Editing Primary sclerosing cholangitis (section)

==Cause==
The exact cause of primary sclerosing cholangitis is  unknown, and its pathogenesis is improperly understood.<ref name="Lazaridis2016"/> Although PSC is thought to be caused by [[autoimmune disease]], it does not demonstrate a clear response to immunosuppressants. Thus, many experts believe it to be a complex, multifactorial (including immune-mediated) disorder and perhaps one that encompasses several different hepatobiliary diseases.<ref name="ReferenceB">{{cite journal | vauthors = Tabibian JH, Lindor KD | title = Primary sclerosing cholangitis: a review and update on therapeutic developments | journal = Expert Review of Gastroenterology & Hepatology | volume = 7 | issue = 2 | pages = 103–114 | date = February 2013 | pmid = 23363260 | doi = 10.1586/egh.12.80 | s2cid = 207210857 }}</ref><ref>{{cite journal | vauthors = O'Hara SP, Tabibian JH, Splinter PL, LaRusso NF | title = The dynamic biliary epithelia: molecules, pathways, and disease | journal = Journal of Hepatology | volume = 58 | issue = 3 | pages = 575–582 | date = March 2013 | pmid = 23085249 | pmc = 3831345 | doi = 10.1016/j.jhep.2012.10.011 }}</ref> Alternatively, some experts have suggested that the reason immunosuppressant medications are ineffective is because PSC almost always remains undiagnosed until a very advanced stage, at which point damage may be irreversible or require more aggressive treatment than other autoimmune diseases.<ref name=":2" />

Data have provided novel insights suggesting:
# an important association between the intestinal [[microbiota]] and PSC<ref>{{cite journal | vauthors = Tabibian JH, O'Hara SP, Lindor KD | title = Primary sclerosing cholangitis and the microbiota: current knowledge and perspectives on etiopathogenesis and emerging therapies | journal = Scandinavian Journal of Gastroenterology | volume = 49 | issue = 8 | pages = 901–908 | date = August 2014 | pmid = 24990660 | pmc = 4210190 | doi = 10.3109/00365521.2014.913189 }}</ref><ref>{{cite journal | vauthors = Tabibian JH, Varghese C, O'Hara SP, LaRusso NF | title = Microbiome-Immune Interactions and Liver Disease | journal = Clinical Liver Disease | volume = 5 | issue = 4 | pages = 83–85 | date = April 2015 | pmid = 29755735 | pmc = 5944616 | doi = 10.1002/cld.453 }}</ref><ref>{{cite journal | vauthors = Tabibian JH, Varghese C, LaRusso NF, O'Hara SP | title = The enteric microbiome in hepatobiliary health and disease | journal = Liver International | volume = 36 | issue = 4 | pages = 480–487 | date = April 2016 | pmid = 26561779 | pmc = 4825184 | doi = 10.1111/liv.13009 }}</ref> and
# a process referred to as [[cellular senescence]] and the senescence-associated secretory phenotype in the pathogenesis of PSC.<ref>{{cite journal | vauthors = Tabibian JH, O'Hara SP, Splinter PL, Trussoni CE, LaRusso NF | title = Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis | journal = Hepatology | volume = 59 | issue = 6 | pages = 2263–2275 | date = June 2014 | pmid = 24390753 | pmc = 4167827 | doi = 10.1002/hep.26993 }}</ref><ref>{{cite journal | vauthors = Tabibian JH, Trussoni CE, O'Hara SP, Splinter PL, Heimbach JK, LaRusso NF | title = Characterization of cultured cholangiocytes isolated from livers of patients with primary sclerosing cholangitis | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 94 | issue = 10 | pages = 1126–1133 | date = October 2014 | pmid = 25046437 | pmc = 4184949 | doi = 10.1038/labinvest.2014.94 }}</ref>
In addition, longstanding, well-recognized associations are seen between PSC and [[human leukocyte antigen]] alleles (A1, B8, and DR3).<ref name=Charatchar/>