【重磅】世界胃腸病學(xué)組織全球指南：幽門螺桿菌

World Gastroenterology Organisation Global Guidelines：Helicobacter pylori

世界胃腸病學(xué)組織全球指南：幽門螺桿菌

中國(guó)幽門螺桿菌分子醫(yī)學(xué)中心（CCHpMM）

鐘子劭、徐包慧 I 譯

郜恒駿 I 審校   

來(lái)源：https://www./guidelines/helicobacter-pylori/helicobacter-pylori-english

1. Summary

1.  摘要

Helicobacter pylori continues to be a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer.

幽門螺桿菌仍然是世界范圍內(nèi)的一個(gè)主要健康問(wèn)題，由于消化性潰瘍病和胃癌導(dǎo)致了相當(dāng)高的發(fā)病率和死亡率。

The burden of disease falls disproportionately on less well-resourced populations. As with most infectious diseases, the greatest impact on reducing this burden comes from improvements in socioeconomic status, which interrupt transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions in which improvements in living standards are slow to occur.

疾病的負(fù)擔(dān)不成比例地落在資源不足的人群身上。與大多數(shù)傳染病一樣，對(duì)減少這種負(fù)擔(dān)的最大影響來(lái)自于社會(huì)經(jīng)濟(jì)地位的改善，以阻斷傳播。在世界許多地區(qū)已經(jīng)觀察到了這一點(diǎn)，但在許多生活水平改善緩慢的地區(qū)，感染率仍然很高。

Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy is still a major issue for clinicians. An effective vaccine also still appears to be elusive.

同時(shí)，最佳的臨床管理和治療路徑仍未確定，并隨著抗生素耐藥性模式的變化而不斷發(fā)展。盡管經(jīng)過(guò)幾十年的研究和臨床實(shí)踐，重大挑戰(zhàn)依然存在。尋求最有效、最安全、最簡(jiǎn)單的療法仍然是臨床醫(yī)生面臨的主要問(wèn)題。一種有效的疫苗似乎也仍然遙不可及。

Clinical guidelines not infrequently proffer discordant advice. It is very difficult for guidelines to achieve relevance across a variety of populations with varying spectrums of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important for pathways to be based on the best available local knowledge, rather than solely extrapolated from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the WGO H. pylori guideline uses a “cascades” approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant, and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.

臨床指南經(jīng)常提供不一致的建議。指南很難在具有不同疾病譜、抗生素耐藥率和巨大的資源差異的各種人群中實(shí)現(xiàn)一致性。由于地區(qū)因素是決定幽門螺桿菌感染的影響和管理策略的核心，因此，重要的是，治療方案應(yīng)基于現(xiàn)有的最佳當(dāng)?shù)卣J(rèn)識(shí)，而不是僅僅從其他地區(qū)制定的指南中推斷出來(lái)，因?yàn)檫@些指南可能不太適用。為此，本次修訂的WGO幽門螺桿菌指南采用了 '級(jí)聯(lián) '方法，旨在總結(jié)管理原則，并根據(jù)既定的關(guān)鍵治療原則，利用當(dāng)?shù)刂R(shí)和現(xiàn)有資源指導(dǎo)地區(qū)實(shí)踐，為務(wù)實(shí)、相關(guān)和可實(shí)現(xiàn)的診斷和治療路徑提供建議。

2.  Introduction

2.  介紹

Helicobacter pylori has been recognized as a major pathogen of humankind for nearly four decades. However, despite the impact of treatment of infected individuals and the reduced transmission of infection in communities in which socioeconomic living standards have improved, it continues to be the most common human bacterial pathogen, infecting perhaps half of the world’s population [1]. As a result, it is still a major cause of morbidity and mortality worldwide.

近四十年來(lái)，幽門螺桿菌被認(rèn)為是人類的主要病原體。然而，盡管對(duì)感染者的治療產(chǎn)生了影響，而且在社會(huì)經(jīng)濟(jì)生活水平提高的社區(qū)，幽門螺桿菌的傳播也有所減少，但它仍然是最常見的人類細(xì)菌病原體，可能感染了世界上一半的人口[1]。因此，它仍然是全世界發(fā)病和死亡的一個(gè)主要原因。

H. pylori infection invariably causes active chronic gastritis. In most people, this may be clinically silent throughout life, but in a substantial minority it causes gastroduodenal diseases, most importantly peptic ulcer disease, noncardia gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It also increases the risk of gastroduodenal ulceration and bleeding in patients who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and is responsible for symptoms in a subset of patients with functional dyspepsia.

幽門螺桿菌感染總是會(huì)引起慢性活動(dòng)性胃炎。在大多數(shù)人中，這可能在臨床上終生無(wú)癥狀，但在相當(dāng)少的人中，它引起胃十二指腸疾病，包括最重要的消化性潰瘍病、非賁門胃癌和胃粘膜相關(guān)淋巴組織（MALT）淋巴瘤。它還增加了正在服用非甾體抗炎藥（NSAIDs）如阿司匹林的病人的胃十二指腸潰瘍和出血的風(fēng)險(xiǎn)，并且是造成一部分功能性消化不良病人癥狀的原因。

H. pylori has been studied intensively. A literature search reveals more than 45,000 publications. A great deal has been learned about the epidemiology of infection, biology, genetics, pathophysiology, disease expression, diagnosis, and treatment. However, major gaps in our knowledge remain. The precise mode of transmission of infection remains unclear, despite many epidemiological studies that identify risk factors for infection. The determinants of disease expression are still incompletely understood, including many aspects of the host–pathogen interaction. The pathophysiology of this interaction is complex and has been reviewed in detail elsewhere [2,3]. The optimal clinical management pathways in different settings are still a matter of debate, and refinements in diagnostic modalities continue to be sought. The quest for the most effective, safe, and simple treatment is still a major issue for clinicians, and the problem of antimicrobial resistance to therapy is a significant challenge. The best method for surveillance of adverse histological changes in the gastric mucosa has not been determined, and the quest for an effective vaccine is ongoing.

幽門螺桿菌已經(jīng)得到了深入的研究。搜索顯示有超過(guò)45,000份研究相關(guān)文獻(xiàn)。在幽門螺桿菌感染的流行病學(xué)、生物學(xué)、遺傳學(xué)、病理生理學(xué)、疾病表達(dá)、診斷和治療方面已經(jīng)有了很大的了解。然而，我們的知識(shí)仍有很大差距。盡管許多流行病學(xué)研究確定了感染的風(fēng)險(xiǎn)因素，但感染的確切傳播方式仍不清楚。疾病表達(dá)的決定因素仍未完全了解，包括宿主-病原體相互作用的許多方面。這種相互作用的病理生理學(xué)是復(fù)雜的，已在其他地方進(jìn)行了詳細(xì)回顧[2,3]。在不同的環(huán)境下，最佳的臨床管理方法仍然是一個(gè)爭(zhēng)論不休的問(wèn)題，且還在繼續(xù)尋求診斷方式的改進(jìn)。追求最有效、最安全、最簡(jiǎn)單的治療方法仍然是臨床醫(yī)生的主要問(wèn)題，而抗生素耐藥對(duì)治療的問(wèn)題也是一個(gè)重大挑戰(zhàn)。監(jiān)測(cè)胃粘膜不良組織學(xué)變化的最佳方法尚未確定，對(duì)有效疫苗的探索也在進(jìn)行。

There have been many reviews and clinical guidelines on H. pylori [4–12]. As the field is changing rapidly, there is a need for periodic updating and revision of these position papers. In addition, it is very difficult for guidelines to achieve relevance across a wide variety of populations with varying spectrums of disease and often with vastly different resources with which to deal with it. Guidelines not infrequently proffer discordant advice. As local factors are central to determining the impact and management strategies for H. pylori infection, this is not surprising. It is important for clinical advice to be based on the best available local data, rather than extrapolated from guidelines formulated in other regions, which may be less applicable. However, in many areas in which the impact of H. pylori infection is greatest, there is a lack of high-quality data to determine the local best practice. Addressing this gap in knowledge is a significant challenge. In the meantime, decisions need to be based on the best available local evidence, extrapolation from higher-quality data from elsewhere, and expert opinion.

目前已經(jīng)有很多關(guān)于幽門螺桿菌的評(píng)論和臨床指南[4-12]。由于該領(lǐng)域變化迅速，有必要定期更新和修訂這些立場(chǎng)文件。此外，指南很難在具有不同疾病譜的各種人群中實(shí)現(xiàn)相關(guān)性，而且通常具有處理疾病的巨大不同資源。指南經(jīng)常提供不一致的建議。由于地區(qū)因素是決定幽門螺桿菌感染的影響和管理策略的核心，這并不令人驚訝。重要的是，臨床建議應(yīng)以當(dāng)?shù)氐淖罴褦?shù)據(jù)為基礎(chǔ)，而不是從其他地區(qū)制定的指南中推斷出來(lái)，因?yàn)檫@些指南可能不太適用。然而，在幽門螺桿菌感染影響最大的許多地區(qū)，缺乏高質(zhì)量的數(shù)據(jù)來(lái)確定當(dāng)?shù)氐淖罴炎龇ā＝鉀Q這一知識(shí)差距是一個(gè)重大挑戰(zhàn)。同時(shí)，幽門螺桿菌治療管理策略需要根據(jù)現(xiàn)有的最佳當(dāng)?shù)刈C據(jù)、其他地方的高質(zhì)量數(shù)據(jù)的推斷和專家意見來(lái)做出決定。

The purpose of this update to the WGO guideline is to summarize and review the evidence from a number of new guidelines that outline best practice and to suggest how these principles may be applied around the world using the “cascades” approach. This approach recognizes variations in the regional prevalence and impact of infection and the vast differences in health resources available to address the problem, which require pragmatic, tailored local approaches. The burden of disease wrought by H. pylori falls disproportionately on less well-resourced regions, which are insufficiently represented in epidemiological surveys and are often not the focus of clinical guidelines.

這次更新WGO指南的目的是總結(jié)和回顧一些新指南的證據(jù)，這些指南概述了最佳做法，并建議如何利用 '級(jí)聯(lián) '方法在世界各地應(yīng)用這些原則。這種方法認(rèn)識(shí)到各地區(qū)感染的流行程度和影響的差異，以及可用于解決該問(wèn)題的衛(wèi)生資源的巨大差異，這就要求采取務(wù)實(shí)的、適合當(dāng)?shù)氐姆椒āＳ拈T螺桿菌造成的疾病負(fù)擔(dān)不成比例地落在資源不足的地區(qū)，而這些地區(qū)在流行病學(xué)調(diào)查中的代表性不足，往往不是臨床指南的重點(diǎn)。

3.  Natural history, transmission and epidemiology—global aspects

3. 自然歷史、傳播和流行病學(xué)-全球方面

3.1  Natural history of infection

3.1  感染的自然史

H. pylori infection usually persists for life, unless it is treated with antibiotics or autoeradication occurs when long-standing infection causes widespread gastric mucosal atrophy and metaplasia with achlorhydria. Transient infection may occur in some infants. Reinfection after treatment in adults is uncommon in both higher-prevalence and lower-prevalence regions. Reinfection may be confused with recrudescence, when infection is suppressed transiently, below the threshold of detection by tests, but has not been eradicated by antibiotics. There are variations in the virulence of different H. pylori strains globally. The interplay between host and environmental factors may result in differences in the expression of disease.

幽門螺桿菌感染通常會(huì)持續(xù)終身，除非用抗生素治療，或者當(dāng)長(zhǎng)期感染導(dǎo)致廣泛的胃粘膜萎縮和腸化并伴有胃酸缺乏癥時(shí)發(fā)生自身消除。一些嬰兒可能發(fā)生短暫的感染。無(wú)論在高發(fā)地區(qū)還是低發(fā)地區(qū)成人治療后的再感染都不常見。再感染可能與復(fù)發(fā)相混淆，復(fù)發(fā)是指感染被暫時(shí)抑制，低于檢測(cè)的閾值，但沒(méi)有被抗生素所根除。在全球范圍內(nèi)，不同的幽門螺桿菌菌株的毒力存在差異。宿主和環(huán)境因素之間的相互作用可能導(dǎo)致疾病表現(xiàn)的差異。

3.2  Transmission of infection

3.2  感染的傳播

Although there are well-described risk factors for infection, and plausible hypotheses, the precise mode of transmission has not been definitively established. Most infection appears to occur in early childhood, with a minority of cases developing in adults. There is strong evidence from epidemiology and genetic studies of person-to-person transmission, particularly within families. Mothers appear to be particularly important in transmission to their young children. Ingestion of the organism seems most plausible via the gastro–oral or oral–oral route. Fecal–oral transmission appears less likely, at least in developed countries. Whether transmission occurs via water, food, household pets, or flies is still a matter of speculation.

雖然有很好的感染風(fēng)險(xiǎn)因素和合理的假說(shuō)，但確切的傳播方式還沒(méi)有明確的確定。大多數(shù)感染似乎發(fā)生在兒童早期，少數(shù)病例發(fā)生在成人。流行病學(xué)和遺傳學(xué)研究有強(qiáng)有力的證據(jù)表明幽門螺桿菌存在人與人之間的傳播，特別是在家庭內(nèi)部。母親似乎在傳染給其年幼子女方面特別重要。通過(guò)胃-口或口-口途徑傳播該生物體似乎是最合理的。糞口傳播似乎不太可能，至少在發(fā)達(dá)國(guó)家是這樣。幽門螺桿菌是否通過(guò)水、食物、家庭寵物或蒼蠅傳播，仍然是一個(gè)猜測(cè)的問(wèn)題。

3.3  Epidemiology

3.3  流行病學(xué)

Although half of the world’s population are thought to be infected with H. pylori, there is widespread variation in the prevalence of infection, between and within countries (Fig. 1). In addition, the prevalence may vary within a single city and also between subgroups within a population (Fig. 2) [13]. For example, there may be wide variations in the prevalence between more affluent urban populations and rural populations.

盡管世界上有一半的人口被認(rèn)為感染了幽門螺桿菌，但在國(guó)家之間和國(guó)家內(nèi)部，感染率存在著廣泛的差異（圖1）。此外，在一個(gè)城市內(nèi)，以及在一個(gè)人口的亞群之間，感染率也會(huì)有所不同（圖2）[13]。例如，較富裕的城市人口和農(nóng)村人口之間的患病率可能有很大差異。

The quality of prevalence data varies. Many studies are not true prevalence studies, but rather audits of clinical subsets. Other studies may not represent a valid cross-section of the population. Moreover, there is significant variability in the quality of reports. In some regions, diagnostic methods may be less reliable, while some countries are poorly represented as they lack any reliable data at all. For all these reasons, a single figure cannot be taken to summarize and represent the prevalence of infection in an entire country and must be applied with caution. For example, a prevalence study from one city in one region of a populous, multiethnic country with wide variation in socioeconomic standards is unlikely to represent the true prevalence across the entire country and cannot reflect high-risk and low-risk subsets. However, countries and regions can usually be characterized as high-prevalence, mid-prevalence, and low-prevalence locations [1].

