Primary sclerosing cholangitis pathophysiology: Difference between revisions
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===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
===Genetics=== | ===Genetics=== | ||
Primary sclerosing cholangitis is associated with environmental as well as genetic factors. The risk of primary sclerosing cholangitis among siblings is estimated to be 9-39 times higher than the general population.<ref name="pmid18674735">{{cite journal |vauthors=Bergquist A, Montgomery SM, Bahmanyar S, Olsson R, Danielsson A, Lindgren S, Prytz H, Hultcrantz R, Lööf LA, Sandberg-Gertzén H, Almer S, Askling J, Ehlin A, Ekbom A |title=Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis |journal=Clin. Gastroenterol. Hepatol. |volume=6 |issue=8 |pages=939–43 |year=2008 |pmid=18674735 |doi=10.1016/j.cgh.2008.03.016 |url=}}</ref> The [[HLA]] locus on [[chromosome]] 6p21<ref name="pmid19944697">{{cite journal |vauthors=Karlsen TH, Franke A, Melum E, Kaser A, Hov JR, Balschun T, Lie BA, Bergquist A, Schramm C, Weismüller TJ, Gotthardt D, Rust C, Philipp EE, Fritz T, Henckaerts L, Weersma RK, Stokkers P, Ponsioen CY, Wijmenga C, Sterneck M, Nothnagel M, Hampe J, Teufel A, Runz H, Rosenstiel P, Stiehl A, Vermeire S, Beuers U, Manns MP, Schrumpf E, Boberg KM, Schreiber S |title=Genome-wide association analysis in primary sclerosing cholangitis |journal=Gastroenterology |volume=138 |issue=3 |pages=1102–11 |year=2010 |pmid=19944697 |doi=10.1053/j.gastro.2009.11.046 |url=}}</ref> and [[genes]] of the [[IL-2]] pathway<ref name="pmid21151127">{{cite journal |vauthors=Melum E, Franke A, Schramm C, Weismüller TJ, Gotthardt DN, Offner FA, Juran BD, Laerdahl JK, Labi V, Björnsson E, Weersma RK, Henckaerts L, Teufel A, Rust C, Ellinghaus E, Balschun T, Boberg KM, Ellinghaus D, Bergquist A, Sauer P, Ryu E, Hov JR, Wedemeyer J, Lindkvist B, Wittig M, Porte RJ, Holm K, Gieger C, Wichmann HE, Stokkers P, Ponsioen CY, Runz H, Stiehl A, Wijmenga C, Sterneck M, Vermeire S, Beuers U, Villunger A, Schrumpf E, Lazaridis KN, Manns MP, Schreiber S, Karlsen TH |title=Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci |journal=Nat. Genet. |volume=43 |issue=1 |pages=17–9 |year=2011 |pmid=21151127 |pmc=4354850 |doi=10.1038/ng.728 |url=}}</ref><ref name="pmid23603763">{{cite journal |vauthors=Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, Andreassen OA, Weersma RK, Weismüller TJ, Eksteen B, Invernizzi P, Hirschfield GM, Gotthardt DN, Pares A, Ellinghaus D, Shah T, Juran BD, Milkiewicz P, Rust C, Schramm C, Müller T, Srivastava B, Dalekos G, Nöthen MM, Herms S, Winkelmann J, Mitrovic M, Braun F, Ponsioen CY, Croucher PJ, Sterneck M, Teufel A, Mason AL, Saarela J, Leppa V, Dorfman R, Alvaro D, Floreani A, Onengut-Gumuscu S, Rich SS, Thompson WK, Schork AJ, Næss S, Thomsen I, Mayr G, König IR, Hveem K, Cleynen I, Gutierrez-Achury J, Ricaño-Ponce I, van Heel D, Björnsson E, Sandford RN, Durie PR, Melum E, Vatn MH, Silverberg MS, Duerr RH, Padyukov L, Brand S, Sans M, Annese V, Achkar JP, Boberg KM, Marschall HU, Chazouillères O, Bowlus CL, Wijmenga