Editing Primary sclerosing cholangitis (section)

==Prognosis==
There are no reliable prognostic models for PSC, owing to the highly variable disease course. Patients who are asymptomatic at the time of diagnosis are known to have better outcomes than those who have symptoms. However, many asymptomatic patients will develop symptoms later in time. Laboratory tests such as [[liver function tests]] are surprisingly unreliable when used as prognostic indicators for PSC.<ref name=":2" />

Estimated median survival from diagnosis until liver transplant or PSC-related death is 21.3 years.<ref>{{cite journal | vauthors = Boonstra K, Weersma RK, van Erpecum KJ, Rauws EA, Spanier BW, Poen AC, van Nieuwkerk KM, Drenth JP, Witteman BJ, Tuynman HA, Naber AH, Kingma PJ, van Buuren HR, van Hoek B, Vleggaar FP, van Geloven N, Beuers U, Ponsioen CY | display-authors = 6 | title = Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis | journal = Hepatology | volume = 58 | issue = 6 | pages = 2045–2055 | date = December 2013 | pmid = 23775876 | doi = 10.1002/hep.26565 | hdl-access = free | s2cid = 205889681 | hdl = 1887/117347 }}</ref> Various models have been developed to help predict survival,<ref>{{cite journal | vauthors = Tornai D, Ven PL, Lakatos PL, Papp M | title = Serological biomarkers for management of primary sclerosing cholangitis | journal = World Journal of Gastroenterology | volume = 28 | issue = 21 | pages = 2291–2301 | date = June 2022 | pmid = 35800183 | pmc = 9185217 | doi = 10.3748/wjg.v28.i21.2291 | doi-access = free }}</ref> but their use is generally best suited for research and not clinical purposes. A serum [[alkaline phosphatase]] less than 1.5 times the upper limit of normal has been associated with better outcomes, but its use in predicting long-term outcomes is unclear.<ref name="Lazaridis2016" /> An [[Immunoglobulin A|IgA]] isotype [[autoantibody]] to the pancreatic [[GP2 (gene)|GP2]] protein (anti-GP2 IgA antibody) is the first verified prognostic biomarker in PSC.<ref name=":1">{{cite journal | vauthors = Tornai D, Papp M | title = Editorial: serologic antibodies in primary sclerosing cholangitis – a tell-tale sign of compromised gut-liver immunity? | journal = Alimentary Pharmacology & Therapeutics | volume = 53 | issue = 2 | pages = 350–351 | date = January 2021 | pmid = 33368511 | doi = 10.1111/apt.16201 | s2cid = 229379767 | doi-access = free }}</ref> The role of anti-GP2 IgA in PSC was simultaneously investigated and reported by two research groups,<ref>{{cite journal | vauthors = Jendrek ST, Gotthardt D, Nitzsche T, Widmann L, Korf T, Michaels MA, Weiss KH, Liaskou E, Vesterhus M, Karlsen TH, Mindorf S, Schemmer P, Bär F, Teegen B, Schröder T, Ehlers M, Hammers CM, Komorowski L, Lehnert H, Fellermann K, Derer S, Hov JR, Sina C | display-authors = 6 | title = Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis | journal = Gut | volume = 66 | issue = 1 | pages = 137–144 | date = January 2017 | pmid = 27406039 | doi = 10.1136/gutjnl-2016-311739 | s2cid = 3479797 | hdl = 10852/62341 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Tornai T, Tornai D, Sipeki N, Tornai I, Alsulaimani R, Fechner K, Roggenbuck D, Norman GL, Veres G, Par G, Par A, Szalay F, Lakatos PL, Antal-Szalmas P, Papp M | display-authors = 6 | title = Loss of tolerance to gut immunity protein, glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis | journal = Scientific Reports | volume = 8 | issue = 1 | pages = 399 | date = January 2018 | pmid = 29321484 | pmc = 5762861 | doi = 10.1038/s41598-017-18622-1 | bibcode = 2018NatSR...8..399T }}</ref> and later confirmed by others.<ref>{{cite journal | vauthors = Sowa M, Kolenda R, Baumgart DC, Pratschke J, Papp M, Tornai T, Suchanski J, Bogdanos DP, Mytilinaiou MG, Hammermann J, Laass MW, Conrad K, Schramm C, Franke A, Roggenbuck D, Schierack P | display-authors = 6 | title = Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype | language = English | journal = Frontiers in Immunology | volume = 9 | pages = 1959 | date = 2018 | pmid = 30233574 | pmc = 6127632 | doi = 10.3389/fimmu.2018.01959 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wunsch E, Norman GL, Milkiewicz M, Krawczyk M, Bentow C, Shums Z, Mahler M, Lopens S, Reinhold D, Franke A, Schramm C, Roggenbuck D, Milkiewicz P | display-authors = 6 | title = Anti-glycoprotein 2 (anti-GP2) IgA and anti-neutrophil cytoplasmic antibodies to serine proteinase 3 (PR3-ANCA): antibodies to predict severe disease, poor survival and cholangiocarcinoma in primary sclerosing cholangitis | journal = Alimentary Pharmacology & Therapeutics | volume = 53 | issue = 2 | pages = 302–313 | date = January 2021 | pmid = 33159471 | pmc = 7821312 | doi = 10.1111/apt.16153 }}</ref> Association was demonstrated between anti-GP2 IgA and progressive liver fibrosis, [[cholangiocarcinoma]] development and shorter transplantation free survival in PSC patients.<ref name=":1" />

