【重磅】世界胃肠病学组织全球指南：幽门螺杆菌

World Gastroenterology Organisation Global Guidelines：Helicobacter pylori

世界胃肠病学组织全球指南：幽门螺杆菌

中国幽门螺杆菌分子医学中心（CCHpMM）

钟子劭、徐包慧 I 译

郜恒骏 I 审校   

来源：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.

幽门螺杆菌仍然是世界范围内的一个主要健康问题，由于消化性溃疡病和胃癌导致了相当高的发病率和死亡率。

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.

疾病的负担不成比例地落在资源不足的人群身上。与大多数传染病一样，对减少这种负担的最大影响来自于社会经济地位的改善，以阻断传播。在世界许多地区已经观察到了这一点，但在许多生活水平改善缓慢的地区，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.

同时，最佳的临床管理和治疗路径仍未确定，并随着抗生素耐药性模式的变化而不断发展。尽管经过几十年的研究和临床实践，重大挑战依然存在。寻求最有效、最安全、最简单的疗法仍然是临床医生面临的主要问题。一种有效的疫苗似乎也仍然遥不可及。

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.

临床指南经常提供不一致的建议。指南很难在具有不同疾病谱、抗生素耐药率和巨大的资源差异的各种人群中实现一致性。由于地区因素是决定幽门螺杆菌感染的影响和管理策略的核心，因此，重要的是，治疗方案应基于现有的最佳当地认识，而不是仅仅从其他地区制定的指南中推断出来，因为这些指南可能不太适用。为此，本次修订的WGO幽门螺杆菌指南采用了 '级联 '方法，旨在总结管理原则，并根据既定的关键治疗原则，利用当地知识和现有资源指导地区实践，为务实、相关和可实现的诊断和治疗路径提供建议。

2.  Introduction

2.  介绍

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.

近四十年来，幽门螺杆菌被认为是人类的主要病原体。然而，尽管对感染者的治疗产生了影响，而且在社会经济生活水平提高的社区，幽门螺杆菌的传播也有所减少，但它仍然是最常见的人类细菌病原体，可能感染了世界上一半的人口[1]。因此，它仍然是全世界发病和死亡的一个主要原因。

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.

幽门螺杆菌感染总是会引起慢性活动性胃炎。在大多数人中，这可能在临床上终生无症状，但在相当少的人中，它引起胃十二指肠疾病，包括最重要的消化性溃疡病、非贲门胃癌和胃粘膜相关淋巴组织（MALT）淋巴瘤。它还增加了正在服用非甾体抗炎药（NSAIDs）如阿司匹林的病人的胃十二指肠溃疡和出血的风险，并且是造成一部分功能性消化不良病人症状的原因。

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.

幽门螺杆菌已经得到了深入的研究。搜索显示有超过45,000份研究相关文献。在幽门螺杆菌感染的流行病学、生物学、遗传学、病理生理学、疾病表达、诊断和治疗方面已经有了很大的了解。然而，我们的知识仍有很大差距。尽管许多流行病学研究确定了感染的风险因素，但感染的确切传播方式仍不清楚。疾病表达的决定因素仍未完全了解，包括宿主-病原体相互作用的许多方面。这种相互作用的病理生理学是复杂的，已在其他地方进行了详细回顾[2,3]。在不同的环境下，最佳的临床管理方法仍然是一个争论不休的问题，且还在继续寻求诊断方式的改进。追求最有效、最安全、最简单的治疗方法仍然是临床医生的主要问题，而抗生素耐药对治疗的问题也是一个重大挑战。监测胃粘膜不良组织学变化的最佳方法尚未确定，对有效疫苗的探索也在进行。

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.

目前已经有很多关于幽门螺杆菌的评论和临床指南[4-12]。由于该领域变化迅速，有必要定期更新和修订这些立场文件。此外，指南很难在具有不同疾病谱的各种人群中实现相关性，而且通常具有处理疾病的巨大不同资源。指南经常提供不一致的建议。由于地区因素是决定幽门螺杆菌感染的影响和管理策略的核心，这并不令人惊讶。重要的是，临床建议应以当地的最佳数据为基础，而不是从其他地区制定的指南中推断出来，因为这些指南可能不太适用。然而，在幽门螺杆菌感染影响最大的许多地区，缺乏高质量的数据来确定当地的最佳做法。解决这一知识差距是一个重大挑战。同时，幽门螺杆菌治疗管理策略需要根据现有的最佳当地证据、其他地方的高质量数据的推断和专家意见来做出决定。

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.

这次更新WGO指南的目的是总结和回顾一些新指南的证据，这些指南概述了最佳做法，并建议如何利用 '级联 '方法在世界各地应用这些原则。这种方法认识到各地区感染的流行程度和影响的差异，以及可用于解决该问题的卫生资源的巨大差异，这就要求采取务实的、适合当地的方法。幽门螺杆菌造成的疾病负担不成比例地落在资源不足的地区，而这些地区在流行病学调查中的代表性不足，往往不是临床指南的重点。

”

Key statement

It is a major challenge for guidelines to achieve relevance across a wide variety of populations with varying spectrums of disease and with vastly different resources with which to deal with it.

关键陈述

对于指南来说，如何在不同的人群中实现相关性是一个重大的挑战，这些人群有着不同的疾病谱，而且处理疾病的资源也大不相同。

3.  Natural history, transmission and epidemiology—global aspects

3. 自然历史、传播和流行病学-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.

幽门螺杆菌感染通常会持续终身，除非用抗生素治疗，或者当长期感染导致广泛的胃粘膜萎缩和肠化并伴有胃酸缺乏症时发生自身消除。一些婴儿可能发生短暂的感染。无论在高发地区还是低发地区成人治疗后的再感染都不常见。再感染可能与复发相混淆，复发是指感染被暂时抑制，低于检测的阈值，但没有被抗生素所根除。在全球范围内，不同的幽门螺杆菌菌株的毒力存在差异。宿主和环境因素之间的相互作用可能导致疾病表现的差异。

3.2  Transmission of infection

3.2  感染的传播

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.

虽然有很好的感染风险因素和合理的假说，但确切的传播方式还没有明确的确定。大多数感染似乎发生在儿童早期，少数病例发生在成人。流行病学和遗传学研究有强有力的证据表明幽门螺杆菌存在人与人之间的传播，特别是在家庭内部。母亲似乎在传染给其年幼子女方面特别重要。通过胃-口或口-口途径传播该生物体似乎是最合理的。粪口传播似乎不太可能，至少在发达国家是这样。幽门螺杆菌是否通过水、食物、家庭宠物或苍蝇传播，仍然是一个猜测的问题。

3.3  Epidemiology

3.3  流行病学

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.

尽管世界上有一半的人口被认为感染了幽门螺杆菌，但在国家之间和国家内部，感染率存在着广泛的差异（图1）。此外，在一个城市内，以及在一个人口的亚群之间，感染率也会有所不同（图2）[13]。例如，较富裕的城市人口和农村人口之间的患病率可能有很大差异。

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].

患病率数据的质量各不相同。许多研究不是真正的流行病研究，而是对临床子集的审核。其他研究可能不代表有效的人口横断面。此外，报告的质量也有很大差异。在一些地区，诊断方法可能不太可靠，而一些国家由于根本没有任何可靠的数据，所以代表性很差。由于所有这些原因，不能用一个数字来概括和代表整个国家的感染率，必须谨慎。例如，在一个人口众多、社会经济水平差异很大的多民族国家的一个地区的一个城市的流行率研究，不太可能代表整个国家的真实流行率，也不能反映高风险和低风险的子集。然而，国家和地区通常可以被描述为高发区、中发区和低发区[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.