患病率數(shù)據(jù)的質(zhì)量各不相同。許多研究不是真正的流行病研究，而是對(duì)臨床子集的審核。其他研究可能不代表有效的人口橫斷面。此外，報(bào)告的質(zhì)量也有很大差異。在一些地區(qū)，診斷方法可能不太可靠，而一些國(guó)家由于根本沒(méi)有任何可靠的數(shù)據(jù)，所以代表性很差。由于所有這些原因，不能用一個(gè)數(shù)字來(lái)概括和代表整個(gè)國(guó)家的感染率，必須謹(jǐn)慎。例如，在一個(gè)人口眾多、社會(huì)經(jīng)濟(jì)水平差異很大的多民族國(guó)家的一個(gè)地區(qū)的一個(gè)城市的流行率研究，不太可能代表整個(gè)國(guó)家的真實(shí)流行率，也不能反映高風(fēng)險(xiǎn)和低風(fēng)險(xiǎn)的子集。然而，國(guó)家和地區(qū)通常可以被描述為高發(fā)區(qū)、中發(fā)區(qū)和低發(fā)區(qū)[1]。

The major determinant of the prevalence of infection is socioeconomic status in childhood. Socioeconomic factors reflect levels of hygiene, sanitation, density of living, and educational level.

感染率的主要決定因素是兒童時(shí)期的社會(huì)經(jīng)濟(jì)因素。社會(huì)經(jīng)濟(jì)因素反映了衛(wèi)生、環(huán)境衛(wèi)生、居住密度和教育水平的水平。

A strong inverse relationship has been consistently reported. Thus, as expected, the prevalence of infection is generally higher in developing countries, and infection is almost ubiquitous in some of the most resource-poor subsets of these populations. Migrants from such regions are recognized as being a high-risk group in more developed, low-prevalence countries.

一直以來(lái)，都有強(qiáng)負(fù)關(guān)系的報(bào)道。因此，正如預(yù)期的那樣，發(fā)展中國(guó)家的感染率普遍較高，而且在一些人口資源最匱乏的人群中，感染幾乎普遍存在。來(lái)自這些地區(qū)的移民被認(rèn)為是較發(fā)達(dá)的低發(fā)病率國(guó)家的高風(fēng)險(xiǎn)群體。

The prevalence of H. pylori infection increases with age. This is mostly due to the cohort effect, in which the risk of acquiring infection was greater during the childhood of those born longer ago in comparison with more recently, rather than reflecting ongoing adult acquisition. Ethnicity has been described as a risk factor, but is most likely closely correlated with socioeconomic status or practices that may increase the risk of transmission, rather than having a genetic basis.

幽門螺桿菌感染的流行率隨著年齡的增長(zhǎng)而增加。這主要是由于隊(duì)列效應(yīng)，即那些出生時(shí)間較久的人在童年時(shí)期獲得感染的風(fēng)險(xiǎn)比最近出生的人要大，而不是反映正在進(jìn)行的成人感染。種族被認(rèn)為是一個(gè)風(fēng)險(xiǎn)因素，但很可能與社會(huì)經(jīng)濟(jì)地位或可能增加傳播風(fēng)險(xiǎn)的做法密切相關(guān)，而不是具有遺傳基礎(chǔ)。

A striking observation has been the change in the prevalence of infection over time in some countries. Reports of rapidly falling infection rates, most marked in children and younger adults, are common from developed countries, and from countries that have undergone rapid economic development that has led to raised socioeconomic standards. In these countries, the prevalence of infection is now low.

一個(gè)引人注目的現(xiàn)象是一些國(guó)家的感染率隨時(shí)間的推移而變化。發(fā)達(dá)國(guó)家和經(jīng)歷了快速經(jīng)濟(jì)發(fā)展導(dǎo)致社會(huì)經(jīng)濟(jì)標(biāo)準(zhǔn)提高的國(guó)家普遍報(bào)告幽門螺桿菌感染率迅速下降，在兒童和年輕成人中最為明顯。在這些國(guó)家，現(xiàn)在的感染率很低。

A gradual fall in the prevalence of peptic ulcer disease and noncardia gastric cancer is predicted by this observation, since in general the prevalence of peptic ulcer disease and gastric cancer reflects the prevalence of H. pylori in a population. Indeed, the prevalence of ulcer disease and gastric cancer have been falling for decades in developed countries. The fall in disease expression lags behind the fall in infection rates for many years. The declining prevalence of infection and disease occurred long before H. pylori was recognized and treatments were developed.

根據(jù)這一觀察，消化性潰瘍病和非賁門胃癌的發(fā)病率會(huì)逐漸下降，因?yàn)橐话銇?lái)說(shuō)，消化性潰瘍病和胃癌的發(fā)病率反映了幽門螺桿菌在人群中的流行情況。事實(shí)上，幾十年來(lái)，發(fā)達(dá)國(guó)家的潰瘍病和胃癌的發(fā)病率一直在下降。通常疾病表達(dá)的下降滯后于感染率的下降很多年。感染率和疾病的下降早在幽門螺桿菌被認(rèn)識(shí)和治療方法被開發(fā)之前就發(fā)生了。

As with most endemic infectious diseases, a decline in prevalence has more to do with improvements in population hygiene and sanitation than with individual, case-by-case treatment, since in most countries, only a minority of infected individuals will ever receive therapy. Notable exceptions are well-resourced high-prevalence countries such as Japan, where screening and treatment is now done systematically in early adulthood. The prevalence of infection appears to be stable in countries in which standards have not improved or have deteriorated, and it is unlikely to fall substantially until improvements do occur. Peptic ulcer disease is still rampant in many of these countries. The burden of gastric cancer also falls disproportionately on these populations.

與大多數(shù)地方性傳染病一樣，流行率的下降更多的是與人口衛(wèi)生和環(huán)境衛(wèi)生的改善有關(guān)，而不是與個(gè)別的、單個(gè)病例治療有關(guān)，因?yàn)樵诖蠖鄶?shù)國(guó)家，只有少數(shù)感染者會(huì)接受治療。值得注意的例外是資源豐富的高發(fā)病率國(guó)家，如日本，已在年輕人中開展系統(tǒng)性的篩查和治療。在那些標(biāo)準(zhǔn)沒(méi)有改善甚至更加惡化的國(guó)家，感染率似乎是穩(wěn)定的，而且在出現(xiàn)改善之前，感染率不太可能大幅下降。在其中許多國(guó)家，消化性潰瘍病仍然很猖獗。胃癌的負(fù)擔(dān)也不成比例地落在這些人口身上。

4.  The impact of H. pylori infection and the effect of eradication

4.  幽門螺桿菌感染的影響和根除的效果

4.1  H. pylori and peptic ulcer disease

4.1  幽門螺桿菌和消化性潰瘍病

The recognition that H. pylori was the cause of most duodenal ulcers and about two-thirds of gastric ulcers was a seminal, Nobel Prize–winning medical breakthrough [14]. In many developed countries with a decreasing prevalence of infection and cure of ulcer patients, the proportion of all peptic ulcers due to H. pylori is falling. In less developed countries, where the prevalence of infection remains high and fewer ulcer sufferers receive curative treatment, peptic ulcer disease (PUD) continues to be a very common and important condition. H. pylori infection has been estimated to confer an individual lifetime risk of peptic ulcer disease of 15–20%. Untreated, PUD is a chronic relapsing and remitting disease that causes major mortality and morbidity due to pain, bleeding, and perforation. It also results in economic losses. Eradication of H. pylori heals most active peptic ulcers and prevents further relapses, thus effecting a cure. Eradication of H. pylori in patients with a history of ulcer disease prevents subsequent relapses.

認(rèn)識(shí)到幽門螺桿菌是大多數(shù)十二指腸潰瘍和大約三分之二的胃潰瘍的原因，是一個(gè)具有開創(chuàng)性的、獲得諾貝爾獎(jiǎng)的醫(yī)學(xué)突破[14]。在許多發(fā)達(dá)國(guó)家，隨著感染率的下降和潰瘍患者的治愈，所有消化性潰瘍中由幽門螺桿菌引起的比例正在下降。在欠發(fā)達(dá)國(guó)家，感染率仍然很高，潰瘍病患者接受治愈性治療的人數(shù)較少，消化性潰瘍病（PUD）仍然是一種非常普遍和重要的疾病。據(jù)估計(jì)，幽門螺桿菌感染使個(gè)體一生中患消化性潰瘍病的風(fēng)險(xiǎn)增加15-20%。如果不加以治療，PUD作為一種慢性復(fù)發(fā)和緩解的疾病，會(huì)引起疼痛、出血和穿孔而導(dǎo)致主要的死亡率和發(fā)病率。它還會(huì)導(dǎo)致經(jīng)濟(jì)損失。根除幽門螺桿菌可以治愈大多數(shù)活動(dòng)性消化性潰瘍，防止進(jìn)一步復(fù)發(fā)，從而達(dá)到治愈的效果。在有潰瘍病史的病人中根除幽門螺桿菌可以防止以后復(fù)發(fā)。

NSAIDs and aspirin cause most other peptic ulcers. H. pylori and NSAIDs act synergistically to increase the risk of ulcers and bleeding. Eradication of H. pylori reduces this risk before the start of chronic NSAID therapy.

非甾體抗炎藥和阿司匹林會(huì)導(dǎo)致大多數(shù)其他的消化性潰瘍。幽門螺桿菌和NSAIDs協(xié)同作用，增加潰瘍和出血的風(fēng)險(xiǎn)。在開始長(zhǎng)期NSAID治療之前，根除幽門螺桿菌可以減少這種風(fēng)險(xiǎn)。

4.2  H. pylori and gastric cancer and MALT lymphoma

4.2  幽門螺桿菌與胃癌和MALT淋巴瘤

In susceptible infected hosts, long-standing active chronic gastritis may result in gastric mucosal atrophy with intestinal metaplasia. In a minority, these premalignant mucosal changes progress to dysplasia and clinically silent, early cancer, followed by advanced gastric cancer. Gastric cancer often presents at an advanced, symptomatic stage and it has a generally poor prognosis. H. pylori has been estimated to confer an individual lifetime risk of gastric cancer of 1.5–2.0% in infected individuals. Despite the relatively low individual risk, as the global number of people infected is estimated in the billions, there is a global burden of gastric cancer of over one million per year, with a high fatality rate (Table 1) [15]. This burden is not distributed evenly. East Asia—Japan, Korea, and eastern China—has the highest prevalence of disease. China suffers 40% of world cases of gastric cancer. Most, but not all, gastric cancers are related to H. pylori. The risk of progression to gastric cancer varies and is related to host and pathogen factors. Host cofactors include smoking and diet. High salt intake, the consumption of pickled foods, and diets low in antioxidants are dietary cofactors. Genetic risk factors in the host that are associated with increased risk include the presence of polymorphisms in genes that determine the expression of interleukin-1 (IL-1; proinflammatory cytokines) and pathogen recognition receptors. Genotyping of strains of H. pylori has revealed differences in virulence factors that promote inflammation and are associated with an increased risk of cancer.

在易受感染的宿主中，長(zhǎng)期慢性活動(dòng)性胃炎可能導(dǎo)致胃粘膜萎縮并伴有腸化生。在少數(shù)情況下，這些惡性腫瘤前的粘膜病變會(huì)發(fā)展成異型增生和臨床上無(wú)癥狀的早期癌癥，然后是晚期胃癌。胃癌常常在晚期、有癥狀階段被診斷出，而且預(yù)后一般較差。據(jù)估計(jì)，在感染者中，幽門螺桿菌使個(gè)人終生患胃癌的風(fēng)險(xiǎn)為1.5-2.0%。盡管個(gè)人風(fēng)險(xiǎn)相對(duì)較低，但由于全球感染者的數(shù)量估計(jì)有數(shù)十億，因此全球每年有超過(guò)一百萬(wàn)的胃癌負(fù)擔(dān)，而且死亡率很高（表1）[15]。這種負(fù)擔(dān)并不是平均分布的。東亞--日本、韓國(guó)和中國(guó)東部--疾病的發(fā)病率最高。中國(guó)的胃癌病例占世界的40%。大多數(shù)（但不是所有）胃癌都與幽門螺桿菌有關(guān)。進(jìn)展為胃癌的風(fēng)險(xiǎn)各不相同，與宿主和病原體因素有關(guān)。宿主的輔助因素包括吸煙和飲食。高鹽攝入、食用腌制食品和低抗氧化劑的飲食是飲食的輔助因素。宿主中與風(fēng)險(xiǎn)增加有關(guān)的遺傳風(fēng)險(xiǎn)因素包括決定白細(xì)胞介素-1（IL-1；促炎癥細(xì)胞因子）和病原體識(shí)別受體表達(dá)的基因存在多態(tài)性。幽門螺桿菌菌株的基因分型顯示了促進(jìn)炎癥的毒力因素的差異，與癌癥風(fēng)險(xiǎn)的增加有關(guān)。

Eradication of H. pylori before the occurrence of adverse, precancerous histological changes has been shown to prevent gastric cancer and is the rationale for mass test-and-treat screening programs in young adults in countries with a high burden of disease and with sufficient resources to devote to this endeavor. In less well-resourced regions with a high burden of gastric cancer, such a strategy remains aspirational rather than feasible, given cost constraints, logistical difficulties, and competing health-care needs.

在出現(xiàn)不良的癌前組織學(xué)變化之前根除幽門螺桿菌已被證明可以預(yù)防胃癌，這也是在疾病負(fù)擔(dān)重且有足夠資源投入這項(xiàng)工作的國(guó)家對(duì)年輕成年人進(jìn)行大規(guī)模檢測(cè)和治療篩查的理由。在資源較少、胃癌負(fù)擔(dān)較重的地區(qū)，考慮到成本限制、后勤困難和相互競(jìng)爭(zhēng)的醫(yī)療需求，這樣的策略仍然是理想的，而不是可行的。

Eradicating H. pylori after mucosal atrophy and/or intestinal metaplasia have developed may reduce the risk of gastric cancer, but does not eliminate it [16]. In any individual, the residual risk is related to the extent and severity of the mucosal changes, as well as other host risk factors. Endoscopic surveillance of intestinal metaplasia may be appropriate in some settings.

在粘膜萎縮和/或腸化生形成后，根除幽門螺桿菌可能會(huì)降低胃癌的風(fēng)險(xiǎn)，但并不能消除它[16]。在任何個(gè)體中，殘留的風(fēng)險(xiǎn)與粘膜變化的范圍和嚴(yán)重程度以及其他宿主風(fēng)險(xiǎn)因素有關(guān)。在某些情況下，內(nèi)鏡監(jiān)測(cè)腸化生可能是合適的。

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is rare. Most cases are a consequence of H. pylori infection, and eradication of H. pylori when the lymphoma is at a low-grade stage results in regression and cure. Late recurrences after eradication have occasionally been reported.

