Primary biliary cirrhosis pathophysiology
|
Primary Biliary Cirrhosis Microchapters |
|
Differentiating Primary Biliary Cirrhosis from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Primary biliary cirrhosis pathophysiology On the Web |
|
American Roentgen Ray Society Images of Primary biliary cirrhosis pathophysiology |
|
Risk calculators and risk factors for Primary biliary cirrhosis pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Please help WikiDoc by adding content here. It's easy! Click here to learn about editing.
Overview
Pathophysiology
The pathogenesis of the disease is unknown at this time, but research indicates that there is an 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 trans peptidase test (GGTP). An increase in GGTP could indicate presence of primary biliary cirrhosis.
57% of patients with acute liver failure have anti-transglutaminase antibodies[1] suggesting a role of gluten sensitivity in primary biliary cirrhosis, and primary biliary cirrhosis is considerable more common in gluten sensitive enteropathy than the normal population.[2][3]
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.[4] Both proteins appear to be prognostic of liver failure relative to anti-mitochondrial antibodies.
In 2003 it was reported that an environmental gram negative alphabacterium — Novosphingobium aromaticivorans[5] was strongly associated with this disease. Subsequent reports appear to have confirmed this finding suggesting an aetiological role for this organism.[6][7][8] The mechanism appears to be a cross reaction between the proteins of the bacterium and the mitochondrial proteins of the liver cells.[9] The gene encoding CD101 may also play a role in host susceptibility to this disease.[10]
Genetics
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 genome scan of PBC patients.[11][12] 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, suggesting future therapeutic targets.
Histopathology
{{#ev:youtube|Jj8ozr_IttM&mode=related&search=}}
References
- ↑ Leung PS, Rossaro L, Davis PA; et al. (2007). "Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis". doi:10.1002/hep.21828. PMID 17657817.
- ↑ Logan RF, Ferguson A, Finlayson ND, Weir DG (1978). "Primary biliary cirrhosis and coeliac disease: an association?". Lancet. 1 (8058): 230–3. PMID 74661.
- ↑ Volta U, Rodrigo L, Granito A; et al. (2002). "Celiac disease in autoimmune cholestatic liver disorders". Am. J. Gastroenterol. 97 (10): 2609–13. PMID 12385447.
- ↑ Nakamura M, Takii Y, Ito M; et al. (2006). "Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis". J. Autoimmun. 26 (2): 138–45. doi:10.1016/j.jaut.2005.10.007. PMID 16337775.
- ↑ Selmi C, Balkwill DL, Invernizzi P; et al. (2003). "Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium". Hepatology. 38 (5): 1250–7. doi:10.1053/jhep.2003.50446. PMID 14578864. Unknown parameter
|month=ignored (help) - ↑ Mohammed JP, Mattner J (2009). "Autoimmune disease triggered by infection with alphaproteobacteria". Expert Rev Clin Immunol. 5 (4): 369–379. doi:10.1586/ECI.09.23. PMC 2742979. PMID 20161124. Unknown parameter
|month=ignored (help) - ↑ Kaplan MM (2004). "Novosphingobium aromaticivorans: a potential initiator of primary biliary cirrhosis". Am. J. Gastroenterol. 99 (11): 2147–9. doi:10.1111/j.1572-0241.2004.41121.x. PMID 15554995. Unknown parameter
|month=ignored (help) - ↑ Selmi C, Gershwin ME (2004). "Bacteria and human autoimmunity: the case of primary biliary cirrhosis". Curr Opin Rheumatol. 16 (4): 406–10. PMID 15201604. Unknown parameter
|month=ignored (help) - ↑ Mattner J, Savage PB, Leung P; et al. (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. Unknown parameter
|month=ignored (help) - ↑ Mohammed JP, Fusakio ME, Rainbow DB; et al. (2011). "Identification of Cd101 as a susceptibility gene for Novosphingobium aromaticivorans-induced liver autoimmunity". J. Immunol. 187 (1): 337–49. doi:10.4049/jimmunol.1003525. PMC 3134939. PMID 21613619. Unknown parameter
|month=ignored (help) - ↑ Hirschfield GM, Liu X, Xu C; et al. (2009). "Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants". N. Engl. J. Med. 360 (24): 2544–55. doi:10.1056/NEJMoa0810440. PMC 2857316. PMID 19458352. Unknown parameter
|month=ignored (help) - ↑ http://www.torontoliver.ca