感染率的主要决定因素是儿童时期的社会经济因素。社会经济因素反映了卫生、环境卫生、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.

一直以来，都有强负关系的报道。因此，正如预期的那样，发展中国家的感染率普遍较高，而且在一些人口资源最匮乏的人群中，感染几乎普遍存在。来自这些地区的移民被认为是较发达的低发病率国家的高风险群体。

”

Key statement

The major determinant of the prevalence of infection is socioeconomic status in childhood.

关键陈述

感染率的主要决定因素是儿童时期的社会经济地位。

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.

幽门螺杆菌感染的流行率随着年龄的增长而增加。这主要是由于队列效应，即那些出生时间较久的人在童年时期获得感染的风险比最近出生的人要大，而不是反映正在进行的成人感染。种族被认为是一个风险因素，但很可能与社会经济地位或可能增加传播风险的做法密切相关，而不是具有遗传基础。

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.

一个引人注目的现象是一些国家的感染率随时间的推移而变化。发达国家和经历了快速经济发展导致社会经济标准提高的国家普遍报告幽门螺杆菌感染率迅速下降，在儿童和年轻成人中最为明显。在这些国家，现在的感染率很低。

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.

根据这一观察，消化性溃疡病和非贲门胃癌的发病率会逐渐下降，因为一般来说，消化性溃疡病和胃癌的发病率反映了幽门螺杆菌在人群中的流行情况。事实上，几十年来，发达国家的溃疡病和胃癌的发病率一直在下降。通常疾病表达的下降滞后于感染率的下降很多年。感染率和疾病的下降早在幽门螺杆菌被认识和治疗方法被开发之前就发生了。

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.

与大多数地方性传染病一样，流行率的下降更多的是与人口卫生和环境卫生的改善有关，而不是与个别的、单个病例治疗有关，因为在大多数国家，只有少数感染者会接受治疗。值得注意的例外是资源丰富的高发病率国家，如日本，已在年轻人中开展系统性的筛查和治疗。在那些标准没有改善甚至更加恶化的国家，感染率似乎是稳定的，而且在出现改善之前，感染率不太可能大幅下降。在其中许多国家，消化性溃疡病仍然很猖獗。胃癌的负担也不成比例地落在这些人口身上。

”

Key statement

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.

关键陈述

与大多数地方性传染病一样，流行率的下降更多的是与人口卫生和环境卫生的改善有关，而不是与个别的、单个病例治疗有关，因为在大多数国家，只有少数感染者会接受治疗。

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

4.  幽门螺杆菌感染的影响和根除的效果

4.1  H. pylori and peptic ulcer disease

4.1  幽门螺杆菌和消化性溃疡病

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.

认识到幽门螺杆菌是大多数十二指肠溃疡和大约三分之二的胃溃疡的原因，是一个具有开创性的、获得诺贝尔奖的医学突破[14]。在许多发达国家，随着感染率的下降和溃疡患者的治愈，所有消化性溃疡中由幽门螺杆菌引起的比例正在下降。在欠发达国家，感染率仍然很高，溃疡病患者接受治愈性治疗的人数较少，消化性溃疡病（PUD）仍然是一种非常普遍和重要的疾病。据估计，幽门螺杆菌感染使个体一生中患消化性溃疡病的风险增加15-20%。如果不加以治疗，PUD作为一种慢性复发和缓解的疾病，会引起疼痛、出血和穿孔而导致主要的死亡率和发病率。它还会导致经济损失。根除幽门螺杆菌可以治愈大多数活动性消化性溃疡，防止进一步复发，从而达到治愈的效果。在有溃疡病史的病人中根除幽门螺杆菌可以防止以后复发。

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.

非甾体抗炎药和阿司匹林会导致大多数其他的消化性溃疡。幽门螺杆菌和NSAIDs协同作用，增加溃疡和出血的风险。在开始长期NSAID治疗之前，根除幽门螺杆菌可以减少这种风险。

4.2  H. pylori and gastric cancer and MALT lymphoma

4.2  幽门螺杆菌与胃癌和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，长期慢性活动性胃炎可能导致胃粘膜萎缩并伴有肠化生。在少数情况下，这些恶性肿瘤前的粘膜病变会发展成异型增生和临床上无症状的早期癌症，然后是晚期胃癌。胃癌常常在晚期、有症状阶段被诊断出，而且预后一般较差。据估计，在感染者中，幽门螺杆菌使个人终生患胃癌的风险为1.5-2.0%。尽管个人风险相对较低，但由于全球感染者的数量估计有数十亿，因此全球每年有超过一百万的胃癌负担，而且死亡率很高（表1）[15]。这种负担并不是平均分布的。东亚--日本、韩国和中国东部--疾病的发病率最高。中国的胃癌病例占世界的40%。大多数（但不是所有）胃癌都与幽门螺杆菌有关。进展为胃癌的风险各不相同，与宿主和病原体因素有关。宿主的辅助因素包括吸烟和饮食。高盐摄入、食用腌制食品和低抗氧化剂的饮食是饮食的辅助因素。宿主中与风险增加有关的遗传风险因素包括决定白细胞介素-1（IL-1；促炎症细胞因子）和病原体识别受体表达的基因存在多态性。幽门螺杆菌菌株的基因分型显示了促进炎症的毒力因素的差异，与癌症风险的增加有关。

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.

在出现不良的癌前组织学变化之前根除幽门螺杆菌已被证明可以预防胃癌，这也是在疾病负担重且有足够资源投入这项工作的国家对年轻成年人进行大规模检测和治疗筛查的理由。在资源较少、胃癌负担较重的地区，考虑到成本限制、后勤困难和相互竞争的医疗需求，这样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.

在粘膜萎缩和/或肠化生形成后，根除幽门螺杆菌可能会降低胃癌的风险，但并不能消除它[16]。在任何个体中，残留的风险与粘膜变化的范围和严重程度以及其他宿主风险因素有关。在某些情况下，内镜监测肠化生可能是合适的。

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.

胃粘膜相关淋巴组织（MALT）淋巴瘤是罕见的。大多数病例是幽门螺杆菌感染的结果，当淋巴瘤处于低级阶段时，根除幽门螺杆菌会导致淋巴瘤消退和治愈。偶尔也有根除后晚期复发的报道。

”

Key statement

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.

关键陈述

在发生不利的、癌前组织学变化之前根除幽门螺杆菌已被证明可以预防胃癌，这也是在疾病负担较重且有足够资源投入这项工作的国家对青壮年进行大规模检测和治疗筛查计划的理由。

4.3  H. pylori–associated dyspepsia

4.3  幽门螺杆菌相关的消化不良

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.

大多数幽门螺杆菌胃炎是无症状的，但是在没有溃疡病的情况下，它通常与上消化道症状有关。然而，只有大约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疗后症状会持续缓解。这是因为功能性消化不良是一种异质性的疾病，可能由不同的机制引起。幽门螺杆菌在一些有症状的病人中可能是因果关系，而在其他病人中症状可能是偶然出现的。然而，经过根除治疗后，受感染的病人中改善的比例要大于那些接受经验性抑酸治疗的病人。此外，患者可能受益于溃疡病和癌症的终生风险降低，特别是如果他们在胃粘膜出现不良组织学变化之前就接受治疗。

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.

最近修订的胃炎分类将幽门螺杆菌相关的消化不良作为一个独立的实体，并被纳入《国际疾病分类》第11版（ICD-11）[11]。该分类还强调了幽门螺杆菌胃炎作为导致消化性溃疡病和胃癌的癌前病变的意义，而不论是否存在症状。

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.

