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| {{Infobox_Disease |
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| Name = {{PAGENAME}} |
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| DiseasesDB = 10615 |
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| ICD10 = {{ICD10|K|74|3|k|70}} |
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| ICD9 = {{ICD9|571.6}} |
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| ICDO = |
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| OMIM = |
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| MeshID = D008105 |
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| {{Search infobox}}
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| {{CMG}}
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| '''Associate Editor-In-Chief:''' {{CZ}}
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| ==Overview==
| | '''For patient information page on this topic, click [[Primary biliary cirrhosis (patient information)|here]].''' |
| | {{Primary biliary cirrhosis}} |
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| '''Primary biliary cirrhosis''' is an [[autoimmune disease]] of the [[liver]] marked by the slow progressive destruction of the small bile ducts ([[bile canaliculi]]) within the liver. When these ducts are damaged [[bile]] builds up in the liver ([[cholestasis]]) and over time damages the tissue. This can lead to scarring, [[fibrosis]], [[cirrhosis]], and ultimately [[liver failure]]. It 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 not less than 9 to 1, women to men (reference: Medical care of the Liver Trasplant Patient, 3rd Edition published 2006, editied by Paul G. Killenberg, page 155).
| | {{CMG}}; {{AE}}{{Anmol}}, {{SH}}, {{AA}}, {{ARK}} |
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| ==Signs and symptoms==
| | {{SK}} Chronic non-suppurative destructive cholangitis, PBC, Primary biliary cholangitis. |
| The following signs may be present in PBC:
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| *[[Fatigue (physical)|Fatigue]]
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| *[[Pruritus]] (itchy skin)
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| *[[Jaundice]] (yellowing of the eyes and skin), due to increased [[bilirubin]] in the blood.
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| *[[Xanthelasma]]ta (focal collections of [[cholesterol]] in the skin, especially around the eyes)
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| * Complications of [[cirrhosis]] and [[portal hypertension]]:
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| ** Fluid retention in the abdomen ([[ascites]])
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| ** [[Esophageal varices]]
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| ** [[Hepatic encephalopathy]], up to coma, in extreme cases.
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| * Association with an extrahepatic autoimmune disorder such as Rheumatoid Arthritis or Sjögren syndrome (up to 80% incidence).
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| ==Diagnosis== | | ==[[Primary biliary cirrhosis overview|Overview]]== |
| To diagnose PBC, distinctions should be established from other conditions with similar symptoms, such as [[autoimmune hepatitis]] or [[primary sclerosing cholangitis]] (PSC).
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| Diagnostic [[blood test]]s include:
| | ==[[Primary biliary cirrhosis historical perspective|Historical Perspective]]== |
| * Deranged [[liver function test]]s (high [[alkaline phosphatase]], elevated AST, ALT)
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| * Presence of certain [[antibodies]]: [[Anti-mitochondrial antibody|antimitochondrial antibody]], [[antinuclear antibody]] (the M2-[[IgG]] antimitochondrial antibody is the most specific test)
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| Abdominal [[medical ultrasonography|ultrasound]] or a [[CT scan]] is usually performed to rule out blockage to the bile ducts. Previously most suspected sufferers underwent a [[liver biopsy]], and - if uncertainty remained - [[endoscopic retrograde cholangiopancreatography]] (ERCP, an [[endoscopy|endoscopic]] investigation of the [[bile duct]]). Now most patients are diagnosed without invasive investigation since the combination of anti-mitochondrial antibodies (see below) and typical (cholestatic) liver function tests are considered diagnostic. However, a liver biopsy is necessary to determine the stage of disease.
| | ==[[Primary biliary cirrhosis classification|Classification]]== |
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| '''[[Anti-nuclear antibodies]]''' appear to be prognostic agents in PBC. [[Anti-glycoprotein-210 antibodies]], and to a lessor degree [[anti-p62 antibodies]] correlate with progression toward end stage liver failure. [[Anti-centromere antibodies]] correlate with developing portal hypertension.<ref name="pmid17187436">{{cite journal | author = Nakamura M, Kondo H, Mori T, ''et al'' | title = Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis | journal = Hepatology | volume = 45 | issue = 1 | pages = 118-27 | year = 2007 | pmid = 17187436 | doi = 10.1002/hep.21472}}</ref>. Anti-np62<ref name="pmid11303304">{{cite journal | author = Nesher G, Margalit R, Ashkenazi YJ | title = Anti-nuclear envelope antibodies: Clinical associations | journal = Semin. Arthritis Rheum. | volume = 30 | issue = 5 | pages = 313-20 | year = 2001 | pmid = 11303304 | doi = 10.1053/sarh.2001.20266}}</ref> and anti-sp100 are also found in association with PBC.
| | ==[[Primary biliary cirrhosis pathophysiology|Pathophysiology]]== |
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| ===Summary of stages=== | | ==[[Primary biliary cirrhosis causes|Causes]]== |
| *''Stage 1 - Portal Stage'': Normal sized triads; portal inflammation, subtle [[bile duct]] damage. [[Granuloma]]s are often detected in this stage.
