活動性巨細胞病毒感染與隨後的自身免疫性疾病風險之間的關聯：全國性人口為基礎的世代研究

Association between prior active cytomegalovirus infection and subsequent autoimmune disease risk: A population-based cohort study in Taiwan

目的：本研究探討活動性巨細胞病毒感染後，與後續自體免疫疾病發生的關聯性。方法：使用台灣全民健保資料庫，找出在2006年到2017年被診斷為巨細胞病毒感染，且使用對應抗病毒藥物治療的患者；再由無被診斷巨細胞病毒感染族群中抽取對照組，在校正年紀、性別、共病後，使用Cox比例風險模型來統計分析活動性巨細胞病毒感染患者相對於對照組發生自體免疫疾病的發生率比值與風險比。結果：至2006到2017年間，共收入1,138位活動性巨細胞感染患者。這批患者無論在器官特異性自體免疫疾病、或者系統性自體免疫疾病都有較高的疾病發生率。其中最顯著差異的包含了艾迪森氏病（aHR＝84.61,95％信賴區間10.58－676.84）、僵直性脊椎炎（aHR＝12.15,95％信賴區間4.50－33.53）、類風溼性關節炎（aHR＝7.79,95％信賴區間1.28－47.47），紅斑性狼瘡（aHR＝10.59,95％信賴區間1.49－75.19）。結論：在活動性巨細胞病毒感染後，患者發生自體免疫疾病的風險較無感染者顯著上升。

Objectives: This study explored the association between active cytomegalovirus (CMV) infection and autoimmune diseases. Methods: By extracting data from Taiwan's National Health Insurance Research Database, we retrospectively analysed patients with CMV infection treated with antiviral drugs from January 1, 2006, to December 31, 2017. These patients were followed up to estimate the incidence of autoimmune disease and compared with those without CMV infection. Incidence rate ratios (IRRs) and adjusted hazard ratios (aHRs) of autoimmune diseases for patients with CMV infection were estimated using the Cox proportional hazard regression model. Results: After 1:10 propensity score matching, the final study population comprised 1,138 patients with active CMV infection and 11,380 without CMV infection. The incidence rates of overall autoimmune diseases were significantly higher in the active CMV cohort than in the non-CMV cohort (881.83 and 425.38 person-years, respectively), including organ-specific and systemic autoimmune diseases. Furthermore, a higher incident subgroup of autoimmune diseases such as Addison's disease (aHR: 84.61, 95% confidence interval [CI]: 10.58-676.84), ankylosing spondylitis (aHR: 12.15, 95% CI: 4.50-33.53), rheumatoid arthritis (aHR: 7.79, 95% CI: 1.28-47.47), and systemic lupus erythematosus (aHR: 10.59, 95% CI: 1.49-75.19) were noted in the active CMV cohort compared with the non-CMV cohort. Conclusions: The risk of autoimmune diseases, including Addison's disease, Ankylosing Spondylitis, Rheumatoid arthritis, Systemic lupus erythematosus, are significantly higher in patients with active CMV infection than in those without.