The new england journal of medicine .
2010;362:1597-1604 April 29, 2010
(Impact Factor ： 54.420)
Kenneth E.L. McColl, M.D.
Speaker


A 29-year-old man presents with intermittent epigastric discomfort, without weight loss or evidence of gastrointestinal bleeding.

He reports no use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs).

Abdominal examination reveals epigastric tenderness.

A serologic test for Helicobacter pylori is positive, and he receives a 10-day course of triple therapy (omeprazole, amoxicillin, and larithromycin).
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Six weeks later, he returns with the same symptoms. How should his case be further evaluated and managed?

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Helicobacter pylori , a gram-negative bacterium found on the luminal surface of the gastric epithelium, was first isolated by
Warren and Marshall in 19831 (Fig. 1).

It induces chronic inflammation of the underlying mucosa (Fig.
2).
Figure 1 Figure 2

 At least 50% of the world’s human population has H. pylori infection.

The organism can survive in the acidic environment of the stomach partly owing to its remarkably high urease activity.

Infection with H. pylori is a cofactor in the development of three important upper gastrointestinal diseases ：
1.
duodenal or gastric ulcers (reported to develop in 1 to 10% of infected patients),
2.
gastric cancer (in 0.1 to 3%),
3.
and gastric mucosa-associated lymphoid-tissue (MALT) lymphoma (in <0.01%).


In patients with duodenal ulcers, the inflammation of the gastric mucosa induced by the infection is most pronounced in the non–acid-secreting antral region of the stomach and stimulates the increased release of gastrin.

The increased gastrin levels in turn stimulate excess acid secretion from the more proximal acid-secreting fundic mucosa, which is relatively free of inflammation.

The increased duodenal acid load damages the duodenal mucosa, causing ulceration and gastric metaplasia.

The metaplastic mucosa can then become colonized by H. pylori, which may contribute to the ulcerative process.

Eradication of the infection provides a long-term cure of duodenal ulcers in more than 80% of patients whose ulcers are not associated with the use of
NSAIDs.

NSAIDs are the main cause of H. pylori–negative ulcers


Extensive epidemiologic data suggest strong associations between H. pylori infection and noncardia gastric cancers (i.e., those distal to the gastroesophageal junction).

The infection is classified as a human carcinogen by the World Health
Organization.

The risk of cancer is highest among patients in whom the infection induces inflammation of both the antral and fundic mucosa and causes mucosal atrophy and intestinal metaplasia.

Eradication of H. pylori infection reduces the progression of atrophic gastritis, but there is little evidence of reversal of atrophy or intestinal metaplasia, and it remains unclear whether eradication reduces the risk of gastric cancer


Epidemiologic studies have also shown strong associations between H. pylori infection and the presence of gastric MALT lymphomas.

Furthermore,eradication of the infection causes regression of most localized gastric MALT lymphomas


Candidates for Testing for H. pylori Infection

Since the vast majority of patients with H. pylori infection do not have any related clinical disease,routine testing is not considered appropriate.


Definite indications for identifying and treating the infection are confirmed ga stric or duodenal ulcers and gastric MALT lymphoma.

In addition, European guidelines recommend eradicating H.
pylori infection in first-degree relatives of patients with gastric cancer and in patients with atrophic gastritis, unexplained irondeficiency anemia, or chronic idiopathic thrombocytopenic purpura.


Patients with accompanying alarm symptom(e.g.,weight loss, persistent vomiting,or gastrointestinal bleeding) or for older patients (≥45 or ≥55 years of age, depending on the specific set of guidelines) with new-onset dyspepsia, in whom endoscopy is warranted.

The nonendoscopic strategy is also not generally recommended for patients with NSAID-associated dyspepsia.


