PBC is now widely accepted to occur as a result of the interaction of one of more environmental triggers with a host who exhibits an individual susceptibility. Much work has been done by UK-PBC and others to explore individual susceptibility.
Genetic factors play a key role in this susceptibility (although PBC is not a genetic disease in the conventional sense and none of the gene variants which confer risk is themselves abnormal). The genes implicated in PBC are almost exclusively ones which play a role in regulating the immune response; an observation which links in with the immune features which are so characteristic of the disease.
Studies are ongoing to see whether genes (the same or different to the ones that put an individual at risk of PBC) also play a role in the severity of liver disease and the development of cirrhosis once the disease has developed.
At present the nature of the trigger for the disease has not been established although evidence has been put forward for viruses, chronic bacterial, infections and environmental chemicals. The phenomenon of disease clustering would be fully in keeping with an environmental trigger.