幽门螺杆菌感染与其他各种疾病有关。在大多数情况下，这种关联并没有被证明是因果关系，共同的疾病将不可避免地在一些病人身上并存。有适度的证据表明幽门螺杆菌与免疫性血小板减少性紫癜有关，而且已经尝试过根除疗法，但效果不一。

5.  Diagnosis of H. pylori infection

5.  幽门螺杆菌感染的诊断

5.1  Who to test and treat?

5.1  谁需要检测和治疗？

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.

是否治疗幽门螺杆菌必须是一个积极的决定，要考虑到患者个人的情况和风险。因此，检测幽门螺杆菌的决定只应出于治疗的目的。

”

Good practice point

The decision to test for H. pylori should only be made with therapeutic intent.

良好实践要点

只有在有治疗意图的情况下，才能决定是否检测幽门螺杆菌。

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总结了检测和治疗幽门螺杆菌的循证适应症[4,17]。每个适应症在不同地区的适用性取决于感染和疾病的流行程度、资源、竞争性需求和患者个体因素。消化性溃疡病是世界上大多数地区的首要适应症。多年来，对一种常见的、慢性的、重要的疾病进行短期治愈性治疗的临床和健康经济效益已得到充分证明。在资源匮乏的地区，应该优先考虑这一治疗指征。

6.  How to test for H. pylori

6.  如何检测幽门螺杆菌

6.1  Endoscopic diagnostic tests

6.1  内窥镜诊断检查

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.

幽门螺杆菌感染的诊断可以是侵入性的（内窥镜）或非侵入性的（非内窥镜）（表3）。内窥镜检查时取的活体组织通常用于组织学分析和尿素酶测试。用于培养的活检较少用于诊断，除非有抗生素耐药性检测，并且需要帮助个人临床决策或确定群体抗生素耐药率。从胃部的两个位置采取两种检测方式的组合通常对诊断最有效。在实践中，这通常意味着从胃窦和胃体取样进行组织学检查，从胃窦取样进行尿素酶测试。当有额外的组织学监测需要时，可以使用更多的结构化活检方案，如胃炎评估手术（OLGA）和胃炎/肠道增生评估手术（OLGIM）方案[18]。组织学检查通常是昂贵的，而且非常依赖操作者，并且不能假设准确性，除非与以前的其他检测方式相比。

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.

在资源有限的地区，依赖尿素酶测试是很常见的。大多数商业性的尿素酶测试的准确度似乎达到了95%左右。尽管它们比组织学的价格要低得多，但在资源匮乏的地区，这些测试仍然会产生巨大的成本负担，特别是当费用由病人承担时。商业性尿素酶检测通常花费5美元。在非熟练工人的平均日收入可能为1-2美元的地区，这可能是负担不起的。幸运的是，有一些非常便宜的普通尿素酶测试已经有很多年了，可以在现场进行，单位成本约为0.20美元。这些通常是无缓液的检测，可以得到非常快速的结果，其灵敏度与商业测试非常相似[19]。非洲、亚洲和太平洋地区的一些国家正在使用它们。

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.

从活检中培养幽门螺杆菌需要特定的运输条件、实验室技术和设备。在专业的中心，培养成功率可能达到90%，但实际情况成功率往往低于专业中心。在专业性不强的实验室中，用于抗生素检测的再培养也不一定成功，因此，在需要时不一定能得到结果。现在有商业化的实时聚合酶链式反应（PCR）检测，能够以较高的灵敏度和特异性检测幽门螺杆菌，也能检测导致克拉霉素耐药的突变[20-22]。这些测试不需要严格的分析前条件，可以在几个小时内完成。 这些快速、廉价的基于试剂盒的活检抗生素耐药性检测的验证和实施有望成为H. pylori感染管理方面的一个重大进展。在耐药性高的地区提供这种测试可能会大大有助于为个别病人选择治疗方法，同时也有利于调查人口的流行情况。

”

Good practice point

The validation and implementation of rapid, inexpensive kit-based PCR diagnostic and antimicrobial resistance tests promises to be a major advance in management.

良好实践要点

快速、便宜的基于试剂盒的PCR诊断和抗生素耐药性检测的验证和实施，有望成为幽门螺杆菌管理上的一大进步。

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).

在一个发病率较高、资源匮乏的地区，对未服用非甾体抗炎药的患者进行十二指肠溃疡病的内镜诊断，预测幽门螺杆菌存在的准确率为95%。虽然确认感染的活检是可取的，但十二指肠溃疡的存在具有与大多数测试相似的预测价值，因此，在不产生进一步费用的情况下进行治疗是合理的（除非有廉价的通用尿素酶测试）。

6.2  Noninvasive diagnostic tests

6.2  无创性诊断检查

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.

当不需要或无法进行内窥镜检查时，可以使用无创性检查。尿素呼气试验（UBTs）是非常有用的，在识别幽门螺杆菌方面比其他无创性试验具有更高的诊断准确性（对于没有胃切除史的病人）。有点令人惊讶的是，在幽门螺杆菌和消化性溃疡病最常见的许多国家，这些检测并不广泛。其原因很复杂，可能包括缺乏建立和运行呼气分析实验室的专业知识或资源，商业套件测试的成本相对较高，或过度依赖经验疗法或内镜检查。在许多情况下，对胃癌的有效焦虑是使用内窥镜检查的主要驱动力（尽管一旦出现症状，胃癌很少能够治愈）。UBTs的费用各不相同。在资源较多的国家，成本与内镜检查相比非常有利，尽管在内镜检查相对便宜的地区，成本优势消失，除非有低成本的UBTs。稳定同位素C13 UBT测试已在多个地方得到详细验证，在资源丰富的地区通常是首选。C14 UBT使用非常低剂量的放射性同位素，通常需要较短的收集时间，但没有得到广泛的验证。它的准确度可能要低一些。C13 UBT的实验室成本较高，因为需要一个质谱仪，而C14 UBT则需要一个成本较低的闪烁计数器。C14同位素的实际（而不是商业）单位成本很低，因此可以使用中央实验室 '枢纽和辐条 '模式提供服务，从整个地区远程收集呼气样本，以非常低的成本提供测试。目前已有商业化的试剂盒和分析仪。准确度各不相同，而且这些试剂盒的单位成本往往很高。

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.

粪便抗原检测是另一种选择。这些测试似乎与UBTs几乎一样准确，但病人和卫生保健及实验室工作人员往往对基于粪便的测试有较低的偏好。在一些地方，成本是一个问题。基于粪便的快速PCR检测也是可用的[21]。尽管这些测试面临同样的接受障碍，以及需要实验室设备和技能，但它们有可能在一次非侵入性测试中提供快速诊断和抗生素耐药性测试。

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%.

血清学抗体检测是很常见的。尽管它们作为血清流行病学调查是有用的，但这些测试往往缺乏对个别病人进行决策所需的敏感性和特异性，一般来说帮助不大。它们需要在特定的地点进行验证，而且由于交叉反应导致的错误结果的问题很少被解决。在幽门螺杆菌中度流行的社区，这些测试的准确性可能不超过50%。

6.3  Testing to assess the outcome after eradication therapy

6.3  测试评估根除疗法后的结果

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稳定，最好对所有的病人进行结果评估，尽管这可能并不普遍可行。应优先考虑那些在感染持续的情况下仍有最高危害风险的患者，如正在接受复杂溃疡病治疗的患者（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.

