Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci

Melum, Espen; Franke, André; Schramm, Christoph; Weismüller, Tobias J.; Gotthardt, Daniel; Offner, Felix; Juran, Brian D.; Laerdahl, Jon K.; Labi, Verena; Bjõrnsson, Einar; Weersma, Rinse K.; Henckaerts, Liesbet; Teufel, Andreas; Rust, Christian; Ellinghaus, Eva; Balschun, Tobias; Boberg, Kirsten Muri; Ellinghaus, David; Bergquist, Annika; Sauer, Peter; Ryu, Euijung; Hov, Johannes R.; Wedemeyer, Jochen; Lindkvist, Björn; Wittig, Michael; Porte, Robert J.; Holm, Kristian; Gieger, Christian; Wichmann, H‐Erich; Stokkers, Pieter; Ponsioen, Cyriel Y.; Runz, Heiko; Stiehl, A.; Wijmenga, Cisca; Sterneck, Martina; Vermeire, Séverine; Beuers, Ulrich; Villunger, Andreas; Schrumpf, E.; Lazaridis, Konstantinos N.; Manns, Michael P.; Schreiber, Stefan; Karlsen, Tom H.

doi:10.1038/ng.728

Cited by 222 publications

(177 citation statements)

References 10 publications

Supporting

Mentioning

169

Contrasting

Unclassified

Order By: Relevance

“…3,[5][6][7] Similar to three other large series, [6][7][8] most of the children (76%) had associated IBD, UC being the most common (70%). So far, all studies have shown that PSC and IBD do not have a common genetic background, 13,14 supporting the paradigm of a unique phenotype of PSC-IBD. 15 As previously reported, the majority of our patients had mild pancolitis, 15 and IBD was diagnosed at the same time as PSC or before the liver disease.…”

Section: Presentation At the Time Of Diagnosismentioning

confidence: 99%

Clinical course and prognosis of pediatric-onset primary sclerosing cholangitis

Tenca

Färkkilä

Arola

et al. 2016

United European Gastroenterology Journal

View full text Add to dashboard Cite

Background: The natural history of pediatric-onset primary sclerosing cholangitis (PSC) and overlap with autoimmune hepatitis (PSC/AIH) is poorly known. Objective: The aim of this study was to evaluate the clinical outcome of patients with pediatric-onset disease in a tertiary referral center. Methods: We traced 33 patients (median age at diagnosis 16 years), with PSC or PSC/AIH in cholangiography and liver histology diagnosed between December 1993 and 2011, at Helsinki University Hospital. Diagnostic procedures and long-term follow-up were reassessed until the end of December 2013. Results: PSC was confirmed in all 33 patients; 19 of them had an overlap with AIH. At diagnosis, three of 33 had cirrhosis. Inflammatory bowel disease (IBD) was associated in 76% of the patients, mostly ulcerative colitis (70%); treatment of IBD being a minor determinant of the clinical outcome of liver disease. In the last follow-up (median nine years), all patients were alive, and no malignancy occurred. Most patients (91%) were on ursodeoxycholic acid and 12 PSC/AIH patients on immunosuppression. Endoscopic retrograde cholangiography during follow-up showed a progression of intra-hepatic disease in 12 patients (36%). Four patients (12%) had undergone liver transplantation, and one was listed; no recurrence of the disease in the graft was seen. Conclusion:The clinical course and outcome of pediatric-onset PSC and PSC/AIH seem to be favourable in the majority of patients until early adulthood. In about one-third of patients, however, PSC is progressive, challenging the current treatment guidelines and warranting further studies on disease pathogenesis.

show abstract

Section: Presentation At the Time Of Diagnosismentioning

confidence: 99%

Clinical course and prognosis of pediatric-onset primary sclerosing cholangitis

Tenca

Färkkilä

Arola

et al. 2016

United European Gastroenterology Journal

View full text Add to dashboard Cite

show abstract

“…Initially, candidate gene studies were employed, followed by genome-wide association studies from Northern Europe [10]. Most recently, an international multicentre immunochip-based study was published, comparing 130,422 single nuclear polymorphisms in 3,789 patients with PSC with 25,079 controls [11].…”

Section: Aetiologymentioning

confidence: 99%

Primary Sclerosing Cholangitis

Williamson

Chapman

2014

Dig Dis

View full text Add to dashboard Cite

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease caused by diffuse inflammation and fibrosis that can involve the entire biliary tree. It is a progressive disorder which can ultimately lead to biliary cirrhosis, portal hypertension and hepatic failure. PSC is a complex genetic disorder with male predominance. Environmental predisposing factors include non-smoking. It is closely associated with inflammatory bowel disease (IBD), particularly ulcerative colitis, which occurs in about two thirds of PSC cases. Recent studies have suggested that PSC-IBD is a separate disease entity from IBD alone with distinctive genetic and phenotypic characteristics. Most PSC patients are asymptomatic at presentation; clinical symptoms include fatigue, jaundice, weight loss, right upper quadrant pain and pruritis. Serum biochemical tests indicate cholestasis, and diagnosis is usually established by cholangiography. In symptomatic patients, median survival from presentation to death or liver transplantation is about 12 years. It is a premalignant condition, and the majority of deaths are from malignancy, particularly cholangiocarcinoma or colonic cancer. PSC has no curative treatment. Medical treatment with ursodeoxycholic acid may slow progression of the disease and reduce colonic dysplasia, though trials lack statistical significance. Liver transplantation is the only option in young patients with PSC and advanced liver disease.

show abstract

“…Наша 4 пацијента, који су имали ове алеле су имали исте хистолошке промене (ПСЦ), а имали су ХТ услед излагања инду-стријским токсинима. Нове GWS студије су указале на потенцијално учешће не-ХЛА гена у настанку ПСЦ 35,36 . ХЛА Б14, ХЛА -ДР3 и ХЛА Б27 су чешћи код пацијената са сликом аутоимуног хепатитиса, који се често јавља код пације-ната са ХТ услед терапије преднизоном 7,8,24,34,37 .…”

unclassified