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 (Holmenfjorden, January 2018)
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.
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 if exisiting drugs targeting gut bacteria can be used to treat primary sclerosing cholangitis (PSC).
Increasing evidence that shared gut and liver antigens drive chronic inflammation in PSC
The exact causes of primary scleorsing cholangitis (PSC) are unclear however PSC is strongly associated with autoantibody production by B cells and inflammatory bowel disease.
We discovered that a significant number of gut and liver B cells in patients with PSC recognize similar antigens. This suggests that antibody-producing B cells circulating amongst the gut and liver may contribute to chronic inflammation in PSC.
Overall these findings support ongoing efforts to better understand B-cell responses in PSC as a means of identifying relevant antigens, knowledge that could inform the development of novel treatments.
NoPSC publishes a comprehensive update on primary sclerosing cholangitis in the Journal of Hepatology
Primary sclerosing cholangitis (PSC) is a rare and progressive liver disease with important knowledge gaps and unmet needs. The close association with inflammatory bowel disease and the high risk of cancer in the liver and gut have strong impact on patients and their follow-up. With limited therapeutic options, PSC has long been the leading indication for liver transplantation in Norway. What is the current state-of-the-art management in PSC and what are the advances in this field?
This article published in the Journal of Hepatology emphasises recent developments related to patient stratification and disease behaviour and provides an overview of management options from a practical, patient-centred perspective. Advances in the understanding of PSC pathogenesis are explained and ongoing efforts to develop effective therapy are summarised.
New Nature Genetics publication on how our genes orchestrate the bacterial landscape in our gut
The human gut microbiota is an important determinant for health and disease but what are the most important factors determining its composition?
Lifestyle, medication and diet are among the factors known to be important contributors and in our new study, we find that genes are also a key factor. We have identified over 40 specific genes that contribute to shaping the gut microbiota. It was somewhat surprising that our genes also seem to be even more important for orchestrating the composition of the gut microbiota than our gender, diet and age combined; all variables that traditionally have been thought to be the strongest determinants of gut microbiota composition in healthy people.
One of the most important genes that were identified was the vitamin D receptor gene which is activated by bile acids made by the bacteria in our gut. It also interacts with several 'healthy' fatty acids, like omega-3 and omega-6 fatty acids found in fish and seafood.
Overall, our study represents an important milestone in the work of understanding how humans interact with all the billions of bacteria that live in our gut, and lays the foundation for tremendous research opportunities in the future.
NoPSC publishes study on the intestinal microbiota in mice with biliary disease in the Journal of Hepatology
Genetically modified mice (NOD.c3c4) that spontaneously develop bile duct disease have a gut microflora (microbiota) that differs substantially from normal mice. When NOD.c3c3 mice are raised in an environment devoid of bacteria, the disease in the bile ducts diminishes. Overall this indicates that gut microbiota may influences the liver disease individuals predisposed for bile duct inflammation.
Study on gut and liver T cells in patients with PSC-IBD published in the Journal of Hepatology
Primary sclerosing cholangitis (PSC) is a devastating liver disease strongly associated with inflammatory bowel disease (IBD). The cause of PSC is unknown, but it has been suggested that the immune reactions in the gut and the liver are connected. Our data demonstrate for the first time that a proportion of the T cells in the gut and the liver react to similar triggers, and that this proportion is particularly high in patients with PSC and IBD.