我國(guó)幽門螺桿菌感染的現(xiàn)狀分析

王 雪， 李異玲， 呂曉輝

中國(guó)醫(yī)科大學(xué)附屬第一醫(yī)院消化內(nèi)科，遼寧 沈陽(yáng) 110000

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專題·幽門螺桿菌

我國(guó)幽門螺桿菌感染的現(xiàn)狀分析

王 雪， 李異玲， 呂曉輝

中國(guó)醫(yī)科大學(xué)附屬第一醫(yī)院消化內(nèi)科，遼寧 沈陽(yáng) 110000

我國(guó)幽門螺桿菌(Helicobacter pylori，H.pylori)的感染率在不同地區(qū)、不同時(shí)期、不同人群中不同，且呈逐年下降趨勢(shì)。目前，由于抗生素的廣泛使用，H.pylori耐藥情況已成為影響其根除率的重要因素，含鉍劑的四聯(lián)療法較標(biāo)準(zhǔn)三聯(lián)療法有更好的治療效果，已作為抗H.pylori治療的首選方案之一；同時(shí)，個(gè)體化治療和輔助用藥越來(lái)越被重視。

中國(guó)；幽門螺桿菌；流行病學(xué)；除菌治療現(xiàn)狀；耐藥情況

幽門螺桿菌(Helicobacter pylori，H.pylori)是一種微需氧、對(duì)生長(zhǎng)條件要求十分苛刻的革蘭陰性桿菌。近年來(lái)，H.pylori與各種疾病的關(guān)系被相繼報(bào)道，尤其是慢性胃炎和胃潰瘍，其在醫(yī)學(xué)研究中的地位越來(lái)越重要。本文就我國(guó)H.pylori感染的現(xiàn)狀進(jìn)行分析。

1 流行病學(xué)

1.1 不同地區(qū)H.pylori感染率 我國(guó)不同地區(qū)H.pylori感染率不同。Tang等[1]在2014年研究了8 365名成都永久居民H.pylori感染情況，其感染率為53.1%。Pan等[2]研究了胃癌高發(fā)區(qū)山東臨朐縣184 786名居民H.pylori感染情況，感染率為57.6%。孟欣穎等[3]從1 813名青島市民中得到的H.pylori感染率為46.8%。斯慶圖娜拉等[4]報(bào)道2012年-2015年鄂爾多斯市H.pylori感染率為45.76%。研究報(bào)道，2014年-2015年沈陽(yáng)市健康人群H.pylori感染率為46.01%[5]。2013年-2014年南京市健康人群H.pylori感染率為43.56%[6]。2014年河南許昌縣健康人群H.pylori感染率48.7%[7]。2012年-2013年江蘇東臺(tái)市、浙江寧波市、武漢地區(qū)健康人群H.pylori感染率分別為44.43%[8]、62.7%[9]和46.8%[10]。

1.2H.pylori感染的發(fā)展趨勢(shì)H.pylori的感染率在不同時(shí)期不同，且呈逐年下降趨勢(shì)。Wang等[11]調(diào)查了1990年-2002年21個(gè)省，25 209人的H.pylori感染情況，平均感染率為58.07%。Zhang等[12]報(bào)道2002年-2004年覆蓋19個(gè)省的26 341人H.pylori感染情況，平均感染率為54.76%。Jiang等[13]綜合了前人對(duì)H.pylori感染情況的調(diào)查，運(yùn)用科學(xué)的統(tǒng)計(jì)方法得到2004年-2008年和2009年-2013年我國(guó)H.pylori平均感染率分別為45.47%和42.06%。從中我們可以看到，從1990年-2002年到2009年-2013年我國(guó)H.pylori的感染率存在有意義的下降。此外，在廣州1993年-2003年(62.5%→49.3%)[14]，中國(guó)香港1997年-2003年(44%→36%)[15]，山東馬平1990年-2006年(73.78%→50.95%)[16]，北京1990年-2006年(55.35%→41.35%)[16]，中國(guó)東南方2003年-2012年(42.40%→23.82%)[17]的H.pylori感染率調(diào)查中，我們也能看到呈下降趨勢(shì)的感染率。

1.3 不同人群H.pylori感染情況 Huang等[18]檢測(cè)了上海市1 988名7～18歲兒童H.pylori感染情況，發(fā)現(xiàn)小學(xué)組(7～12歲)、初中組(13～15歲)、高中組(16～18歲)感染率分別為27.4%、33.6%和45.1%，可見(jiàn)H.pylori感染率隨年齡增加而升高。Zhang等[19]在376名兒童中觀察到3～7歲、8～12歲、13～16歲H.pylori的感染率分別為39.5%、41.0%、54.5%，隨著年齡增加，H.pylori感染率也增加。此外，Ding等[20]在研究3 491名0～18歲兒童中，Xu等[21]在觀察1 442名兒童中，Hou等[22]在研究394名1～13歲的兒童中，Wong等[23]對(duì)1997年-2004年159名兒童進(jìn)行回顧性分析中，均發(fā)現(xiàn)隨年齡增加，H.pylori感染率也增加。醫(yī)務(wù)工作者，尤其是胃腸道和口腔醫(yī)師要比非醫(yī)務(wù)工作者有較高的H.pylori感染率[24]。

