Updated review provides new insights into PSC
Primary sclerosing cholangitis (PSC) is a rare but serious liver disease for which there is currently no effective disease-modifying treatment. In a new review article published in The Lancet, researchers from Karolinska Institutet and international colleagues summarise the latest knowledge on the disease, its causes and potential future treatments.
Primary sclerosing cholangitis (PSC) is a chronic disease affecting the bile ducts and the liver. Despite many years of research, knowledge remains limited regarding why the disease develops and how it can best be treated.
In the new review article, the researchers compiled current evidence through a comprehensive review of scientific literature from MEDLINE, PubMed and other databases. The work is based on discussions and joint analyses among researchers from several countries.
The researchers describe how PSC is likely to develop through a complex interplay between genetic factors, the immune system, the bile ducts and the gut microbiome, that is, the bacteria and other microorganisms found in the intestine.
“PSC is a disease for which much still remains unclear. By summarising the knowledge available today, we hope to contribute to a better understanding of the disease and help ensure that people with PSC receive better care within the healthcare system,” says Annika Bergquist, Professor at the Department of Medicine, Huddinge, Karolinska Institutet.
Several new treatment strategies under investigation
The article also highlights the rapid progress being made in the field. After decades without effective disease-modifying treatments, several new strategies are now being investigated. These include drugs that affect bile acid metabolism, the gut microbiota and the development of fibrosis, that is, scarring of the liver.
According to the researchers, norucholic acid has shown particularly promising results in a phase III study.
The review also provides updated guidance on patient follow-up and on how prognostic information can be communicated.
“There is a major need for better treatments and for methods to detect the disease and its complications at an earlier stage. It is also important to develop reliable biomarkers that can be used in future clinical trials,” says Annika Bergquist.
The next steps for research are to increase understanding of the underlying biological mechanisms of the disease, improve opportunities for the early detection of PSC and bile duct cancer, and develop treatments that can slow disease progression and reduce the risk of complications.
The review article was written by Erik von Seth and Annika Bergquist at Karolinska Institutet in collaboration with Tom H. Karlsen at the University of Oslo, Atsushi Tanaka at Teikyo University School of Medicine in Tokyo, and Cyriel Ponsioen at Amsterdam University Medical Centers.
Publication
Primary sclerosing cholangitis, Erik von Seth, Tom H Karlsen, Astushi Tanaka, Cyriel Ponsioen, Annika Bergquist, The Lancet, 18 April 2026, doi: 10.1016/S0140-6736(25)02582-6