UDCA Use in Primary Biliary Cholangitis Associated With Reduced Cancer Risk: JAMA
USA: A large retrospective, propensity score–matched cohort study found that ursodeoxycholic acid (UDCA) use in patients with primary biliary cholangitis (PBC) was associated with a significantly lower incidence of breast and gastrointestinal cancers, suggesting a potential chemopreventive effect. However, the authors caution that prospective studies are needed to confirm this association.
UDCA is the established first-line therapy for PBC, a chronic autoimmune liver disease, due to its ability to slow disease progression, delay liver damage, and improve survival. Its relationship with cancer risk has remained uncertain, as prior studies were limited by small sample sizes and inadequate control of confounding. To overcome these limitations, researchers conducted a large real-world cohort analysis using electronic health record data.
Published in JAMA Network Open, the research letter analyzed data from the TriNetX Research Network, which encompasses de-identified records from 109 healthcare organizations worldwide. From a pool of about 156 million patients, more than 48,000 adults diagnosed with PBC between 2005 and 2025 were identified. Participants were aged 18–89 years, had no prior cancer diagnosis, and survived at least one year after PBC diagnosis.
Patients were classified based on the initiation of UDCA within six months of PBC diagnosis and matched 1:1 using propensity scores to balance demographic, socioeconomic, clinical, lifestyle, medication, and surgical factors. Cancer risk was assessed using Cox proportional hazards models for new diagnoses occurring at least one year after the index date.
The key findings were as follows:
- After propensity score matching, both the UDCA and non-UDCA cohorts comprised 6,057 patients each, with a mean age of around 57 years and a predominance of female participants.
- UDCA use was associated with a 41% reduction in the risk of overall gastrointestinal cancers compared with nonuse.
- A comparable reduction in risk was observed for liver cancer among patients receiving UDCA.
- Among female patients, UDCA treatment was linked to a substantially lower incidence of breast cancer.
- No statistically significant association was found between UDCA use and colorectal cancer risk.
- The observed associations remained consistent across alternative analytical approaches, including models using pre-matched data with extensive adjustment for confounding factors.
- Sensitivity analyses using PBC diagnosis as the index date for both cohorts showed similar directional trends, although with weaker statistical significance.
The authors noted key strengths such as the large sample size, robust confounder adjustment, and use of harmonized global EHR data. Limitations included residual confounding, possible self-selection bias, lack of data on treatment duration and adherence, and limited follow-up for long-term cancer outcomes.
Overall, the findings suggest that UDCA may confer protective effects beyond liver disease management, potentially through anti-inflammatory, antiproliferative, or cytoprotective mechanisms. The researchers emphasized the need for prospective studies or randomized trials to validate these observations, particularly for liver and breast cancer.
Reference:
Su L, Patel PJ, Shu X. Use of Ursodeoxycholic Acid and Cancer Risk for Patients With Primary Biliary Cholangitis. JAMA Netw Open. 2025;8(12):e2550907. doi:10.1001/jamanetworkopen.2025.50907
Next Story