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Seasonal variation in the diagnosis of primary biliary cirrhosis: further evidence for an environmental component to etiology
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Dr Richard McNally
Dr Peter James
Emeritus Professor Oliver James
McNally RJQ, James PW, Ducker S, James OFW
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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 (1987–2003). Date of diagnosis was defined as the earliest date at which the patient was found to have fulfilled any two of three diagnostic criteria (AMA positive titre ≥ 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 non-uniform variation and also for individual months. Poisson regression analysis was used to fit a sinusoidal (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 = 115, E = 84.7, O/E = 1.36, P = 0.001). Furthermore, there was evidence of a sinusoidal pattern with a June peak (P = 0.012). In conclusion, these highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC.
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