胃粘膜相關(guān)淋巴組織（MALT）淋巴瘤是罕見的。大多數(shù)病例是幽門螺桿菌感染的結(jié)果，當(dāng)淋巴瘤處于低級(jí)階段時(shí)，根除幽門螺桿菌會(huì)導(dǎo)致淋巴瘤消退和治愈。偶爾也有根除后晚期復(fù)發(fā)的報(bào)道。

4.3  H. pylori–associated dyspepsia

4.3  幽門螺桿菌相關(guān)的消化不良

Most H. pylori gastritis is asymptomatic, but it is commonly associated with upper gut symptoms in the absence of ulcer disease. However, only about one-third or less of infected patients with “functional dyspepsia” experience sustained relief of symptoms after eradication therapy. This is because functional dyspepsia is a heterogeneous condition that may be caused by different mechanisms. H. pylori may be causal in some patients with symptoms and may be present incidentally in others. However, the proportion of infected patients who improve after eradication therapy is greater than those who are given empirical acid-suppressive therapy. In addition, patients may benefit from a reduced lifetime risk of ulcer disease and cancer, especially if they are treated before adverse histological changes have developed in the gastric mucosa.

大多數(shù)幽門螺桿菌胃炎是無(wú)癥狀的，但是在沒(méi)有潰瘍病的情況下，它通常與上消化道癥狀有關(guān)。然而，只有大約三分之一或更少的患有 '功能性消化不良 '的感染者在接受根除治療后癥狀會(huì)持續(xù)緩解。這是因?yàn)楣δ苄韵涣际且环N異質(zhì)性的疾病，可能由不同的機(jī)制引起。幽門螺桿菌在一些有癥狀的病人中可能是因果關(guān)系，而在其他病人中癥狀可能是偶然出現(xiàn)的。然而，經(jīng)過(guò)根除治療后，受感染的病人中改善的比例要大于那些接受經(jīng)驗(yàn)性抑酸治療的病人。此外，患者可能受益于潰瘍病和癌癥的終生風(fēng)險(xiǎn)降低，特別是如果他們?cè)谖刚衬こ霈F(xiàn)不良組織學(xué)變化之前就接受治療。

A recent revised classification of gastritis has recognized H. pylori–associated dyspepsia as a distinct entity, and it has been incorporated into the 11th revision of the International Classification of Diseases (ICD-11) [11]. The classification also highlights the significance of H. pylori gastritis as the precursor lesion that leads to peptic ulcer disease and gastric cancer, irrespective of whether symptoms are present.

最近修訂的胃炎分類將幽門螺桿菌相關(guān)的消化不良作為一個(gè)獨(dú)立的實(shí)體，并被納入《國(guó)際疾病分類》第11版（ICD-11）[11]。該分類還強(qiáng)調(diào)了幽門螺桿菌胃炎作為導(dǎo)致消化性潰瘍病和胃癌的癌前病變的意義，而不論是否存在癥狀。

H. pylori infection has been associated with a variety of other conditions. In most cases, the association has not been shown to be causal, and common conditions will inevitably coexist in some patients. There is modest evidence linking H. pylori to immune thrombocytopenic purpura, and eradication therapy has been tried, with variable results.

幽門螺桿菌感染與其他各種疾病有關(guān)。在大多數(shù)情況下，這種關(guān)聯(lián)并沒(méi)有被證明是因果關(guān)系，共同的疾病將不可避免地在一些病人身上并存。有適度的證據(jù)表明幽門螺桿菌與免疫性血小板減少性紫癜有關(guān)，而且已經(jīng)嘗試過(guò)根除療法，但效果不一。

5.  Diagnosis of H. pylori infection

5.  幽門螺桿菌感染的診斷

5.1  Who to test and treat?

5.1  誰(shuí)需要檢測(cè)和治療？

The decision on whether or not to treat H. pylori must be an active one that takes into account the individual patient’s circumstances and risks. The decision to test for H. pylori should therefore only be made with therapeutic intent.

是否治療幽門螺桿菌必須是一個(gè)積極的決定，要考慮到患者個(gè)人的情況和風(fēng)險(xiǎn)。因此，檢測(cè)幽門螺桿菌的決定只應(yīng)出于治療的目的。

Evidence-based indications for testing for and treating H. pylori are summarized in Table 2 [4,17]. The applicability of each indication in different regions will depend on the prevalence of infection and disease, resources, competing needs, and individual patient factors. Peptic ulcer disease is the prime indication in most of the world. The clinical and health-economic benefits of short-term curative therapy for a common, chronic, important disease have been amply demonstrated over many years. In resource-poor regions, this indication for therapy should be prioritized.

表2總結(jié)了檢測(cè)和治療幽門螺桿菌的循證適應(yīng)癥[4,17]。每個(gè)適應(yīng)癥在不同地區(qū)的適用性取決于感染和疾病的流行程度、資源、競(jìng)爭(zhēng)性需求和患者個(gè)體因素。消化性潰瘍病是世界上大多數(shù)地區(qū)的首要適應(yīng)癥。多年來(lái)，對(duì)一種常見的、慢性的、重要的疾病進(jìn)行短期治愈性治療的臨床和健康經(jīng)濟(jì)效益已得到充分證明。在資源匱乏的地區(qū)，應(yīng)該優(yōu)先考慮這一治療指征。

6.  How to test for H. pylori

6.  如何檢測(cè)幽門螺桿菌

6.1  Endoscopic diagnostic tests

6.1  內(nèi)窺鏡診斷檢查

Diagnostic tests for H. pylori infection may be invasive (endoscopic) or noninvasive (nonendoscopic) (Table 3). Biopsies taken at endoscopy are most commonly for histological analysis and urease testing. Biopsies for culture are less often used for diagnosis, unless antimicrobial resistance testing is available and is needed to aid individual clinical decision-making or determine population resistance rates. A combination of two testing modalities taken from two topographic locations in the stomach is generally most effective for diagnosis. In practice, this usually means biopsies taken from the antrum and body of the stomach for histology and from the antrum for a urease test. More structured biopsy protocols may be used when there is an additional need for histological surveillance, as in the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis/Intestinal-Metaplasia Assessment (OLGIM) protocols [18]. Histology is usually costly and very operator-dependent, and accuracy cannot be assumed except in comparison with other previous testing modalities.

幽門螺桿菌感染的診斷可以是侵入性的（內(nèi)窺鏡）或非侵入性的（非內(nèi)窺鏡）（表3）。內(nèi)窺鏡檢查時(shí)取的活體組織通常用于組織學(xué)分析和尿素酶測(cè)試。用于培養(yǎng)的活檢較少用于診斷，除非有抗生素耐藥性檢測(cè)，并且需要幫助個(gè)人臨床決策或確定群體抗生素耐藥率。從胃部的兩個(gè)位置采取兩種檢測(cè)方式的組合通常對(duì)診斷最有效。在實(shí)踐中，這通常意味著從胃竇和胃體取樣進(jìn)行組織學(xué)檢查，從胃竇取樣進(jìn)行尿素酶測(cè)試。當(dāng)有額外的組織學(xué)監(jiān)測(cè)需要時(shí)，可以使用更多的結(jié)構(gòu)化活檢方案，如胃炎評(píng)估手術(shù)（OLGA）和胃炎/腸道增生評(píng)估手術(shù)（OLGIM）方案[18]。組織學(xué)檢查通常是昂貴的，而且非常依賴操作者，并且不能假設(shè)準(zhǔn)確性，除非與以前的其他檢測(cè)方式相比。

In resource-limited regions, reliance on urease tests is common. Most commercial urease tests appear to be accurate to a sensitivity of about 95%. Although they are much less expensive than histology, these tests may still incur a significant cost burden in resource-poor regions, especially when the cost is borne by the patient. A commercial test typically costs US$ 5. In regions where the average daily income for an unskilled worker may be $1–2, this may not be affordable. Fortunately, there are very inexpensive generic urease tests that have been available for many years and can be done on site, with a unit cost of about $0.20. These are usually unbuffered tests that give a very rapid result and have a sensitivity very similar to that of commercial tests [19]. They are in use in some countries in Africa, Asia, and the Pacific region.

在資源有限的地區(qū)，依賴尿素酶測(cè)試是很常見的。大多數(shù)商業(yè)性的尿素酶測(cè)試的準(zhǔn)確度似乎達(dá)到了95%左右。盡管它們比組織學(xué)的價(jià)格要低得多，但在資源匱乏的地區(qū)，這些測(cè)試仍然會(huì)產(chǎn)生巨大的成本負(fù)擔(dān)，特別是當(dāng)費(fèi)用由病人承擔(dān)時(shí)。商業(yè)性尿素酶檢測(cè)通常花費(fèi)5美元。在非熟練工人的平均日收入可能為1-2美元的地區(qū)，這可能是負(fù)擔(dān)不起的。幸運(yùn)的是，有一些非常便宜的普通尿素酶測(cè)試已經(jīng)有很多年了，可以在現(xiàn)場(chǎng)進(jìn)行，單位成本約為0.20美元。這些通常是無(wú)緩液的檢測(cè)，可以得到非常快速的結(jié)果，其靈敏度與商業(yè)測(cè)試非常相似[19]。非洲、亞洲和太平洋地區(qū)的一些國(guó)家正在使用它們。

Culturing H. pylori from biopsies requires specific transport conditions, laboratory skills, and equipment. Culture success rates may reach 90% in expert centers, but are often lower than that in less expert centers. Subculturing for antimicrobial testing may also not always be successful in less expert laboratories, so that results may not always be obtained when required. There are now commercially available real-time polymerase chain reaction (PCR) tests that allow the detection of H. pylori with high levels of sensitivity and specificity, and also of mutations that cause clarithromycin resistance [20–22]. These tests do not require strict preanalytic conditions and they can be performed in a few hours.  The validation and implementation of these rapid, inexpensive kit-based point-of-care antimicrobial resistance tests promises to be a major advance in management. The availability of such tests in regions of high resistance may greatly aid the choice of therapy for individual patients, while also facilitating surveys of population prevalence.

從活檢中培養(yǎng)幽門螺桿菌需要特定的運(yùn)輸條件、實(shí)驗(yàn)室技術(shù)和設(shè)備。在專業(yè)的中心，培養(yǎng)成功率可能達(dá)到90%，但實(shí)際情況成功率往往低于專業(yè)中心。在專業(yè)性不強(qiáng)的實(shí)驗(yàn)室中，用于抗生素檢測(cè)的再培養(yǎng)也不一定成功，因此，在需要時(shí)不一定能得到結(jié)果。現(xiàn)在有商業(yè)化的實(shí)時(shí)聚合酶鏈?zhǔn)椒磻?yīng)（PCR）檢測(cè)，能夠以較高的靈敏度和特異性檢測(cè)幽門螺桿菌，也能檢測(cè)導(dǎo)致克拉霉素耐藥的突變[20-22]。這些測(cè)試不需要嚴(yán)格的分析前條件，可以在幾個(gè)小時(shí)內(nèi)完成。 這些快速、廉價(jià)的基于試劑盒的活檢抗生素耐藥性檢測(cè)的驗(yàn)證和實(shí)施有望成為H. pylori感染管理方面的一個(gè)重大進(jìn)展。在耐藥性高的地區(qū)提供這種測(cè)試可能會(huì)大大有助于為個(gè)別病人選擇治療方法，同時(shí)也有利于調(diào)查人口的流行情況。

Endoscopic diagnosis of duodenal ulcer disease in a higher-prevalence, poorly resourced region, in a patient who is not taking NSAIDs, has an accuracy of 95% for predicting the presence of H. pylori. While a biopsy-based test to confirm infection is desirable, the presence of the duodenal ulcer has a predictive value similar to that of most tests, and so it is reasonable to treat without incurring further costs (unless inexpensive generic urease tests are available).

在一個(gè)發(fā)病率較高、資源匱乏的地區(qū)，對(duì)未服用非甾體抗炎藥的患者進(jìn)行十二指腸潰瘍病的內(nèi)鏡診斷，預(yù)測(cè)幽門螺桿菌存在的準(zhǔn)確率為95%。雖然確認(rèn)感染的活檢是可取的，但十二指腸潰瘍的存在具有與大多數(shù)測(cè)試相似的預(yù)測(cè)價(jià)值，因此，在不產(chǎn)生進(jìn)一步費(fèi)用的情況下進(jìn)行治療是合理的（除非有廉價(jià)的通用尿素酶測(cè)試）。

6.2  Noninvasive diagnostic tests

6.2  無(wú)創(chuàng)性診斷檢查

When endoscopy is not required or not available, noninvasive tests may be used. Urea breath tests (UBTs) are very useful and have higher diagnostic accuracy than other noninvasive tests for identifying H. pylori (in patients without a history of gastrectomy). Somewhat surprisingly, these are not widely available in many countries in which H. pylori and peptic ulcer disease are most common. The reasons for this are complex, and may include a lack of expertise or resources to set up and operate breath analysis laboratories, the relatively high cost of commercial kit tests, or overreliance on either empirical therapy or endoscopy. In many cases, valid anxiety about gastric cancer is a major driver of the use of endoscopy (although once they become symptomatic, gastric cancers are rarely curable). The costs of UBTs vary. In higher-resource countries, costs compare very favorably with endoscopy, although in regions in which endoscopy is relatively inexpensive, the cost advantage disappears unless low-cost UBTs are available. The stable isotope C13 UBT test has been validated in detail in multiple locations, and is often preferred in well-resourced regions. The C14 UBT uses a very low dose of radioactive isotope and usually has a shorter collection time, but has not been as extensively validated. It may be somewhat less accurate. The laboratory set-up costs for C13 UBTs are higher, as a mass spectrometer is required, whereas a less expensive scintillation counter is needed for C14 UBTs. The real (rather than commercial) unit cost of the C14 isotope is low, so the test could be provided at a very low cost using a central laboratory “hub and spoke” model for service delivery, with remotely collected breath samples being delivered from throughout a region. Point-of-care commercial kits and analyzers are available. The accuracy varies, and the unit cost of these kits is often high.