C, Schrumpf E, Vermeire S, Albrecht M, Rioux JD, Alexander G, Bergquist A, Cho J, Schreiber S, Manns MP, Färkkilä M, Dale AM, Chapman RW, Lazaridis KN, Franke A, Anderson CA, Karlsen TH |title=Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis |journal=Nat. Genet. |volume=45 |issue=6 |pages=670–5 |year=2013 |pmid=23603763 |pmc=3667736 |doi=10.1038/ng.2616 |url=}}</ref> are associated with increased susceptibility to the development of primary sclerosing cholangitis. In addition, the following 16 [[gene]] [[Locus (genetics)|loci]] are associated with increased risk of primary sclerosing cholangitis. | Primary sclerosing cholangitis is associated with environmental as well as genetic factors. The risk of primary sclerosing cholangitis among siblings is estimated to be 9-39 times higher than the general population.<ref name="pmid18674735">{{cite journal |vauthors=Bergquist A, Montgomery SM, Bahmanyar S, Olsson R, Danielsson A, Lindgren S, Prytz H, Hultcrantz R, Lööf LA, Sandberg-Gertzén H, Almer S, Askling J, Ehlin A, Ekbom A |title=Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis |journal=Clin. Gastroenterol. Hepatol. |volume=6 |issue=8 |pages=939–43 |year=2008 |pmid=18674735 |doi=10.1016/j.cgh.2008.03.016 |url=}}</ref> The [[HLA]] locus on [[chromosome]] 6p21<ref name="pmid19944697">{{cite journal |vauthors=Karlsen TH, Franke A, Melum E, Kaser A, Hov JR, Balschun T, Lie BA, Bergquist A, Schramm C, Weismüller TJ, Gotthardt D, Rust C, Philipp EE, Fritz T, Henckaerts L, Weersma RK, Stokkers P, Ponsioen CY, Wijmenga C, Sterneck M, Nothnagel M, Hampe J, Teufel A, Runz H, Rosenstiel P, Stiehl A, Vermeire S, Beuers U, Manns MP, Schrumpf E, Boberg KM, Schreiber S |title=Genome-wide association analysis in primary sclerosing cholangitis |journal=Gastroenterology |volume=138 |issue=3 |pages=1102–11 |year=2010 |pmid=19944697 |doi=10.1053/j.gastro.2009.11.046 |url=}}</ref> and [[genes]] of the [[IL-2]] pathway<ref name="pmid21151127">{{cite journal |vauthors=Melum E, Franke A, Schramm C, Weismüller TJ, Gotthardt DN, Offner FA, Juran BD, Laerdahl JK, Labi V, Björnsson E, Weersma RK, Henckaerts L, Teufel A, Rust C, Ellinghaus E, Balschun T, Boberg KM, Ellinghaus D, Bergquist A, Sauer P, Ryu E, Hov JR, Wedemeyer J, Lindkvist B, Wittig M, Porte RJ, Holm K, Gieger C, Wichmann HE, Stokkers P, Ponsioen CY, Runz H, Stiehl A, Wijmenga C, Sterneck M, Vermeire S, Beuers U, Villunger A, Schrumpf E, Lazaridis KN, Manns MP, Schreiber S, Karlsen TH |title=Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci |journal=Nat. Genet. |volume=43 |issue=1 |pages=17–9 |year=2011 |pmid=21151127 |pmc=4354850 |doi=10.1038/ng.728 |url=}}</ref><ref name="pmid23603763">{{cite journal |vauthors=Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, Andreassen OA, Weersma RK, Weismüller TJ, Eksteen B, Invernizzi P, Hirschfield GM, Gotthardt DN, Pares A, Ellinghaus D, Shah T, Juran BD, Milkiewicz P, Rust C, Schramm C, Müller T, Srivastava B, Dalekos G, Nöthen MM, Herms S, Winkelmann J, Mitrovic M, Braun F, Ponsioen CY, Croucher PJ, Sterneck M, Teufel A, Mason AL, Saarela