当需要进行内镜检查时，基于活检的检测可用于确定根除治疗后的结果（例如评估胃溃疡愈合和排除肿瘤，或调查不良组织学）。否则，首选非侵入性检查。UBTs和粪便检测应在根除疗法完成后不少于1个月进行。为了尽量减少假阴性结果，患者在检测前至少一个月内不应服用抗生素或铋化合物，并且至少在一周内，最好是两周内避免使用质子泵抑制剂（PPI）。血清学对评估结果没有用，因为抗体水平往往在治疗后持续多年。尽管无创诊断测试，特别是呼气测试得到了广泛的验证，但在世界许多地方仍然无法以低廉的价格获得这些测试，这仍然是一个未满足的主要临床需求。

6.4  Diagnostic pathways

6.4  诊断途径

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.

诊断测试的选择在很大程度上取决于临床环境、可用性、专业知识和成本。如果所有的诊断方式都可用，关键问题是是否需要内镜检查来调查上消化道疾病的症状或体征。在发病率低、较发达的国家，对胃食管反流（GERD）、功能性消化不良、贲门癌和食管癌的担忧进行评估是内镜检查的常见指征，而且通常在那个时候对胃部进行幽门螺杆菌活检。幽门螺杆菌在这些地区仍然是一个问题，特别是在高风险的人群，如老年患者和社会经济地位较低的人，或来自高发地区的移民。在这些国家，使用UBTs的无创 '测试和治疗 '策略已在年轻患者中得到验证，并具有成本效益，尽管这一策略的使用可能正在下降。经验性的PPI治疗试验常常在初级保健中进行，如果症状没有得到缓解，就会求助于内窥镜检查。虽然这种做法很受欢迎，但如果症状不是胃食管反流病的典型症状，就会出现问题，而且这种治疗试验的理想时间也不清楚。这可能会导致幽门螺杆菌的诊断失败。尽管该有机体可能是偶然出现的，但在年轻的成年人中，治疗与明显的长期风险降低有关。在资源丰富、发病率较低的国家，幽门螺杆菌的管理策略的成本效益随当地的医疗费用而变化。

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.

在发病率较高的国家，由于对胃癌的恐惧，医生和病人通常都明显倾向于及时进行内镜检查--尽管如前所述，当病人出现症状时，这是否能提高生存率尚不确定。对于个人决策来说，必须考虑感染的预检概率、病人的年龄、症状或体征的性质，以及当地溃疡病和胃癌的发病率。

6.5  Empirical therapy in low-resource regions

6.5  低资源地区的经验性治疗

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

在内窥镜或无创诊断幽门螺杆菌感染的手段非常有限的地方，必须根据临床情况做出经验性的决定。当有明确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时，可以从临床角度强烈怀疑消化性溃疡病。在已知幽门螺杆菌流行率高且消化性溃疡病常见的地区，对消化性溃疡病的临床推定诊断采用经验性根除疗法是合理的（图3）。如此治疗的人群将包括许多患有消化性溃疡病的人，他们将获得很大的好处。它还包括一些患有幽门螺杆菌相关的胃炎但没有活动性溃疡的人。在这一群体中，症状的解决比使用任何其他疗法（通常是PPIs）更频繁，重要的是，成功的治疗可以减少消化性溃疡病和胃癌的终身风险。消化性溃疡病和胃炎的治疗也已被证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.

在经验性的基于症状的根除疗法中，会有一部分接受治疗的患者，他们没有被感染，可能有其他诊断。这个群体不会从根除疗法中受益，而且涉及到成本和不必要的抗生素使用，但造成重大伤害的可能性很低，而且接受治疗的群体的整体利益证明这种方法是合理的。事实上，在幽门螺杆菌和消化性溃疡病很常见的地区，由于经济或地理原因，许多人没有机会接受调查，亚太幽门螺杆菌共识小组特别赞同这种方法。经验性地使用PPI治疗可能不如初始治疗有益。这种方法应该得到教育保健工作者的计划的支持，以识别更可能是由溃疡病引起的症状，并有选择地应用这种策略。在这些资源匮乏的地区，用这种方法治疗所有的上消化道症状是比较困难的。

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.

非甾体抗炎药的使用很普遍，与非甾体抗炎药相关的消化性溃疡病很常见，并且可能与幽门螺杆菌感染同时存在。在怀疑有溃疡病的情况下，当NSAIDs（包括阿司匹林）被使用时，合理的做法是既要治疗幽门螺杆菌，又要解决NSAID的风险，即停止使用这些药物，在完成根除治疗后的几周内给病人使用PPI。

”

Good practice point

In resource-poor, high-prevalence regions in which diagnostic testing is not available, a history suggesting chronic ulcer disease—periodic upper gut pain and/or past or present melena—suggests a high likelihood of H. pylori ulcer disease and justifies empirical eradication therapy, especially in patients with no history or NSAID or aspirin use.

良好实践要点

在资源匮乏、发病率高的地区，如果无法进行诊断性检测，那么暗示慢性溃疡病的病史--周期性上消化道疼痛和/或过去或现在的血便--表明幽门螺杆菌溃疡病的可能性很大，有理由进行经验性根除治疗，特别是对于没有NSAID或阿司匹林使用史的患者。

7. Treatment of H. pylori infection

7. 幽门螺杆菌感染的治疗

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.

大量的研究已经解决了幽门螺杆菌的治疗问题，并且有许多专家指南推荐了治疗的选择。然而，大部分的文献和建议都来自于资源丰富的发达国家，而来自于资源匮乏的发展中国家的文献和建议相对较少，而这些国家承担着幽门螺杆菌感染相关疾病的主要负担。目前已经确立了普遍适用的抗生素治疗原则。然而，有一些关键问题必须在当地解决，以确定当地的最佳做法，因为抗生素耐药模式以及幽门螺杆菌根除率在各地区有所不同，并且如药物成本和药品可获得性等其他问题，也会影响治疗的选择。表4概述了指导选择根除疗法的关键原则。

Table 4  Key principles guiding the choice of H. pylori eradication therapy

表4   指导选择幽门螺杆菌根除疗法的关键原则

1. Randomized controlled treatment trials and meta-analyses provide the highest level of evidence, but are not available for。many regions. Local audits of treatment outcome are useful.

随机对照治疗试验和Meta分析提供了最高水平的证据，但许多地区没有相应的证据。本地对治疗结局的审核是有用的。

2. Treatment recommendations based on resistance patterns and outcome data from one region may not be applicable elsewhere, due to variation in resistance rates and other factors.

由于耐药率和其他因素的变化，基于一个地区的耐药模式和根除率数据的治疗推荐可能不适用于其他地区。

3. Generating high-quality local data and monitoring antibiotic resistance and treatment outcomes are priorities.

获得高质量的本地治疗数据并监测抗生素耐药率和根除率是优先事项。

4. Ad hoc, unproven therapies should be avoided.

尤其应避免临时性的、未经证实的治疗方法。

5. The main determinant of eradication success is pretreatment antibiotic resistance.

根除成功的主要决定因素是在治疗前了解抗生素耐药性。

6. Primary resistance to clarithromycin, metronidazole, and levofloxacin varies widely regionally. 

对克拉霉素、甲硝唑和左氧氟沙星的原发耐药在各地区差异很大。

7. Major determinants of primary resistance appear to be the magnitude and duration of community usage of these antibiotics as monotherapy for other indications.

原发性耐药的主要决定因素似乎是社区使用这些抗生素作为其他适应症的单一疗法的程度和持续时间。

8. Prior personal exposure of a patient to these drugs is likely to result in resistance and increases the chance of treatment failure.

