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| '''For patient information page on this topic, click [[Primary biliary cirrhosis (patient information)|here]].''' | | '''For patient information page on this topic, click [[Primary biliary cirrhosis (patient information)|here]].''' |
| {{Primary biliary cirrhosis}} | | {{Primary biliary cirrhosis}} |
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| {{CMG}} '''Associate Editor(s)-In-Chief:''' {{CZ}} [[User: Prashanthsaddala|Prashanth Saddala M.B.B.S]] | | {{CMG}}; {{AE}}{{Anmol}}, {{SH}}, {{AA}}, {{ARK}} |
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| {{SK}} Chronic non-suppurative destructive cholangitis, PBC | | {{SK}} Chronic non-suppurative destructive cholangitis, PBC, Primary biliary cholangitis. |
| ==Causes==
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| ==Diagnosis== | | ==[[Primary biliary cirrhosis overview|Overview]]== |
| ===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=== | |
| 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 historical perspective|Historical Perspective]]== |
| 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 classification|Classification]]== |
| * 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|antinuclear antibodies]] like [[Anti-glycoprotein-210 antibodies]], [[Anti-centromere antibodies]], anti-sp100. (the M2-[[IgG]] antimitochondrial antibody is the most specific test)
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| ===Liver Biopsy===
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| Primary biliary cirrhosis is characterized by interlobular bile duct destruction. [[Histopathologic]] findings of primary biliary cirrhosis include:<ref name=pmid10976014>{{cite journal | pmid = 10976014 | doi=10.1053/bega.2000.0103 | volume=14 | issue=4 | title=Destruction of bile ducts in primary biliary cirrhosis | year=2000 | month=August | author=Nakanuma Y, Tsuneyama K, Sasaki M, Harada K | journal=Baillieres Best Pract Res Clin Gastroenterol | pages=549–70}}</ref> | |
| *Inflammation of the bile ducts, characterized by intraepithelial [[lymphocyte]]s, and
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| *Periductal [[epithelioid]] [[granulomata]].
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| A liver biopsy is necessary to determine the stage of disease.
| | ==[[Primary biliary cirrhosis pathophysiology|Pathophysiology]]== |
| ===Other Diagnostic studies=== | |
| 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]]).
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| 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 causes|Causes]]== |
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| '''MR images of a patient with primary biliary cirrhosis'''
| | ==[[Primary biliary cirrhosis differential diagnosis|Differentiating Primary Biliary Cirrhosis from other Diseases]]== |
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| <gallery>
| | ==[[Primary biliary cirrhosis epidemiology and demographics|Epidemiology and Demographics]]== |
| Image:
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| Primary biliary cirrhosis 001.jpg|T2 | | ==[[Primary biliary cirrhosis risk factors|Risk Factors]]== |
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| Image:
| | ==[[Primary biliary cirrhosis screening|Screening]]== |
| Primary biliary cirrhosis 002.jpg|T2Image: | |
| Primary biliary cirrhosis 003.jpg|T1 preImage:
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| Primary biliary cirrhosis 004.jpg|T1 postImage:
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| Primary biliary cirrhosis 005.jpg|T1 postImage:
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| Primary biliary cirrhosis 006.jpg|T1 postImage:
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| Primary biliary cirrhosis 007.jpg|T1 post</gallery>
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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. Specific treatment for fatigue, which may be debilitating in some patients, is limited and currently undergoing trials.
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| * 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.
| | ==Diagnosis== |
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| * 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. Alternative agents include [[naltrexone]] and [[rifampicin]].
