We read with great interest the updated American Association for the Study of Liver Diseases practice guidelines on primary biliary cirrhosis (PBC) and congratulate the authors for their comprehensive review and, in particular, for their clear discussion of special cases and patients with overlap syndrome and for exhaustive and practical approaches to therapy.1
However, we consider being familiar with the common extrahepatic manifestations of this disease to be of the upmost clinical relevance in medical practice. PBC is often associated with other diseases or syndromes, many of which are considered to be mediated by immunological mechanisms and some of which are classified within the spectrum of collagen vascular diseases. Accordingly, with the striking defects of immune regulation found in these patients, it has been proposed that PBC can be classified as a model autoimmune disease.2–5 Furthermore, although PBC is primarily a disease of the liver, there can be extrahepatic manifestations of this disease.
The prevalence of other diseases in patients with PBC varies in different series between 15% and 100%. This wide variation in prevalence may be due, at least in part, to whether associated diseases that were subclinical were diagnosed and included in published series. More than 84% of PBC patients have been reported to exhibit features of at least one nonhepatic autoimmune disease sometime during the clinical course, and in about 40% of PBC cases, evidence of two or more nonhepatic autoimmune diseases can be found.6 It has been suggested that some of the more frequently associated diseases share a common pathogenic mechanism with PBC. In contrast, most of the rare associations of PBC with other diseases have been described in isolated case reports. In such reports, it is uncertain whether an association is related to a common pathogenic factor or is purely fortuitous.
In conclusion, the occurrence of associated disorders with immunological features that do not primarily affect the liver provides support for the hypothesis that PBC is a systemic disease with an autoimmune basis. In individual patients, either PBC or another autoimmune disease may be clinically silent, so the true incidence of the association of PBC with other disorders having immunological features will be apparent only if appropriate tests for relevant asymptomatic diseases are conducted. Multicenter, prospective studies are warranted.