患者既往抗生素使用可能会导致耐药，并增加治疗失败的机会。

9. Primary clarithromycin resistance (CR) is reported to have increased in many countries over relatively few years, while remaining stable in other countries.

据报道，部分国家克拉霉素原发性耐药（CR）在数年内有所增加，而在其他国家则保持稳定。

10. Primary or secondary resistance to amoxicillin and tetracycline are so rare as to not affect treatment choices.

阿莫西林和四环素的原发性或继发性耐药性非常罕见，以至于不影响治疗选择。

11. Since much treatment is given presumptively or after noninvasive H. pylori testing, the choice of therapy will be based on knowledge of likely local antimicrobial resistance patterns.

由于许多治疗是假定性的或在非侵入性幽门螺杆菌检测后进行的，因此治疗的选择往往是基于当地抗生素耐药模式。

12. When endoscopy is carried out, culture is not often done routinely prior to first-line therapy in most places, but this will vary according to skills, resources, local knowledge of resistance rates, and outcomes. Ideally, culture should also be used to monitor local resistance trends over time.

在进行内窥镜检查时，大多数地方通常不会在一线治疗前进行常规药敏培养，但这会因技术、资源、当地对耐药率和治疗结局而有所不同。理想情况下，药敏培养也应该被用来监测当地抗生素耐药性随时间变化的趋势。

13. The availability of rapid, inexpensive, point-of-care PCR antimicrobial resistance testing may change individual treatment choices and facilitate the surveillance of trends in resistance.

快速、便宜、即时的PCR抗生素耐药性检测的出现可能会改变个人治疗的选择，并会促进对耐药性趋势的监测。

14. Secondary resistance after treatment failure is very common with clarithromycin, metronidazole, and perhaps levofloxacin.

对于克拉霉素、甲硝唑，或左氧氟沙星在治疗失败后产生继发性耐药是非常常见的。

15. Repeating the same therapy has a low likelihood of success and should be avoided.

重复同一疗法的根除成功率很低，应避免重复的疗法。

16. The choice of second-line and subsequent therapies, if needed, should follow a logical decision path that involves using the most effective drugs first, avoiding repeating the same therapy, and using evidence-based choices of subsequent therapies.

如果需要，二线和后续疗法的选择应遵循一个合理的决策路径，即首先使用最有效的药物，避免重复相同的疗法，并使用基于证据的后续疗法选择。

17. Culture has a very limited role in determining the choice of salvage therapies.

药敏培养在决定补救治疗选择方面的作用非常有限。

18. The dosage and duration of therapy will influence outcomes.

治疗的剂量和持续时间会影响结果。

19. Treatment should be preceded by an informed consent process that outlines the potential risks and benefits of therapy to the patient.

治疗前应进行知情同意程序，并概述治疗对病人的潜在风险和益处。

20. Compliance is a major modifiable determinant of eradication success and should be supported with clear verbal and written information.

依从性是根除成功的一个主要的可改变的决定因素，患者应得到明确的口头和书面信息的支持。

21. Smoking has an adverse effect on eradication success.

吸烟对根除治疗有不利影响。

22. Unmodifiable risk factors for treatment failure may include CYP2C19 polymorphisms and the virulence factors of the organism.

治疗失败不可改变的风险因素可能包括CYP2C19基因多态性和幽门螺杆菌的毒力因素。

23. The role and value of potassium-competitive acid blockers such as vonoprazan is still emerging. These drugs are not affected by CYP2C19 polymorphisms and result in more uniform and potent inhibition of gastric acid secretion.

钾竞争性酸阻断剂（如沃诺拉赞）的作用和价值仍在不断显现。这些药物不受CYP2C19基因多态性的影响，对胃酸分泌的抑制更加均匀和有效。

24. Costs may be minimized by using high-quality generic drugs, especially in resource-poor regions. 

使用高质量的非专利药物，可以最大限度地降低患者治疗成本，特别是在资源匮乏的地区。

25. The drugs required should be on essential drug lists and be widely available.

治疗所需药物应在基本药物清单上，并能广泛获得。

8.  Translating treatment principles into therapeutic choices

8.  将治疗原则转化为治疗选择

8.1  Choice of first-line eradication therapy

8.1  一线根除疗法的选择

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].

应用这些治疗原则将确保可能的最佳结果。在资源丰富的地区，治疗可能基于高质量的试验和审核及药敏培养数据；在资源匮乏的地区，依靠对社区或个人抗生素使用情况的了解以及任何当地的审核结果都会影响其他地方的指南所推荐的疗法的使用[4-12]。

8.1.1  PPI, amoxicillin, clarithromycin triple therapy

8.1.1  PPI、阿莫西林、克拉霉素三联疗法

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.

在世界许多地方，由质子泵抑制剂（PPI）与阿莫西林和克拉霉素（PPI-AC）组成的三联疗法仍然是最常用的一线疗法。这种组合是第一个非常广泛推荐的疗法，并取代了不太有效的三联疗法。多年来，它得到了很好的评估。该组合根除成功的主要决定因素是治疗前的克拉霉素耐药性（CR）。世界各地的抗生素耐药性，特别是克拉霉素耐药性的流行程度差异很大（表5）。在克拉霉素已经并正在作为单一疗法用于其他感染的地方，CR的水平通常很高，而且在不断增加。有观点认为，在已知原发性CR率为15-20%或更高的地区应放弃这种疗法，因为这对根除率有影响。一个有点主观的最低根除率，即在意向性治疗的基础上达到80%，常常被引用为可接受疗法的基准。在CR率中等或较低（即低于15-20%）的地区，这是PPI-AC在真实世界研究中的一个常见根除率。在CR发生率较高的国家，可能会出现不可接受的较低的根除结果。

”

Key statement

The major determinant of eradication success with PPI-AC is pretreatment clarithromycin resistance.

关键陈述

使用PPI-AC根除成功的主要决定因素是治疗前的克拉霉素是否耐药。

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.

最佳的治疗时间是一个有争议的问题。最近关于普及14天PPI-AC治疗的呼吁通常来自于CR较高的地区。最初的研究多为7天，尽管这一期限可能受到注册试验设计的影响。支持的人指出，在系统回顾中较长的疗程通常都有较高根除率。然而，还有其他考虑因素影响着治疗的持续时间，特别是在资源匮乏的国家。增加第二周的治疗疗程可能会提高根除率，通常约为10%。这意味着，为了多获得一次治疗成功，需要多治疗一周的病人数量是10名。如果达到这种更高的根除率，其代价包括治疗费用翻倍，这在资源匮乏的地区是一个主要问题。(应该指出的是，在资源非常匮乏的地区，一周的三联疗法的费用可能与最低收入者每周的收入一样多）。长时间使用抗生素，不良反应的风险会大大增加，不遵守规定的可能性也会大大增加。另一种方法是给予较短的治疗，这样依从性可能会更高，不良反应和费用会更少，但有一点可以理解，那就是可能会有10%的病人需要二线抢救治疗。只要一线根除率至少适中，第二种策略的总体抗生素使用量将大大降低。在一些资源丰富的国家，通常推荐使用较长的疗程，但在资源贫乏的地区，还需要对较短的疗程进行更多的模拟研究。还必须注意的是，一些国家已经报告了1周PPI-AC治疗的可接受的根除率，而更长疗程的增量效益还没有研究。PPI（标准或大剂量）和克拉霉素（250毫克或500毫克，每天两次）的最佳剂量在大多数地区尚未确定。在CR高的地区，这种治疗的一周或两周可能都不能达到可接受的根除率。在这种地方，对一线疗法的选择是不同的。

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].

