Patients with primary biliary cholangitis (PBC) face a higher risk of lacunar stroke, a type of small vessel stroke, according to new genetic research published recently in iScience.
This study used a Mendelian randomization approach, which leverages inherited genetic differences to evaluate causal relationships, to confirm that PBC is not just associated with stroke but may actively increase risk.
The analysis drew on multiple large-scale genome-wide association studies to identify genetic markers linked to PBC and test their impact on lacunar stroke risk. Across three independent datasets, the findings were consistent.
“Individuals with PBC have an elevated risk of lacunar strokes,” explained the study’s authors.
For example, in the discovery analysis, genetically predicted PBC raised stroke risk with an odds ratio of 1.0635, meaning patients with PBC had about a 6% higher chance of lacunar stroke compared with those without PBC.
“It is essential to implement early screening for lacunar stroke in patients with PBC to enable preemptive prevention and intervention,” the authors further noted.
Read more about the prognosis of PBC
This study also tested for potential bias from horizontal pleiotropy, a genetic effect that could confound results, and found none. Sensitivity analyses, including leave-one-out testing, confirmed that no single genetic variant was driving the results. Researchers further ruled out reverse causation, showing that the genetic link went from PBC to stroke rather than the other way around.
These results highlight the importance of early cardiovascular monitoring for people with PBC. While previous observational studies sometimes failed to detect an increased stroke risk, likely due to small sample sizes, treatment effects or misclassified strokes, the genetic approach captures lifelong disease exposure and provides more robust evidence. Patients with PBC may benefit from stroke prevention strategies including careful management of blood pressure, cholesterol and other vascular risk factors.
The research also points to potential biological mechanisms connecting PBC and stroke. Chronic inflammation, endothelial dysfunction, and altered lipid metabolism in PBC may damage small cerebral arteries, creating conditions conducive to lacunar stroke. Elevated inflammatory markers like interleukin-6 and tumor necrosis factor-alpha, along with impaired cholesterol transport, may collectively contribute to vascular injury over time.
Although these findings strengthen science’s understanding of systemic risks in PBC, limitations remain. The study relied on summary-level genetic data and could not account for individual treatments or disease severity. Further research in diverse populations is needed to confirm these results and guide patient care. Nonetheless, this work underscores that PBC patients may need proactive vascular risk management alongside routine liver-focused care.
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