重视幽门螺杆菌感染根除治疗中的几个问题

2014-02-25 胡伏莲 中华医学杂志

幽门螺杆菌(H·pylori)与多种上胃肠道疾病及胃肠道外疾病密切相关已被临床医生周知,H·pylori的根除治疗也成为消化科医生重要的临床工作部分。随着人们对H·pylori研究的不断深入,H·pylori根除治疗已取得了巨大进展。然而,目前H·pylori的治疗中仍然存在不少问题,H·pylori根除治疗反复失败也是临床医生经常遇到的难题。 一、耐药性是导致根除率下降的主要原因

幽门螺杆菌(H·pylori)与多种上胃肠道疾病及胃肠道外疾病密切相关已被临床医生周知,H·pylori的根除治疗也成为消化科医生重要的临床工作部分。随着人们对H·pylori研究的不断深入,H·pylori根除治疗已取得了巨大进展。然而,目前H·pylori的治疗中仍然存在不少问题,H·pylori根除治疗反复失败也是临床医生经常遇到的难题。

一、耐药性是导致根除率下降的主要原因

在早期的研究中,质子泵抑制剂(PPI)标准三联疗法的根除率可以达到90%,甚至95%以上,但是随着H·pylori根除治疗的广泛开展,三联疗法的根除率逐渐下降,在亚洲、欧洲和美洲某些地区的根除率不到80%,甚至低于70%。根据Graham评分系统,不到80%的根除率属于最低的F级,是完全不能接受的。影响H·pylori根除治疗效果的主要因素包括H·pylori菌株本身的因素、宿主因素等,其中甲硝唑和克拉霉素耐药菌株增加是导致根除率下降最主要的原因。我国的耐药流行病学调查表明,甲硝唑耐药率达到60%~70%,克拉霉素耐药率达到20%~38%,左氧氟沙星在H·pylori根除治疗中使用较晚,但耐药率也达到30%~38%。近年来国际上推荐了一些新的根除方案,包括序贯疗法及伴同疗法,以克服H·pylori抗生素耐药,提高根除率。

序贯治疗最初的目的是克服克拉霉素耐药,在治疗的前5 d使用PPI和阿莫西林治疗。阿莫西林攻击细菌细胞壁,防止形成克拉霉素泵出通道,从而减少细菌的耐药。之后的5d,停用阿莫西林,改用克拉霉素和甲硝唑,PPI则贯穿整个疗程。序贯治疗最早应用于意大利,报道可以获得90%左右的根除率,但是在我国进行的多中心随机对照临床研究中,序贯疗法与PPI三联疗法相比并未显示优势。伴同疗法是让患者在10 d疗程中同时服用PPI及序贯疗法中的3种抗生素,实际上是由PPI和3种抗生素组成的四联疗法。有荟萃分析显示,伴同疗法根除率可以到90%,优于标准三联方案,并且有良好的安全性,但其纳入的原始研究都是在2000年左右进行的,当时克拉霉素耐药情况远没有现在这么严重。另外伴同疗法中抗生素总量较序贯治疗增加了1倍,不仅加大了患者的经济负担,而且可能会加重H·pylori耐药形势。伴同疗法同时使用3种抗菌药物,还存在用药安全性问题,而且在抗生素的选择上会更加困难。在Maastrieht IV共识中伴同疗法是在缺乏铋剂无法应用含铋四联的情况下推荐使用的,我国由于有铋剂,并考虑其安全性,所以不推荐伴同疗法。

在H·pylori高耐药率的情况下,铋剂四联方案受到重视。研究显示铋剂对H·pylori标准菌株及临床分离的H·pylori耐药菌株均有体外抑菌和杀菌作用,并且与甲硝唑或克拉霉素联用对标准菌株及临床分离的H·pylori耐药菌株具有体外协同抑菌或杀菌作用。PPI四联1周疗法用于H·pylori感染的初治,疗效明显高于PPI三联1周疗法,是一种可供选择的一线治疗方案。在Maastrieht 1V共识中,在高克拉霉素耐药地区(>15%~20%)首先推荐铋剂四联方案。我国井冈山共识推荐含铋四联疗法用于H·pylori根除治疗。由于铋剂的安全性不宜用于特殊人群,所以在儿童中仍推荐PPI三联疗法。有荟萃分析喁。显示,含铋剂方案与不含铋剂方案,除铋剂使粪便变黑之外,两者的不良反应并无差异性,提示铋剂在H·pylori根除治疗中有较好的安全性。

二、抑酸治疗是影响根除治疗效果的重要因素

胃内pH直接影响到抗生素的治疗效果,因此PPI是H·pylori根除方案的重要组成部分。研究表明增加PPI的剂量可以提高H·pylori根除率,一项荟萃分析比较了在PPI三联疗法中单次和双次给予标准剂量PPI对H·pylori根除率的影响,其共纳入13个原始研究,包含了2391例患者,结果显示无论按意向分析,还是按符合方案分析双次PPI给药方案根除率均明显优于单次PPI给药。还有荟萃分析显示,适当提高PPI的标准剂量可以使PPI标准三联疗法H·pylori根除率增加6%~10%。

