Abstract

Background & AimsThe epidemiology of autoimmune liver disease (AILD) is challenging to study because of the diseases’ rarity and because of cohort selection bias. Increased incidence farther from the Equator has been reported for multiple sclerosis, another autoimmune disease. We assessed the incidence of primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) in relation to latitude.MethodsWe performed a retrospective cohort study using anonymized UK primary care records from January 1, 2002, to May 10, 2016. All adults without a baseline diagnosis of AILD were included and followed up until the first occurrence of an AILD diagnosis, death, or they left the database. Latitude was measured as registered general practice rounded down to whole degrees.ResultsThe cohort included 8,590,421 records with 53.3 × 107 years of follow-up evaluation from 694 practices. There were 1314 incident cases of PBC, 396 of PSC, and 1034 of AIH. Crude incidences were as follows: PBC, 2.47 (95% CI, 2.34–2.60); PSC, 0.74 (95% CI, 0.67–0.82); and AIH, 1.94 (95% CI, 1.83–2.06) per 100,000 per year. PBC incidence correlated with female sex, smoking, and deprivation; PSC incidence correlated with male sex and non-smoking; AIH incidence correlated with female sex and deprivation. A more northerly latitude was associated strongly with incidence of PBC: 2.16 (95% CI, 1.79–2.60) to 4.86 (95% CI, 3.93–6.00) from 50°N to 57°N (P = .002) and incidence of AIH: 2.00 (95% CI, 1.65–2.43) to 3.28 (95% CI, 2.53–4.24) (P = .003), but not incidence of PSC: 0.82 (95% CI, 0.60–1.11) to 1.02 (95% CI, 0.64–1.61) (P = .473). Incidence after adjustment for age, sex, smoking, and deprivation status showed similar positive correlations for PBC and AIH with latitude, but not PSC. Incident AIH cases were younger at more northerly latitude.ConclusionsWe describe an association in the United Kingdom between more northerly latitude and the incidence of PBC and AIH that requires both confirmation and explanation.

Highlights

  • BACKGROUND & AIMSThe epidemiology of autoimmune liver disease (AILD) is challenging to study because of the diseases’ rarity and because of cohort selection bias

  • primary biliary cholangitis (PBC) incidence correlated with female sex, smoking, and deprivation; primary sclerosing cholangitis (PSC) incidence correlated with male sex and non-smoking; autoimmune hepatitis (AIH) incidence correlated with female sex and deprivation

  • A more northerly latitude was associated strongly with incidence of PBC: 2.16 to 4.86 from 50N to 57N (P [ .002) and incidence of AIH: 2.00 to 3.28 (P [ .003), but not incidence of PSC: 0.82 to 1.02 (P [ .473)

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Summary

Introduction

The epidemiology of autoimmune liver disease (AILD) is challenging to study because of the diseases’ rarity and because of cohort selection bias. Increased incidence farther from the Equator has been reported for multiple sclerosis, another autoimmune disease. We assessed the incidence of primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) in relation to latitude. Disease risk in primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis is insufficiently explained by genetic factors. In other autoimmune diseases such as multiple sclerosis, geographic latitude correlates with disease risk

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