An increased risk of urinary tract infection precedes development of primary biliary cirrhosis

Primary Biliary Cirrhosis (PBC) is an idiopathic chronic liver disease associated with destruction of small intrahepatic bile ducts [1]. Both genetic [2] and environmental factors [3] have been implicated in its aetiology but no complete explanation is yet accepted. It seems however likely that the aetiology is a complex interplay between multiple factors.

There has been recent epidemiological interest in the spatio-temporal clustering of cases, which might indicate involvement of a transient toxic or transmissible agent [4, 5]. The agent involved however is as yet uncertain. A number of potential infectious precipitants have however previously been considered [6] including organisms such as Mycoplasma [7] and Novosphingobium.aromaticivorans[8]. Another group of infections which have received attention are Urinary Tract Infections (UTIs)[9]. A number of studies have suggested a specific link with Escherichia .Coli[10, 11] which is the commonest urinary isolate in the UK [12], and it has been suggested that this may occur via a mechanism of molecular mimicry [13]. Epidemiologically it has been known for some time, that patients with PBC are at increased risk of urinary tract infection after diagnosis [14] and four case control studies in recent years have confirmed the presence of an association [15-18]. They have been unable however to clearly suggest whether it is a cause or consequence of PBC since all of these studies have been retrospective case control studies with exposure to UTI ascertained by questionnaire at unspecified points in the disease course; i.e. at any time during life. In each study therefore, it is possible that the UTIs recorded occurred after diagnosis, rather than before onset of the disease, and each was inevitably susceptible to recall bias. Since an exposure can be the cause only of outcomes which occur after it, this means that one cannot ascribe causality based upon these studies. Further though Burroughs and colleagues, in their pioneering work in this area, showed that after diagnosis PBC was associated with UTI in a manner not seen for other chronic liver disease [14], such specificity would also need to be shown for any antecedent association if it were to be believed causal.

We have therefore set out to establish whether the epidemiology of the relationship between PBC and UTI is consistent with a causal relationship both by better defining the temporal relationship between PBC and UTI and by establishing whether any relationship is specific to PBC among liver disease. To achieve this we have carried out a large population based case-control study nested in the United Kingdom General Practice Research Database.

This post was last modified on December 5, 2024 3:49 am