Welcome to the Norwegian PSC Research Center homepage



The Norwegian PSC Research Center (NoPSC) was established on the 19th of May 2008 at the Medical Department, Rikshospitalet upon signing of a contract between the University of Oslo and Rikshospitalet on the handling of funds from Canica A/S. The funds are exclusively dedicated to research related to basic and clinical aspects of the chronic liver disease primary sclerosing cholangitis (PSC).

NoPSC is now a separate center within the Clinic of Surgery, Inflammatory Medicine and Transplantation at Oslo University Hospital (OUH) Rikshospitalet, and is also affiliated with the Research Institute for Internal Medicine, OUH Rikshospitalet and the Institute of Clinical Medicine at the University of Oslo.

NoPSC has a broad range of both local and international collaborators (see annual reports for more information). NoPSC has also established the International PSC Study Group (www.ipscsg.org).


Norwegian PSC Research Center annual retreat (Holmenkollen, January 2019)

Recent News

Lipids in bile activate natural killer T cells

Natural killer T (NKT) cells are abundant immune cells in liver and activated by lipids (fat molecules).

To determine if activating lipids are found in liver bile, we co-cultured NKT cell lines with bile collected from the gallbaldder of patients undergoing liver transplantation, including those with PSC.

We found that patient bile samples can activate several NKT cell lines at very low concentrations suggesting that activating lipids are present and highly potent in bile. Activating lipids in bile may originate from bacteria as one third of activating bile samples (4 of 12) contained microbial DNA.

Our results reveal lipids in bile can activate NKT cells in liver patients and these findings further support the role of NKT cells in hepatobiliary diseases such as PSC.

For more information, please visit the following link: https://onlinelibrary.wiley.com/doi/10.1111/cei.13541

New members join NoPSC

NoPSC welcomes Marco Sanduzzi-Zampareilli (Visiting Scholar, BCLC group, Hospital Clinic of Barcelona) and several new members to the group - onwards and upwards to a brighter 2021.

Endogenous lipid expression regulates invariant natural killer T cells

Invariant natural killer T (iNKT) cells are a highly enriched immune subset found in the liver and unique because they recognize lipids (fat molecules) presented by CD1d. Features governing iNKT cell development and function are poorly understood, however, iNKT cells are thought to regulate liver inflammation in diseases such as primary sclerosing cholangitis (PSC).

To better understand the development and function of iNKT cells, we studied humans and mice lacking acid sphingomyelinase (ASM).

We discovered that iNKT cell numbers and activity were significantly reduced in ASM-deficient humans and treatment with ASM restored iNKT cell levels in ASM-deficient mice.

These results show that self-lipids are critical for the development and function of iNKT cells and suggest that expression of self-lipids may contribute to the control of liver inflammation in PSC.

For more information, please visit the following link:  https://www.nature.com/articles/s41590-019-0504-0


Autotaxin activity predicts disease severity in PSC

Disease activity in PSC shows large variations over time and very few tools are available that help predict prognosis and treatment responses in patients.

A protein called autotaxin (ATX) was recently described as a marker of liver injury therefore we explored if autotaxin could be used as a potential biomarker for disease severity in PSC.

In both a discovery and valdiation cohort, we saw increased serum autotaxin activity was associated with reduced liver transplant-free survival independent of other markers of inflammation and fibrosis suggesting that autotaxin could have utility as a future clinical biomarker in PSC.

For more information, please see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559994/


GPR35 risk variant for PSC enhances cellular metabolism and proliferation

Genetic variations in G protein–coupled receptor 35 (GPR35) are associated with an increased risk for primary sclerosing cholangitis (PSC) and related cancers however the general function of GPR35 is poorly understood.

Using Gpr35-deficient mice, we found that GPR35 promotes the activity of sodium/potassium-ATPase, a ubiquitous and essential transmembrane pump that regulates cellular metabolism and proliferation.

A genetic variant of GPR35 associated with PSC heightens sodium/potassium-ATPase activity, enhancing glycolysis and proliferation of intestinal epithelial cells compared to non-PSC-associated GPR35.

Intriguingly, treatment reducing GPR35 activity decreased tumor burden in mice suggesting that GPR35 could be an attractive target for the treatment of PSC and related cancers.

For more information, please see: http://stke.sciencemag.org/content/12/562/eaau9048



Circulating markers of gut dysfunction associate with disease severity in PSC

Bacterial products from inflamed leaky gut are hypothesized to contribute to bone duct inflammation. To test this hypothesis, we investigated whether circulating markers or bacterial translocation associated with transplant-free survival in patients with primary sclerosing cholangitis (PSC).

Compared to healthy controls, PSC patients show increased levels of the bacterial translocation markers CD14 and LBP. High levels of CD14 and LBP were associated with poor transplant-free survival, independent from Mayo risk score, indicating that ongoing gut leakage could impact the pathophysiology or PSC.

For more information, please see:  https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.13979




Natural killer T cells mediate liver inflammation in the bile ducts

Natural killer T (NKT) cells represent a major lymphocyte population in the liver that likely regulate immune-driven liver diseases such as primary sclerosing cholangitis (PSC).

In our present study, we explored if NKT cells elicit liver inflammation by treating mice with the NKT cell agonist oxazolone. We found that animals with NKT cells (WT) developed acute cholangitis following oxazolone injection after seven days whereas NKT cell-deficient animals (Cd1d-/-) did not develop disease.

Our findings implicate that NKT cells are involved in liver inflammation. The elucidation of this biliary immune pathway may be important to better understand PSC pathogenesis and lead to the development of new therapeutic approaches for cholangiopathies.

For more information: https://www.nature.com/articles/s41385-018-0066-8


Johannes Hov awarded prestigious ERC research grant to study cause and treatments for PSC

NoPSC group leader Johannes Hov has received a Starting Grant of 1.5 million EUR from the European Research Council (ERC) to investigate the importance of intestinal bacteria in disease and determine whether exiting drug targeting gut bacteria can be used to treat primary sclerosing cholangitis (PSC) .

For more information, please see:  https://www.med.uio.no/english/about/news-and-events/news/2018/erc-starting-grant-for-johannes-hov.html