Seasonal variation in the patient diagnosis of primary biliary cirrhosis: Further evidence for an environmental component to etiology

Abstract

The etiology of primary biliary cirrhosis (PBC) is far from clear. Both genetic and environmental factors are likely to be involved. We have previously reported evidence of space-time clustering, suggesting that a transient environmental agent may be involved in etiology. To further examine whether a seasonally varying environmental agent may contribute to the etiology of PBC, we have analyzed seasonal variation with respect to month of diagnosis using population-based data from northeast England over a defined period (1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003). Date of diagnosis was defined as the earliest date at which the patient was found to have fulfilled any two of three diagnostic criteria (i.e., antimitochondrial antibody-positive titer 1 in 40, cholestatic liver blood tests, diagnostic or compatible liver histology). Monthly expected (E) numbers of cases were calculated under an assumption of a uniform distribution throughout the year. Observed counts (O) were compared with the expected numbers. The chi-squared heterogeneity test was used to test for overall nonuniform variation and also for individual months. Poisson regression analysis was used to fit a sinusoidal (i.e., harmonic) model to the data, using month of diagnosis as a covariate in the model. There was a marked peak for diagnoses in the month of June (O 5 115, E 5 84.7, O/E 5 1.36; P 5 0.001). Furthermore, there was evidence of a sinusoidal pattern with a June peak (P 5 0.012). Conclusion: These highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC.

Does primary biliary cirrhosis cluster in time?

“…This was the first study to find space-time clustering of this disease and suggests that transient environmental agents might play a role in the aetiology of this disease. Further analysis of this population-based cohort found marked seasonal variation in diagnoses of PBC, with a peak in June (McNally et al, 2011). This suggests the involvement of a seasonally varying agent occurring at different locations in the environment.…”

“…The present study is concerned with the detection of irregular temporal distributions of cases of PBC, as opposed to regular seasonal patterns or space-time clustering as addressed previously (McNally et al, 2009(McNally et al, , 2011, or individual temporal clusters. A general irregular temporal distribution of cases that is not confined to one particular time period or period of each year is known as 'temporal clustering' (Muirhead et al, 2013).…”

Frequent detection of immunoglobulin M anti-herpes simplex viral antibody in patients with primary biliary cirrhosis

“…We read with great interest the article by McNally et al, 1 who reported the involvement of a seasonally varying environmental agent in the etiology of primary biliary cirrhosis (PBC), and who have reported previously that a transient environmental agent may be involved in the etiology using a space-time clustering method among cases of PBC in a defined geographical population of northeast England. 2 A combination of genetic predisposition and environmental factors are thought to contribute the etiology of PBC.…”

What Is New in Primary Biliary Cirrhosis?

“…Space-clustering occurs when there is an excess of cases of a given disease within a restricted geographical area, at a specified period of time. The study by McNally et al [54] suggests space-clustering of PBC which cannot be attributed to variations in population density. According to the authors, these findings are suggestive of a widespread but transient causative agent (such as a virus) in a localized geographical area, which is consistent with a short ‘lag time’ between exposure to a particular agent followed by diagnosis at a later date, or a longer but constant ‘lag time’ between exposure to the agent and subsequent diagnosis.…”

“…Recent data from a group in Newcastle appears to characterize the contribution of environmental (likely infectious) agents in the pathogenesis of PBC in a cluster of patients. McNally et al [54] analyzed space-time clustering using population-based data from northeast England over a period from 1987 to 2003. Space-clustering occurs when there is an excess of cases of a given disease within a restricted geographical area, at a specified period of time.…”