Potential Roles for Infectious Agents in the Pathophysiology of Primary Biliary Cirrhosis: What's New?

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease serologically characterized by the presence of high-titer antimitochondrial antibodies and, histologically by chronic nonsuppurative cholangitis and granulomata. The aetiology of the disease remains elusive, although genetic, epigenetic, environmental, and infectious factors have been considered important for the induction of the disease in genetically prone individuals. The disease shows a striking female predominance and becomes clinically overt at the fourth to sixth decade. These characteristics have prompted investigators to consider infections that predominate in women at these ages as the likely candidates for triggering the disease. Recurrent urinary tract infections due to Escherichia coli were the first infections to be considered pathogenetically relevant. Over the years, several other microorganisms have been linked to the pathogenesis of PBC owing to epidemiological, immunological, microbiological, or experimental findings in animal models. Recent studies have provided data supporting the pathogenic role of Novosphingobium aromaticivorans and betaretroviruses. Several reports have linked other organisms to the induction of the disease and/or the maintenance of the auto-aggressive responses that are perpetuated over the course of the disease. This review highlights the findings of the most recent studies investigating the link between infections and PBC. We also discuss the close interplay of the infectious agents with other environmental and genetic factors, which may explain the multifaceted nature of this puzzling disease.