背景及目的：埃及斑蚊及白線斑蚊為登革病毒主要的傳染媒介，隨著全球暖化，氣候的變遷改善蚊子的生長條件，使其可生存地區擴大到100多個國家，全球約有一半的人口處於登革病毒感染風險中，且發生率急遽攀升，成為這些地區兒童及成年人死亡的原因之一，帶來巨大的健康、經濟和社會負擔，登革熱成為全球關注的公共衛生議題。嚴重登革熱可能會發生出血和休克等危及生命的併發症，但大多數感染者會在發燒期過後自動康復，因此，登革熱被視為沒有長期後遺症的急性發熱性疾病，但陸續有一些研究在探討感染登革病毒痊癒後是否有一些長期的影響；而消化道出血是登革熱常見的併發症之一，但目前尚未有研究探討登革熱患者是否有較高的腸胃道出血長期風險，因此，本研究探討感染登革病毒後，短期、中期與長期發生腸胃道出血的風險。

方法：本研究使用回溯性世代追蹤研究法，申請使用行政院衛生福利資料科學中心的全民健康保險研究資料庫，並從1998-2015年的法定傳染病個案通報系統資料庫-機敏資料庫中，找出2002-2012年登革熱新發個案作為病例世代，再自2000-2015年的全民健保承保檔，用個別配對1:4配對年齡、性別、居住地區及發病年月，再串門急診及西醫住院檔，找出非登革熱病患的人作為對照世代。自配對的發病日開始追蹤至發生腸胃道出血、死亡或2015年12月31日，將追蹤時間分成發病後≤60天與>60天，而大於60天又再分為61-365和>365天。我們使用多變量Cox比例風險模型(Cox proportional hazard model)控制性別、年齡、居住地區及與腸胃道出血相關的疾病和藥物後，分別估計不同追蹤時段的風險比(Hazard Ratio, HR)及95%信賴區間(Confidence interval, CI)。我們也考慮發病後以30日為時間切點，探討發病後≤30天與>30天(>30天又再分為31-365天和>365天)發生腸胃道出血的風險。另外考量死亡為競爭風險，使用次分佈瞬間危險函數(SubDistribution Hazard Function, SDH)進行敏感度分析。

結果：本研究納入登革熱新發病患13,207人及配對的非登革熱對照組52,828人，而病例世代和對照世代追蹤時間的中位數和四分位距分別為8.12年(IQR 5.09-13.10)及8.13年(IQR 5.11-13.11)。在控制干擾因子後，登革熱在感染後短期60天內有較高的腸胃道出血風險(HR 27.44, 95% CI 18.40-40.93)，但中長期超過60天後登革熱與腸胃道出血無顯著相關(HR 0.95, 95% CI 0.83-1.10)，而感染61-365天之HR 0.79, 95% CI 0.49-1.28，超過365天之HR 0.98, 95% CI 0.85-1.13。若以30天為切點，在感染後短期30天內也有較高的腸胃道出血風險(HR 53.92, 95% CI 31.25-93.04)，而中長期超過30天後登革熱與腸胃道出血也無顯著相關(HR 0.95, 95% CI 0.83-1.09)，感染31-365天HR 0.80, 95% CI 0.50-1.25。使用次分佈瞬間危險函數進行敏感度分析發現結果與使用多變量Cox比例風險模型的結果差異不大。

結論：本研究發現登革熱患者在發病後短期60天內發生腸胃道出血的風險較非登革熱患者高，超過60天後則無風險，顯示登革病毒對於消化道出血沒有長期的風險，讓患者較安心痊癒後較不會有腸胃道出血的併發症，但仍需注意短期發生腸胃道出血的危險性。

This retrospective cohort study, including 13,207 newly diagnosed dengue patients and 52,828 non-dengue matched controls, was conducted to investigate the long-term risk of gastrointestinal bleeding among dengue patients. The median and interquartile range of follow-up time between dengue patients and non-dengue controls were 8.12 years (IQR 5.09-13.10) and 8.13 years (IQR 5.11-13.11). After controlling for potential confounders, dengue patients had a higher risk of GI bleeding within 60 days after infection, but there was no significant association between dengue and GI bleeding after 60 day. It seems that dengue virus infection does not increase the long-term risk of GI bleeding among infected people.

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