J, Leppa V, Dorfman R, Alvaro D, Floreani A, Onengut-Gumuscu S, Rich SS, Thompson WK, Schork AJ, Næss S, Thomsen I, Mayr G, König IR, Hveem K, Cleynen I, Gutierrez-Achury J, Ricaño-Ponce I, van Heel D, Björnsson E, Sandford RN, Durie PR, Melum E, Vatn MH, Silverberg MS, Duerr RH, Padyukov L, Brand S, Sans M, Annese V, Achkar JP, Boberg KM, Marschall HU, Chazouillères O, Bowlus CL, Wijmenga C, Schrumpf E, Vermeire S, Albrecht M, Rioux JD, Alexander G, Bergquist A, Cho J, Schreiber S, Manns MP, Färkkilä M, Dale AM, Chapman RW, Lazaridis KN, Franke A, Anderson CA, Karlsen TH |title=Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis |journal=Nat. Genet. |volume=45 |issue=6 |pages=670–5 |year=2013 |pmid=23603763 |pmc=3667736 |doi=10.1038/ng.2616 |url=}}</ref> are associated with increased susceptibility to the development of primary sclerosing cholangitis. In addition, the following 16 [[gene]] [[Locus (genetics)|loci]] are associated with increased risk of primary sclerosing cholangitis.<ref name="pmid19944697">{{cite journal |vauthors=Karlsen TH, Franke A, Melum E, Kaser A, Hov JR, Balschun T, Lie BA, Bergquist A, Schramm C, Weismüller TJ, Gotthardt D, Rust C, Philipp EE, Fritz T, Henckaerts L, Weersma RK, Stokkers P, Ponsioen CY, Wijmenga C, Sterneck M, Nothnagel M, Hampe J, Teufel A, Runz H, Rosenstiel P, Stiehl A, Vermeire S, Beuers U, Manns MP, Schrumpf E, Boberg KM, Schreiber S |title=Genome-wide association analysis in primary sclerosing cholangitis |journal=Gastroenterology |volume=138 |issue=3 |pages=1102–11 |year=2010 |pmid=19944697 |doi=10.1053/j.gastro.2009.11.046 |url=}}</ref><ref name="pmid21151127">{{cite journal |vauthors=Melum E, Franke A, Schramm C, Weismüller TJ, Gotthardt DN, Offner FA, Juran BD, Laerdahl JK, Labi V, Björnsson E, Weersma RK, Henckaerts L, Teufel A, Rust C, Ellinghaus E, Balschun T, Boberg KM, Ellinghaus D, Bergquist A, Sauer P, Ryu E, Hov JR, Wedemeyer J, Lindkvist B, Wittig M, Porte RJ, Holm K, Gieger C, Wichmann HE, Stokkers P, Ponsioen CY, Runz H, Stiehl A, Wijmenga C, Sterneck M, Vermeire S, Beuers U, Villunger A, Schrumpf E, Lazaridis KN, Manns MP, Schreiber S, Karlsen TH |title=Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci |journal=Nat. Genet. |volume=43 |issue=1 |pages=17–9 |year=2011 |pmid=21151127 |pmc=4354850 |doi=10.1038/ng.728 |url=}}</ref><ref name="pmid23603763">{{cite journal |vauthors=Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, Andreassen OA, Weersma RK, Weismüller TJ, Eksteen B, Invernizzi P, Hirschfield GM, Gotthardt DN, Pares A, Ellinghaus D, Shah T, Juran BD, Milkiewicz P, Rust C, Schramm C, Müller T, Srivastava B, Dalekos G, Nöthen MM, Herms S, Winkelmann J, Mitrovic M, Braun F, Ponsioen CY, Croucher PJ, Sterneck M, Teufel A, Mason AL, Saarela J, Leppa V, Dorfman R, Alvaro D, Floreani A, Onengut-Gumuscu S, Rich SS, Thompson WK, Schork AJ, Næss S, Thomsen I, Mayr G, König IR, Hveem K, Cleynen I, Gutierrez-Achury J, Ricaño-Ponce I, van Heel D, Björnsson E, Sandford RN, Durie PR, Melum E, Vatn MH, Silverberg MS, Duerr RH, Padyukov L, Brand S, Sans M, Annese V, Achkar JP, Boberg KM, Marschall HU, Chazouillères O, Bowlus CL, Wijmenga C, Schrumpf E, Vermeire S, Albrecht M, Rioux JD, Alexander G, Bergquist A, Cho J, Schreiber S, Manns MP, Färkkilä M, Dale AM, Chapman RW, Lazaridis KN, Franke A, Anderson CA, Karlsen TH |title=Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis |journal=Nat. Genet. |volume=45 |issue=6 |pages=670–5 |year=2013 |pmid=23603763 |pmc=3667736 |doi=10.1038/ng.2616 |url=}}</ref> | ||