在任何根除疗法中，钾竞争性阻酸剂（如vonoprazan）代替PPI的作用和价值正在显现。这些药物不受CYP2C19多态性的影响，对胃酸分泌的抑制作用更加均匀和有效[25]。

8.1.2  Bismuth-based quadruple therapies

8.1.2  铋剂四联疗法

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.

一线治疗的另一个核心选择，特别是在原发性CR高的地区，仍然是以铋剂为基础的四联疗法。研究的最好的方案涉及PPI、铋剂、四环素和甲硝唑（PPI-BTM）。这种治疗方法经受住了时间的考验，因为无论原发性甲硝唑耐药性（MR）如何，它都能带来可靠和可接受的根除率，因为在BTM中加入PPI似乎可以克服MR。7天的治疗已经取得了良好的效果，尽管也有人主张采用更长的治疗时间（10-14天）。这种疗法的主要缺点是笨拙的剂量方案（因为它通常每天用药四次）和常见但通常是轻微的不良反应，这可能会影响坚持治疗。在一些地方，铋剂和四环素的供应减少可能会限制这种疗法的使用。然而，当这些药物不容易获得或没有注册时，经有关部门许可，以低价进口非专利药物往往是可行的。

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

用阿莫西林替代四环素的四联疗法（PPI-BAM）早有报道，使用较少，但可能提供可接受的结果。

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，有报道称通过添加铋剂（B+PPI-AC）将标准的PPI-AC三联疗法转换为四联疗法，在某些地方取得了良好的效果[26]。这对克服CR的价值还没有完全确定，但值得详细评估。

8.1.3  Nonbismuth quadruple therapies

8.1.3  非铋剂四联疗法

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.

有主张采用非铋剂四联疗法--通常是指在PPI-AC三联疗法（PPI-ACM）中加入甲硝唑。如果MR率较低或中等，这可能会提高根除率，但对于世界上许多原发性MR和/或CR较高的地区来说，不太可能有很大帮助。此外，治疗失败的病人往往会被发现有双重耐药性。在资源丰富的国家已经对这种类型的伴随治疗进行了研究，但在资源贫乏的国家很少。对序贯或混合疗法的研究较少，似乎不能提供卓越的根除效果，开药也很笨拙，并对依从性构成了一定的挑战。因此，不推荐使用这些方案。

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.

如果通过对病人的检测知道了甲硝唑的敏感性，PPI-AM可以作为一线治疗，并取得合理的效果。它也适用于已知人群中MR值较低的地方。

8.1.4  Levofloxacin triple therapy

8.1.4  左氧氟沙星三联疗法

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.

左氧氟沙星三联疗法（PPI、阿莫西林和左氧氟沙星，PPI-AL为10-14天）在已知或推测左氧氟沙星耐药性（LR）较低时被用于一线治疗，但该组合在这一作用中没有被广泛研究，大多数报告与二线治疗有关。一些国家关于左氧氟沙星耐药率高的报道将限制这种疗法在这些地方的应用。该疗法的耐受性一般较好。最近人们对使用氟喹诺酮类药物的风险表示关注。对于左氧氟沙星，这与罕见的肌腱炎或肌炎的风险有关。这种不良反应的确切发生率没有很好的记录，但在老年人和有炎症性关节炎或肾功能损害的人中似乎更常见，如果有其他选择，最好在这些高风险人群中避免使用。更大剂量的左氧氟沙星和可能的大剂量PPI可能与卓越的根除成功率有关。莫西沙星是一种相关的喹诺酮类药物，也已被使用。对它的研究较少，而且它的抗菌谱较广，所以一般不比左氧氟沙星更受欢迎。

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.

还有其他一些研究不充分的治疗方法，但在各种评论中被推荐。例如，呋喃唑酮已被用于CR和LR较高的地方，但与已有的疗法相比，证明其价值的高质量数据很少，而且其确切的作用仍有待确定。

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.

当使用通过培养或快速PCR检测抗生素耐药性时，可以为个别病人开出有针对性的疗法。这可能在原发性CR较高的地区具有最大的价值，以避免在一线治疗中使用克拉霉素。对基于粪便的PCR检测的验证和接受提供了将这一好处扩展到基础保健和不需要或不能进行内镜检查的情况下的前景。

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

表6和表7提供了一线治疗方案及其组成的概述和总结。

8.2  Choice of second and subsequent eradication therapies

8.2  二线和后续根除疗法的选择

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].

一些地方对一线根除失败后的二线或补救疗法进行了充分的研究，但对于许多资源匮乏的地区来说，完全缺乏数据[4-12]。

8.2.1  Bismuth-based quadruple therapy and levofloxacin triple therapy

8.2.1  铋剂四联疗法和左氧氟沙星三联疗法

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线疗法包括标准的铋剂四联疗法7-14天和左氧氟沙星三联疗法10-14天。两者都已被证明能达到80%以上的根除率。两者之间的选择取决于是否了解当地原发性左氧氟沙星耐药率、药物可得到性、经验、依从性和成本。通常推荐较长的治疗时间（即14天），但需要关于当地结果、成本和依从性的数据。当这些治疗方法失败时，其他疗法通常是第三种选择。在有经验的中心，在一线治疗失败后，明智地选择的疗法的总根除率应该在最多三个疗程后接近98%。

8.2.2  Other salvage therapies

8.2.2  其他补救性疗法

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.

已使用的其他补救疗法包括以利福布汀为基础的三联疗法（PPI-AR）。一般来说，它的疗效较差，显著中性粒细胞减少的风险可能高达1%，这往往会限制其使用。在结核病高发地区通常要避免使用。大剂量二联PPI加阿莫西林治疗（PPI-A）已经取得了一些成功。非铋剂四联疗法作为补救治疗通常是无效的，原因是继发性CR和MR。在检测后知道甲硝唑敏感性的情况下，PPI-AM可作为二线治疗，效果合理，但一般不用于经验性的二线治疗。呋喃唑酮已经被使用，并且在一些地区被推荐作为治疗的一个组成部分。包括这种药物的高质量根除研究很少，随机试验也很缺乏。对其安全性和使用的担忧导致其在美国和欧盟无法使用。

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.

当遵循适当的治疗途径且治疗失败时，应避免处方者一时兴起的临时治疗，除非有亚专业的专业知识或临床试验，否则应接受持续感染的状态。在一些患者中，如那些复发的溃疡病患者，根治失败可能导致需要维持抗酸分泌治疗。

8.3  Treatment choices for patients with penicillin allergy

8.3  青霉素过敏患者的治疗选择

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.

对于青霉素过敏的病人，可以用甲硝唑代替阿莫西林，并与PPI和克拉霉素联合使用（PPI-MC）。然而，原发性MR会降低其疗效。铋剂四联疗法是一个非常好的替代选择（PPI-BTM）。如果上述两种疗法都失败了，进一步的选择就很有限了。对于那些病史较久远、不确定的或不可能的青霉素过敏史的病人，如果有资源可用，可以进行1型青霉素过敏的正式评估。这包括测量青霉素抗体，然后进行皮肤点刺试验，如果阴性，则进行监督下的口服试验。当在低风险患者中开展这项工作时，多达80%的此类患者被证明对青霉素不过敏，他们可以根据需要安全地使用含阿莫西林的治疗方法（如果最初没有使用克拉霉素，通常是PPI-AL或PPI-AC）。这样的策略已被证明可以在大多数病人中成功地进行根除治疗。如果以前有明确的1型反应史，则可假定为过敏，而不需要进行测试。

8.4  Treatment pathways

8.4  治疗途径

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.

