The Epidemiology of UK Autoimmune Liver Disease Varies With Geographic Latitude

Abstract

Background & aims: 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.

Methods: We 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.

Results: The 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.

Conclusions: We describe an association in the United Kingdom between more northerly latitude and the incidence of PBC and AIH that requires both confirmation and explanation.

Keywords: Autoimmune Hepatitis; Autoimmune Liver Disease; Latitude; Primary Biliary Cholangitis; Primary Sclerosing Cholangitis.

Figure 1

Incidence of autoimmune liver disease by latitude. Top row: Plots denote crude incidence of (A) primary biliary cholangitis (PBC), (B) primary sclerosing cholangitis (PSC), and (C) autoimmune hepatitis (AIH). (D–F) Bottom row: Plots denote adjusted incidence after adjustment for sex, age, smoking status, and Townsend deprivation quintile. For PBC and AIH there was a significant increase in incidence at more northerly latitudes both before and after adjustment; for PSC a significant correlation was not present.

Figure 2

Maps of the United Kingdom showing the crude incidence of autoimmune liver diseases. Incidences are for the whole study period and shown as cases per 100,000/y. The density of shading corresponds to incidence as denoted in each panel: (A) primary biliary cholangitis (PBC), (B) primary sclerosing cholangitis (PSC), and (C) autoimmune hepatitis (AIH). The locations of major cities are shown for reference.

Figure 3

Prevalence of autoimmune liver disease by latitude. Top row: Plots denote crude prevalence at the end of 2015 of (A) primary biliary cholangitis (PBC), (B) primary sclerosing cholangitis (PSC), and (C) autoimmune hepatitis (AIH). (D–F) Bottom row: Plots denote adjusted incidence after adjustment for sex, age, smoking status, and Townsend deprivation quintile. For PBC, 5.89 (2.51–9.27) per 100,000 per degree (r² = 0.752; P = .005); PSC, 0.62 (-0.18 to 1.41) per 100,000 per degree (r² = 0.375; P = .107); and AIH, 1.92 (0.150–3.69) per 100,000 per degree (r² = 0.540; P = .038).