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!Locus | !Locus | ||
Revision as of 18:54, 9 December 2016
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Primary sclerosing cholangitis Microchapters |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]
Overview
Pathophysiology
Pathogenesis
Gross Pathology
Microscopic Pathology
Genetics
Primary sclerosing cholangitis is associated with environmental as well as genetic factors. The risk of primary sclerosing cholangitis among siblings is estimated to be 9-39 times higher than the general population.[1] The HLA locus on chromosome 6p21[2] and genes of the IL-2 pathway[3][4] are associated with increased susceptibility to the development of primary sclerosing cholangitis. In addition, the following 16 gene loci are associated with increased risk of primary sclerosing cholangitis.[2][3][4]
| Locus | Gene |
|---|---|
| 1p36 | MMEL1 |
| 2q13 | BCL2L11 |
| 2q33 | CD28 |
| 2q37 | GPR35 |
| 3p21 | MST1 |
| 4q27 | IL2 / IL21 |
| 6p21 | HLA B |
| 6q15 | BACH2 |
| 10p15 | IL2RA |
| 11q23 | SIK2 |
| 12q13 | HDAC7 |
| 12q24 | SH2B3 |
| 18q21 | TCF4 |
| 18q22 | CD226 |
| 19q13 | PRKD2 |
| 21q22 | PSMG1 / ETS2 |
Associated Conditions
Some of the conditions associated with primary sclerosing cholangitis include:[5]
- Inflammatory bowel disease (IBD): approximately 70-80% of patients with primary sclerosing cholangitis have IBD (Crohn's disease and ulcerative colitis).[6]
- Autoimmune hepatitis: approximately 35% of children with primary sclerosing cholangitis have associated autoimmune hepatitis[7], while only 5% of adults have combined primary sclerosing cholangitis with associated autoimmune hepatitis.[8]
- Gallbladder disease: this includes gallbladder stones and cholecystitis, polyps and cancer.[9][10]
References
- ↑ Bergquist A, Montgomery SM, Bahmanyar S, Olsson R, Danielsson A, Lindgren S, Prytz H, Hultcrantz R, Lööf LA, Sandberg-Gertzén H, Almer S, Askling J, Ehlin A, Ekbom A (2008). "Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis". Clin. Gastroenterol. Hepatol. 6 (8): 939–43. doi:10.1016/j.cgh.2008.03.016. PMID 18674735.
- ↑ 2.0 2.1 Karlsen TH, Franke A, Melum E, Kaser A, Hov JR, Balschun T, Lie BA, Bergquist A, Schramm C, Weismüller TJ, Gotthardt D, Rust C, Philipp EE, Fritz T, Henckaerts L, Weersma RK, Stokkers P, Ponsioen CY, Wijmenga C, Sterneck M, Nothnagel M, Hampe J, Teufel A, Runz H, Rosenstiel P, Stiehl A, Vermeire S, Beuers U, Manns MP, Schrumpf E, Boberg KM, Schreiber S (2010). "Genome-wide association analysis in primary sclerosing cholangitis". Gastroenterology. 138 (3): 1102–11. doi:10.1053/j.gastro.2009.11.046. PMID 19944697.