當(dāng)不需要或無(wú)法進(jìn)行內(nèi)窺鏡檢查時(shí)，可以使用無(wú)創(chuàng)性檢查。尿素呼氣試驗(yàn)（UBTs）是非常有用的，在識(shí)別幽門螺桿菌方面比其他無(wú)創(chuàng)性試驗(yàn)具有更高的診斷準(zhǔn)確性（對(duì)于沒(méi)有胃切除史的病人）。有點(diǎn)令人驚訝的是，在幽門螺桿菌和消化性潰瘍病最常見的許多國(guó)家，這些檢測(cè)并不廣泛。其原因很復(fù)雜，可能包括缺乏建立和運(yùn)行呼氣分析實(shí)驗(yàn)室的專業(yè)知識(shí)或資源，商業(yè)套件測(cè)試的成本相對(duì)較高，或過(guò)度依賴經(jīng)驗(yàn)療法或內(nèi)鏡檢查。在許多情況下，對(duì)胃癌的有效焦慮是使用內(nèi)窺鏡檢查的主要驅(qū)動(dòng)力（盡管一旦出現(xiàn)癥狀，胃癌很少能夠治愈）。UBTs的費(fèi)用各不相同。在資源較多的國(guó)家，成本與內(nèi)鏡檢查相比非常有利，盡管在內(nèi)鏡檢查相對(duì)便宜的地區(qū)，成本優(yōu)勢(shì)消失，除非有低成本的UBTs。穩(wěn)定同位素C13 UBT測(cè)試已在多個(gè)地方得到詳細(xì)驗(yàn)證，在資源豐富的地區(qū)通常是首選。C14 UBT使用非常低劑量的放射性同位素，通常需要較短的收集時(shí)間，但沒(méi)有得到廣泛的驗(yàn)證。它的準(zhǔn)確度可能要低一些。C13 UBT的實(shí)驗(yàn)室成本較高，因?yàn)樾枰粋€(gè)質(zhì)譜儀，而C14 UBT則需要一個(gè)成本較低的閃爍計(jì)數(shù)器。C14同位素的實(shí)際（而不是商業(yè)）單位成本很低，因此可以使用中央實(shí)驗(yàn)室 '樞紐和輻條 '模式提供服務(wù)，從整個(gè)地區(qū)遠(yuǎn)程收集呼氣樣本，以非常低的成本提供測(cè)試。目前已有商業(yè)化的試劑盒和分析儀。準(zhǔn)確度各不相同，而且這些試劑盒的單位成本往往很高。

Stool antigen testing is another option. These tests appear to be almost as accurate as UBTs, but patients and health-care and laboratory workers often have a lower preference for stool-based tests. Cost is an issue in some locations. Stool-based rapid PCR tests are also available [21]. Although these tests face the same acceptance barriers, as well as requiring laboratory equipment and skills, they have the potential to provide rapid diagnosis and antimicrobial resistance testing in a single noninvasive test.

糞便抗原檢測(cè)是另一種選擇。這些測(cè)試似乎與UBTs幾乎一樣準(zhǔn)確，但病人和衛(wèi)生保健及實(shí)驗(yàn)室工作人員往往對(duì)基于糞便的測(cè)試有較低的偏好。在一些地方，成本是一個(gè)問(wèn)題。基于糞便的快速PCR檢測(cè)也是可用的[21]。盡管這些測(cè)試面臨同樣的接受障礙，以及需要實(shí)驗(yàn)室設(shè)備和技能，但它們有可能在一次非侵入性測(cè)試中提供快速診斷和抗生素耐藥性測(cè)試。

Serological antibody tests are commonly available. Although they are useful as seroepidemiological surveys, these tests often lack the sensitivity and specificity required for decision-making in individual patients and are generally not very helpful. They need to be validated for specific locations, and the issue of false results due to cross-reactivity has rarely been addressed. In a community with moderate H. pylori prevalence, the accuracy of these tests may not exceed 50%.

血清學(xué)抗體檢測(cè)是很常見的。盡管它們作為血清流行病學(xué)調(diào)查是有用的，但這些測(cè)試往往缺乏對(duì)個(gè)別病人進(jìn)行決策所需的敏感性和特異性，一般來(lái)說(shuō)幫助不大。它們需要在特定的地點(diǎn)進(jìn)行驗(yàn)證，而且由于交叉反應(yīng)導(dǎo)致的錯(cuò)誤結(jié)果的問(wèn)題很少被解決。在幽門螺桿菌中度流行的社區(qū)，這些測(cè)試的準(zhǔn)確性可能不超過(guò)50%。

6.3  Testing to assess the outcome after eradication therapy

6.3  測(cè)試評(píng)估根除療法后的結(jié)果

As the success of eradication is very variable, outcome assessment should ideally be done in all patients, although this may not be feasible universally. Priority should be given to those who remain at highest risk for harm if the infection is ongoing, such as those who are being treated for complicated ulcer disease (bleeding or perforation).

由于根除的成功率很不穩(wěn)定，最好對(duì)所有的病人進(jìn)行結(jié)果評(píng)估，盡管這可能并不普遍可行。應(yīng)優(yōu)先考慮那些在感染持續(xù)的情況下仍有最高危害風(fēng)險(xiǎn)的患者，如正在接受復(fù)雜潰瘍病治療的患者（出血或穿孔）。

Biopsy-based testing may be used to determine the outcome after eradication therapy when endoscopy is required (to assess gastric ulcer healing and exclude neoplasia, or to survey adverse histology, for example). Otherwise, noninvasive tests are preferred. UBTs and stool tests should be done not less than 1 month after the completion of eradication therapy. To minimize false-negative results, no antibiotics or bismuth compounds should be taken by the patient for at least a month before testing, and proton-pump inhibitor (PPI) use should be avoided for at least one and preferably two weeks. Serology is not useful for assessing the outcome, as antibody levels often persist for years after therapy. Despite the widespread validation of noninvasive diagnostic tests, and of breath tests in particular, they are still not available at low cost in many places around the world, and this remains a major unmet clinical need.

當(dāng)需要進(jìn)行內(nèi)鏡檢查時(shí)，基于活檢的檢測(cè)可用于確定根除治療后的結(jié)果（例如評(píng)估胃潰瘍愈合和排除腫瘤，或調(diào)查不良組織學(xué)）。否則，首選非侵入性檢查。UBTs和糞便檢測(cè)應(yīng)在根除療法完成后不少于1個(gè)月進(jìn)行。為了盡量減少假陰性結(jié)果，患者在檢測(cè)前至少一個(gè)月內(nèi)不應(yīng)服用抗生素或鉍化合物，并且至少在一周內(nèi)，最好是兩周內(nèi)避免使用質(zhì)子泵抑制劑（PPI）。血清學(xué)對(duì)評(píng)估結(jié)果沒(méi)有用，因?yàn)榭贵w水平往往在治療后持續(xù)多年。盡管無(wú)創(chuàng)診斷測(cè)試，特別是呼氣測(cè)試得到了廣泛的驗(yàn)證，但在世界許多地方仍然無(wú)法以低廉的價(jià)格獲得這些測(cè)試，這仍然是一個(gè)未滿足的主要臨床需求。

6.4  Diagnostic pathways

6.4  診斷途徑

The choice of diagnostic test depends to a large extent on the clinical context, availability, expertise, and cost. If all modalities for diagnosis are available, the key issue is whether endoscopy is required to investigate symptoms or signs of upper gut disease. In low-prevalence, more developed countries, assessment for gastroesophageal reflux (GERD), functional dyspepsia, cardia and esophageal cancer concerns are common indications for endoscopy, and it is usual to biopsy the stomach for H. pylori at that time. H. pylori is still an issue in such regions, particularly in higher-risk subgroups such as older patients and those with lower socioeconomic status, or migrants from high-prevalence regions. In these countries, a noninvasive “test-and-treat” strategy using UBTs have been validated in younger patients and are cost-effective, although the use of this strategy may be declining. An empirical trial of PPI therapy is often done in primary care instead, with recourse to endoscopy if the symptoms are not relieved. Although popular, this is problematic when the symptoms are not typical of GERD, and the ideal duration of such a treatment trial is unclear. It may lead to failure to diagnose H. pylori. Although the organism may be incidental to the presentation, treatment in younger adults is associated with significant long-term risk reduction. The cost-effectiveness of management strategies for H. pylori in well-resourced, lower-prevalence countries varies with local health-care costs.

診斷測(cè)試的選擇在很大程度上取決于臨床環(huán)境、可用性、專業(yè)知識(shí)和成本。如果所有的診斷方式都可用，關(guān)鍵問(wèn)題是是否需要內(nèi)鏡檢查來(lái)調(diào)查上消化道疾病的癥狀或體征。在發(fā)病率低、較發(fā)達(dá)的國(guó)家，對(duì)胃食管反流（GERD）、功能性消化不良、賁門癌和食管癌的擔(dān)憂進(jìn)行評(píng)估是內(nèi)鏡檢查的常見指征，而且通常在那個(gè)時(shí)候?qū)ξ覆窟M(jìn)行幽門螺桿菌活檢。幽門螺桿菌在這些地區(qū)仍然是一個(gè)問(wèn)題，特別是在高風(fēng)險(xiǎn)的人群，如老年患者和社會(huì)經(jīng)濟(jì)地位較低的人，或來(lái)自高發(fā)地區(qū)的移民。在這些國(guó)家，使用UBTs的無(wú)創(chuàng) '測(cè)試和治療 '策略已在年輕患者中得到驗(yàn)證，并具有成本效益，盡管這一策略的使用可能正在下降。經(jīng)驗(yàn)性的PPI治療試驗(yàn)常常在初級(jí)保健中進(jìn)行，如果癥狀沒(méi)有得到緩解，就會(huì)求助于內(nèi)窺鏡檢查。雖然這種做法很受歡迎，但如果癥狀不是胃食管反流病的典型癥狀，就會(huì)出現(xiàn)問(wèn)題，而且這種治療試驗(yàn)的理想時(shí)間也不清楚。這可能會(huì)導(dǎo)致幽門螺桿菌的診斷失敗。盡管該有機(jī)體可能是偶然出現(xiàn)的，但在年輕的成年人中，治療與明顯的長(zhǎng)期風(fēng)險(xiǎn)降低有關(guān)。在資源豐富、發(fā)病率較低的國(guó)家，幽門螺桿菌的管理策略的成本效益隨當(dāng)?shù)氐尼t(yī)療費(fèi)用而變化。

In higher-prevalence countries, there is often a distinct preference by both doctor and patient for prompt endoscopy, due to the fear of gastric cancer—although as noted, it is not certain whether this improves survival when patients present with symptoms. For individual decision-making, the pretest probability of infection, the patient’s age, the nature of symptoms or signs, and the local prevalence of ulcer disease and gastric cancer must be considered.

在發(fā)病率較高的國(guó)家，由于對(duì)胃癌的恐懼，醫(yī)生和病人通常都明顯傾向于及時(shí)進(jìn)行內(nèi)鏡檢查--盡管如前所述，當(dāng)病人出現(xiàn)癥狀時(shí)，這是否能提高生存率尚不確定。對(duì)于個(gè)人決策來(lái)說(shuō)，必須考慮感染的預(yù)檢概率、病人的年齡、癥狀或體征的性質(zhì)，以及當(dāng)?shù)貪儾『臀赴┑陌l(fā)病率。

6.5  Empirical therapy in low-resource regions

6.5  低資源地區(qū)的經(jīng)驗(yàn)性治療

Where there is very limited access to endoscopic or noninvasive means of diagnosing H. pylori infection, decision-making must be empirical, based on the clinical setting. Peptic ulcer disease may be strongly suspected on clinical grounds when there is a clear history of periodic upper gut pain and/or any earlier or recent history of upper gastrointestinal bleeding. In regions in which it is known that the prevalence of H. pylori is high and peptic ulcer disease is common, it is reasonable to use empirical eradication therapy for the presumptive clinical diagnosis of peptic ulcer disease (Fig. 3). The cohort so treated will include many with peptic ulcer disease, who will gain major benefit. It will also include some who have H. pylori–associated gastritis but no active ulcer. In this group, symptom resolution occurs more frequently than with the use of any other therapy (commonly PPIs), and importantly, successful therapy reduces lifelong risks of peptic ulcer disease and gastric cancer. Treatment of both peptic ulcer disease and gastritis has also been shown to be cost-effective

在內(nèi)窺鏡或無(wú)創(chuàng)診斷幽門螺桿菌感染的手段非常有限的地方，必須根據(jù)臨床情況做出經(jīng)驗(yàn)性的決定。當(dāng)有明確的周期性上消化道疼痛史和/或任何早期或近期的上消化道出血史時(shí)，可以從臨床角度強(qiáng)烈懷疑消化性潰瘍病。在已知幽門螺桿菌流行率高且消化性潰瘍病常見的地區(qū)，對(duì)消化性潰瘍病的臨床推定診斷采用經(jīng)驗(yàn)性根除療法是合理的（圖3）。如此治療的人群將包括許多患有消化性潰瘍病的人，他們將獲得很大的好處。它還包括一些患有幽門螺桿菌相關(guān)的胃炎但沒(méi)有活動(dòng)性潰瘍的人。在這一群體中，癥狀的解決比使用任何其他療法（通常是PPIs）更頻繁，重要的是，成功的治療可以減少消化性潰瘍病和胃癌的終身風(fēng)險(xiǎn)。消化性潰瘍病和胃炎的治療也已被證明是具有成本效益的。

With empirical symptom-based eradication therapy, there will be a subgroup treated who are not infected and may have other diagnoses. This group will not benefit from eradication therapy, and there are costs and the unnecessary use of antibiotics involved, but the likelihood of major harm is low and the overall benefit to the treated group justifies this approach. Indeed, the Asia–Pacific Consensus Group on H. pylori has specifically endorsed such an approach in regions in which H. pylori and peptic ulcer disease are common and many people have no access to investigations, for either economic or geographic reasons. Empirical use of PPI therapy is likely to be less beneficial than the initial treatment. Such an approach should be supported by programs for educating health-care workers to recognize symptoms that are more likely to be due to ulcer disease and to apply this strategy selectively. In these resource-poor regions, treating all upper gut symptoms with such an approach is harder to justify.

在經(jīng)驗(yàn)性的基于癥狀的根除療法中，會(huì)有一部分接受治療的患者，他們沒(méi)有被感染，可能有其他診斷。這個(gè)群體不會(huì)從根除療法中受益，而且涉及到成本和不必要的抗生素使用，但造成重大傷害的可能性很低，而且接受治療的群體的整體利益證明這種方法是合理的。事實(shí)上，在幽門螺桿菌和消化性潰瘍病很常見的地區(qū)，由于經(jīng)濟(jì)或地理原因，許多人沒(méi)有機(jī)會(huì)接受調(diào)查，亞太幽門螺桿菌共識(shí)小組特別贊同這種方法。經(jīng)驗(yàn)性地使用PPI治療可能不如初始治療有益。這種方法應(yīng)該得到教育保健工作者的計(jì)劃的支持，以識(shí)別更可能是由潰瘍病引起的癥狀，并有選擇地應(yīng)用這種策略。在這些資源匱乏的地區(qū)，用這種方法治療所有的上消化道癥狀是比較困難的。

NSAID use is widespread, and NSAID-related peptic ulcer disease is common and may coexist with H. pylori infection. In an empirical setting of suspected ulcer disease, when NSAIDs (including aspirin) are being used, it is reasonable both to treat for H. pylori and to address the NSAID risk by ceasing the use of these agents and treating the patient with PPIs for a few weeks after the completion of eradication therapy.

非甾體抗炎藥的使用很普遍，與非甾體抗炎藥相關(guān)的消化性潰瘍病很常見，并且可能與幽門螺桿菌感染同時(shí)存在。在懷疑有潰瘍病的情況下，當(dāng)NSAIDs（包括阿司匹林）被使用時(shí)，合理的做法是既要治療幽門螺桿菌，又要解決NSAID的風(fēng)險(xiǎn)，即停止使用這些藥物，在完成根除治療后的幾周內(nèi)給病人使用PPI。

7. Treatment of H. pylori infection

7. 幽門螺桿菌感染的治療

A vast number of studies have addressed therapy issues, and numerous expert guidelines recommending choices of therapy are available. However, much of the literature and advice derives from well-resourced countries, with relatively little coming from the poorly-resourced countries that bear the major burden of diseases caused by H. pylori. Principles for antibiotic therapy that apply universally have been established. However, there are key issues that must be addressed locally in order to determine the best local practice, as antimicrobial resistance patterns and therefore eradication rates vary regionally [23,24] and other local issues such as the cost and availability of drugs influence the choice of therapy. The key principles that guide the choice of eradication therapy are outlined in Table 4.