大部分PPI是通过细胞色素P450 2C19(CYP2C19)代谢的。CYP2C19的基因型(强和弱代谢基因型)会影响PPI的抑酸效果,从而影响H·pylori根除治疗效果。CYP2C19表型在不同地区有较大差别,在白种人中弱和强代谢型分别占2%~4%和18%~27%,但是在亚洲黄种人中占14%~20%和<1.3%。这解释了为什么白种人比亚洲黄种人需要更高剂量的PPI以及为什么第一代PPI疗效有较大的个体差异。虽然在亚洲黄种人群中,强代谢型患者比例较低,但这可能正是某些患者反复且H·pylor根除治疗失败的原因之一。

还有一个要特别强调的重要问题是在患者接受H·pylori根除治疗之前,不仅必须停用抗生素至少1个月,而且还必须停用所有对H·pylori有抑制作用的药物至少2周,包括PPI、H2受体抑制剂(H2RA)、铋剂以及对H·pylori有杀灭作用的中药,上述药物可使H·pylori发生球形变而导致根除冶疗失败。

三、患者依从性是容易被忽略的影响因素

我们在临床工作中体会到,同样的治疗方案老年感染者可以获得较年轻人高的H·pylori根除率。一方面这可能和老年患者肌酐清除率降低,抗菌药物有更高的血药浓度有关,另一方面老年患者对自己的健康情况更为关注,并且有更多的精力遵守医嘱。相对而言,年轻患者不太在意自己的健康情况,或因工作繁忙不能严格按时服药。还有研究表明,年轻患者根除H·pylori治疗不良反应发生率高于老年患者,这也是影响年轻患者依从性的重要因素。

从医生角度来增加患者依从性至关重要,医生在治疗中要仔细说明服药时间和方法,强调按时服药的重要性,而且在治疗期间要定期随访,了解患者的用药情况及治疗中发生的不良反应,医生对患者病情的重视是增加患者依从性的关键。

四、正确认识和应用共识意见

1999年中华医学会消化分会H·pylori学组制定了我国第1个H·pylori感染有关问题的共识意见,并于2003年、2008年及2012年3次对共识意见进行了修订。H·pylori感染共识为提高我国H·pylori感染的诊治水平做出了巨大的贡献。

共识的制定是基于循证医学证据,涵盖了H·pylori处理的各个方面,具有临床指导价值,对规范临床医生对H·pylori的处理有重要意义。在临床实践中,原则上按照共识意见指导治疗,但是并不是共识适合所有患者,某一个方案也不能适合所有患者,医生运用共识不能照搬。对于治疗方案的选择并非千篇一律,不是***一药,万人一方,应该因地区而异,因人而异,必须强调个体化治疗,根据患者具体情况进行处理。此外任何共识都需要验证、需要经过一段时间的检验证实其客观性和有效性,有些问题还可能存在争议而需要进一步修改,这就说明了为什么对共识3~5年就需要修订一次。

五、探讨H·pylor治疗新路径

传统上H·pylor感染的治疗都是应用抗生素,但除抗生素之外,是否还存在其他药物,如某些能影响H·pylor黏附定植,使其排出体外从而治疗H·pylor感染的药物。“H·pylor治疗新路径”主要包括中医中药、益生菌、胃黏膜保护剂等在H·pylor治疗中的地位和作用,还有口腔H·pylor是否影响H·pylor的问题也值得探讨。探索“H·pylor治疗新路径”是应对H·pylor耐药,提高H·pylor根除率的新思路和新手段。

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    2018-03-28 zanzaifeng

    hp俨然已经成为许多人日常生活中需要面对的常见难题.期待早日得到有效的根治性切除.

