Annika Bergquist

Primary sclerosing cholangitis (PSC) is a chronic liver disease with a greatly increased risk of developing cirrhosis and bile duct cancer. Cancer is often detected in advanced stages and there is no effective chemotherapy and early cancer diagnosis is crucial for curative surgical treatment to be offered. In a previous study, we evaluated a surveillance program with annual MRI and blood samples, which now created a unique opportunity to further study blood and MRI-based markers for early cancer. We are a leading research group in this field and a national reference center for this disease. We are studying a unique collection of material from more than 500 people with PSC collected between 2012-2020, where we have saved MRI images, blood and information about disease progression and cancer. We are evaluating a newly developed way of assessing MR images - the so-called DiStrict Score, developing blood-based markers for early cancer diagnosis and testing them in this group. We are also conducting a clinical trial based on our own hypothesis-generated registry data in patients with PSC, where patients are randomized between simvastatin and placebo with the hope of being able to show that simvastatin protects against rapid disease progression and cancer The purpose of the research program is to develop methods and strategies for early tumor diagnosis and improve prognosis in PSC. We hope that we can develop blood-based so-called methylation signatures in blood that can become markers for early tumor development, show that our newly developed MR score can be used in clinical practice. We also hope to show that simvastatin protects against disease progression and cancer.

Scandinavia is the part of the world where primary sclerosing cholangitis (PSC) is most frequent. The etiology is unknown which limits the development of targeted therapy. There is a very high risk of developing cholangiocarcinoma (CCA). The disease progression to liver failure of CCA is highly unpredictable. PSC is a unique model to understand the development of CCA that otherwise is so rare that longitudinal studies are impossible. There is no predictor, medical treatment, early diagnostic tool, or good animal model for PSC/CCA. It is an urgent need to the uncover the biology underlining the heterogeneity of the disease to increase the precision and efficiency of patient’s management. The purpose of this proposal is to join clinical and basic expertise in the study of these two severe diseases. We aim to define the in-depth biological heterogeneity of PSC and CCA, and to uncover new disease entities suitable for targeted diagnosis, and management. We will tackle this challenge using a combination of genome-scale molecular and biological methods and state-of-art multidimensional analysis. We aim to perform the first genome-wide methylation and genome-scale autoantibody profiling in PSC and CCA as well as a multi-OMIC integration of large-scale metabolomic, molecular and inflammatory mediators. To achieve these aims, we possess both bioinformatic expertise and one of the world-largest PSC/CCA cohorts and biobank built over the last 20 years.

Primary sclerosing cholangitis (PSC) is a chronic liver disease with a greatly increased risk of liver failure and bile duct cancer. If the tumor can be found early, the cancer can be cured with surgery or a liver transplant. One problem is that tumors are often detected late and tests that find tumors in early stages are lacking. Medical treatment that slows progression to liver failure and bile duct cancer is also lacking. Cholesterol-lowering treatment with statins can have a positive effect in chronic liver disease and possibly also protect against bile duct cancer. We recently demonstrated an association between statin use and prognosis in PSC. In a national surveillance study with MRI examination and collection of blood samples annually for 5 years in over 600 patients with PSC, we create an opportunity to develop markers for early cancer diagnosis and assessment of prognosis. We are going to conduct a study in which people draw lots between treatment with simvastatin 40 mg daily and a placebo. 700 patients are treated for 5 years. Start of studies is estimated for August 2020. Through studies in Swedish registers, we investigate how big the cancer risk is for tumor forms other than bile duct cancer and whether the risk of bile duct cancer in PSC patients is affected by whether bile duct cancer is present in the family. The research program aims to increase knowledge about cancer risk, develop strategies for early tumor diagnosis and improve prognosis in PSC.

Primary sclerosing cholangitis (PSC) is a chronic liver disease that mainly affects young men with chronic intestinal inflammation. The cause of the PSC is unknown, the disease leads to cirrhosis and medical treatment is lacking. Liver failure requires liver transplantation. The PSC also involves a greatly increased risk of cancer of the bile duct and colon. It is of the utmost importance to discover precursors of bile duct cancer in order to provide cure treatment with liver transplantation. There is no good method that identifies early cancer development in the biliary tract and no way to predict who is at risk of developing cancer. We conduct a national surveillance study for 5 years to evaluate whether annual PSC surveys at the PSC can lead to previous discovery of biliary cancer in order to provide patients with liver transplantation. We are studying the inflammatory attack on the biliary tract to increase knowledge of disease mechanisms and investigate how new endoscopic techniques can be used for early tumor diagnosis. Through register studies, we also study how heredity for cancer affects cancer risk in the PSC, whether colectomy and drug use can be linked to prognosis at the PSC. We are investigating what support PSC patients are demanding for increased quality of life. Through these studies, we hope to develop strategies for improved monitoring and follow-up of patients with PSC with the aim of earlier detecting tumors with the aim of being able to offer curative treatment. We hope to improve our diagnostic tools in investigating the suspected tumor at the PSC. Through increased knowledge of why the disease occurs, we hope to contribute to creating new treatment strategies and concepts and help patients to live with their chronic disease while maintaining and maintaining high quality of life.