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| * To relieve fatigue associated with primary biliary cirrhosis, current studies indicate that Provigil (modafinil) may be effective without damaging the liver.<ref>[[Modafinil#Primary_biliary_cirrhosis]]<br/>{{cite journal |author=Ian Gan S, de Jongh M, Kaplan MM |title=Modafinil in the treatment of debilitating fatigue in primary biliary cirrhosis: a clinical experience |journal=Dig. Dis. Sci. |volume=54 |issue=10 |pages=2242–6 |year=2009 |month=October |pmid=19082890 |doi=10.1007/s10620-008-0613-3 |url=http://www.springerlink.com/content/f0207x6110847113/}}<br/>{{cite journal |author=Kumagi T, Heathcote EJ |title=Primary biliary cirrhosis |journal=Orphanet J Rare Dis |volume=3 |pages=1 |year=2008 |pmid=18215315 |pmc=2266722 |doi=10.1186/1750-1172-3-1 |url=http://www.ojrd.com/content/3//1 |quote=[http://www.ojrd.com/content/3/1/1#B157 Ref 157 viz:]}}<br/>{{cite journal |author=Jones DE, Newton JL |title=An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis |journal=Aliment. Pharmacol. Ther. |volume=25 |issue=4 |pages=471–6 |year=2007 |month=February |pmid=17270003 |doi=10.1111/j.1365-2036.2006.03223.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0269-2813&date=2007&volume=25&issue=4&spage=471}}</ref> 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.<ref>[[Modafinil#Patent_protection_and_antitrust_litigation]]<br/>{{cite journal |author=Carrier MA |title=Provigil: A Case Study of Anticompetitive Behavior |journal=Hastings Science & Technology Law Journal |volume=3 |issue=2 |pages=441–452 |year=2011 |url=http://hstlj.org/content/vol3/iss2/v3i2carrier.pdf |format=PDF}}</ref> The FTC has filed suit against Cephalon alleging anti-competitive behavior.<ref>http://www.ftc.gov/os/caselist/0610182/080213complaint.pdf</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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| * Patients with PBC have poor lipid-dependent absorption of Vitamins A, D, E, K.<ref name="BaconO'Grady2006">{{cite book|author1=Bruce R. Bacon|author2=John G. O'Grady|title=Comprehensive clinical hepatology|url=http://books.google.com/?id=ec0G9HGiR8MC&pg=PA283|accessdate=29 June 2010|year=2006|publisher=Elsevier Health Sciences|isbn=978-0-323-03675-7|pages=283–}}</ref> Appropriate supplementation is recommended when bilirubin is elevated<ref>{{cite journal|last=Lindor|first=KD|coauthors=Gershwin, ME; Poupon, R; Kaplan, M; Bergasa, NV; Heathcote, EJ; American Association for Study of Liver, Diseases|title=Primary biliary cirrhosis.|journal=Hepatology (Baltimore, Md.)|date=2009 Jul|volume=50|issue=1|pages=291-308|pmid=19554543|doi=10.1002/hep.22906}}</ref>. Multivitamins (esp. Vitamin D) and calcium are also recommended.
| | ==Treatment== |
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| * Patients with PBC are at elevated risk of developing [[osteoporosis]]<ref>{{cite journal|last=Collier|first=Jane|title=Guidelines on the management of osteoporosis associated with chronic liver disease|journal=Gut|year=2002|volume=50|pages=i1-i9|pmid=11788576|accessdate=14 June 2012|pmc=1867644}}</ref> and [[esophageal varices]]<ref>{{cite journal|last=Ali|first=AH|coauthors=Sinakos, E; Silveira, MG; Jorgensen, RA; Angulo, P; Lindor, KD|title=Varices in early histological stage primary biliary cirrhosis.|journal=Journal of Clinical Gastroenterology|date=2011 Aug|volume=45|issue=7|pages=e66-71|pmid=20856137|doi=10.1097/MCG.0b013e3181f18c4e}}</ref> 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.
| | [[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]] |
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| *As in all liver diseases, [[alcoholic beverage]]s are contraindicated.
| | ==Case Studies== |
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| As in all liver diseases, excessive consumption of [[alcohol]] is contraindicated.
| | [[Primary biliary cirrhosis case study one|Case #1]] |
| | | ==Related Chapters== |
| In advanced cases, a [[Liver transplantation|liver transplant]], if successful, results in a favorable 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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| [[Obeticholic acid]] is in phase III clinical trials for PBC.<ref>http://www.genengnews.com/gen-news-highlights/dainippon-sumitomo-pays-intercept-15m-for-phase-iii-liver-disease-drug/81244901/</ref>
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| ==References==
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| <div class="references-small"><references/></div>
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| ==Sources==
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| ===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===
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| *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== | |
| *[[Bile canaliculus]] | | *[[Bile canaliculus]] |
| | <br> |
| | [[de:Primär biliäre Zirrhose]] |
| | [[pl:Pierwotna marskość żółciowa wątroby]] |
| | [[sv:primär biliär cirrhos]] |
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| ==External Links==
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| * [http://pbcers.org PBCers.org] - patients' organisation
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| * [http://www.pbcfoundation.org.uk/ PBC Foundation UK]
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| [[Category:Autoimmune diseases]]
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