大量的研究已經(jīng)解決了幽門螺桿菌的治療問(wèn)題，并且有許多專家指南推薦了治療的選擇。然而，大部分的文獻(xiàn)和建議都來(lái)自于資源豐富的發(fā)達(dá)國(guó)家，而來(lái)自于資源匱乏的發(fā)展中國(guó)家的文獻(xiàn)和建議相對(duì)較少，而這些國(guó)家承擔(dān)著幽門螺桿菌感染相關(guān)疾病的主要負(fù)擔(dān)。目前已經(jīng)確立了普遍適用的抗生素治療原則。然而，有一些關(guān)鍵問(wèn)題必須在當(dāng)?shù)亟鉀Q，以確定當(dāng)?shù)氐淖罴炎龇ǎ驗(yàn)榭股啬退幠Ｊ揭约坝拈T螺桿菌根除率在各地區(qū)有所不同，并且如藥物成本和藥品可獲得性等其他問(wèn)題，也會(huì)影響治療的選擇。表4概述了指導(dǎo)選擇根除療法的關(guān)鍵原則。

8.  Translating treatment principles into therapeutic choices

8.  將治療原則轉(zhuǎn)化為治療選擇

8.1  Choice of first-line eradication therapy

8.1  一線根除療法的選擇

Application of these principles of therapy will ensure the best outcomes possible. In well-resourced regions, treatment may be based on high-quality trials and audit and culture data; in resource-poor regions, reliance on a knowledge of community or personal antibiotic usage and any local audit of outcomes will influence the use of therapies recommended in guidelines from elsewhere [4–12].

應(yīng)用這些治療原則將確保可能的最佳結(jié)果。在資源豐富的地區(qū)，治療可能基于高質(zhì)量的試驗(yàn)和審核及藥敏培養(yǎng)數(shù)據(jù)；在資源匱乏的地區(qū)，依靠對(duì)社區(qū)或個(gè)人抗生素使用情況的了解以及任何當(dāng)?shù)氐膶徍私Y(jié)果都會(huì)影響其他地方的指南所推薦的療法的使用[4-12]。

8.1.1  PPI, amoxicillin, clarithromycin triple therapy

8.1.1  PPI、阿莫西林、克拉霉素三聯(lián)療法

In many parts of the world, triple therapy, comprising a proton-pump inhibitor (PPI) with amoxicillin and clarithromycin (PPI-AC), is still the most commonly used first-line therapy. This combination was the first very widely recommended therapy and superseded less effective triple therapies. It has been very well evaluated over the years. The major determinant of eradication success with this combination is pretreatment clarithromycin resistance (CR). The prevalence of antibiotic resistance, particularly CR, varies widely around the world (Table 5). Where clarithromycin has been and is used commonly as monotherapy for other infections, the level of CR is often high and increasing. There are views that this therapy should be abandoned in areas where the primary CR rates are known to be 15–20% or greater, because of the impact this has on eradication rates. A somewhat arbitrary minimum eradication rate of 80% on an intention-to-treat basis is often quoted as a benchmark for an acceptable therapy. This is a common eradication rate for PPI-AC in real-world studies in areas where CR rates are moderate or low (i.e., below 15–20%). Unacceptably lower eradication results may occur in countries in which the prevalence of CR is higher.

在世界許多地方，由質(zhì)子泵抑制劑（PPI）與阿莫西林和克拉霉素（PPI-AC）組成的三聯(lián)療法仍然是最常用的一線療法。這種組合是第一個(gè)非常廣泛推薦的療法，并取代了不太有效的三聯(lián)療法。多年來(lái)，它得到了很好的評(píng)估。該組合根除成功的主要決定因素是治療前的克拉霉素耐藥性（CR）。世界各地的抗生素耐藥性，特別是克拉霉素耐藥性的流行程度差異很大（表5）。在克拉霉素已經(jīng)并正在作為單一療法用于其他感染的地方，CR的水平通常很高，而且在不斷增加。有觀點(diǎn)認(rèn)為，在已知原發(fā)性CR率為15-20%或更高的地區(qū)應(yīng)放棄這種療法，因?yàn)檫@對(duì)根除率有影響。一個(gè)有點(diǎn)主觀的最低根除率，即在意向性治療的基礎(chǔ)上達(dá)到80%，常常被引用為可接受療法的基準(zhǔn)。在CR率中等或較低（即低于15-20%）的地區(qū)，這是PPI-AC在真實(shí)世界研究中的一個(gè)常見根除率。在CR發(fā)生率較高的國(guó)家，可能會(huì)出現(xiàn)不可接受的較低的根除結(jié)果。

The optimal duration of therapy is a matter of contention. Recent calls for universal 14-day PPI-AC therapy usually originate from regions with higher CR. Initial studies were mostly for 7 days, although that duration may have been influenced by registration trial design. Proponents of the longer duration of therapy point to somewhat higher eradication rates in systematic reviews. However, there are other considerations that influence the duration of therapy, particularly in resource-poor countries. Adding a second week of therapy may increase eradication rates, typically by about 10%. This means that the number of patients needed to treat with an extra week of therapy in order to achieve one more treatment success is 10. The price of this higher eradication rate, if achieved, includes a doubling of the cost of treatment, which is a major issue in resource-poor regions. (It should be noted that the cost of a week of triple therapy in very resource-poor regions may be as much as weekly earnings for the lowest paid.) The risk of adverse effects increases considerably with protracted antibiotics, as does the likelihood of noncompliance. An alternative is to give shorter therapy where compliance is likely to be greater and adverse effects and costs fewer, with the understanding that 10% more patients may need a second-line salvage therapy. Overall antibiotic use will be much lower with the second strategy, as long as first-line eradication rates are at least moderately high. The longer therapy is usually recommended in some well-resourced countries, but more modeling of shorter courses in resource poor-regions is needed. It must also be noted that acceptable eradication rates with 1-week PPI-AC therapy have been reported from several countries, and the incremental benefit of a longer course has not been studied. The optimal dosage for the PPI (standard or high dose) and clarithromycin (250 mg or 500 mg twice daily) has not been determined in most locations. In high CR regions, neither one nor two weeks of this therapy may achieve acceptable eradication rates. In such places, the choice for first-line therapy varies.

最佳的治療時(shí)間是一個(gè)有爭(zhēng)議的問(wèn)題。最近關(guān)于普及14天PPI-AC治療的呼吁通常來(lái)自于CR較高的地區(qū)。最初的研究多為7天，盡管這一期限可能受到注冊(cè)試驗(yàn)設(shè)計(jì)的影響。支持的人指出，在系統(tǒng)回顧中較長(zhǎng)的療程通常都有較高根除率。然而，還有其他考慮因素影響著治療的持續(xù)時(shí)間，特別是在資源匱乏的國(guó)家。增加第二周的治療療程可能會(huì)提高根除率，通常約為10%。這意味著，為了多獲得一次治療成功，需要多治療一周的病人數(shù)量是10名。如果達(dá)到這種更高的根除率，其代價(jià)包括治療費(fèi)用翻倍，這在資源匱乏的地區(qū)是一個(gè)主要問(wèn)題。(應(yīng)該指出的是，在資源非常匱乏的地區(qū)，一周的三聯(lián)療法的費(fèi)用可能與最低收入者每周的收入一樣多）。長(zhǎng)時(shí)間使用抗生素，不良反應(yīng)的風(fēng)險(xiǎn)會(huì)大大增加，不遵守規(guī)定的可能性也會(huì)大大增加。另一種方法是給予較短的治療，這樣依從性可能會(huì)更高，不良反應(yīng)和費(fèi)用會(huì)更少，但有一點(diǎn)可以理解，那就是可能會(huì)有10%的病人需要二線搶救治療。只要一線根除率至少適中，第二種策略的總體抗生素使用量將大大降低。在一些資源豐富的國(guó)家，通常推薦使用較長(zhǎng)的療程，但在資源貧乏的地區(qū)，還需要對(duì)較短的療程進(jìn)行更多的模擬研究。還必須注意的是，一些國(guó)家已經(jīng)報(bào)告了1周PPI-AC治療的可接受的根除率，而更長(zhǎng)療程的增量效益還沒(méi)有研究。PPI（標(biāo)準(zhǔn)或大劑量）和克拉霉素（250毫克或500毫克，每天兩次）的最佳劑量在大多數(shù)地區(qū)尚未確定。在CR高的地區(qū)，這種治療的一周或兩周可能都不能達(dá)到可接受的根除率。在這種地方，對(duì)一線療法的選擇是不同的。

The role and value of potassium-competitive acid blockers such as vonoprazan in place of PPIs in any eradication therapy is emerging. These drugs are not affected by CYP2C19 polymorphisms and result in more uniform and potent inhibition of gastric acid secretion [25].

在任何根除療法中，鉀競(jìng)爭(zhēng)性阻酸劑（如vonoprazan）代替PPI的作用和價(jià)值正在顯現(xiàn)。這些藥物不受CYP2C19多態(tài)性的影響，對(duì)胃酸分泌的抑制作用更加均勻和有效[25]。

8.1.2  Bismuth-based quadruple therapies

8.1.2  鉍劑四聯(lián)療法

The other core choice for first-line therapy, especially in regions with high primary CR, is still bismuth-based quadruple therapy. The best-studied regimen involves a PPI, bismuth, tetracycline, and metronidazole (PPI-BTM). This treatment has stood the test of time, since it leads to reliable and acceptable eradication rates irrespective of primary metronidazole resistance (MR), as the addition of a PPI to BTM appears to overcome MR. Good results have been achieved with 7-day therapy, although there are proponents of longer (10–14-day) treatments. The major drawbacks of this therapy are the clumsy dosage regimen (as it is usually dosed four times daily) and common but usually mild adverse effects, which may impair adherence. Reduced access to bismuth and tetracycline may limit the use of this treatment in some places. However, when these drugs are not readily available or not registered, it is often feasible to import generic drugs at low cost, with the permission of the relevant authorities.

一線治療的另一個(gè)核心選擇，特別是在原發(fā)性CR高的地區(qū)，仍然是以鉍劑為基礎(chǔ)的四聯(lián)療法。研究的最好的方案涉及PPI、鉍劑、四環(huán)素和甲硝唑（PPI-BTM）。這種治療方法經(jīng)受住了時(shí)間的考驗(yàn)，因?yàn)闊o(wú)論原發(fā)性甲硝唑耐藥性（MR）如何，它都能帶來(lái)可靠和可接受的根除率，因?yàn)樵贐TM中加入PPI似乎可以克服MR。7天的治療已經(jīng)取得了良好的效果，盡管也有人主張采用更長(zhǎng)的治療時(shí)間（10-14天）。這種療法的主要缺點(diǎn)是笨拙的劑量方案（因?yàn)樗ǔＣ刻煊盟幩拇危┖统Ｒ姷ǔＪ禽p微的不良反應(yīng)，這可能會(huì)影響堅(jiān)持治療。在一些地方，鉍劑和四環(huán)素的供應(yīng)減少可能會(huì)限制這種療法的使用。然而，當(dāng)這些藥物不容易獲得或沒(méi)有注冊(cè)時(shí)，經(jīng)有關(guān)部門許可，以低價(jià)進(jìn)口非專利藥物往往是可行的。

A quadruple therapy substituting amoxicillin for tetracycline (PPI-BAM) has long been reported and is less used, but may provide acceptable outcomes.

用阿莫西林替代四環(huán)素的四聯(lián)療法（PPI-BAM）早有報(bào)道，使用較少，但可能提供可接受的結(jié)果。

More recently, converting standard PPI-AC triple therapy to a quadruple therapy by adding bismuth (B+PPI-AC) has been reported, with favorable results in some locations [26]. The value of this in overcoming CR has yet to be fully determined, but it merits detailed evaluation.

最近，有報(bào)道稱通過(guò)添加鉍劑（B+PPI-AC）將標(biāo)準(zhǔn)的PPI-AC三聯(lián)療法轉(zhuǎn)換為四聯(lián)療法，在某些地方取得了良好的效果[26]。這對(duì)克服CR的價(jià)值還沒(méi)有完全確定，但值得詳細(xì)評(píng)估。

8.1.3  Nonbismuth quadruple therapies

8.1.3  非鉍劑四聯(lián)療法

There are advocates of nonbismuth quadruple therapies—usually meaning the addition of metronidazole to PPI-AC triple therapy (PPI-ACM). This may increase eradication rates if MR rates are low or moderate, but is unlikely to be very helpful in the many regions of the world where primary MR and/or CR are high. Moreover, patients in whom the treatment fails will often be found to have dual resistance. This type of concomitant therapy has been studied in well-resourced countries, but rarely in poorly resourced countries. Sequential or hybrid regimens are less well studied, appear not to offer superior eradication, are clumsy to prescribe, and pose particular challenges with adherence. As a result, they are not recommended.

有主張采用非鉍劑四聯(lián)療法--通常是指在PPI-AC三聯(lián)療法（PPI-ACM）中加入甲硝唑。如果MR率較低或中等，這可能會(huì)提高根除率，但對(duì)于世界上許多原發(fā)性MR和/或CR較高的地區(qū)來(lái)說(shuō)，不太可能有很大幫助。此外，治療失敗的病人往往會(huì)被發(fā)現(xiàn)有雙重耐藥性。在資源豐富的國(guó)家已經(jīng)對(duì)這種類型的伴隨治療進(jìn)行了研究，但在資源貧乏的國(guó)家很少。對(duì)序貫或混合療法的研究較少，似乎不能提供卓越的根除效果，開藥也很笨拙，并對(duì)依從性構(gòu)成了一定的挑戰(zhàn)。因此，不推薦使用這些方案。

Where metronidazole sensitivity is known from testing in a patient, PPI-AM may be used as a first-line treatment with reasonable outcomes. It is also suitable in locations where MR is known to be low in the population.

如果通過(guò)對(duì)病人的檢測(cè)知道了甲硝唑的敏感性，PPI-AM可以作為一線治療，并取得合理的效果。它也適用于已知人群中MR值較低的地方。

8.1.4  Levofloxacin triple therapy

8.1.4  左氧氟沙星三聯(lián)療法

Levofloxacin triple therapy (PPI, amoxicillin and levofloxacin, PPI-AL for 10–14 days) has been used in first-line therapy when levofloxacin resistance (LR) is known or presumed to be low, but the combination has not been studied extensively in this role, with most reports relating to second-line therapy. Reports of high levofloxacin resistance rates in some countries will limit the usefulness of this therapy in these locations. The treatment is generally well tolerated. There have been recent concerns about the risks of fluoroquinolone use. With levofloxacin, this is related to the rare risk of tendinitis or myositis. The precise prevalence of this adverse effect is not well documented, but it appears more common in the elderly and those with inflammatory arthritis or renal impairment and is best avoided in these high-risk subgroups if alternatives exist. A higher dose of levofloxacin and possibly high-dose PPI may be associated with superior eradication success. Moxifloxacin, a related quinolone, has also been used. It has been less studied and has a broader spectrum of activity, so is generally not preferred over levofloxacin.

