早期根除治療幽門桿菌對系統性紅斑狼瘡風險的影響

研究目的我們先前的研究顯示幽門桿菌(Helicobacter pylori, HP)感染會增加患者的系統性紅斑狼瘡(Systemic lupus erythematosus, SLE)風險。本研究進一步探討早期根除治療幽門桿菌是否會影響幽門桿菌感染患者的系統性紅斑狼瘡風險。方法我們在台灣分析了從2000年至2013年確診為幽門桿菌感染的41653位患者。這些對象來自台灣全民健康保險研究數據庫（National Taiwan Insurance Research Database, NHIRD）的百萬歸人檔縱向健康保險數據庫(Longitudinal Health Insurance Database, LHID 2000）。進一步將幽門桿菌感染患者族群分為早期（3個月內）和晚期（3個月後）接受幽門桿菌根除療法兩組。通過使用傾向評分分析入組年份，年齡，性別，收入，都市化程度，合併症(包括類風濕關節炎，乾燥症，高血壓，糖尿病，高脂血症，冠心病，骨質疏鬆症，腦血管病變，哮喘，慢性阻塞性肺疾病，慢性腎臟病，慢性肝病，慢性蕁麻疹，結核病，肺炎，敗血症和帶狀皰疹等)和醫療就診的使用以1：1比例匹配。我們進一步採用多變項Cox回歸分析估計系統性紅斑狼瘡的風險值，透過Kaplan-Meier analysis和log-rank test計算系統性紅斑狼瘡的存活分析與累積發生率。並且以敏感性分析和分層分析，來評估系統性紅斑狼瘡調整後的風險比（adjusted hazard ratio, aHR）。結果在早期根除治療幽門桿菌族群中，系統性紅斑狼瘡的相對風險為0.75（95％CI：0.43-1.31）。經過多變項調整後，早期根除治療幽門桿菌組的系統性紅斑狼瘡風險低於晚期根除治療幽門桿菌族群（aHR：0.74，95％CI：0.42-1.29）。進一步分層分析中顯示，在前3年的追蹤期內，早期根除治療幽門桿菌可顯著降低系統性紅斑狼瘡風險（aHR：0.16，95％CI：0.05-0.53，相互作用p：0.0013）。與在診斷後3個月內即早期根除治療幽門桿菌者相比，在診斷後3–36個月內和> 36個月後才進行根除治療者在最初3年的追蹤期內系統性紅斑狼瘡的aHR分別為4.78（95％CI：1.19-19.20）和7.66（95％CI：2.17–27.05）。結論我們的回顧性世代研究發現幽門桿菌感染會增加患者的系統性紅斑狼瘡風險。而早期根除治療幽門桿菌可以顯著降低系統性紅斑狼瘡風險，尤其是在最初的3年追蹤期中。這是第一篇探討幽門桿菌早期根除療法是否會影響幽門桿菌感染患者的系統性紅斑狼瘡風險的文章。希望藉由這個研究結果呼籲幽門桿菌早期根除治療的重要性。

Objectives: Our previous study demonstrated that Helicobacter pylori (HP) infection was associated with a 1.63-fold increased systemic lupus erythematosus (SLE) risk. We thus hypothesized that a longer period of Helicobacter pylori exposure leads to a higher SLE risk compared to a shorter period of Helicobacter pylori exposure. Consequently, we evaluated whether early eradication influences SLE risk in patients with Helicobacter pylori infection by using a nationwide population-based cohort study.Materials and methods: We identified 41,653 patients with Helicobacter pylori infection in Taiwan between 2000 and 2013 from the Longitudinal Health Insurance Database of the National Taiwan Insurance Research Database. The patient population was divided into early (within 3 months) and late (after 3 months) eradication cohorts; age, sex, comorbidities, and medical visits were matched at a 1:1 ratio. Multiple Cox regression, sensitivity and stratified analysis were used to estimate SLE adjusted hazard ratio (aHR).Results: The relative risk of SLE was 0.75 (95% CI: 0.43–1.31) in the early eradication cohort. After multivariate adjustment, the SLE risk was non-significantly lower in the early eradication cohort than in the late eradication cohort (aHR: 0.74, 95% CI: 0.42–1.29). Stratified analysis revealed that early eradication could significantly reduce SLE risk during the 3-year follow-up period (aHR: 0.16, 95% CI: 0.05–0.53, p for interaction: 0.0013). Compared with eradication within 3 months of diagnosis, eradication within 3–36 months and >36 months corresponded with SLE aHR of 4.78 (95% CI: 1.19–19.20) and 7.66 (95% CI: 2.17–27.05), respectively, when follow-up period was <3 years. The overall long-term SLE risk was not significantly different between the cohorts.Conclusion: Based on this real-world, nationwide population-based longitudinal study and adjustment of possible confounding variables, we found early Helicobacter pylori eradication could significantly reduce the risk of SLE within 3-year follow-up. We recommend administering early eradication and provide appropriate monitoring of SLE in patients with Helicobacter pylori infection during follow-up.