Challenges are manifold, but the lack of diagnostic markers for PSC and for cholangiocarcinoma in PSC means that both conditions are diagnosed late. The lack of effective medical treatment of PSC means that, unfortunately, PSC is the leading indication for liver transplantation in Norway.
About the project
PSC is a slowly progressive disease with a course of one to two decades from the identification of early stages of disease manifestations until end-stage liver disease. This results in difficulties in establishing a robust level of evidence for the benefit of any treatment in delaying liver transplantation. At present, no medical therapy with proven efficacy is available. Several compounds are being investigated in phase I and phase II trials.
The Norwegian PSC research center has participated in the nor-ursodeoxycholic acid trial from the Falk Pharmaceutical company and look forward to be a part of more clinical trials in the near future. Ongoing studies also aim to determine the optimal mode of endoscopic therapy for narrow structures (dilatation or stenting).
Another key topic for the clinical research group is to determine biomarkers for disease severity, including markers that can be used to determine the effect of medical treatment. This includes biomarkers in blood and bile, along with evaluation of novel imaging modalities. Patients are also closely followed after liver transplantation to determine factors that contribute to the development of the recurrent disease (occurring in 15-30%).
Objectives and collaboration
Establishing diagnostic markers for PSC in patients with inflammatory bowel disease could serve crucial for diagnosing patients before the scarring of the bile ducts has become irreversible. In collaboration with the Inflammatory Bowel Disease in South Eastern Norway (IBSEN) study group, ongoing efforts aim to determine factors that correlate with even sub-clinical bile duct changes on cholangiography in patients with inflammatory bowel disease.
Likewise, it is a priority topic to determine biomarkers for pre-clinical cholangiocarcinoma in patients with PSC to allow for effective treatments (see Genomics and metagenomics in inflammatory disorders).
All studies within the clinical research groups are performed in close collaboration with the International PSC study group (www.ipscsg.org). Key investigators are clinicians, typically funded by Oslo University Hospital and Haukeland University Hospital. Some dedicated time for research is supported by the Norwegian PSC research center.
- Bende F, Mulabecirovic A, Sporea I, Popescu A, Sirli R, Gilja OH, Vesterhus M, Havre RF (2017) Assessing Liver Stiffness by 2-D Shear Wave Elastography in a Healthy Cohort Ultrasound Med Biol, 44 (2), 332-341
- Carpino G, Cardinale V, Folseraas T, Overi D, Floreani A, Franchitto A, Onori P, Cazzagon N, Berloco PB, Karlsen TH, Alvaro D, Gaudio E (2017) Hepatic stem/progenitor cell activation differs between primary sclerosing and primary biliary cholangitis Am J Pathol (in press)
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- Karlsen TH, Folseraas T, Thorburn D, Vesterhus M (2017) Primary sclerosing cholangitis - a comprehensive review J Hepatol, 67 (6), 1298-1323
- Alberts R, de Vries EMG, Goode EC, Jiang X, Sampaziotis F, Rombouts K, Böttcher K, Folseraas T, Weismüller TJ, Mason AL, Wang W, Alexander G, Alvaro D, Bergquist A, Björkström NK, Beuers U, Björnsson E, Boberg KM, Bowlus CL, Bragazzi MC, Carbone M, Chazouillères O, Cheung A, Dalekos G, Eaton J, Eksteen B, Ellinghaus D, Färkkilä M, Festen EAM, Floreani A, Franceschet I, Gotthardt DN, Hirschfield GM, Hoek BV, Holm K, Hohenester S, Hov JR, Imhann F, Invernizzi P, Juran BD, Lenzen H, Lieb W, Liu JZ, Marschall HU, Marzioni M, Melum E, Milkiewicz P, Müller T, Pares A, Rupp C, Rust C, Sandford RN, Schramm C, Schreiber S, Schrumpf E, Silverberg MS, Srivastava B, Sterneck M, Teufel A, Vallier L, Verheij J, Vila AV, Vries B, Zachou K; International PSC Study Group, The UK PSC Consortium, Chapman RW, Manns MP, Pinzani M, Rushbrook SM, Lazaridis KN, Franke A, Anderson CA, Karlsen TH, Ponsioen CY, Weersma RK (2017) Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis Gut (in press)
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- Trivedi PJ, Tickle J, Vesterhus MN, Eddowes PJ, Bruns T, Vainio J, Parker R, Smith D, Liaskou E, Thorbjørnsen LW, Hirschfield GM, Auvinen K, Hubscher SG, Salmi M, Adams DH, Weston CJ (2017) Vascular adhesion protein-1 is elevated in primary sclerosing cholangitis, is predictive of clinical outcome and facilitates recruitment of gut-tropic lymphocytes to liver in a substrate-dependent manner Gut (in press)
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- Rizvi SMH, Aagnes B, Holdaas H,Gude E, Boberg KM, Bjørtuft Ø, Helsing P, Leivestad T, Møller B, Gjersvik P. Long-term change in the risk of skin cancer after organ transplantation JAMA Dermatology (in press)
- Vesterhus M, Folseraas T (2017) PSC and differential diagnosis (Norwegian) NGF-nytt, Oct 2017
- Vesterhus M, Hov, JR (2017) Anti-GP2 IgA auto antibodies are associated with a reduced survival and cholangiocarcinoma in primary sclerosing cholangitis (Norwegian). Best Practice Gastroenterologi, Feb 2017.