    0

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  3. [GetPortalCommentsPageByObjectIdResponse(id=300464, encodeId=b71d30046485, content=hp俨然已经成为许多人日常生活中需要面对的常见难题.期待早日得到有效的根治性切除., beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/03/24/965105b95fe53b6329b522fe372907a2.jpg, createdBy=34621617558, createdName=zanzaifeng, createdTime=Wed Mar 28 07:55:51 CST 2018, time=2018-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2027377, encodeId=9042202e377de, content=<a href='/topic/show?id=80e262286bf' target=_blank style='color:#2F92EE;'>#根除治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62286, encryptionId=80e262286bf, topicName=根除治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Wed Apr 16 12:04:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1683623, encodeId=5f53168362319, content=<a href='/topic/show?id=c2fc6228167' target=_blank style='color:#2F92EE;'>#根除#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62281, encryptionId=c2fc6228167, topicName=根除)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07d627990740, createdName=风铃830, createdTime=Fri Jul 04 22:04:00 CST 2014, time=2014-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995421, encodeId=dcf8199542125, content=<a href='/topic/show?id=cba649104ea' target=_blank style='color:#2F92EE;'>#幽门螺杆菌感染根除#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49104, encryptionId=cba649104ea, topicName=幽门螺杆菌感染根除)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Wed Feb 04 17:04:00 CST 2015, time=2015-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1811679, encodeId=82b818116e9ba, content=<a href='/topic/show?id=751f8889423' target=_blank style='color:#2F92EE;'>#螺杆菌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88894, encryptionId=751f8889423, topicName=螺杆菌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87b1109, createdName=kcb069, createdTime=Sun Nov 30 19:04:00 CST 2014, time=2014-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348698, encodeId=d8811348698e5, content=<a href='/topic/show?id=cfeb49103af' target=_blank style='color:#2F92EE;'>#幽门螺杆菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49103, encryptionId=cfeb49103af, topicName=幽门螺杆菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Thu Feb 27 02:04:00 CST 2014, time=2014-02-27, status=1, ipAttribution=)]
    2014-07-04 风铃830
  4. [GetPortalCommentsPageByObjectIdResponse(id=300464, encodeId=b71d30046485, content=hp俨然已经成为许多人日常生活中需要面对的常见难题.期待早日得到有效的根治性切除., beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/03/24/965105b95fe53b6329b522fe372907a2.jpg, createdBy=34621617558, createdName=zanzaifeng, createdTime=Wed Mar 28 07:55:51 CST 2018, time=2018-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2027377, encodeId=9042202e377de, content=<a href='/topic/show?id=80e262286bf' target=_blank style='color:#2F92EE;'>#根除治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62286, encryptionId=80e262286bf, topicName=根除治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Wed Apr 16 12:04:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1683623, encodeId=5f53168362319, content=<a href='/topic/show?id=c2fc6228167' target=_blank style='color:#2F92EE;'>#根除#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62281, encryptionId=c2fc6228167, topicName=根除)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07d627990740, createdName=风铃830, createdTime=Fri Jul 04 22:04:00 CST 2014, time=2014-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995421, encodeId=dcf8199542125, content=<a href='/topic/show?id=cba649104ea' target=_blank style='color:#2F92EE;'>#幽门螺杆菌感染根除#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49104, encryptionId=cba649104ea, topicName=幽门螺杆菌感染根除)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Wed Feb 04 17:04:00 CST 2015, time=2015-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1811679, encodeId=82b818116e9ba, content=<a href='/topic/show?id=751f8889423' target=_blank style='color:#2F92EE;'>#螺杆菌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88894, encryptionId=751f8889423, topicName=螺杆菌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87b1109, createdName=kcb069, createdTime=Sun Nov 30 19:04:00 CST 2014, time=2014-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348698, encodeId=d8811348698e5, content=<a href='/topic/show?id=cfeb49103af' target=_blank style='color:#2F92EE;'>#幽门螺杆菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49103, encryptionId=cfeb49103af, topicName=幽门螺杆菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Thu Feb 27 02:04:00 CST 2014, time=2014-02-27, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=300464, encodeId=b71d30046485, content=hp俨然已经成为许多人日常生活中需要面对的常见难题.期待早日得到有效的根治性切除., beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/03/24/965105b95fe53b6329b522fe372907a2.jpg, createdBy=34621617558, createdName=zanzaifeng, createdTime=Wed Mar 28 07:55:51 CST 2018, time=2018-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2027377, encodeId=9042202e377de, content=<a href='/topic/show?id=80e262286bf' target=_blank style='color:#2F92EE;'>#根除治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62286, encryptionId=80e262286bf, topicName=根除治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Wed Apr 16 12:04:00 CST 2014, time=2014-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1683623, encodeId=5f53168362319, content=<a href='/topic/show?id=c2fc6228167' target=_blank style='color:#2F92EE;'>#根除#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62281, encryptionId=c2fc6228167, topicName=根除)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07d627990740, createdName=风铃830, createdTime=Fri Jul 04 22:04:00 CST 2014, time=2014-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995421, encodeId=dcf8199542125, content=<a href='/topic/show?id=cba649104ea' target=_blank style='color:#2F92EE;'>#幽门螺杆菌感染根除#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49104, encryptionId=cba649104ea, topicName=幽门螺杆菌感染根除)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Wed Feb 04 17:04:00 CST 2015, time=2015-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1811679, encodeId=82b818116e9ba, content=<a href='/topic/show?id=751f8889423' target=_blank style='color:#2F92EE;'>#螺杆菌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88894, encryptionId=751f8889423, topicName=螺杆菌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87b1109, createdName=kcb069, createdTime=Sun Nov 30 19:04:00 CST 2014, time=2014-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348698, encodeId=d8811348698e5, content=<a href='/topic/show?id=cfeb49103af' target=_blank style='color:#2F92EE;'>#幽门螺杆菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49103, encryptionId=cfeb49103af, topicName=幽门螺杆菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Thu Feb 27 02:04:00 CST 2014, time=2014-02-27, status=1, ipAttribution=)]
    2014-11-30 kcb069
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