Infectious triggers of primary biliary cirrhosis: Do we know enough?

Abstract

Primary biliary cirrhosis (PBC) is an immune mediated liver disease directed against the biliary epithelial cells of the small bile ducts. The disease is characterised by circulating antimitochondrial antibodies (AMA), as well as antinuclear antibodies (ANA). AMA is considered pathognomonic for PBC, with AMA positivity predicting disease development in asymptomatic individuals. Middle aged females are most commonly affected, with increased incidence in families. Sisters and daughters of PBC patients are especially at risk. Epidemiological and twin studies have demonstrated that genetic predisposition, combined with environmental factors likely act together in the disease initiation. Among the environmental risk factors, infectious agents have been implicated. The mechanism by which infectious agents contribute to the pathogenesis of PBC appears to be through molecular-mimicry, and cross reactivity to antigenic epitopes of mitochondrial antigens. Although several bacterial and viral pathogens have been identified with PBC, Escherichia coli, Novosphingobium aromaticivorans, and Lactobacillus delbrueckii subspecies bulgaricus have been considered the most significant infectious triggers, and have also been the most studied. The pathogenic significance of these bacteria may be reflective of their relationship with other identified risk factors, such as recurrent urinary tract infections and alterations in oestrogen metabolism. This review will examine the literature surrounding the epidemiological and molecular studies which have characterised the role of these bacteria in the pathogenesis of PBC.