this stage.
  • Stage 2 — Periportal Stage: Enlarged triads; periportal fibrosis and/or inflammation. Typically characterized by the finding of a proliferation of small bile ducts.
  • Stage 3 — Septal Stage: Active and/or passive fibrous septa.
  • Stage 4 — Biliary Cirrhosis: Nodules present; garland or jigsaw puzzle pattern.

Treatment

There is no known cure, but medication may slow the progression so that a normal lifespan and quality of life may be attainable for many patients.[26][27]

  • Ursodeoxycholic acid (Ursodiol) is the most frequently used treatment. This helps reduce the cholestasis and improves blood test results (liver function tests). It has a minimal effect on symptoms and whether it improves prognosis is controversial.[28]
  • Specific treatment for fatigue, which may be debilitating in some patients, is limited and undergoing trials.[30] Some studies indicate that Provigil (modafinil) may be effective without damaging the liver.[31] Though off-patent, the limiting factor in the use of modafinil in the U.S. is cost. The manufacturer, Cephalon, has made agreements with manufacturers of generic modafinil to provide payments in exchange for delaying their sale of modafinil.[32] The FTC has filed suit against Cephalon alleging anti-competitive behavior.[33]
  • Patients with PBC have poor lipid-dependent absorption of Vitamins A, D, E, K.[34] Appropriate supplementation is recommended when bilirubin is elevated.[35]
  • Patients with PBC are at elevated risk of developing osteoporosis[36] and esophageal varices[37] as compared to the general population and others with liver disease. Screening and treatment of these complications is an important part of the management of PBC.

As in all liver diseases, consumption of alcohol is contraindicated.

In advanced cases, a liver transplant, if successful, results in a favorable prognosis.[38]

The farnesoid X receptor agonist, obeticholic acid, which is a modified bile acid, is in phase III clinical trials for PBC.[39]

Epidemiology

PBC is a chronic autoimmune liver disease with a female gender predominance with female:male ratio is at least 9:1 and a peak incidence in the fifth decade of life.[40] In some areas of the US and UK the prevalence is estimated to be as high as 1 in 4000. This is much more common than in South America or Africa, which may be due to better recognition in the US and UK. First-degree relatives may have as much as a 500 times increase in prevalence, but there is debate if this risk is greater in the same generation relatives or the one that follows.[4]

Prognosis

The serum bilirubin level is an indicator of the prognosis of PBC, with levels of 2–6 mg/dL having a mean survival time of 4.1 years, 6–10 mg/dL having 2.1 years and those above 10 mg/dL having a mean survival time of 1.4 years.[41]

After liver transplant, the recurrence rate may be as high as 18% at 5 years, and up to 30% at 10 years. There is no consensus on risk factors for recurrence of the disease.[42]

Patients with PBC have an increased risk of hepatocellular carcinoma compared to the general population, as is found in other cirrhotic patients. In patients with advanced disease, one series found an incidence of 20% in men and 4% in women.[43]

History

Addison and Gull in 1851 described the clinical picture of progressive obstructive jaundice in the absence of mechanical obstruction of the large bile ducts. Ahrens et al in 1950 coined the term primary biliary cirrhosis for this disease. The association with anti-mitochondrial antibodies was first reported in 1965[44] and their presence was recognized as a marker of early, pre-cirrhotic disease.[45]

Society and culture

Patient support groups

The PBC Foundation

The PBC Foundation is a UK-based international charity offering support and information to people with PBC, their families and friends.[46] It campaigns for increasing recognition of the disorder, improved diagnosis and treatments, and estimates over 8000 people are undiagnosed in the UK.[47][48] The Foundation has supported research into PBC including the development of the PBC-40 quality of life measure published in 2004[49] and helped establish the PBC Genetics Study.[50][15] It was founded by Collette Thain in 1996, after she was diagnosed with the condition.[47] Thain was awarded an MBE Order of the British Empire in 2004 for her work with the Foundation.[51]

In 2014, the PBC Foundation, along with the US-based advocacy group, the PBCers, launched an initiative to change the name from "primary biliary cirrhosis" to "primary biliary cholangitis".[5][6][52] Clinician support for this name change has come from the American Association for the Study of Liver Diseases[7] and the European Association for the Study of the Liver, and it is proposed that this change be reflected in the International Classification of Disease (ICD11).

