Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom.
Hepatology. 2011 Dec;54(6):2099-103. doi: 10.1002/hep.24597.
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 (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 = 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).
These highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC.
原发性胆汁性肝硬化（PBC）的病因尚不清楚。遗传和环境因素都可能与之相关。我们之前曾报告过时空聚集的证据，表明可能存在一种短暂的环境因素参与其病因。为了进一步研究季节性变化的环境因素是否可能导致 PBC 的病因，我们使用来自英格兰东北部的基于人群的数据，分析了在特定时间段（1987-2003 年）中与诊断月份相关的季节性变化。诊断日期定义为最早发现患者符合以下三个诊断标准中的任意两个的日期（即抗线粒体抗体滴度≥1:40，胆汁淤积性肝功能检查，诊断或符合的肝脏组织学）。假设全年均匀分布，计算每个月的预期（E）病例数。将观察到的病例数（O）与预期数进行比较。卡方异质性检验用于检验总体非均匀性变化，也用于检验个别月份。使用诊断月份作为模型中的协变量，对数据进行正弦（即谐波）模型拟合的泊松回归分析。6 月份的诊断明显出现高峰（O=115，E=84.7，O/E=1.36；P=0.001）。此外，存在 6 月高峰的正弦模式的证据（P=0.012）。
这些非常新颖的结果进一步证明季节性变化的环境因素可能参与 PBC 的病因。
