Bile analysis identifies patients at risk of developing an aggressive liver cancer subject

An international study, coordinated by the Cima University of Navarrademonstrates that the analysis of free bile DNA can identify patients at risk of developing an aggressive liver cancer subject . Specifically, the work suggests that the detection of mutations in patients with primary sclerosing cholangitis (PSC) could help in the early diagnosis of cholangiocarcinoma.

PSC is a rare chronic liver disease characterized by inflammation and fibrosis (scarring) of the bile ducts. It is associated with an increased risk of developing cholangiocarcinoma, an aggressive liver tumor with a very poor prognosis, the usual treatment for which is liver transplantation.

Early detection of this disease is difficult, as current diagnostic techniques have limited sensitivity. "Patients with PSC often undergo endoscopic explorations of the bile duct. In these interventions it is possible to collect bile and we have taken advantage of this sample to analyze, in an essay we call Bilemut, the presence of mutations that would come from the tumor DNA", explains Dr. María Arechederra, researcher of the Hepatology group : liquid biopsy and carcinogenesis at Cima and first author of the work. and first author of the work.

Early detection of cancer

"One of the most relevant findings of this work is that three of the four patients with PSC studied in the Bilemut project developed cholangiocarcinoma during follow-up. Moreover, in two of them, the detection of mutations occurred between five and seven months before the clinical diagnosis of the tumor," emphasizes Prof. Carmen Berasainain. Prof. Carmen Berasainco-director of the study together with Prof. Matias Avila Prof. Matías Ávila. 

Although additional programs of study are needed, the results suggest that this subject analysis could be incorporated as a screening tool to identify patients with PSC who require closer monitoring or further diagnostic testing. The results have been published in the scientific journal Liver International.

The work, carried out in the framework the Cancer Center Clínica Universidad de Navarra and the CIBER in Liver and Digestive Diseases (CIBERehd), has counted with the partnership the Medical University of Warsaw and the Pomeranian Medical University (Poland), and the University of Duisburg-Essen and the University Hospital RWTH Aachen (Germany), among other international centers. 

The research has been funded by public and private entities such as the European Unionproject Transcan Project and Euroregion New Aquitaine-Euskadi-Navarre), the Instituto de Salud Carlos III and the department of Health of the Government of Navarra, as well as by the Spanish association Against Cancer, Thermo Fisher and the Rolf M. Schwiete Foundation.

Bile bank

Cima researchers together with the group Dr. Jesús Urman, from the University Hospital of Navarra, are promoters of the usefulness of bile as a liquid biopsy and, in partnership with the University Hospital of Galdakao (Basque Country) and the Centre Hospitalier de Bordeaux (France), have founded the BileBank project (https://bilebank.org/), to promote the collection and use of bile for diagnostic and therapeutic purposes. Several centers from all over Europe have joined this project .

reference letter of the article:
Arechederra M, Bik E, Rojo C, et al. Mutational Analysis of Bile Cell-Free DNA in Primary Sclerosing Cholangitis: A Pilot Study. Liver International. 2025; 45:e70049. https://doi.org/10.1111/liv.70049