不同亞型H.pylori混合感染的問(wèn)題存在于臨床中[25]，成功根除后再感染問(wèn)題也同樣存在。Zhang等[26]通過(guò)文獻(xiàn)檢索對(duì)36篇文章的原始數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析，發(fā)現(xiàn)在成人中再感染率為0～23.4%，兒童為1.9%～9.6%。此外，H.pylori感染率還與BMI[27]、家庭收入、飲食衛(wèi)生、教育、婚姻狀況[28]、家庭聚集[29]等有關(guān)。

2 H.pylori除菌治療現(xiàn)狀

2000年，EHSG第3次Maastricht共識(shí)會(huì)議建議將PPI、克拉霉素、阿莫西林或甲硝唑結(jié)合的標(biāo)準(zhǔn)三聯(lián)療法作為根除H.pylori的一線治療方案[30]。但由于近年來(lái)抗生素的廣泛應(yīng)用，H.pylori耐藥率不斷增長(zhǎng)，其根除率不斷下降。2012年我國(guó)標(biāo)準(zhǔn)三聯(lián)療法H.pylori根除率只有73.5%[31]。左氧氟沙星是具有廣譜抗菌作用的喹諾酮類抗生素，已被建議取代克拉霉素在三聯(lián)療法中的位置[32]。14 d含左氧氟沙星的三聯(lián)療法，根除率達(dá)95%[32]，但僅建議應(yīng)用在對(duì)喹諾酮敏感的菌株或根除率<90%且對(duì)喹諾酮敏感的地區(qū)[33]。

2012年，我國(guó)第4次全國(guó)幽門螺桿菌共識(shí)[34]指出三聯(lián)療法已不適合作為一線治療方案，伴同療法缺乏我國(guó)資料，序貫療法與標(biāo)準(zhǔn)三聯(lián)療法相比在我國(guó)多中心的研究中也并未顯示出優(yōu)勢(shì)[35]，含鉍劑的四聯(lián)療法可作為抗H.pylori治療的首選方案之一[36]。經(jīng)典的鉍劑四聯(lián)方案包括鉍劑、PPI、四環(huán)素和甲硝唑。但我國(guó)由于四環(huán)素不易獲得，H.pylori對(duì)甲硝唑的高耐藥性[37]及其不耐受的不良反應(yīng)，經(jīng)典鉍劑四聯(lián)方案在我國(guó)難以實(shí)行。呋喃唑酮由于臨床上較少應(yīng)用，其敏感性接近100%[38]。含呋喃唑酮鉍劑四聯(lián)療法得到越來(lái)越多的重視。一項(xiàng)424例的單中心隨機(jī)研究得出，2周含呋喃唑酮鉍劑四聯(lián)療法H.pylori根除率為95.2%(PP)和99.0%(ITT)[39]。鉍劑、阿莫西林、克拉霉素、PPI的結(jié)合也被作為一種治療手段，在低耐藥區(qū)，其根除率為81.3%(ITT)和89.7%(PP)[40]。但由于克拉霉素的耐藥性較高，此方案不作為經(jīng)驗(yàn)治療[39]。不含鉍劑的四聯(lián)療法，如雷貝拉唑、阿莫西林、左氧氟沙星、呋喃唑酮[41]在研究中被證實(shí)有94.3%的根除率。此外，阿莫西林和四環(huán)素結(jié)合的四聯(lián)療法也獲得較高的根除率[41]。同一種治療方案，不同的療程會(huì)有不同的治療效果。兩個(gè)多變量的回顧性分析均顯示，同一治療方案，隨著治療療程的增加，根除率提高[42]。

由于H.pylori根除率存在個(gè)體差異，個(gè)體化治療越來(lái)越被重視。一項(xiàng)含有3 512例患者，13個(gè)臨床對(duì)照試驗(yàn)的分析顯示，依據(jù)敏感性、CYP2C19基因型檢測(cè)、分子檢測(cè)或培養(yǎng)結(jié)果制定的個(gè)體化治療均比經(jīng)驗(yàn)治療的除菌率高[43]。