In a placebo-controlled trial of empirical treatment involving 294 patients with uninvestigated dyspepsia and a positive H. pylori breath test, the 1-year rate of symptom resolution was 50% in those receiving H.
pylori –eradication therapy, as compared with 36% of those receiving placebo (P = 0.02)

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 平時，胃黏膜細胞上的 氫離子幫浦會將酸排入胃中，
降低胃中的 pH 值
 幽門桿菌雖然居於胃部，卻不耐酸，最適合的酸鹼
範圍為 pH5-7.5
 具有「尿素 酶」 ，能將人體 內的尿素 分解，尿素分
解後會 產生二氧化碳與 氨，使得細菌體周邊的環境
不至於過酸，細菌也就得以存活。



The urea breath test involves drinking 13 C-labeled or 14 C-labeled urea, which is converted to labeled carbon dioxide by the urease in H.
pylori . The labeled gas is measured in a breath sample.

 用 ELASA 偵測糞便中是否存有幽門螺旋桿菌

 包括 esomeprazole （本院藥品：耐適恩 Nexium ）、 lansoprazole （本院藥品：泰克胃通 Takepron ）、 omeprazole 、 pantoprazole （本院藥品：保衛康
治潰 樂
Pantoloc ）、 rabeprazole 。
 針對中 度至嚴重的胃食道逆流 ，且抑制胃酸分 泌
的效果長。
 常 見的 副作用包括頭痛、疲倦
、噁心、 便秘或腹瀉等 。

 為一種「盤尼西林」類的抗生素。
 藉著破壞圍繞細菌外圍的細胞壁，使細菌的細胞壁
不能正常地生長，最後達到消滅細菌的作用。


Clarithromycin
 抑制細菌蛋白質的 產生，使細菌不能正常地生長與繁殖，因
而造成細菌的死亡。
 可與 Takepron 併用治療與幽門螺旋桿菌 (H. pylori) 有關之消化
性潰瘍。

Tetracycline
 結構類似四個環狀所以又通稱為「四環類」抗生素。
 藥理作用是能 夠抑制細菌蛋白質的產生，使細菌不能正常地
生長與繁殖，最後導致死亡。


It is important to confirm the eradication of H. pylori infection in patients who have had an H. pylori –associated ulcer or gastric MALT lymphoma or who have undergone resection for early gastric cancer.

To avoid repeated treatment of patients whose symptoms are not attributable to H. pylori, follow-up testing is indicated in patients whose symptoms persist after H. pylori eradication treatment for dyspepsia.


Before prescribing a second course of therapy, it is important to confirm that the infection is still present and consider whether additional antimicrobial treatment is appropriate.

Treatment failure is often related to H. pylori resistance to clarithromycin or metronidazole (or both agents). If initial therapy did not include a bismuth salt,bismuth-based quadruple therapy is commonly used as second-line therapy, with eradication rates in case series ranging from 57 to 95%.


Triple therapies have also been tested as secondline therapies in patients in whom initial therapy failed. A proton-pump inhibitor used in combination with metronidazole and either amoxicillin or tetracycline is recommended in patients previously treated with a proton-pump inhibitor, amoxicillin, and clarithromycin.

 非侵入式檢驗用 : 尿素呼吸試驗、糞便抗原試驗和血清學試
驗，而血清學試驗是最不準確的。
 然而最常使用的療法三合一療法，是利用 proton-pump inhibitor, clarithromycin, and amoxicillin or metronidazole 來
作用在第一線的治療，而前題是使用幽門桿菌對於 clarithromycin 沒有抗藥性的情況下。

 在治療根除後復發或症狀持續存在並不太可能是因
為治療失敗，而是這些症狀不是 H. pylori 感染造成的。
進一步的治療是不應該考慮的，除非是確認又被 H.
pylori 感染。
 對於被感染 H. pylori 並進行非侵入性檢測和治療後的
復發或者持續性的消化不良，後續處理知識是缺乏
的。而檢測治療包括胃酸抑制劑、胃鏡，來檢 查潛
在的潰瘍或其他導致的症狀。並且重複對於 H. pylori
的檢測和治療。對其他潛在的原因導致的症狀也應
該一併考慮！

 幽門桿菌感染後，一定要按時吃藥才能痊癒，否則
讓幽門桿菌 產生抗藥性後 ，又要在重複一次療程。