Observed counts (O) were compared with the expected Selleck RG-7204 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 = 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). Conclusion: These highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC. (HEPATOLOGY 2011) The etiology of primary biliary cirrhosis (PBC) is not clear.1 Both genetic2-4 and environmental factors are likely to be involved. We have

previously reported evidence of space-time clustering among cases of PBC in a defined geographical population of northeast England.5 This finding suggested that one or more transient environmental agents may play a role in etiology. Putative agents, suggested by other studies, include infections, such as Escherichia coli, mycobacteria, and a retrovirus.6-9 An earlier small study from northeast England BEZ235 nmr of 117 cases of PBC diagnosed during 1966-1979 had shown evidence of seasonality in symptom development, particularly in the spring and early summer,10 although this finding has never been confirmed. If seasonally varying transient environmental agents contribute to the etiology of a disease, then the distribution of cases may exhibit seasonal patterning. However, such seasonality would only happen under very specific conditions. In the case of PBC, this would imply the following: (1) the agent would have a seasonal pattern of occurrence; (2) the latent period

from exposure to diagnosis would be relatively Sorafenib datasheet constant; and (3) because PBC is a relatively uncommon disease, the onset of PBC would result as a rare consequence of exposure to the transient environmental agent. Examples of agents that may exhibit a seasonal pattern include infections, air pollution, and dietary factors. The aim of the present study was to investigate seasonal variation in the incidence of PBC by month of diagnosis among cases diagnosed during 1987-2003 in a well-defined geographical area of northeast England. AMA, antimitochondrial antibody; E, expected number of cases; ICD, International Classification of Diseases; O, observed number of cases; ONS, Office for National Statistics; PBC, primary biliary cirrhosis. For this study, we included both cases defined as “definite PBC” and “probable PBC” in our original case-finding study.11 Definite PBC is all three of the following: antimitochondrial antibody (AMA) positive titer ≥1 in 40, cholestatic liver blood tests, and diagnostic or compatible liver histology.