Urinary tract infection as a risk factor for autoimmune liver disease: from bench to bedside

Autoimmune liver diseases include autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis. A variety of environmental and genetic risk factors have been associated with these conditions. Recurrent urinary tract infections (rUTI) have been strongly associated with PBC, and to a lesser extent with AIH. These observations were initially based on the observation of significant bacteriuria in female patients with PBC. Larger epidemiological studies demonstrated that there was indeed a strong correlation between recurrent UTI and PBC. AIH has not been linked to recurrent UTI in epidemiological studies; however treatment of UTI with nitrofurantoin can induce AIH. As Escherichia coli is the most prevalent organism isolated in women with UTI, it has been suggested that molecular mimicry between microbial and human PDC-E2 (the main autoantigenic target in PBC) epitopes may explain the link between UTI and PBC. Multiple studies have demonstrated molecular mimicry and immunological cross-reactivity involving microbial and self-antigen mimics. This review will examine the literature surrounding UTI and autoimmune liver disease. This will include case reports and epidemiological studies, as well as experimental data.