PBCers

This is a US-based patient support group.[53] It was founded in 1996 and advocates for greater awareness of the disease and new treatments.[54] It has been a major force behind the initiative for a change in name.[6]

References

  1. ^ Hirschfield GM, Gershwin ME (Jan 2013). "The immunobiology and pathophysiology of primary biliary cirrhosis". Annual Review of Pathology. 8: 303–30. doi:10.1146/annurev-pathol-020712-164014. PMID 23347352.
  2. ^ Dancygier, Henryk (2010). Clinical Hepatology Principles and Practice of. Springer. pp. 895–. ISBN 978-3-642-04509-7. Retrieved 29 June 2010.
  3. ^ Saxena R, Theise N (Feb 2004). "Canals of Hering: recent insights and current knowledge". Seminars in Liver Disease. 24 (1): 43–8. doi:10.1055/s-2004-823100. PMID 15085485.
  4. ^ a b Clavien, Pierre-Alain; Killenberg, Paul G. (2006). Medical Care of the Liver Transplant Patient: Total Pre-, Intra- and Post-Operative Management. Wiley-Blackwell. p. 155. ISBN 1-4051-3032-6. {{cite book}}: Invalid |ref=harv (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  5. ^ a b PBC Foundation (UK). "PBC Name Change Press Release". Retrieved 8 July 2015.
  6. ^ a b c PBCers Organization. "Primary Biliary Cirrhosis Name Change Initiative" (PDF).
  7. ^ a b AASLD. "A name change for PBC: cholangitis replacing cirrhosis". Retrieved 6 July 2015.
  8. ^ a b Floreani A, Franceschet I, Cazzagon N (Aug 2014). "Primary biliary cirrhosis: overlaps with other autoimmune disorders". Seminars in Liver Disease. 34 (3): 352–60. doi:10.1055/s-0034-1383734. PMID 25057958.
  9. ^ Watt FE, James OF, Jones DE (Jul 2004). "Patterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study". Qjm. 97 (7): 397–406. PMID 15208427.
  10. ^ Logan RF, Ferguson A, Finlayson ND, Weir DG (Feb 1978). "Primary biliary cirrhosis and coeliac disease: an association?". Lancet. 1 (8058): 230–3. doi:10.1016/S0140-6736(78)90480-4. PMID 74661.
  11. ^ Volta U, Rodrigo L, Granito A, Petrolini N, Muratori P, Muratori L, Linares A, Veronesi L, Fuentes D, Zauli D, Bianchi FB (Oct 2002). "Celiac disease in autoimmune cholestatic liver disorders". The American Journal of Gastroenterology. 97 (10): 2609–13. doi:10.1111/j.1572-0241.2002.06031.x. PMID 12385447. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
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  14. ^ http://www.uk-pbc.com
  15. ^ a b Liu JZ, Almarri MA, Gaffney DJ, Mells GF, Jostins L, Cordell HJ, Ducker SJ, Day DB, Heneghan MA, Neuberger JM, Donaldson PT, Bathgate AJ, Burroughs A, Davies MH, Jones DE, Alexander GJ, Barrett JC, Sandford RN, Anderson CA (Oct 2012). "Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis". Nature Genetics. 44 (10): 1137–41. doi:10.1038/ng.2395. PMC 3459817. PMID 22961000. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  16. ^ Juran BD, Hirschfield GM, Invernizzi P, Atkinson EJ, Li Y, Xie G, Kosoy R, Ransom M, Sun Y, Bianchi I, Schlicht EM, Lleo A, Coltescu C, Bernuzzi F, Podda M, Lammert C, Shigeta R, Chan LL, Balschun T, Marconi M, Cusi D, Heathcote EJ, Mason AL, Myers RP, Milkiewicz P, Odin JA, Luketic VA, Bacon BR, Bodenheimer HC, Liakina V, Vincent C, Levy C, Franke A, Gregersen PK, Bossa F, Gershwin ME, deAndrade M, Amos CI, Lazaridis KN, Seldin MF, Siminovitch KA (Dec 2012). "Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants". Human Molecular Genetics. 21 (23): 5209–21. doi:10.1093/hmg/dds359. PMC 3490520. PMID 22936693. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
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  19. ^ Kaplan MM (Nov 2004). "Novosphingobium aromaticivorans: a potential initiator of primary biliary cirrhosis". The American Journal of Gastroenterology. 99 (11): 2147–9. doi:10.1111/j.1572-0241.2004.41121.x. PMID 15554995.
  20. ^ Selmi C, Gershwin ME (Jul 2004). "Bacteria and human autoimmunity: the case of primary biliary cirrhosis". Current Opinion in Rheumatology. 16 (4): 406–10. doi:10.1097/01.bor.0000130538.76808.c2. PMID 15201604.