初次H.pylori治療失敗需進(jìn)行H.pylori復(fù)治的情況存在于臨床中。在不同的研究中，與其他療法相比獲得較高的根除率并可作為二線治療的方案有：14 d蘭索拉唑+阿莫西林+呋喃唑酮+鉍劑(根除率ITT 90.35%和PP 91.96%)[44]、10 d埃索美拉唑+呋喃唑酮+阿莫西林+鉍劑(根除率ITT 83.8%和PP 88.2%)[45]、含莫西沙星的三聯(lián)療法(根除率79.03%)[46]、10 d雷貝拉唑+鉍劑+阿莫西林+米諾環(huán)素(根除率ITT 84.1%和PP 88.3%)[47]和4 d蘭索拉唑+鉍劑+四環(huán)素+甲硝唑(根除率ITT 90.6%和PP 88.1%)[48]。

此外，作為輔助藥物，益生菌[49]、依卡倍特鈉[50]、荊花胃康[51]、殺菌肽[52]、重組人乳鐵蛋白[53]等均對(duì)H.pylori的消除有一定作用，但需要更多的研究證實(shí)這一結(jié)論。

3 耐藥情況

H.pylori的治療效果與其對(duì)抗生素的耐藥性有直接聯(lián)系。2012年，第4次全國(guó)幽門螺桿菌感染處理共識(shí)報(bào)告[34]指出，用于根除H.pylori的6種藥物中，甲硝唑耐藥率為60%～70%，左氧氟沙星為30%～38%，克拉霉素為20%～38%，呋喃唑酮、阿莫西林、四環(huán)素的耐藥率仍很低[37]。

不同時(shí)期、不同地區(qū)H.pylori對(duì)抗生素的耐藥性不同。Zhang等[54]分別研究了北京地區(qū)2009年-2010年和2013年-2014年371例和950例H.pylori陽(yáng)性患者。在2009年-2010年，H.pylori對(duì)甲硝唑、克拉霉素、左氧氟沙星、利福平、阿莫西林、四環(huán)素的耐藥率分別為66.8%、39.9%、34.5%、15.4%、6.7%、4.9%，2013年-2014年，耐藥率變?yōu)?3.4%、52.6%、54.8%、18.2%、4.4%、7.3%，且在2009年-2010年，對(duì)單種、2種、3種、4種、5種、6種抗生素敏感的H.pylori菌株分別為33.7%、28.3%、16.7%、6.2%、0.3%和0.3%。到2013年-2014年，敏感率變?yōu)?7.6%、28.4%、24.9%、7.3%、2.3%和0.1%。研究還顯示，非潰瘍患者H.pylori對(duì)克拉霉素的耐藥性高于潰瘍患者。左氧氟沙星和甲硝唑耐藥在女性和中老年患者中更常見(jiàn)。Sun等[55]研究了上海地區(qū)2000年-2009年H.pylori對(duì)甲硝唑、克拉霉素、阿莫西林、呋喃唑酮、左氧氟沙星、四環(huán)素的耐藥性。對(duì)克拉霉素的耐藥率變化從8.6%、9.0%到20.7%，對(duì)左氧氟沙星耐藥率變化從10.3%、24.0%到32.5%，對(duì)甲硝唑的耐藥率較穩(wěn)定，維持在40%～50%，所有菌株均對(duì)阿莫西林和呋喃唑酮敏感[37]。

我國(guó)H.pylori感染率在不同時(shí)期不同且呈逐年下降趨勢(shì)。由于抗生素的廣泛使用，標(biāo)準(zhǔn)三聯(lián)療法已不能達(dá)到滿意的根除率，含鉍劑的四聯(lián)療法成為抗H.pylori的首選方案之一。H.pylori對(duì)抗生素的耐藥情況是影響其根除率的重要因素，規(guī)范使用抗生素問(wèn)題應(yīng)該被重視。此外，益生菌、荊花胃康、殺菌肽等輔助用藥對(duì)H.pylori的根除有一定的效果，但需大樣本的研究證實(shí)。

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(責(zé)任編輯：馬 軍)

Analysis of Helicobacter pylori infection in China

WANG Xue, LI Yiling, LV Xiaohui

Department of Gastroenterology, the First Affiliated Hospital of China Medical University, Shenyang 110000, China

The infection rate of Helicobacter pylori (H.pylori) in China has a difference in different regions, periods and populations. At present, due to the widespread use of antibiotics, drug resistance ofH.pylorihas became an important factor affecting the eradication rate. Bismuth-containing quadruple therapy has a better therapeutic effect than standard triple therapy and becomes one of the preferred options for anti-H.pyloritreatment. At the same time, individualized treatment and adjuvant drugs are gaining more and more attention.

China; Helicobacter pylori; Epidemiology; Sterilization treatment status; Drug resistance

10.3969/j.issn.1006-5709.2017.06.006

王雪，研究方向：消化系統(tǒng)疾病。E-mail：2571222989@qq.com

呂曉輝，副教授，副主任醫(yī)師，研究方向：各種消化系統(tǒng)疾病診斷及治療。E-mail：Lvxiaohui1122@163.com

R378

A

1006-5709(2017)06-0640-04

2017-04-01