- 學位論文
利用胃液聚合酶鏈鎖反應來診斷曾經治療過的幽門螺旋桿菌：一個準確且符合臨床需求的診斷方式
An accurate solution to the clinical unmet need for the diagnosis of treatment-experienced Helicobacter Pylori:Gastric juice-based PCR assay
摘要
(前言) 幽門螺旋桿菌一旦治療失敗後，臨床上就非常著重細菌培養的方式，因為細菌培養能夠提供藥物敏感度測試做為後續再次治療的用藥依據。然而，細菌培養的準確度很低，尤其是對於治療過的幽門螺旋桿菌而言，準確度更低。目前臨床上所需的，是一個能夠提供高準確度，而且也能同時提供抗生素藥物敏感度試驗的工具。理論而言，胃液聚合酶鏈鎖反應能同時提供這兩個優勢，但是目前沒有臨床數據來證實。這篇研究的目標就是提供關於胃液聚合酶鏈鎖反應的診斷數據，並且將這個結果跟傳統的培養方式做比較。 (方法) 此研究總共收入了711位病人，並且將這些病人根據之前的治療經驗區分為以下四群：尚未治療過，曾經接受一線治療，曾經接受兩線治療，曾經接受三線治療。在每位病人中，若符合以下的臨床黃金標準，則定義為幽門螺旋桿菌感染：(1)組織學與快速尿素酶同時陽性或是(2)組織學或快速尿素酶之一陽性並且合併尿素酶吹氣測試陽性。爾後，我們在每位幽門桿菌陽性以及陰性病人身上，採集胃液做胃液聚合酶鏈鎖反應，也採集胃組織檢體做組織培養。根據結果計算出胃液聚合酶鏈鎖反應以及組織培養的敏感性，專一性，陽性預測值，陰性預測值以及準確度。再利用統計檢定比較其結果。 (結果) 我們的結果顯示胃液聚合酶鏈鎖反應的準確度比傳統組織培養還要高。在尚未治療過的病人當中，胃液聚合酶鏈鎖反應的準確度為96%，傳統組織培養的準確度為87%，此比較的統計p值為0.0001。在接受過1線治療的病人，胃液聚合酶鏈鎖反應的準確度為97%，傳統組織培養的準確度為79%，此比較的統計p值為0.0002。在接受過2線治療的病人，胃液聚合酶鏈鎖反應的準確度為96%，傳統組織培養的準確度為77%，此比較的統計p值為0.0012。在接受過3線治療的病人，胃液聚合酶鏈鎖反應的準確度為100%，傳統組織培養的準確度為70%，此比較的統計p值為0.0092。此外，胃液聚合酶鏈鎖反應檢測的敏感度也是優於傳統組織培養。在尚未治療過的病人當中，胃液聚合酶鏈鎖反應的敏感度為92%，傳統組織培養的準確度為58%，此比較的統計p值小於0.0001。在接受過1線治療的病人，胃液聚合酶鏈鎖反應的敏感度為90%，傳統組織培養的準確度為35%，此比較的統計p值小於0.0001。在接受過2線治療的病人，胃液聚合酶鏈鎖反應的敏感度為93%，傳統組織培養的準確度為60%，此比較的統計p值小於0.0006。在接受過3線治療的病人，胃液聚合酶鏈鎖反應的敏感度為100%，傳統組織培養的準確度為22%，此比較的統計p值小於0.00023。特異度，陽性預測值，陰性預測值也都有計算。以上的結果都顯示出，在治療過的幽門螺旋桿菌感染當中，胃液聚合酶鏈鎖反應的診斷都比傳統組織細菌培養法來的好。 (結論) 對於曾經治療過的幽門螺旋桿菌而言，胃液聚合酶鏈鎖反應的診斷率比傳統組織細菌培養法來的有效，而且胃液聚合酶鏈鎖反應不會隨著治療次數增加而有所影響。反之，傳統組織細菌培養法會因為治療次數越多，診斷準確率會下降。我們的研究證實，在曾經治療過的幽門桿菌感染的族群中，胃液聚合酶鏈鎖反應是個準確的診斷方式而且符合目前臨床需求，具有被廣泛運用的潛力。
並列摘要
Background The culture method has been strongly emphasized in the clinical setting of Helicobacter pylori (H. pylori) eradication failure because retreatment strategy can be tailored based on the culture antibiotics susceptibility test. However, the culture method yields low accuracy, especially in treatment-experienced H. pylori infection. The current clinical unmet need in the setting of treatment-experienced H. pylori infection is one diagnostic method with satisfying accuracy as well as the ability to perform the antibiotics susceptibility test. Theoretically, gastric juiced-based PCR is able to provide both strengths, but there is no clinical data. Our study intended to provide the data regarding the diagnostic accuracy of gastric juice-based PCR in the treatment-experienced H. pylori infection and compare the results of gastric juice-based PCR with that of the culture method. Methods We included 711 patients and categorized them into 4 groups based on their previous treatment history: treatment-naïve, post 1st line therapy, post 2nd line therapy and post 3rd line therapy. The status of H. pylori infection in each subject was confirmed according to the following clinical gold standards: concordant positive histology and rapid urease test or positive urease breath test. We performed gastric juice-based PCR and culture in each subject and then calculated the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of gastric juice-based PCR as well as culture method. Finally, we compared the results with Fisher’s exact test. Results Our findings demonstrated that the accuracy of gastric juice-based PCR was higher than that of the traditional culture method in treatment-naïve patients (96% vs 87%, p values = 0.0001), in patients post 1st line therapy (97% vs 79%, p values = 0.0002), in patients post 2nd line therapy (96% vs 77%, p values = 0.0012) and in patients post 3rd line therapy (100% vs 70%, p values = 0.0092). The sensitivity of gastric juice-based PCR was also better than that of the traditional culture method in treatment-naïve patients (92% vs 58%, p values < 0.0001), in patients post 1st line therapy (90% vs 35%, p values < 0.0001), in patients post 2nd line therapy (93% vs 60%, p values = 0.0006) and in patients post 3rd line therapy (100% vs 22%, p values = 0.0023). The specificity, positive predictive and negative predictive values were calculated as well. The results indicated that gastric juice-based PCR outperformed the traditional culture method in diagnosis of treatment-experienced H pylori. Conclusion The gastric juice-based PCR yields more accurate diagnosis in treatment-experienced H. pylori than the traditional culture method and also provides the anti-microbial susceptibility test to guide subsequent retreatment therapy. Our study demonstrated that gastric juice-based PCR suits the current unmet need for the management of treatment-experienced H pylori and has very promising potential for widespread application in the setting of treatment failure.