Primary sclerosing cholangitis (PSC) is a chronic liver disease that mainly affects young men with chronic intestinal inflammation. The cause of the PSC is unknown, the disease leads to cirrhosis and medical treatment is lacking. Liver failure requires liver transplantation. The PSC also involves a greatly increased risk of cancer of the bile duct and colon. It is of the utmost importance to discover precursors of bile duct cancer in order to provide cure treatment with liver transplantation. There is no good method that identifies early cancer development in the biliary tract and no way to predict who is at risk of developing cancer. We conduct a national surveillance study for 5 years to evaluate whether annual PSC surveys at the PSC can lead to previous discovery of biliary cancer in order to provide patients with liver transplantation. We are studying the inflammatory attack on the biliary tract to increase knowledge of disease mechanisms and investigate how new endoscopic techniques can be used for early tumor diagnosis. Through register studies, we also study how heredity for cancer affects cancer risk in the PSC, whether colectomy and drug use can be linked to prognosis at the PSC. We are investigating what support PSC patients are demanding for increased quality of life. Through these studies, we hope to develop strategies for improved monitoring and follow-up of patients with PSC with the aim of earlier detecting tumors with the aim of being able to offer curative treatment. We hope to improve our diagnostic tools in investigating the suspected tumor at the PSC. Through increased knowledge of why the disease occurs, we hope to contribute to creating new treatment strategies and concepts and help patients to live with their chronic disease while maintaining and maintaining high quality of life.

Primary sclerosing cholangitis (PSC) is a chronic liver disease that mainly affects young men with chronic intestinal inflammation. The cause of PSC is unknown, treatment is missing and liver failure requires liver transplantation. The PSC involves a greatly increased risk of cancer of the bile duct and colon. It is of the utmost importance to detect biliary cancer early in order to provide cure treatment with a combination of radiation, chemotherapy and transplantation. There is no good method that identifies early cancer development in the biliary tract. Patients with intestinal inflammation are examined annually by colonoscopy to identify and treat tumor precursors. We conduct a National Surveillance Study for 5 years to evaluate whether annual CCS examinations and blood samples at the PSC can lead to previous discovery of biliary cancer in order to provide patients with liver transplantation. Through studies of new techniques (direct microscopy of the mucosa) in connection with colonoscopy, we try to improve the possibility of finding early cancer changes in the colon. We want to investigate what support these patients need to improve the quality of life. Through these studies we hope to develop strategies for improved tumor diagnosis, investigation and treatment and at the PSC in order to be able to offer curative treatment before a cancer has developed. Through increased knowledge of why the disease occurs, we hope to contribute to creating new treatment strategies and concepts. There is currently no curative treatment and we know that patients with PSC have lowered quality of life. We hope to create knowledge about intervention and care that can improve the quality of life even if the disease cannot be cured.

Primary sclerosing cholangitis (PSC) is a chronic liver disease that mainly affects young men with chronic intestinal inflammation. The cause of PSC is unknown, treatment is missing and liver failure requires liver transplantation. The PSC involves a greatly increased risk of cancer of the bile duct and colon. It is of the utmost importance to detect biliary cancer early in order to provide cure treatment with a combination of radiation, chemotherapy and transplantation. There is no good method that identifies early cancer development in the biliary tract. Patients with intestinal inflammation are examined annually by colonoscopy to identify and treat tumor precursors. We conduct a National Surveillance Study for 5 years to evaluate whether annual CCS examinations and blood samples at the PSC can lead to previous discovery of biliary cancer in order to provide patients with liver transplantation. Through studies of new techniques (direct microscopy of the mucosa) in connection with colonoscopy, we try to improve the possibility of finding early cancer changes in the colon. We want to investigate what support these patients need to improve the quality of life. Through these studies we hope to develop strategies for improved tumor diagnosis, investigation and treatment and at the PSC in order to be able to offer curative treatment before a cancer has developed. Through increased knowledge of why the disease occurs, we hope to contribute to creating new treatment strategies and concepts. There is currently no curative treatment and we know that patients with PSC have lowered quality of life. We hope to create knowledge about intervention and care that can improve the quality of life even if the disease cannot be cured.

Primary sclerosing cholangitis (PSC) is a chronic liver disease that mainly affects young men with chronic intestinal inflammation. The cause of PSC is unknown, treatment is missing and liver failure requires liver transplantation. The PSC involves a greatly increased risk of cancer of the bile duct and colon. It is of the utmost importance to detect biliary cancer early in order to provide cure treatment with a combination of radiation, chemotherapy and transplantation. There is no good method that identifies early cancer development in the biliary tract. Patients with intestinal inflammation are examined annually by colonoscopy to identify and treat tumor precursors. We conduct a National Surveillance Study for 5 years to evaluate whether annual CCS examinations and blood samples at the PSC can lead to previous discovery of biliary cancer in order to provide patients with liver transplantation. Through studies of new techniques (direct microscopy of the mucosa) in connection with colonoscopy, we try to improve the possibility of finding early cancer changes in the colon. We want to investigate what support these patients need to improve the quality of life. Through these studies we hope to develop strategies for improved tumor diagnosis, investigation and treatment and at the PSC in order to be able to offer curative treatment before a cancer has developed. Through increased knowledge of why the disease occurs, we hope to contribute to creating new treatment strategies and concepts. There is currently no curative treatment and we know that patients with PSC have lowered quality of life. We hope to create knowledge about intervention and care that can improve the quality of life even if the disease cannot be cured.