总之，在资源丰富的地区，当地的CR和MR（有时是LR）率是已知的，在CR较低的地区，基于证据的治疗选择通常是PPI-AC作为第一线，PPI-BTM或PPI-AL疗法作为第二和第三线，顺序不限。在CR水平较高的地区，可使用PPI-BTM。B+PPI-AC或PPI-AL可能是备选的一线疗法。二线选择取决于首先一线治疗的方案。如果以前没有使用过，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.

在资源匮乏的地区，社区CR和MR尚未建立或已知较高的情况下，治疗方法的选择是基于对根除率的经验性统计、个别病人作为单一疗法接触抗生素的个人药物使用史、社区使用此类药物的情况、可用性和成本（表8）。PPI-AC仍然被广泛地选择，并且PPI-BTM或PPI-AL，甚至非铋剂四联疗法作为替代的一线或补救疗法。然而，当已知克拉霉素的一线治疗根除率不佳时，可首选所述的其他疗法之一。现在非常需要有关左氧氟沙星耐药率的数据，因为LR在许多地区似乎很普遍，而且一些已发表的数据的质量也不确定。因此，PPI-BTM四联疗法可能是一个很好的首选和后续选择，因为它避免了因耐药而导致的根除率低的问题。然而，其使用有时会受到可用性、依从性和不良反应的限制。无论选择哪种治疗途径，关键是不要重复相同的治疗，因为在一线治疗失败后，由于继发性抗生素耐药，这是一个非常低价值的策略。例如，用PPI-AC根除的成功率在一线治疗中可能是80%或更多，但在一线治疗失败后重复治疗时，成功率低至8%。这其中大部分可归因于继发性CR。不幸的是，这种做法在一些地方仍然很普遍，但应该加以阻止。最后，在许多地区，患者获得廉价的非专利药物和医疗教育仍然是需要克服的重大挑战。

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

图4中概述了选择治疗的适当途径。

8.5  The role of culture

8.5  药敏培养的用途

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.

调查幽门螺杆菌的耐药性模式，以确定人口感染率和其变化，将指导治疗选择。在一些资源充足的国家，有可能在治疗前对内窥镜活检的个体抗生素敏感性测试的基础上进行个性化的治疗。然而，这并不是临床实践中的常规做法，而且在任何情况下，用于耐药性测试的培养和亚培养在不太专业的实验室里可能会失败。此外，许多治疗是在基础保健中进行的，并且在那里进行无创检测和治疗。在治疗失败后，从培养的活体组织中进行的抗生素敏感性测试不太可能在临床决策中发挥重要作用。如果使用克拉霉素治疗失败，继发性CR非常普遍，因此对其进行检测是无益的，应选择不同的治疗。如果PPI-AM可能是一种选择，评估MR或许是有用的，但它并不影响PPI-BTM的选择，因为该疗法不受MR的影响。左氧氟沙星在大多数地区都是经验性使用，在这些地区已知LR很低。此外，幽门螺杆菌对其他抗生素的体外敏感性并不意味着治疗的成功，不应该以这种方式设计临时性的治疗方案。

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.

如果点活检（或基于粪便的）分子技术（PCR）可广泛用于快速评估耐药性，这些技术可能会改变实践，对治疗选择产生重大影响。这种测试有可能取代尿素酶测试，确认感染的存在，并提供快速的抗菌素耐药性数据以指导个体化治疗，其成本仅比目前的商业尿素酶测试高一点。基于粪便的测试将使在基础保健中根据每个病人的抗生素敏感性进行治疗成为可能，而不需要进行内窥镜检查。

8.6  Compliance

8.6  依从性

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.

无论开出哪种疗法，都必须尽一切努力最大限度地提高依从性。这意味着处方者必须花时间与病人解释接受所有治疗和不中断治疗的重要性。这在抗生素使用规定可能不严格或不执行的地区尤其重要，因为在这些地区，抗生素可以从药店的柜台获得。患者可以购买少量的药物用于一两天的治疗，如果症状没有立即得到缓解或出现任何不良反应，就有可能无法坚持下去。显然，整个疗程应该在发病时开出处方并配药。应预计到并解释不良反应，如克拉霉素和甲硝唑常见的短暂味觉障碍，以便其发生时不会导致治疗的停止。为患者提供书面信息包括剂量和用药信息已被发现是有用的。众所周知，吸烟是一个不利于治疗结果的预测因素，在治疗前和治疗期间停止吸烟可能会改善治疗结果，尽管这还没有得到很好的研究。戒烟也有助于溃疡的愈合。有人声称益生菌在减少不良反应（并可能改善结果）方面的作用，但这需要更多和更好质量的证据。

”

Good practice point

Patients should always be advised that successful eradication depends on compliance with the treatment. Time should be taken to counsel the patient, explaining how to take the multidrug therapy and anticipating adverse side effects. The need to complete the treatment should be emphasized. Written or pictorial information may also aid compliance.

良好实践要点

应始终告知患者，成功根除取决于对治疗的依从性。应该花时间对病人进行咨询，解释如何服用治疗和预测不良副作用。应强调完成治疗的必要性。书面或图片信息也可以帮助患者提高依从性。

8.7  After treatment

8.7  治疗后

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.

理想情况下，应对所有接受治疗的病人进行根除结果评估，尽管在实践中很多地方并不具备这种条件。当最初进行了内镜检查，发现胃萎缩和/或肠化生时，需要决定进行内镜下的粘膜监测[27]。这可能会使个别患者受益，但胃癌导致的死亡率总体上的降低还没有得到明确的证明。当发现局灶性高等级胃粘膜异型增生时，可以通过内镜切除这些区域，但更高级的肿瘤需要手术。异型增生可使用增强成像技术检测，或通过映射活检标本，但没有内镜下可见的离散性病变。这些患者需要在内镜下重新评估，最好是用图像增强和放大内镜，高级别异型增生在6个月内，低级别异型增生在12个月内。

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.

由于萎缩和肠化生很常见，内窥镜监测将占用大量的内窥镜资源，并对其他保健需求产生机会成本。因此，一般来说，只有高风险个体才会被提供监测。高风险通常意味着存在更广泛的胃粘膜变化（涉及胃窦和胃体）和/或有胃癌家族史。理想的策略还没有确定。准确的内窥镜检测和粘膜变化的特征需要特定的培训和现代内窥镜，以及熟练的病理学家。

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

9. 基于当地数据和资源的最佳实践根除疗法的区域观点

9.1  Australia

9.1  澳大利亚

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.

在澳大利亚，克拉霉素耐药率低（6-8%），甲硝唑耐药率高（45-50%）。有关左氧氟沙星的数据很少，原发性耐药性似乎很低，但来自高耐药性地区的移民中的耐药率可能例外。因此，PPI、阿莫西林和克拉霉素的标准三联疗法仍然是推荐的一线疗法，除非出现克拉霉素耐药性上升的证据。据报道，7天的根除率为80-87%。14天的治疗还没有正式研究过。补救治疗包括左氧氟沙星三联疗法10天（根除率为80-90%）和标准剂量四联疗法（PPI、铋剂、四环素和甲硝唑）7-14天，其结果相似。左氧氟沙星、四环素和铋剂没有在当地注册，所以不常被用于一线治疗。这些药物必须通过特别准入计划从国外获得，或者在需要进行补救治疗时通过复合药房获得。利福布汀三联疗法使用得不太普遍（76%的根除率）。当地还没有研究过伴随疗法。

9.2  Pacific region

9.2  太平洋地区

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.

