Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterised serologically by cholestasis and the presence of high-titre antimitochondrial antibodies, and histologically by chronic nonsuppurative cholangitis and granulomata. As PBC is a granulomatous disease and Mycobacterium tuberculosis is the most frequent cause of granulomata, a causal relation between tuberculosis and PBC has been suggested. Attempts to find serological evidence of PBC-specific autoantibodies such as AMA have been made and, conversely, granulomatous livers from patients with PBC have been investigated for molecular evidence of Mycobacterium tuberculosis. This paper discusses in detail the reported data in support or against an association between Mycobacterium tuberculosis infection and PBC. We discuss the immunological and microbiological data exploring the association of PBC with exposure to Mycobacterium tuberculosis. We also discuss the findings of large epidemiologic studies investigating the association of PBC with preexistent or concomitant disorders and the relevance of these findings with tuberculosis. Genome-wide association studies in patients with tuberculosis as well as in patients with PBC provide conclusive hints regarding the assumed association between exposure to this mycobacterium and the induction of PBC. Analysis of these data suggest that Mycobacterium tuberculosis is an unlikely infectious trigger of PBC. 1. Introduction Primary biliary cirrhosis (PBC) is a chronic cholestatic, autoimmune liver disease characterised by progressive inflammatory destruction of the small and medium intrahepatic bile ducts and subsequent fibrosis, cirrhosis [1–5], and eventually liver failure [6, 7]. The disease predominantly affects middle-aged women and is practically absent in children or youngsters [8–11]. PBC affects more than one member within the same family, and several reports indicate that first degree relatives of PBC patients have an increased risk of developing the disease [12, 13]. The prevalence of the disease varies among countries, with a recent systematic review indicating prevalence to be 1.91–40.2 per 100,000 inhabitants, and the incidence to be 0.33–5.8 per 100,000 inhabitants/year, in European and North American cohorts (although a breakdown of ethnicity was not provided) [14]. There is a consensus, however, that despite the heterogeneity in the estimated prevalence and incidence amongst ethnic groups, the incidence and prevalence of PBC is increasing [14–18]. The reasons for this increase are poorly understood. Whether there is a
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