  21. ^ Mattner J, Savage PB, Leung P, Oertelt SS, Wang V, Trivedi O, Scanlon ST, Pendem K, Teyton L, Hart J, Ridgway WM, Wicker LS, Gershwin ME, Bendelac A (May 2008). "Liver autoimmunity triggered by microbial activation of natural killer T cells". Cell Host & Microbe. 3 (5): 304–15. doi:10.1016/j.chom.2008.03.009. PMC 2453520. PMID 18474357. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  22. ^ Mohammed JP, Fusakio ME, Rainbow DB, Moule C, Fraser HI, Clark J, Todd JA, Peterson LB, Savage PB, Wills-Karp M, Ridgway WM, Wicker LS, Mattner J (Jul 2011). "Identification of Cd101 as a susceptibility gene for Novosphingobium aromaticivorans-induced liver autoimmunity". Journal of Immunology. 187 (1): 337–49. doi:10.4049/jimmunol.1003525. PMC 3134939. PMID 21613619. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  23. ^ Nakamura M, Kondo H, Mori T, Komori A, Matsuyama M, Ito M, Takii Y, Koyabu M, Yokoyama T, Migita K, Daikoku M, Abiru S, Yatsuhashi H, Takezaki E, Masaki N, Sugi K, Honda K, Adachi H, Nishi H, Watanabe Y, Nakamura Y, Shimada M, Komatsu T, Saito A, Saoshiro T, Harada H, Sodeyama T, Hayashi S, Masumoto A, Sando T, Yamamoto T, Sakai H, Kobayashi M, Muro T, Koga M, Shums Z, Norman GL, Ishibashi H (Jan 2007). "Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis". Hepatology. 45 (1): 118–27. doi:10.1002/hep.21472. PMID 17187436. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  24. ^ Nesher G, Margalit R, Ashkenazi YJ (Apr 2001). "Anti-nuclear envelope antibodies: Clinical associations". Seminars in Arthritis and Rheumatism. 30 (5): 313–20. doi:10.1053/sarh.2001.20266. PMID 11303304.
  25. ^ Nakanuma Y, Tsuneyama K, Sasaki M, Harada K (Aug 2000). "Destruction of bile ducts in primary biliary cirrhosis". Baillière's Best Practice & Research. Clinical Gastroenterology. 14 (4): 549–70. doi:10.1053/bega.2000.0103. PMID 10976014.
  26. ^ a b Levy C, Lindor KD (Apr 2003). "Treatment Options for Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis". Current Treatment Options in Gastroenterology. 6 (2): 93–103. doi:10.1007/s11938-003-0010-0. PMID 12628068.
  27. ^ a b Oo YH, Neuberger J (2004). "Options for treatment of primary biliary cirrhosis". Drugs. 64 (20): 2261–71. doi:10.2165/00003495-200464200-00001. PMID 15456326.
  28. ^ Gluud C, Christensen E (2002). "Ursodeoxycholic acid for primary biliary cirrhosis". The Cochrane Database of Systematic Reviews (1): CD000551. doi:10.1002/14651858.CD000551. PMID 11869580.
  29. ^ Walt RP, Daneshmend TK, Fellows IW, Toghill PJ (Feb 1988). "Effect of stanozolol on itching in primary biliary cirrhosis". British Medical Journal. 296 (6622): 607. PMC 2545238. PMID 3126923.
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  31. ^ Modafinil#Primary biliary cirrhosis
    Ian Gan S, de Jongh M, Kaplan MM (Oct 2009). "Modafinil in the treatment of debilitating fatigue in primary biliary cirrhosis: a clinical experience". Digestive Diseases and Sciences. 54 (10): 2242–6. doi:10.1007/s10620-008-0613-3. PMID 19082890.
    Kumagi T, Heathcote EJ (2008). "Primary biliary cirrhosis". Orphanet Journal of Rare Diseases. 3: 1. doi:10.1186/1750-1172-3-1. PMC 2266722. PMID 18215315. Ref 157 viz: {{cite journal}}: External link in |quote= (help)CS1 maint: unflagged free DOI (link)
    Jones DE, Newton JL (Feb 2007). "An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis". Alimentary Pharmacology & Therapeutics. 25 (4): 471–6. doi:10.1111/j.1365-2036.2006.03223.x. PMID 17270003.
  32. ^ Modafinil#Patent protection and antitrust litigation
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  41. ^ Primary Biliary Cirrhosis~followup at eMedicine
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  46. ^ Association of Medical Research Charities. "The PBC Foundation". Retrieved 12 July 2015.
  47. ^ a b Staff of The Scotsman, January 3, 2008. Dealing with a silent killer
  48. ^ Thain, Collette (2015). "Primary biliary cirrhosis: getting a diagnosis" (online). At Home Magazine. Retrieved 28 July 2015.
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  50. ^ Mells GF, Floyd JA, Morley KI, Cordell HJ, Franklin CS, Shin SY, Heneghan MA, Neuberger JM, Donaldson PT, Day DB, Ducker SJ, Muriithi AW, Wheater EF, Hammond CJ, Dawwas MF, Jones DE, Peltonen L, Alexander GJ, Sandford RN, Anderson CA (Apr 2011). "Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis". Nature Genetics. 43 (4): 329–32. doi:10.1038/ng.789. PMC 3071550. PMID 21399635. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  51. ^ Barry Gordon for The Scotsman. 31 December 2003 A royal seal of approval
  52. ^ PBC Foundation. "EASL Name Change Presentation". Retrieved 8 July 2015.
  53. ^ PBCers.org. "Home page". Retrieved 4 August 2015.
  54. ^ Kim, Margot. "New hope for PBC liver disease". ABC30 Action news. Retrieved 4 August 2015.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Primary_biliary_cholangitis&oldid=674516969"