目前缺乏当地的耐药性数据，也没有什么系统的数据来评估治疗的结果。因此，治疗方法的选择通常是从国际指南中推断出来的，并由药物的可用性决定。通常选择克拉霉素三联疗法，加上PPI和阿莫西林或甲硝唑，尽管临床上怀疑高MR影响了后者的疗效。成本、可得性、当地的专业知识和对治疗的坚持都是有效治疗的障碍。没有经过审查的补救治疗数据。不鼓励在一线治疗失败后采取临时性治疗和重复的克拉霉素治疗。

9.3  Southeast Asia

9.3  东南亚

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.

有很好的证据表明，阿莫西林和四环素的耐药性较低且稳定（<5%），但MR普遍较高（30-100%）。CR一直在增加，但在东南亚国家中差异很大（从2%到43%不等）。对于大多数治疗方案，应使用14天的疗程，除非当地有证据证明较短疗程的可靠根除率。理想情况下，由于各国的抗生素耐药性差异很大，应根据当地的抗生素耐药率来考虑一线治疗方案。据报道，PPI-BTM的成功率一直高于90%。二线治疗方案应包含以前没有使用过的抗生素，或那些不太可能产生耐药性的抗生素，如阿莫西林或四环素。如果尚未使用过PPI-BTM，应考虑使用。在结核分枝杆菌高发的地区不应考虑使用利福布汀。如果在第二次尝试后根除治疗失败，应考虑进行抗生素药敏试验。

9.4  Eurasia

9.4  欧亚大陆

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.

根据一项试点研究，亚美尼亚健康成年人中幽门螺杆菌血清阳性率为41.5%，随年龄增长而增加（18-25岁年龄组为13.6%，65岁以上为83.3%）。2018年对克拉霉素的耐药率低至3.6%，对氟喹诺酮的耐药率为12.8%。然而，新的研究是有必要的，特别是在COVID-19大流行期间，该国初级医疗保健提供者对大环内酯类和呼吸道氟喹诺酮类药物的处方数量空前增加。四环素只有100毫克的药片，这使得传统的四联疗法非常不方便。改编自马斯特里赫特指南的当地建议提出将14天的克拉霉素三联疗法作为一线治疗，并将改良的铋剂四联疗法（PPI、铋剂、阿莫西林和甲硝唑）作为备选一线疗法。二线选择包括左氧氟沙星的三联或四联疗法。这些根除方案都没有在当地进行过疗效研究。

9.5  Western Europe

9.5  西欧

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对于选择一线治疗是高度相关的。这在欧洲国家之间和内部都有差异。因此，对抗生素耐药性的监测在人群层面上仍然是至关重要的。最近的欧洲注册数据，来自27个国家的3万多名患者[28]，表明克拉霉素的原发耐药率为23%，甲硝唑为32%，13%的患者有双重耐药性。中欧和北欧的CR较低；在德国，原发CR仍低于15%的临界水平。用阿莫西林和克拉霉素进行为期14天的三联疗法在这些情况下仍然有效，通常被用作一线治疗。在原发性CR>15%的地区，建议将铋剂四联疗法作为一线治疗，持续10天（或14天，如果该方案的组成部分单独使用）。在大多数国家，包括三种抗生素而不是铋剂四联疗法中使用的两种抗生素的联合疗法是不受欢迎的。PPI三联疗法中的甲硝唑大多已被放弃，现在只保留给个别病例（如对阿莫西林过敏或证实对甲硝唑敏感的病例）。

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.

对左氧氟沙星的耐药性不断增加，使这种抗生素被排除在任何一线治疗方案的组成部分之外。它的使用正变得越来越令人担忧，即使它被用作二线治疗。利福布汀在三线治疗中是有效的，并被推荐作为反复治疗失败后挽救方案的一个组成部分。

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.

欧洲的建议把重点放在检测（13C-UBT）上以评估个体治疗反应。鼓励在治疗失败后对常用的抗生素进行耐药性检测。

9.6  Southern Europe

9.6  南欧

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.

抗生素耐药性的上升是主要问题。在一线治疗前应确定克拉霉素的抗生素敏感性，但目前对大多数患者来说是不可行的。因此，治疗的选择是基于当地CR的耐药情况。然而，在意大利的大多数地区缺乏这方面的信息；在一些中部和南部地区有高耐药率（30%）的报道。当CR>15%或未知时，建议采用10天或14天的铋剂四联疗法或非铋剂四联疗法作为一线治疗。这两种方案的疗效不受CR或MR的影响，当存在双重耐药时，铋基四联疗法表现良好。因此，铋剂四联疗法可被认为是意大利经验性一线治疗的最佳选择。

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.

标准三联疗法--PPI加克拉霉素和阿莫西林或甲硝唑/替硝唑--对克拉霉素敏感菌株有效，但当出现CR时就失效了。只有在已知CR较低（<15%）的地区、以前没有使用过大环内酯类药物的患者，或在该方案已被证明能达到高根除率的地区，才应将14天标准三联疗法作为一线治疗。

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.

序贯治疗，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，这是一种旨在克服克拉霉素耐药问题的方案。然而，有关其疗效的数据是相互矛盾的。尽管来自意大利的一些报告指出，即使在CR情况下其根除率也在90%左右，但最近的指南还是不鼓励使用该方案。二线治疗包括含左氧氟沙星的三联疗法和铋剂四联疗法。为了减少抗生素相关的不良事件，可以使用益生菌补充剂。

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.

北美的克拉霉素耐药性不一（在不同的研究中为17-32%），甲硝唑耐药性高（44%）。在最近的一项研究中，阿莫西林的耐药性被报道为6%，利福布汀的耐药性为0%。美国指南建议，对于一线治疗，克拉霉素三联疗法应限于以前没有大环内酯类药物接触史、居住在已知克拉霉素对幽门螺杆菌分离物耐药性较低的地区的患者。一些郊区和农村地区符合这些标准。在大多数地区，推荐使用铋剂四联疗法或由PPI、克拉霉素、阿莫西林和甲硝唑组成的联合疗法作为一线治疗。在美国，利福布汀、阿莫西林和奥美拉唑的组合已经被批准用于治疗幽门螺杆菌。它在初次治疗中的作用还有待确定。

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.

对南美洲和中美洲的克拉霉素耐药性的研究仍然很少，一些报告的耐药率已经超过20%。墨西哥、哥伦比亚、阿根廷和巴西的耐药率最高。滥用阿奇霉素（一种低成本的药物）可能会选择性导致大环内酯耐药突变，加剧CR率。有文献记载，阿莫西林的耐药率很低，但一些研究显示巴西的耐药率很高。如果这一趋势得到证实，由于这些抗生素疗法的核心作用，这将是一个令人震惊的情况。

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.

经典的三联疗法包括PPI、阿莫西林和克拉霉素，为期7-14天，仍然是最广泛使用的方案，其次是铋剂四联疗法作为替代或二线疗法，以及以左氧氟沙星为基础的疗法作为挽救方案。据报道，对左氧氟沙星的耐药性很少，但在秘鲁已经有高水平的描述。甲硝唑的相关使用在一线四联疗法中很常见，但在中美洲、墨西哥以及南美洲的一些国家，如巴西和哥伦比亚，报告的耐药率超过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.

据报道，每年的复发率超过3-5%，而且在地域上存在差异；许多地区缺乏数据。需要克服的障碍包括药物治疗的费用，提高医生对指南的遵守程度，许多地区缺乏UBT，一些国家没有铋盐、呋喃唑酮和利福布汀，以及缺乏高质量的本地研究来验证幽门螺杆菌根除疗法。该地区的大多数卫生保健系统在这些问题上的运作仍不尽如人意。

10 Abbreviations used in this WGO guideline

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