左氧氟沙星三聯(lián)療法（PPI、阿莫西林和左氧氟沙星，PPI-AL為10-14天）在已知或推測(cè)左氧氟沙星耐藥性（LR）較低時(shí)被用于一線治療，但該組合在這一作用中沒(méi)有被廣泛研究，大多數(shù)報(bào)告與二線治療有關(guān)。一些國(guó)家關(guān)于左氧氟沙星耐藥率高的報(bào)道將限制這種療法在這些地方的應(yīng)用。該療法的耐受性一般較好。最近人們對(duì)使用氟喹諾酮類藥物的風(fēng)險(xiǎn)表示關(guān)注。對(duì)于左氧氟沙星，這與罕見的肌腱炎或肌炎的風(fēng)險(xiǎn)有關(guān)。這種不良反應(yīng)的確切發(fā)生率沒(méi)有很好的記錄，但在老年人和有炎癥性關(guān)節(jié)炎或腎功能損害的人中似乎更常見，如果有其他選擇，最好在這些高風(fēng)險(xiǎn)人群中避免使用。更大劑量的左氧氟沙星和可能的大劑量PPI可能與卓越的根除成功率有關(guān)。莫西沙星是一種相關(guān)的喹諾酮類藥物，也已被使用。對(duì)它的研究較少，而且它的抗菌譜較廣，所以一般不比左氧氟沙星更受歡迎。

There are a number of other less well studied treatments that have nonetheless been recommended in various reviews. Furazolidone, for example, has been used in locations where CR and LR are high, but quality data attesting to its value are meager in comparison with established therapies, and its precise role remains to be defined.

還有其他一些研究不充分的治療方法，但在各種評(píng)論中被推薦。例如，呋喃唑酮已被用于CR和LR較高的地方，但與已有的療法相比，證明其價(jià)值的高質(zhì)量數(shù)據(jù)很少，而且其確切的作用仍有待確定。

When antimicrobial resistance by culture or rapid PCR testing is used, tailored therapy may be prescribed to individual patients. This is likely to have the most value in regions of higher primary CR, to allow avoidance of clarithromycin use in first-line therapy. Validation and acceptance of stool-based PCR testing offers the prospect of extending this benefit to primary care and in circumstances in which endoscopy is not required or accessible.

當(dāng)使用通過(guò)培養(yǎng)或快速PCR檢測(cè)抗生素耐藥性時(shí)，可以為個(gè)別病人開出有針對(duì)性的療法。這可能在原發(fā)性CR較高的地區(qū)具有最大的價(jià)值，以避免在一線治療中使用克拉霉素。對(duì)基于糞便的PCR檢測(cè)的驗(yàn)證和接受提供了將這一好處擴(kuò)展到基礎(chǔ)保健和不需要或不能進(jìn)行內(nèi)鏡檢查的情況下的前景。

Tables 6 and 7 provide an overview and summary of first-line treatment regimens and their composition.

表6和表7提供了一線治療方案及其組成的概述和總結(jié)。

8.2  Choice of second and subsequent eradication therapies

8.2  二線和后續(xù)根除療法的選擇

Second-line or salvage therapies after the failure of first-line eradication have been well studied in some locations, but there is a complete lack of data for many resource-poor regions [4–12].

一些地方對(duì)一線根除失敗后的二線或補(bǔ)救療法進(jìn)行了充分的研究，但對(duì)于許多資源匱乏的地區(qū)來(lái)說(shuō)，完全缺乏數(shù)據(jù)[4-12]。

8.2.1  Bismuth-based quadruple therapy and levofloxacin triple therapy

8.2.1  鉍劑四聯(lián)療法和左氧氟沙星三聯(lián)療法

The most commonly studied and used second-line therapies include standard bismuth-based quadruple therapy for 7–14 days and levofloxacin triple therapy for 10–14 days, as described above. Both have been shown to achieve eradication rates above 80%. The choice between the two depends on whether or not there is knowledge of local primary levofloxacin resistance rates, availability, experience, adherence, and cost. A longer duration of therapy (i.e., 14 days) is often recommended, but data on local outcomes, costs and adherence are needed. When these treatments fail, the other therapy is the usual third choice. In experienced centers, overall eradication rates with judiciously chosen therapies after first-line failure should approach 98% after up to three treatments.

如上所述，最常研究和使用的二線療法包括標(biāo)準(zhǔn)的鉍劑四聯(lián)療法7-14天和左氧氟沙星三聯(lián)療法10-14天。兩者都已被證明能達(dá)到80%以上的根除率。兩者之間的選擇取決于是否了解當(dāng)?shù)卦l(fā)性左氧氟沙星耐藥率、藥物可得到性、經(jīng)驗(yàn)、依從性和成本。通常推薦較長(zhǎng)的治療時(shí)間（即14天），但需要關(guān)于當(dāng)?shù)亟Y(jié)果、成本和依從性的數(shù)據(jù)。當(dāng)這些治療方法失敗時(shí)，其他療法通常是第三種選擇。在有經(jīng)驗(yàn)的中心，在一線治療失敗后，明智地選擇的療法的總根除率應(yīng)該在最多三個(gè)療程后接近98%。

8.2.2  Other salvage therapies

8.2.2  其他補(bǔ)救性療法

Other salvage therapies that have been used include a rifabutin-based triple therapy (PPI-AR). It is generally less effective, and the risk of significant neutropenia may be as high as 1%, which tends to limit its use. It is usually avoided in regions with a high prevalence of tuberculosis. High-dose dual PPI with amoxicillin therapy (PPI-A) has been used with some success. Nonbismuth quadruple therapies are generally ineffective as salvage therapies, due to secondary CR and MR. Where metronidazole sensitivity is known after testing, PPI-AM may be used as a second-line treatment with reasonable outcomes, but it is generally not used for second-line therapy empirically. Furazolidone has been used and is recommended as a component of therapy in some regions. There are few high-quality eradication studies that include this drug, and there is a dearth of randomized trials. Concern about its safety and use has led to it becoming unavailable in the United States and the European Union.

已使用的其他補(bǔ)救療法包括以利福布汀為基礎(chǔ)的三聯(lián)療法（PPI-AR）。一般來(lái)說(shuō)，它的療效較差，顯著中性粒細(xì)胞減少的風(fēng)險(xiǎn)可能高達(dá)1%，這往往會(huì)限制其使用。在結(jié)核病高發(fā)地區(qū)通常要避免使用。大劑量二聯(lián)PPI加阿莫西林治療（PPI-A）已經(jīng)取得了一些成功。非鉍劑四聯(lián)療法作為補(bǔ)救治療通常是無(wú)效的，原因是繼發(fā)性CR和MR。在檢測(cè)后知道甲硝唑敏感性的情況下，PPI-AM可作為二線治療，效果合理，但一般不用于經(jīng)驗(yàn)性的二線治療。呋喃唑酮已經(jīng)被使用，并且在一些地區(qū)被推薦作為治療的一個(gè)組成部分。包括這種藥物的高質(zhì)量根除研究很少，隨機(jī)試驗(yàn)也很缺乏。對(duì)其安全性和使用的擔(dān)憂導(dǎo)致其在美國(guó)和歐盟無(wú)法使用。

When appropriate treatment pathways have been followed and therapy has failed, ad hoc therapies at the whim of the prescriber should be avoided, and ongoing infection should be accepted unless subspecialty expertise or a clinical trial is available. In some patients—such as those with relapsing ulcer disease—eradication failure may result in a need for maintenance antisecretory therapy.

當(dāng)遵循適當(dāng)?shù)闹委熗緩角抑委熓r(shí)，應(yīng)避免處方者一時(shí)興起的臨時(shí)治療，除非有亞專業(yè)的專業(yè)知識(shí)或臨床試驗(yàn)，否則應(yīng)接受持續(xù)感染的狀態(tài)。在一些患者中，如那些復(fù)發(fā)的潰瘍病患者，根治失敗可能導(dǎo)致需要維持抗酸分泌治療。

8.3  Treatment choices for patients with penicillin allergy

8.3  青霉素過(guò)敏患者的治療選擇

For patients with penicillin allergy, metronidazole may be substituted for amoxicillin and combined with a PPI and clarithromycin (PPI-MC). However, primary MR reduces the efficacy of this. Bismuth quadruple therapy is a very good alternative (PPI-BTM). If both of these therapies fail, there are limited further options. In patients who have a remote, uncertain, or unlikely history of penicillin allergy and when resources are available, formal assessment for type 1 penicillin allergy may be done. This involves measurement of penicillin antibodies, followed by skin-prick testing and if negative, a supervised oral challenge. When this is carried out in lower-risk patients, up to 80% of such patients have been shown not to be allergic to penicillin, and they may be treated safely with amoxicillin-containing therapies as required (usually PPI-AL or PPI-AC if clarithromycin was not used initially). Such a strategy has been shown to allow successful eradication therapy in most patients. Where there is a clear history of a type 1 reaction previously, allergy is assumed, and testing is not indicated.

對(duì)于青霉素過(guò)敏的病人，可以用甲硝唑代替阿莫西林，并與PPI和克拉霉素聯(lián)合使用（PPI-MC）。然而，原發(fā)性MR會(huì)降低其療效。鉍劑四聯(lián)療法是一個(gè)非常好的替代選擇（PPI-BTM）。如果上述兩種療法都失敗了，進(jìn)一步的選擇就很有限了。對(duì)于那些病史較久遠(yuǎn)、不確定的或不可能的青霉素過(guò)敏史的病人，如果有資源可用，可以進(jìn)行1型青霉素過(guò)敏的正式評(píng)估。這包括測(cè)量青霉素抗體，然后進(jìn)行皮膚點(diǎn)刺試驗(yàn)，如果陰性，則進(jìn)行監(jiān)督下的口服試驗(yàn)。當(dāng)在低風(fēng)險(xiǎn)患者中開展這項(xiàng)工作時(shí)，多達(dá)80%的此類患者被證明對(duì)青霉素不過(guò)敏，他們可以根據(jù)需要安全地使用含阿莫西林的治療方法（如果最初沒(méi)有使用克拉霉素，通常是PPI-AL或PPI-AC）。這樣的策略已被證明可以在大多數(shù)病人中成功地進(jìn)行根除治療。如果以前有明確的1型反應(yīng)史，則可假定為過(guò)敏，而不需要進(jìn)行測(cè)試。

8.4  Treatment pathways

8.4  治療途徑

In summary, in well-resourced regions in which local rates of CR and MR (and sometimes LR) are known, the evidence-based treatment choice in regions with lower CR is usually PPI-AC as the first line, with PPI-BTM or PPI-AL therapies as the second and third line, in either order. In regions with higher levels of CR, PPI-BTM may be used. B+PPI-AC or PPI-AL may be alternative first-line therapies. Second-line choices depend on what was used first: PPI-BTM or PPI-AL may be used if not used previously.

總之，在資源豐富的地區(qū)，當(dāng)?shù)氐腃R和MR（有時(shí)是LR）率是已知的，在CR較低的地區(qū)，基于證據(jù)的治療選擇通常是PPI-AC作為第一線，PPI-BTM或PPI-AL療法作為第二和第三線，順序不限。在CR水平較高的地區(qū)，可使用PPI-BTM。B+PPI-AC或PPI-AL可能是備選的一線療法。二線選擇取決于首先一線治療的方案。如果以前沒(méi)有使用過(guò)，可以使用PPI-BTM或PPI-AL。

In resource-poor regions in which community CR and MR have not been established or are known to be high, the choice of therapy is based on empirical audits of outcomes, an individual patient’s personal history of antibiotic exposure as monotherapy, known levels of community use of such drugs, availability and cost (Table 8). PPI-AC is still widely chosen with PPI-BTM or PPI-AL, or even nonbismuth quadruple therapies as alternative first-line or salvage therapies. However, when it is known that first-line therapy with clarithromycin results in poor outcomes, one of the other therapies described may be preferred. Data on the rates of levofloxacin resistance are sorely needed, as LR appears to be common in many regions, and the quality of some published data are uncertain. PPI-BTM quadruple therapy is therefore likely to be a good first and subsequent choice, as it avoids the issue of poor outcomes due to resistance. However, its use is sometimes limited by availability, compliance, and adverse effects. Whichever therapeutic pathway is chosen, it is crucial not to repeat the same therapy, as this is a very low-value strategy after first-line failure, due to secondary antibiotic resistance. The success rate for eradication with PPI-AC, for example, may be 80% or more in first-line treatment, but as low as 8% when the treatment is repeated after the first line has failed. Most of this is attributable to secondary CR. This practice is unfortunately still widespread in some places, but should be discouraged. Lastly, patients’ access to inexpensive generic medications and medical education continue to be significant challenges that need to be overcome in many regions.

在資源匱乏的地區(qū)，社區(qū)CR和MR尚未建立或已知較高的情況下，治療方法的選擇是基于對(duì)根除率的經(jīng)驗(yàn)性統(tǒng)計(jì)、個(gè)別病人作為單一療法接觸抗生素的個(gè)人藥物使用史、社區(qū)使用此類藥物的情況、可用性和成本（表8）。PPI-AC仍然被廣泛地選擇，并且PPI-BTM或PPI-AL，甚至非鉍劑四聯(lián)療法作為替代的一線或補(bǔ)救療法。然而，當(dāng)已知克拉霉素的一線治療根除率不佳時(shí)，可首選所述的其他療法之一。現(xiàn)在非常需要有關(guān)左氧氟沙星耐藥率的數(shù)據(jù)，因?yàn)長(zhǎng)R在許多地區(qū)似乎很普遍，而且一些已發(fā)表的數(shù)據(jù)的質(zhì)量也不確定。因此，PPI-BTM四聯(lián)療法可能是一個(gè)很好的首選和后續(xù)選擇，因?yàn)樗苊饬艘蚰退幎鴮?dǎo)致的根除率低的問(wèn)題。然而，其使用有時(shí)會(huì)受到可用性、依從性和不良反應(yīng)的限制。無(wú)論選擇哪種治療途徑，關(guān)鍵是不要重復(fù)相同的治療，因?yàn)樵谝痪€治療失敗后，由于繼發(fā)性抗生素耐藥，這是一個(gè)非常低價(jià)值的策略。例如，用PPI-AC根除的成功率在一線治療中可能是80%或更多，但在一線治療失敗后重復(fù)治療時(shí)，成功率低至8%。這其中大部分可歸因于繼發(fā)性CR。不幸的是，這種做法在一些地方仍然很普遍，但應(yīng)該加以阻止。最后，在許多地區(qū)，患者獲得廉價(jià)的非專利藥物和醫(yī)療教育仍然是需要克服的重大挑戰(zhàn)。

An appropriate pathway for choosing therapy is outlined in Fig. 4.

