Geo-epidemiology and environmental co-variate mapping of primary biliary cholangitis and primary sclerosing cholangitis

Background & Aims: Autoimmune liver disease (AILD) is thought to result from a complex interplay between genetics and the environment. Studies to date have focussed on primary biliary cholangitis (PBC) and demonstrated higher disease prevalence in more urban, polluted, and socially deprived areas. This study utilises a large cohort of patients with PBC and primary sclerosing cholangitis (PSC) to investigate potential environmental contributors to disease and to explore whether the geo-epidemiology of PBC and PSC are disease-specific or pertain to cholestatic AILD in general. Methods: All adult patients with PBC and PSC in a tightly defined geographical area within the UK were identified. Point- and area-based analyses and structural equation modelling (SEM) were used to investigate for disease clustering and examine for relationships between prevalence, distribution of environmental contaminants, and socio-economic status. Results: We identified 2,150 patients with PBC and 472 with PSC. Significant spatial clustering was seen for each disease. A high prevalence of PBC was found in urban, post-industrial areas with a strong coal-mining heritage and increased environmental cadmium levels, whereas a high PSC prevalence was found in rural areas and inversely associated with social deprivation. Conclusions: This study demonstrates spatial clustering of PBC and PSC and adds to our understanding of potential environmental co-variates for both diseases. Disease clustering, within the same geographical area but over different scales, is confirmed for each disease with distinct risk profiles identified and associations with separate putative environmental factors and socio-economic status. This suggests that different triggers and alternative pathways determine phenotypic expression of autoimmunity in the affected population. Co-variate analysis points towards the existence of specific disease triggers. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).

Automated summary

This study investigates the potential environmental contributors to autoimmune liver diseases (AILD) such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Significant spatial clustering of PBC and PSC patients was observed, with distinct risk profiles and associations with different environmental factors and socio-economic statuses identified. This suggests different triggers and alternative pathways determine the phenotypic expression of autoimmunity in the affected population.