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| *''Stage 2 - Periportal Stage'': Enlarged triads; periportal [[fibrosis]] and/or [[inflammation]]. Typically characterized by the finding of a proliferation of small bile ducts.
| | ==[[Primary biliary cirrhosis differential diagnosis|Differentiating Primary Biliary Cirrhosis from other Diseases]]== |
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| *''Stage 3 - Septal Stage'': Active and/or passive fibrous [[septa]].
| | ==[[Primary biliary cirrhosis epidemiology and demographics|Epidemiology and Demographics]]== |
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| *''Stage 4 - Biliary Cirrhosis'': Nodules present; garland or jigsaw pattern.
| | ==[[Primary biliary cirrhosis risk factors|Risk Factors]]== |
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| ==Etiology== | | ==[[Primary biliary cirrhosis screening|Screening]]== |
| The cause of the disease is unknown at this time, but research indicates that there is an [[Immunology|immunological]] basis for the [[disease]], making it an [[autoimmune disorder]]. Most of the patients (>90%) seem to have anti-mitochondrial antibodies (AMAs) against [[pyruvate dehydrogenase complex]] (PDC-E2), an enzyme complex that is found in the [[mitochondria]]. In addition, a more specific test to confirm this disease from a bone disorder such as Paget's (disease of bone) which also has increases in Alkaline phosphatase is the [[Gamma glutamyl transpeptidase|Gamma-glutamyl trans peptidase]] test (GGTP). An increase in GGTP could indicate presence of Primary Biliary Cirrhosis.
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| 57% of patients with acute liver failure have [[anti-transglutaminase antibodies]]<ref name="pmid17657817">{{cite journal | author = Leung PS, Rossaro L, Davis PA, ''et al'' | title = Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis | journal = | volume = | issue = | pages = | year = 2007 | pmid = 17657817 | doi = 10.1002/hep.21828}}</ref> suggesting a role of [[gluten sensitivity]] in primary biliary cirrhosis, and primary biliary cirrhosis is considerable more common in [[Gluten-sensitive enteropathy associated conditions#Diseases of the pancreas.2C gall bladder.2C bile duct|gluten sensitive enteropathy]] than the normal population.<ref name="pmid74661">{{cite journal | author = Logan RF, Ferguson A, Finlayson ND, Weir DG | title = Primary biliary cirrhosis and coeliac disease: an association? | journal = Lancet | volume = 1 | issue = 8058 | pages = 230-3 | year = 1978 | pmid = 74661 | doi = }}</ref><ref name="pmid12385447">{{cite journal | author = Volta U, Rodrigo L, Granito A, ''et al'' | title = Celiac disease in autoimmune cholestatic liver disorders | journal = Am. J. Gastroenterol. | volume = 97 | issue = 10 | pages = 2609-13 | year = 2002 | pmid = 12385447 | doi = }}</ref> In some cases of disease protein expression may cause an [[immune tolerance]] failure, as might be the case with [[nucleoporin 210kDa| gp210]] and [[nucleoporin 62|p62]], nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients.<ref name="pmid16337775">{{cite journal | author = Nakamura M, Takii Y, Ito M, ''et al'' | title = Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis | journal = J. Autoimmun. | volume = 26 | issue = 2 | pages = 138-45 | year = 2006 | pmid = 16337775 | doi = 10.1016/j.jaut.2005.10.007}}</ref> Both proteins appear to be prognostic of liver failure relative to anti-mitochondrial antibodies.
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| ==Therapy== | | ==[[Primary biliary cirrhosis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| 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. However, specific treatment for fatigue, which may be invalidating in some patients, is unavailable. 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 of symptoms and whether it improves prognosis is controversial. To relieve itching caused by bile acids in circulation, which would normally be removed by the liver, [[cholestyramine]] (a [[bile acid sequestrant]]) may be prescribed to absorb bile acids in the gut and be eliminated, rather than re-enter the blood stream. As in all liver diseases, [[alcoholic beverage]]s are contraindicated. In advanced cases, a [[liver transplant]], if successful, results in a favourable prognosis.