Other markers which may be measured and monitored are a [[complete blood count]], serum [[liver enzyme]]s, [[bilirubin]] levels (usually grossly elevated), [[kidney function]], and [[electrolyte]]s. However, none of these tests are reliable indicators of prognosis, as they are either specific to certain disease [[Complication (medicine)|complications]] or have a tendency to fluctuate over time, irrespective of the actual disease progression.<ref name=":2" /> [[Fecal fat]] measurement is occasionally ordered when symptoms of malabsorption (e.g., gross [[steatorrhea]]) are prominent.{{cn|date=September 2022}}

=== Cancer ===
[[Cholangiocarcinoma]], a major complication of PSC, is associated with a very poor prognosis. Approximately 80% of patients diagnosed with PSC-associated cholangiocarcinoma die within 1 year.<ref name=":3" />

The development of any of the cancers associated with PSC predicts a poor prognosis. Complications from PSC-associated cancers account for 40% of deaths from PSC.<ref name="Folseraas2016" /> Primary sclerosing cholangitis is one of the major known risk factors for cholangiocarcinoma,<ref name="Tsaitas2014">{{cite journal | vauthors = Tsaitas C, Semertzidou A, Sinakos E | title = Update on inflammatory bowel disease in patients with primary sclerosing cholangitis | journal = World Journal of Hepatology | volume = 6 | issue = 4 | pages = 178–187 | date = April 2014 | pmid = 24799986 | pmc = 4009473 | doi = 10.4254/wjh.v6.i4.178 | doi-access = free }}</ref> a cancer of the biliary tree, for which the lifetime risk among patients with PSC is 10-15%.<ref name="Kummen2013" /> This represents a 400-fold greater risk of developing cholangiocarcinoma compared to the general population.<ref name="Lazaridis2016" />  Surveillance for cholangiocarcinoma in patients with PSC is encouraged, with some experts recommending annual surveillance with a specialized imaging study and serum markers,<ref>Tabibian JH, Lindor KD. Challenges of Cholangiocarcinoma Detection in Patients with Primary Sclerosing Cholangitis. J Analytical Oncology. 2012;1(1):50–55.</ref> although consensus regarding the modality and interval has yet to be established.{{citation needed|date=October 2013}} Similarly, a screening [[colonoscopy]] is recommended in people who receive a new diagnosis of primary sclerosing cholangitis since their risk of colorectal cancer is 10 times higher than that of the general population.<ref name="Lazaridis2016" />

=== Related diseases ===
PSC is strongly associated with IBD, in particular [[ulcerative colitis]] (UC) and to a lesser extent [[Crohn's disease]]. As many as 5% of patients with IBD are co-diagnosed with PSC,<ref>{{cite journal | vauthors = Olsson R, Danielsson A, Järnerot G, Lindström E, Lööf L, Rolny P, Rydén BO, Tysk C, Wallerstedt S | display-authors = 6 | title = Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis | journal = Gastroenterology | volume = 100 | issue = 5 Pt 1 | pages = 1319–1323 | date = May 1991 | pmid = 2013375 | doi = 10.1016/0016-5085(91)90784-I }}</ref> and approximately 70% of people with PSC have IBD.<ref name=Robbins/> Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood.<ref>{{cite journal | vauthors = Boonstra K, Weersma RK, van Erpecum KJ, Rauws EA, Spanier BW, Poen AC, van Nieuwkerk KM, Drenth JP, Witteman BJ, Tuynman HA, Naber AH, Kingma PJ, van Buuren HR, van Hoek B, Vleggaar FP, van Geloven N, Beuers U, Ponsioen CY | display-authors = 6 | title = Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis | journal = Hepatology | volume = 58 | issue = 6 | pages = 2045–2055 | date = December 2013 | pmid = 23775876 | doi = 10.1002/hep.26565 | hdl-access = free | s2cid = 205889681 | hdl = 1887/117347 }}</ref> Close monitoring of PSC patients is vital.

Various forms of gallbladder disease such as [[gallstone]]s and gallbladder [[Polyp (medicine)|polyp]]s are also common in those with PSC.<ref name="Lazaridis2016"/> Approximately 25% of people with PSC have gallstones.<ref name="Lazaridis2016"/> Ultrasound surveillance of the gallbladder every year is recommended for people with PSC.<ref name="Lazaridis2016"/> Any person with PSC who is found to have a mass in the gallbladder should undergo [[cholecystectomy|surgical removal of the gallbladder]] due to the high risk of cholangiocarcinoma.<ref name="Lazaridis2016"/> [[Osteoporosis]] (hepatic osteodystrophy) and [[hypothyroidism]] are also associated with PSC.{{cn|date=September 2022}}

A 2–3:1 male-to-female predilection occurs in primary sclerosing cholangitis.<ref name=Robbins/>  PSC can affect men and women at any age, although it is commonly diagnosed in the fourth decade of life, most often in the presence of IBD.<ref name=":0" />  PSC progresses slowly and is often asymptomatic, so it can be present for years before it is diagnosed and before it causes clinically significant consequences.  Relatively few data are available on the [[Prevalence (epidemiology)|prevalence]] and [[Incidence (epidemiology)|incidence]] of PSC, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, the risk is likely higher in populations where UC is more common.<ref>{{cite journal | vauthors=Feld JJ, Heathcote EJ |title=Epidemiology of autoimmune liver disease |journal= Journal of Gastroenterology and Hepatology|volume=18 |issue=10 |pages=1118–28 |date=October 2003 |pmid=12974897 |doi=10.1046/j.1440-1746.2003.03165.x |s2cid=24075827 |doi-access= }}</ref>  In the United States, an estimated 29,000 individuals have PSC.<ref name="Lazaridis2016"/>