Researchers have mapped out the strongest genetic connections to primary biliary cholangitis (PBC), providing patients and clinicians with the clearest picture yet of how inherited factors influence this chronic liver disease, according to a systematic literature review published recently in Frontiers in Immunology.
These results point to specific immune-related genes that appear to either raise or lower the likelihood of developing PBC.
“Our findings not only consolidate the current understanding of PBC susceptibility but also uncover previously unappreciated genetic features underlying disease pathogenesis,” explained the authors.
This large-scale review analyzed more than 70,000 cases of PBC and 140,000 controls across 105 studies. Investigators found 44 genetic variants strongly tied to PBC risk, including 30 within immune system genes known as HLA and 14 in other regions of the genome. Importantly, some variants were consistently identified by multiple types of genetic studies, strengthening confidence that they play a true role in disease risk.
Read more about causes and risk factors for PBC
The study showed that certain HLA gene variants, such as DRB10801, tripled the risk of PBC, while others like DQB10604 appeared to protect against it. Outside the HLA region, the strongest evidence was for variants in the CTLA4 and VDR genes, both known to affect immune regulation. These results suggest that patients who inherit certain genetic combinations are more vulnerable to the disease, although not everyone with these variants will develop PBC.
For patients, this growing understanding of genetic risk may translate into earlier detection and more tailored care in the future. Identifying individuals at high risk could help doctors monitor liver health more closely or intervene before symptoms worsen. This study also suggests possible new treatment targets by highlighting biological pathways that control immune cell activity.
The analysis further revealed that some genetic changes linked to PBC are also connected to thyroid disorders, as well as melanoma, hinting at shared roots among different autoimmune conditions. This overlap may explain why patients with PBC often face other immune-related health problems.
While these results do not immediately change treatment, they represent a step toward more personalized approaches. By connecting the dots between specific genes and disease development, researchers hope to eventually reduce the uncertainty patients face when living with PBC and open new paths to prevention and therapy.
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