圖4中概述了選擇治療的適當(dāng)途徑。

8.5  The role of culture

8.5  藥敏培養(yǎng)的用途

Surveying H. pylori resistance patterns in order to define population prevalence and changes in prevalence will guide treatment choices. In some well-resourced countries, it is possible to tailor therapy on the basis of individual antimicrobial sensitivity testing of endoscopic biopsies prior to treatment. This is not the norm in clinical practice, however, and in any case, culture and subculture for resistance testing may fail in less expert laboratories. Moreover, much treatment is given in primary care, where noninvasive testing and treating is conducted. After treatment failure, antibiotic sensitivity testing from cultured biopsies is unlikely to play a major role in clinical decision-making. If clarithromycin has been used and failed, secondary CR is so common as to make testing for it unhelpful, and a different therapy should be chosen. Assessing MR is occasionally useful if PPI-AM might be an option, but it does not influence the choice of PPI-BTM, as that therapy is unaffected by MR. Levofloxacin is used empirically in most regions in which the prevalence of LR is known to be low. In addition, the in vitro sensitivity of H. pylori to other antibiotics does not imply therapeutic success, and ad hoc regimens should not be designed in this way.

調(diào)查幽門螺桿菌的耐藥性模式，以確定人口感染率和其變化，將指導(dǎo)治療選擇。在一些資源充足的國(guó)家，有可能在治療前對(duì)內(nèi)窺鏡活檢的個(gè)體抗生素敏感性測(cè)試的基礎(chǔ)上進(jìn)行個(gè)性化的治療。然而，這并不是臨床實(shí)踐中的常規(guī)做法，而且在任何情況下，用于耐藥性測(cè)試的培養(yǎng)和亞培養(yǎng)在不太專業(yè)的實(shí)驗(yàn)室里可能會(huì)失敗。此外，許多治療是在基礎(chǔ)保健中進(jìn)行的，并且在那里進(jìn)行無(wú)創(chuàng)檢測(cè)和治療。在治療失敗后，從培養(yǎng)的活體組織中進(jìn)行的抗生素敏感性測(cè)試不太可能在臨床決策中發(fā)揮重要作用。如果使用克拉霉素治療失敗，繼發(fā)性CR非常普遍，因此對(duì)其進(jìn)行檢測(cè)是無(wú)益的，應(yīng)選擇不同的治療。如果PPI-AM可能是一種選擇，評(píng)估MR或許是有用的，但它并不影響PPI-BTM的選擇，因?yàn)樵摨煼ú皇躆R的影響。左氧氟沙星在大多數(shù)地區(qū)都是經(jīng)驗(yàn)性使用，在這些地區(qū)已知LR很低。此外，幽門螺桿菌對(duì)其他抗生素的體外敏感性并不意味著治療的成功，不應(yīng)該以這種方式設(shè)計(jì)臨時(shí)性的治療方案。

If inexpensive point-of-care biopsy (or stool-based) molecular techniques (PCR) become widely available for rapid assessment of resistance, these may change practice by having a major impact on treatment selection. It is possible that such tests could replace urease tests by confirming the presence of infection and providing rapid antimicrobial resistance data to guide individualized therapy, at a cost only a little more than the current commercial urease tests. Stool-based tests would make it possible to carry out treatment tailored to the individual patient’s antimicrobial sensitivity in primary care, without the need for endoscopy.

如果點(diǎn)活檢（或基于糞便的）分子技術(shù)（PCR）可廣泛用于快速評(píng)估耐藥性，這些技術(shù)可能會(huì)改變實(shí)踐，對(duì)治療選擇產(chǎn)生重大影響。這種測(cè)試有可能取代尿素酶測(cè)試，確認(rèn)感染的存在，并提供快速的抗菌素耐藥性數(shù)據(jù)以指導(dǎo)個(gè)體化治療，其成本僅比目前的商業(yè)尿素酶測(cè)試高一點(diǎn)。基于糞便的測(cè)試將使在基礎(chǔ)保健中根據(jù)每個(gè)病人的抗生素敏感性進(jìn)行治療成為可能，而不需要進(jìn)行內(nèi)窺鏡檢查。

8.6  Compliance

8.6  依從性

Whichever therapy is prescribed, every effort must be made to maximize compliance. This means that the prescriber has to spend time with the patient to explain the importance of taking all of the therapy and not interrupting treatment. This is particularly important in regions in which regulations governing antibiotic use may be lax or not enforced, and where antibiotics can be obtained over the counter from pharmacies. Patients may buy drugs in small quantities for a day or two, with a risk of nonpersistence if symptoms are not immediately relieved or if any adverse effects occur. Clearly, the whole course of therapy should be prescribed and dispensed at the onset. Nuisance adverse effects—such as a transient taste disturbance, which is common with clarithromycin and metronidazole—should be anticipated and explained so that their occurrence does not lead to cessation of therapy. Providing printed material for dosage support and information has been found to be useful. As cigarette smoking is known to be an adverse predictive factor for the outcome, stopping smoking before and during therapy may improve outcomes, although this has not been well studied. Smoking cessation also aids ulcer healing. A role for probiotics in reducing adverse effects (and possibly improving outcomes) has been claimed, but this needs more and better-quality evidence.

無(wú)論開出哪種療法，都必須盡一切努力最大限度地提高依從性。這意味著處方者必須花時(shí)間與病人解釋接受所有治療和不中斷治療的重要性。這在抗生素使用規(guī)定可能不嚴(yán)格或不執(zhí)行的地區(qū)尤其重要，因?yàn)樵谶@些地區(qū)，抗生素可以從藥店的柜臺(tái)獲得。患者可以購(gòu)買少量的藥物用于一兩天的治療，如果癥狀沒(méi)有立即得到緩解或出現(xiàn)任何不良反應(yīng)，就有可能無(wú)法堅(jiān)持下去。顯然，整個(gè)療程應(yīng)該在發(fā)病時(shí)開出處方并配藥。應(yīng)預(yù)計(jì)到并解釋不良反應(yīng)，如克拉霉素和甲硝唑常見的短暫味覺(jué)障礙，以便其發(fā)生時(shí)不會(huì)導(dǎo)致治療的停止。為患者提供書面信息包括劑量和用藥信息已被發(fā)現(xiàn)是有用的。眾所周知，吸煙是一個(gè)不利于治療結(jié)果的預(yù)測(cè)因素，在治療前和治療期間停止吸煙可能會(huì)改善治療結(jié)果，盡管這還沒(méi)有得到很好的研究。戒煙也有助于潰瘍的愈合。有人聲稱益生菌在減少不良反應(yīng)（并可能改善結(jié)果）方面的作用，但這需要更多和更好質(zhì)量的證據(jù)。

8.7  After treatment

8.7  治療后

Ideally, outcome assessment should be carried out in all treated patients, although in practice this is not available in many places. When endoscopy has been conducted initially and gastric atrophy and/or intestinal metaplasia was identified, a decision needs to be made about endoscopic mucosal surveillance [27]. This may benefit individual patients, but an overall reduction in the mortality due to gastric cancer has yet to be clearly demonstrated. When focal high-grade gastric mucosal dysplasia is found, the areas may be removed endoscopically, but more advanced neoplasia requires surgery. Dysplasia may be detected using enhanced imaging, or by mapping biopsy specimens without discrete endoscopically visible lesions. These patients require endoscopic reassessment, preferably with image-enhanced and magnifying endoscopy, within 6 months for high-grade dysplasia and 12 months for low-grade dysplasia.

理想情況下，應(yīng)對(duì)所有接受治療的病人進(jìn)行根除結(jié)果評(píng)估，盡管在實(shí)踐中很多地方并不具備這種條件。當(dāng)最初進(jìn)行了內(nèi)鏡檢查，發(fā)現(xiàn)胃萎縮和/或腸化生時(shí)，需要決定進(jìn)行內(nèi)鏡下的粘膜監(jiān)測(cè)[27]。這可能會(huì)使個(gè)別患者受益，但胃癌導(dǎo)致的死亡率總體上的降低還沒(méi)有得到明確的證明。當(dāng)發(fā)現(xiàn)局灶性高等級(jí)胃粘膜異型增生時(shí)，可以通過(guò)內(nèi)鏡切除這些區(qū)域，但更高級(jí)的腫瘤需要手術(shù)。異型增生可使用增強(qiáng)成像技術(shù)檢測(cè)，或通過(guò)映射活檢標(biāo)本，但沒(méi)有內(nèi)鏡下可見的離散性病變。這些患者需要在內(nèi)鏡下重新評(píng)估，最好是用圖像增強(qiáng)和放大內(nèi)鏡，高級(jí)別異型增生在6個(gè)月內(nèi)，低級(jí)別異型增生在12個(gè)月內(nèi)。

As atrophy and intestinal metaplasia are common, endoscopic surveillance will consume considerable endoscopy resources and will have an opportunity cost against other health-care needs. Generally only higher risk-individuals are therefore usually offered surveillance. High risk usually means the presence of more extensive gastric mucosal changes (involving the antrum and body of the stomach) and/or a family history of gastric cancer. The ideal strategy has yet to be determined. Accurate endoscopic detection and characterization of mucosal changes requires specific training and modern endoscopes, as well as skilled pathologists.

由于萎縮和腸化生很常見，內(nèi)窺鏡監(jiān)測(cè)將占用大量的內(nèi)窺鏡資源，并對(duì)其他保健需求產(chǎn)生機(jī)會(huì)成本。因此，一般來(lái)說(shuō)，只有高風(fēng)險(xiǎn)個(gè)體才會(huì)被提供監(jiān)測(cè)。高風(fēng)險(xiǎn)通常意味著存在更廣泛的胃粘膜變化（涉及胃竇和胃體）和/或有胃癌家族史。理想的策略還沒(méi)有確定。準(zhǔn)確的內(nèi)窺鏡檢測(cè)和粘膜變化的特征需要特定的培訓(xùn)和現(xiàn)代內(nèi)窺鏡，以及熟練的病理學(xué)家。

9. Regional views for best-practice eradication therapy based on local data and resources

9. 基于當(dāng)?shù)財(cái)?shù)據(jù)和資源的最佳實(shí)踐根除療法的區(qū)域觀點(diǎn)

9.1  Australia

9.1  澳大利亞

Low rates of clarithromycin resistance (6–8%) and high rates of metronidazole resistance (45–50%) have been reported in Australia. Data on levofloxacin are sparse, but primary resistance seems to be very low, with the possible exception of rates in migrants from high-resistance regions. As a result, standard triple therapy with PPI, amoxicillin, and clarithromycin is still the recommended first-line therapy, unless and until evidence of rising clarithromycin resistance emerges. Reported 7-day eradication rates are 80–87%. Fourteen-day therapy has not been studied formally. Salvage therapies include levofloxacin triple therapy for 10 days (eradication rate 80–90%) and standard-dose quadruple therapy (PPI, bismuth, tetracycline, and metronidazole) for 7–14 days, with similar outcomes. Levofloxacin, tetracycline, and bismuth are not registered locally, so are not often used in first-line therapy. These drugs have to be obtained via a special-access scheme from abroad, or via compounding pharmacies, when required for salvage treatments. Rifabutin triple therapy has been used less commonly (76% eradication). Concomitant therapies have not been studied locally.

在澳大利亞，克拉霉素耐藥率低（6-8%），甲硝唑耐藥率高（45-50%）。有關(guān)左氧氟沙星的數(shù)據(jù)很少，原發(fā)性耐藥性似乎很低，但來(lái)自高耐藥性地區(qū)的移民中的耐藥率可能例外。因此，PPI、阿莫西林和克拉霉素的標(biāo)準(zhǔn)三聯(lián)療法仍然是推薦的一線療法，除非出現(xiàn)克拉霉素耐藥性上升的證據(jù)。據(jù)報(bào)道，7天的根除率為80-87%。14天的治療還沒(méi)有正式研究過(guò)。補(bǔ)救治療包括左氧氟沙星三聯(lián)療法10天（根除率為80-90%）和標(biāo)準(zhǔn)劑量四聯(lián)療法（PPI、鉍劑、四環(huán)素和甲硝唑）7-14天，其結(jié)果相似。左氧氟沙星、四環(huán)素和鉍劑沒(méi)有在當(dāng)?shù)刈?cè)，所以不常被用于一線治療。這些藥物必須通過(guò)特別準(zhǔn)入計(jì)劃從國(guó)外獲得，或者在需要進(jìn)行補(bǔ)救治療時(shí)通過(guò)復(fù)合藥房獲得。利福布汀三聯(lián)療法使用得不太普遍（76%的根除率）。當(dāng)?shù)剡€沒(méi)有研究過(guò)伴隨療法。

9.2  Pacific region

9.2  太平洋地區(qū)

There is currently a lack of local resistance data, and there are few systematic data for assessing the outcome of therapy. The choice of therapy is therefore usually extrapolated from international guidelines and determined by drug availability. Clarithromycin triple therapy is commonly chosen, with PPI and amoxicillin or metronidazole, despite a clinical suspicion of high MR affecting the efficacy of the latter. Cost, availability, local expertise, and adherence to therapy are all barriers to effective treatment. There are no audited salvage therapy data. Ad hoc therapies and repeat clarithromycin therapy after first-line failure are discouraged.

目前缺乏當(dāng)?shù)氐哪退幮詳?shù)據(jù)，也沒(méi)有什么系統(tǒng)的數(shù)據(jù)來(lái)評(píng)估治療的結(jié)果。因此，治療方法的選擇通常是從國(guó)際指南中推斷出來(lái)的，并由藥物的可用性決定。通常選擇克拉霉素三聯(lián)療法，加上PPI和阿莫西林或甲硝唑，盡管臨床上懷疑高M(jìn)R影響了后者的療效。成本、可得性、當(dāng)?shù)氐膶I(yè)知識(shí)和對(duì)治療的堅(jiān)持都是有效治療的障礙。沒(méi)有經(jīng)過(guò)審查的補(bǔ)救治療數(shù)據(jù)。不鼓勵(lì)在一線治療失敗后采取臨時(shí)性治療和重復(fù)的克拉霉素治療。

9.3  Southeast Asia

9.3  東南亞

There is good evidence that amoxicillin and tetracycline resistance is low and stable ( 90%. Second-line regimens should contain antibiotics not used previously, or those against which resistance is unlikely to develop, such as amoxicillin or tetracycline. PPI-BTM should be considered if it has not yet been used. Rifabutin should not be considered in regions with a high prevalence of Mycobacterium tuberculosis. If eradication treatment fails after a second attempt, antibiotic susceptibility tests should be considered.

