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| {{Infobox_Disease |
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| Name = {{PAGENAME}} |
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| Caption = |
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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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| MedlinePlus = |
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| MeshID = D008105 |
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| {{Search infobox}}
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| {{CMG}}
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| '''Associate Editor(s)-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''' 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]]. | | {{Primary biliary cirrhosis}} |
| ==Historical Perspective==
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| 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 1986.<ref name=Mitchison1986>{{cite journal |author=Mitchison HC, Bassendine MF, Hendrick A, ''et al.'' |title=Positive antimitochondrial antibody but normal alkaline phosphatase: is this primary biliary cirrhosis? |journal=Hepatology |volume=6 |issue=6 |pages=1279–84 |year=1986 |pmid=3793004 |doi=10.1002/hep.1840060609}}</ref>
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| ==Causes==
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| 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]].
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| 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.
| | {{CMG}}; {{AE}}{{Anmol}}, {{SH}}, {{AA}}, {{ARK}} |
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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>
| | {{SK}} Chronic non-suppurative destructive cholangitis, PBC, Primary biliary cholangitis. |
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| 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.
| | ==[[Primary biliary cirrhosis overview|Overview]]== |
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| ==Epidemiology and Demographics== | | ==[[Primary biliary cirrhosis historical perspective|Historical Perspective]]== |
| The female:male ratio is at least 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.
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| ==Natural history, Complications and Prognosis==
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| ===Complicatons===
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| Patients with primary biliary cirrhosis have an increased risk of [[hepatocellular carcinoma]].
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| ===Prognosis===
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| The serum [[bilirubin]] level is an indicator of the prognosis of primary biliary cirrhosis, 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.<ref>[http://emedicine.medscape.com/article/171117-followup eMedicine > Primary Biliary Cirrhosis: Follow-up] Author: Nikolaos T Pyrsopoulos. Coauthor: K Rajender Reddy. Updated: Dec 23, 2009</ref>
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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 name="k&c-p429">Killenberg & Clavien (2006), p. 429.</ref>
| | ==[[Primary biliary cirrhosis classification|Classification]]== |
| ==Diagnosis== | |
| ===History and Symptoms===
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| The following symptoms 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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| * Association with an extrahepatic autoimmune disorder such as Rheumatoid Arthritis or Sjögren syndrome (up to 80% incidence).
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| ===Physical Examination===
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| On physical examination, the following may be present
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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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| **[[Esophageal varices]]
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| ** Fluid retention in the abdomen ([[ascites]])
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| ** [[Hepatic encephalopathy]], up to coma, in extreme cases.
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| ===Laboratory tests=== | | ==[[Primary biliary cirrhosis pathophysiology|Pathophysiology]]== |
| 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 causes|Causes]]== |
| * 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]], [[Anti-glycoprotein-210 antibodies]], [[Anti-centromere antibodies]], anti-sp100. (the M2-[[IgG]] antimitochondrial antibody is the most specific test)
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| ===Ultrasound===
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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.
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| | ==[[Primary biliary cirrhosis differential diagnosis|Differentiating Primary Biliary Cirrhosis from other Diseases]]== |
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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 epidemiology and demographics|Epidemiology and Demographics]]== |
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| ===Summary of stages=== | | ==[[Primary biliary cirrhosis risk factors|Risk Factors]]== |
| *''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 screening|Screening]]== |
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| *''Stage 3 - Septal Stage'': Active and/or passive fibrous [[septa]].
| | ==[[Primary biliary cirrhosis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| *''Stage 4 - Biliary Cirrhosis'': Nodules present; garland or jigsaw pattern.
| | ==Diagnosis== |
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| ==Therapy== | |
| 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. 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>
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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.
| | [[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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| ==References== | | ==Treatment== |
| <div class="references-small"><references/></div>
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| ==Sources==
| | [[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]] |
| ===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=== | | ==Case Studies== |
| *Sanjiv Chopra. ''The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery'', Atria, 2002, ISBN 0-7434-0585-4
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| *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== | | [[Primary biliary cirrhosis case study one|Case #1]] |
| | ==Related Chapters== |
| *[[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:Autoimmune diseases]]
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