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| Multivitamins (esp. Vitamin D) and calcium are also recommended as patients with PBC have poor lipid-dependent absorption of Vitamins A, D, E, K.
| | ==Diagnosis== |
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| ==Statistics== | |
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| The female:male ratio is not less than 9:1. 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. <ref>Medical care of the Liver Trasplant Patient, 3rd Edition published 2006, editied by Paul G. Killenberg, page 155</ref>
| | [[Primary biliary cirrhosis diagnostic study of choice|Diagnostic Study of Choice]] | [[Primary biliary cirrhosis history and symptoms|History and Symptoms]] | [[Primary biliary cirrhosis physical examination|Physical Examination]] | [[Primary biliary cirrhosis laboratory findings|Laboratory Findings]] | [[Primary biliary cirrhosis electrocardiogram|Electrocardiogram]] | [[Primary biliary cirrhosis x ray|X Ray]] | [[Primary biliary cirrhosis CT|CT]] | [[Primary biliary cirrhosis MRI|MRI]] | [[Primary biliary cirrhosis ultrasound|Ultrasound]] | [[Primary biliary cirrhosis other imaging findings|Other Imaging Findings]] | [[Primary biliary cirrhosis other diagnostic studies|Other Diagnostic Studies]] |
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| 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 <ref>Medical care of the Liver Trasplant Patient, 3rd Edition published 2006, editied by Paul G. Killenberg, page 429</ref>
| | ==Treatment== |
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| ==References==
| | [[Primary biliary cirrhosis medical therapy|Medical Therapy]] | [[Primary biliary cirrhosis surgery|Surgery]] | [[Primary biliary cirrhosis primary prevention|Primary Prevention]] | [[Primary biliary cirrhosis secondary prevention|Secondary Prevention]] | [[Primary biliary cirrhosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Primary biliary cirrhosis future or investigational therapies|Future or Investigational Therapies]] |
| <div class="references-small"><references/></div>
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| ==Sources== | | ==Case Studies== |
| ===Medical===
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| *{{OMIM|109720}}
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| *M. Eric Gershwin, John M. Vierling, Michael P. Manns, eds. ''Liver Immunology''. Philadelphia, Pa.: Hanley and Belfus, 2003. ISBN 1-56053-499-0. (State of the art; technical.)
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| *Marshall M. Kaplan, and M. Eric Gershwin, "Primary Biliary Cirrhosis", ''New Engl. J. of Medicine'', 353:1261-1273 September 22, 2005 Number 12 . Review article
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| *Carlo Selmi, Ross L. Coppel, and M. Eric Gershwin, "Primary Biliary Cirrhosis", in Noel R. Rose, Ian R. Mackey, eds, ''The Autoimmune Diseases'', 4th edition, Academic Press, 2006
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| ===General===
| | [[Primary biliary cirrhosis case study one|Case #1]] |
| *Sanjiv Chopra. ''The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery'', Atria, 2002, ISBN 0-7434-0585-4
| | ==Related Chapters== |
| *Melissa Palmer. ''Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease: What You Need to Know'', Avery Publishing Group; Revised edition May 24, 2004, ISBN 1-58333-188-3. [http://www.liverdisease.com her webpage].
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| *Howard J. Worman. ''The Liver Disorders Sourcebook'', McGraw-Hill, 1999, ISBN 0-7373-0090-6.
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| ==See also== | |
| *[[Bile canaliculus]] | | *[[Bile canaliculus]] |
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| ==External links==
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| * [http://pbcers.org PBCers.org] - patients' organisation
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| ** [http://pbcers.org/research.htm A summary of relevant research] (2004)
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| ** [http://pbcers.org/currentresearch.htm Current PBC clinical trials]
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| ** [http://pbcers.org/2005MC.htm June 2005 National (USA) PBC conference]
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| * [http://internalmedicine.ucdmc.ucdavis.edu/who/rheumatology/PBC_Lab/ Dr. Gershwin's research lab at UC Davis] Many research papers online.
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| * [http://www.pbcfoundation.org.uk/ PBC Foundation UK]
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| * [http://cpmcnet.columbia.edu/dept/gi/PBC.html Howard J. Worman's Columbia University web site, with a clear overview of PBC]
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| *[http://www.ii.bham.ac.uk/clinicalimmunology/CISimagelibrary/mito.htm AMA staining patterns]
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| *[http://www.youtube.com/watch?v=Jj8ozr_IttM&mode=related&search= Histopathology lecture on PBC]
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| {{SIB}}
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| {{Gastroenterology}}
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| [[Category:Gastroenterology]]
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| [[Category:Hepatology]]
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| [[Category:Autoimmune diseases]]
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| [[de:Primär biliäre Zirrhose]] | | [[de:Primär biliäre Zirrhose]] |
| [[pl:Pierwotna marskość żółciowa wątroby]] | | [[pl:Pierwotna marskość żółciowa wątroby]] |
| [[sv:primär biliär cirrhos]] | | [[sv:primär biliär cirrhos]] |
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