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

Jessica Katharine Dyson; Alasdair Blain; Mark David Foster Shirley; Mark Hudson; Steven Rushton; David Emrys Jeffreys Jones

doi:10.1016/j.jhepr.2020.100202

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

JHEP Rep. 2020 Nov 4;3(1):100202. doi: 10.1016/j.jhepr.2020.100202. eCollection 2021 Feb.

Authors

Jessica Katharine Dyson^{1

2}, Alasdair Blain³, Mark David Foster Shirley⁴, Mark Hudson^{1

2}, Steven Rushton⁴, David Emrys Jeffreys Jones^{1

2}

Affiliations

¹ Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK.
² Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.
³ Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle-upon-Tyne, UK.
⁴ School of Natural and Environmental Sciences, Newcastle University, Newcastle-upon-Tyne, UK.

Abstract

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.

Lay summary: This study looked for potential environmental triggers in patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) living in the north-east of England and north Cumbria. We found that PBC was more common in urban areas with a history of coal mining and high levels of cadmium whereas PSC was more common in rural areas with lower levels of social deprivation.

Keywords: AHSN NENC, Academic Health Science Network for the North East and North Cumbria; AIH, autoimmune hepatitis; AILD, autoimmune liver disease; Autoimmune hepatitis; BECs, biliary epithelial cells; CFI, comparative fit index; Cadmium; DIC, deviance information criterion; Geo-epidemiology; IMD, Index of Multiple Deprivation; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; Primary biliary cholangitis; Primary sclerosing cholangitis; RMSEA, root mean square error of association; Rural; SEM, structural equation modelling; SFS, superfund toxic waste site; Socio-economic status; Urban.