- ↑ 3.0 3.1 Melum E, Franke A, Schramm C, Weismüller TJ, Gotthardt DN, Offner FA, Juran BD, Laerdahl JK, Labi V, Björnsson E, Weersma RK, Henckaerts L, Teufel A, Rust C, Ellinghaus E, Balschun T, Boberg KM, Ellinghaus D, Bergquist A, Sauer P, Ryu E, Hov JR, Wedemeyer J, Lindkvist B, Wittig M, Porte RJ, Holm K, Gieger C, Wichmann HE, Stokkers P, Ponsioen CY, Runz H, Stiehl A, Wijmenga C, Sterneck M, Vermeire S, Beuers U, Villunger A, Schrumpf E, Lazaridis KN, Manns MP, Schreiber S, Karlsen TH (2011). "Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci". Nat. Genet. 43 (1): 17–9. doi:10.1038/ng.728. PMC 4354850. PMID 21151127.
- ↑ 4.0 4.1 Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, Andreassen OA, Weersma RK, Weismüller TJ, Eksteen B, Invernizzi P, Hirschfield GM, Gotthardt DN, Pares A, Ellinghaus D, Shah T, Juran BD, Milkiewicz P, Rust C, Schramm C, Müller T, Srivastava B, Dalekos G, Nöthen MM, Herms S, Winkelmann J, Mitrovic M, Braun F, Ponsioen CY, Croucher PJ, Sterneck M, Teufel A, Mason AL, Saarela J, Leppa V, Dorfman R, Alvaro D, Floreani A, Onengut-Gumuscu S, Rich SS, Thompson WK, Schork AJ, Næss S, Thomsen I, Mayr G, König IR, Hveem K, Cleynen I, Gutierrez-Achury J, Ricaño-Ponce I, van Heel D, Björnsson E, Sandford RN, Durie PR, Melum E, Vatn MH, Silverberg MS, Duerr RH, Padyukov L, Brand S, Sans M, Annese V, Achkar JP, Boberg KM, Marschall HU, Chazouillères O, Bowlus CL, Wijmenga C, Schrumpf E, Vermeire S, Albrecht M, Rioux JD, Alexander G, Bergquist A, Cho J, Schreiber S, Manns MP, Färkkilä M, Dale AM, Chapman RW, Lazaridis KN, Franke A, Anderson CA, Karlsen TH (2013). "Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis". Nat. Genet. 45 (6): 670–5. doi:10.1038/ng.2616. PMC 3667736. PMID 23603763.
- ↑ Lazaridis KN, LaRusso NF (2016). "Primary Sclerosing Cholangitis". N. Engl. J. Med. 375 (12): 1161–70. doi:10.1056/NEJMra1506330. PMID 27653566.
- ↑ Molodecky NA, Kareemi H, Parab R, Barkema HW, Quan H, Myers RP, Kaplan GG (2011). "Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis". Hepatology. 53 (5): 1590–9. doi:10.1002/hep.24247. PMID 21351115.
- ↑ Feldstein AE, Perrault J, El-Youssif M, Lindor KD, Freese DK, Angulo P (2003). "Primary sclerosing cholangitis in children: a long-term follow-up study". Hepatology. 38 (1): 210–7. doi:10.1053/jhep.2003.50289. PMID 12830004.
- ↑ Kaya M, Angulo P, Lindor KD (2000). "Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system". J. Hepatol. 33 (4): 537–42. PMID 11059857.
- ↑ Buckles DC, Lindor KD, Larusso NF, Petrovic LM, Gores GJ (2002). "In primary sclerosing cholangitis, gallbladder polyps are frequently malignant". Am. J. Gastroenterol. 97 (5): 1138–42. doi:10.1111/j.1572-0241.2002.05677.x. PMID 12014717.
- ↑ Said K, Glaumann H, Bergquist A (2008). "Gallbladder disease in patients with primary sclerosing cholangitis". J. Hepatol. 48 (4): 598–605. doi:10.1016/j.jhep.2007.11.019. PMID 18222013.