有很好的證據(jù)表明，阿莫西林和四環(huán)素的耐藥性較低且穩(wěn)定（<5%），但MR普遍較高（30-100%）。CR一直在增加，但在東南亞國(guó)家中差異很大（從2%到43%不等）。對(duì)于大多數(shù)治療方案，應(yīng)使用14天的療程，除非當(dāng)?shù)赜凶C據(jù)證明較短療程的可靠根除率。理想情況下，由于各國(guó)的抗生素耐藥性差異很大，應(yīng)根據(jù)當(dāng)?shù)氐目股啬退幝蕘?lái)考慮一線治療方案。據(jù)報(bào)道，PPI-BTM的成功率一直高于90%。二線治療方案應(yīng)包含以前沒(méi)有使用過(guò)的抗生素，或那些不太可能產(chǎn)生耐藥性的抗生素，如阿莫西林或四環(huán)素。如果尚未使用過(guò)PPI-BTM，應(yīng)考慮使用。在結(jié)核分枝桿菌高發(fā)的地區(qū)不應(yīng)考慮使用利福布汀。如果在第二次嘗試后根除治療失敗，應(yīng)考慮進(jìn)行抗生素藥敏試驗(yàn)。

9.4  Eurasia

9.4  歐亞大陸

On the basis of a pilot study, the prevalence of H. pylori seropositivity among healthy adults in Armenia is 41.5%, increasing with age (13.6% in the 18–25-year-old age group and 83.3% in those aged over 65). The rate of resistance to clarithromycin in 2018 was as low as 3.6%, and to fluoroquinolones 12.8%. However, new research is warranted, especially during the COVID-19 pandemic when there has been an unprecedented increase in the number of prescriptions for macrolides and respiratory fluoroquinolones by primary-care providers in the country. Tetracycline is only available in 100-mg tablets, making conventional quadruple regimen highly inconvenient. Local recommendations that are adapted from the Maastricht guidelines propose 14-day clarithromycin triple therapy as the first-line treatment and a modified bismuth quadruple therapy (PPI, bismuth, amoxicillin, and metronidazole) as an alternative first-line therapy. Second-line options include triple or quadruple treatment with levofloxacin. None of the eradication regimens has been studied locally for efficacy.

根據(jù)一項(xiàng)試點(diǎn)研究，亞美尼亞健康成年人中幽門螺桿菌血清陽(yáng)性率為41.5%，隨年齡增長(zhǎng)而增加（18-25歲年齡組為13.6%，65歲以上為83.3%）。2018年對(duì)克拉霉素的耐藥率低至3.6%，對(duì)氟喹諾酮的耐藥率為12.8%。然而，新的研究是有必要的，特別是在COVID-19大流行期間，該國(guó)初級(jí)醫(yī)療保健提供者對(duì)大環(huán)內(nèi)酯類和呼吸道氟喹諾酮類藥物的處方數(shù)量空前增加。四環(huán)素只有100毫克的藥片，這使得傳統(tǒng)的四聯(lián)療法非常不方便。改編自馬斯特里赫特指南的當(dāng)?shù)亟ㄗh提出將14天的克拉霉素三聯(lián)療法作為一線治療，并將改良的鉍劑四聯(lián)療法（PPI、鉍劑、阿莫西林和甲硝唑）作為備選一線療法。二線選擇包括左氧氟沙星的三聯(lián)或四聯(lián)療法。這些根除方案都沒(méi)有在當(dāng)?shù)剡M(jìn)行過(guò)療效研究。

9.5  Western Europe

9.5  西歐

CR is highly relevant for the selection of first-line therapy. This varies among and within European countries. Monitoring of antibiotic resistance is therefore still essential at the population level. Recent European registry data, from > 30,000 patients in 27 countries [28], indicated pretreatment resistance rates of 23% for clarithromycin, 32% for metronidazole, and dual resistance in 13%. There is a dichotomy, with lower CR in central and northern Europe; in Germany, primary CR is still below the cut-off level of 15%. Triple therapy with amoxicillin and clarithromycin for 14 days is still effective in these conditions and is commonly used as first-line treatment. In areas where primary CR is > 15%, bismuth quadruple treatments for 10 days (or 14 days if components of this regimen are administered individually) is recommended as first-line treatment. Concomitant therapy, which includes three antibiotics instead of the two used in the bismuth-based quadruple treatment, is unpopular in most countries. Metronidazole in PPI triple therapies has been mostly abandoned and is now reserved for individual cases (e.g., in cases of amoxicillin allergy or proven susceptibility to metronidazole).

CR對(duì)于選擇一線治療是高度相關(guān)的。這在歐洲國(guó)家之間和內(nèi)部都有差異。因此，對(duì)抗生素耐藥性的監(jiān)測(cè)在人群層面上仍然是至關(guān)重要的。最近的歐洲注冊(cè)數(shù)據(jù)，來(lái)自27個(gè)國(guó)家的3萬(wàn)多名患者[28]，表明克拉霉素的原發(fā)耐藥率為23%，甲硝唑?yàn)?2%，13%的患者有雙重耐藥性。中歐和北歐的CR較低；在德國(guó)，原發(fā)CR仍低于15%的臨界水平。用阿莫西林和克拉霉素進(jìn)行為期14天的三聯(lián)療法在這些情況下仍然有效，通常被用作一線治療。在原發(fā)性CR>15%的地區(qū)，建議將鉍劑四聯(lián)療法作為一線治療，持續(xù)10天（或14天，如果該方案的組成部分單獨(dú)使用）。在大多數(shù)國(guó)家，包括三種抗生素而不是鉍劑四聯(lián)療法中使用的兩種抗生素的聯(lián)合療法是不受歡迎的。PPI三聯(lián)療法中的甲硝唑大多已被放棄，現(xiàn)在只保留給個(gè)別病例（如對(duì)阿莫西林過(guò)敏或證實(shí)對(duì)甲硝唑敏感的病例）。

Increasing resistance to levofloxacin has excluded this antibiotic as a component in any first-line regimen. Its use is becoming increasingly worrisome, even if it is used as second-line treatment. Rifabutin is effective in third-line treatment and is recommended as a component of a rescue regimen after repeated treatment failure.

對(duì)左氧氟沙星的耐藥性不斷增加，使這種抗生素被排除在任何一線治療方案的組成部分之外。它的使用正變得越來(lái)越令人擔(dān)憂，即使它被用作二線治療。利福布汀在三線治療中是有效的，并被推薦作為反復(fù)治療失敗后挽救方案的一個(gè)組成部分。

European recommendations put the emphasis on testing (13C-UBT) for assessing the individual treatment response. Resistance testing of the commonly used antibiotics is encouraged after treatment failures.

歐洲的建議把重點(diǎn)放在檢測(cè)（13C-UBT）上以評(píng)估個(gè)體治療反應(yīng)。鼓勵(lì)在治療失敗后對(duì)常用的抗生素進(jìn)行耐藥性檢測(cè)。

9.6  Southern Europe

9.6  南歐

Rising antibiotic resistance is the main issue. Pretreatment antibiotic susceptibility for clarithromycin should be determined before first-line treatment, but is not currently feasible for most patients. The choice of treatment is therefore based on the local prevalence of CR. However, this information is lacking in most regions of Italy; high prevalence (30%) has been reported in some central and southern regions. A 10- or 14-day bismuth-based quadruple therapy or nonbismuth concomitant quadruple therapy is recommended as the first-line treatment when CR is > 15% or unknown. The efficacy of these two regimens is not affected by CR or MR, and bismuth-based quadruple therapy performs well when there is dual resistance. Thus, bismuth quadruple therapy may be considered the best choice for empirical first-line treatment in Italy.

抗生素耐藥性的上升是主要問(wèn)題。在一線治療前應(yīng)確定克拉霉素的抗生素敏感性，但目前對(duì)大多數(shù)患者來(lái)說(shuō)是不可行的。因此，治療的選擇是基于當(dāng)?shù)谻R的耐藥情況。然而，在意大利的大多數(shù)地區(qū)缺乏這方面的信息；在一些中部和南部地區(qū)有高耐藥率（30%）的報(bào)道。當(dāng)CR>15%或未知時(shí)，建議采用10天或14天的鉍劑四聯(lián)療法或非鉍劑四聯(lián)療法作為一線治療。這兩種方案的療效不受CR或MR的影響，當(dāng)存在雙重耐藥時(shí)，鉍基四聯(lián)療法表現(xiàn)良好。因此，鉍劑四聯(lián)療法可被認(rèn)為是意大利經(jīng)驗(yàn)性一線治療的最佳選擇。

The standard triple therapy—PPI plus clarithromycin and amoxicillin or metronidazole/tinidazole—is effective in clarithromycin-sensitive strains, but fails when there is CR. A 14-day standard triple therapy should be used as the first-line treatment only in areas with a known low prevalence of CR (< 15%), in patients without previous use of macrolides, or in areas where this regimen has been proven to achieve high eradication rates.

標(biāo)準(zhǔn)三聯(lián)療法--PPI加克拉霉素和阿莫西林或甲硝唑/替硝唑--對(duì)克拉霉素敏感菌株有效，但當(dāng)出現(xiàn)CR時(shí)就失效了。只有在已知CR較低（<15%）的地區(qū)、以前沒(méi)有使用過(guò)大環(huán)內(nèi)酯類藥物的患者，或在該方案已被證明能達(dá)到高根除率的地區(qū)，才應(yīng)將14天標(biāo)準(zhǔn)三聯(lián)療法作為一線治療。

Sequential therapy, with PPI plus amoxicillin for 5–7 days followed by PPI plus metronidazole and clarithromycin for 5–7 days, is a regimen designed to overcome the issue of clarithromycin resistance. However, data concerning its efficacy are contradictory. Recent guidelines have discouraged its use, despite some reports from Italy of eradication rates around 90%, even with CR. Second-line treatments include levofloxacin-containing triple therapy and bismuth quadruple therapy. Probiotic supplementation may be used in order to reduce antibiotic-related adverse events.

序貫治療，即PPI加阿莫西林5-7天，然后是PPI加甲硝唑和克拉霉素5-7天，這是一種旨在克服克拉霉素耐藥問(wèn)題的方案。然而，有關(guān)其療效的數(shù)據(jù)是相互矛盾的。盡管來(lái)自意大利的一些報(bào)告指出，即使在CR情況下其根除率也在90%左右，但最近的指南還是不鼓勵(lì)使用該方案。二線治療包括含左氧氟沙星的三聯(lián)療法和鉍劑四聯(lián)療法。為了減少抗生素相關(guān)的不良事件，可以使用益生菌補(bǔ)充劑。

9.7  North America

9.7  北美

North America has variable clarithromycin resistance (17–32% in different studies) and high metronidazole resistance (44%). Amoxicillin resistance was reported to be 6% in a recent study, and rifabutin resistance was 0%. U.S. guidelines recommend that for first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who live in areas in which clarithromycin resistance against H. pylori isolates is known to be low. Some suburban and rural areas of the country meet these criteria. First-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole is recommended as first-line therapy in most areas. A combination of rifabutin, amoxicillin, and omeprazole has been approved for H. pylori treatment in the United States. Its role in initial therapy remains to be determined.

北美的克拉霉素耐藥性不一（在不同的研究中為17-32%），甲硝唑耐藥性高（44%）。在最近的一項(xiàng)研究中，阿莫西林的耐藥性被報(bào)道為6%，利福布汀的耐藥性為0%。美國(guó)指南建議，對(duì)于一線治療，克拉霉素三聯(lián)療法應(yīng)限于以前沒(méi)有大環(huán)內(nèi)酯類藥物接觸史、居住在已知克拉霉素對(duì)幽門螺桿菌分離物耐藥性較低的地區(qū)的患者。一些郊區(qū)和農(nóng)村地區(qū)符合這些標(biāo)準(zhǔn)。在大多數(shù)地區(qū)，推薦使用鉍劑四聯(lián)療法或由PPI、克拉霉素、阿莫西林和甲硝唑組成的聯(lián)合療法作為一線治療。在美國(guó)，利福布汀、阿莫西林和奧美拉唑的組合已經(jīng)被批準(zhǔn)用于治療幽門螺桿菌。它在初次治療中的作用還有待確定。

9.8  South and Central America

9.8  南美洲和中美洲

Studies on clarithromycin resistance in South and Central America remain sparse, with some reported rates already exceeding 20%. The highest prevalences are described in Mexico, Colombia, Argentina, and Brazil. The indiscriminate use of azithromycin (a low-cost drug) may select macrolide-resistant mutants and aggravate CR rates. Low resistance rates for amoxicillin have been documented, but some studies show a high percentage in Brazil. If this trend is confirmed, it would be an alarming situation, due to the central role of these antibiotic therapies.

對(duì)南美洲和中美洲的克拉霉素耐藥性的研究仍然很少，一些報(bào)告的耐藥率已經(jīng)超過(guò)20%。墨西哥、哥倫比亞、阿根廷和巴西的耐藥率最高。濫用阿奇霉素（一種低成本的藥物）可能會(huì)選擇性導(dǎo)致大環(huán)內(nèi)酯耐藥突變，加劇CR率。有文獻(xiàn)記載，阿莫西林的耐藥率很低，但一些研究顯示巴西的耐藥率很高。如果這一趨勢(shì)得到證實(shí)，由于這些抗生素療法的核心作用，這將是一個(gè)令人震驚的情況。

The classic triple regimen with PPI, amoxicillin, and clarithromycin for 7–14 days is still the most widely used regimen, followed by bismuth quadruple therapy as an alternative or second-line therapy and levofloxacin-based therapy as a salvage option. Resistance to levofloxacin is reported to be scarce, but high levels have been described in Peru. The associated use of metronidazole is common for first-line quadruple therapy, but the reported prevalence of resistance is above 50% in Central America, Mexico, and in some countries in South America such as Brazil and Colombia.

經(jīng)典的三聯(lián)療法包括PPI、阿莫西林和克拉霉素，為期7-14天，仍然是最廣泛使用的方案，其次是鉍劑四聯(lián)療法作為替代或二線療法，以及以左氧氟沙星為基礎(chǔ)的療法作為挽救方案。據(jù)報(bào)道，對(duì)左氧氟沙星的耐藥性很少，但在秘魯已經(jīng)有高水平的描述。甲硝唑的相關(guān)使用在一線四聯(lián)療法中很常見，但在中美洲、墨西哥以及南美洲的一些國(guó)家，如巴西和哥倫比亞，報(bào)告的耐藥率超過(guò)50%。

Recurrence rates of more than 3–5% per annum, with geographic variability, have been reported; data are lacking from many regions. Barriers that need to be overcome include the cost of medication, improving adherence to guidelines by physicians, a lack of UBTs in many regions, unavailability of bismuth salts, furazolidone, and rifabutin in some countries, and an absence of high-quality local studies to validate anti-H. pylori regimens. Most health-care systems in the region are still operating suboptimally on these issues.

據(jù)報(bào)道，每年的復(fù)發(fā)率超過(guò)3-5%，而且在地域上存在差異；許多地區(qū)缺乏數(shù)據(jù)。需要克服的障礙包括藥物治療的費(fèi)用，提高醫(yī)生對(duì)指南的遵守程度，許多地區(qū)缺乏UBT，一些國(guó)家沒(méi)有鉍鹽、呋喃唑酮和利福布汀，以及缺乏高質(zhì)量的本地研究來(lái)驗(yàn)證幽門螺桿菌根除療法。該地區(qū)的大多數(shù)衛(wèi)生保健系統(tǒng)在這些問(wèn)題上的運(yùn)作仍不盡如人意。

10 Abbreviations used in this WGO guideline

參考文獻(xiàn)：