表1(Table 1)
引用本文
胡佳丽, 兰春慧, 张昊翔, 沈才飞, 王璞, 冯吉, 代剑华, 闫武, 夏一菊, 何金龙, 陈文生, 房殿春.
不同疗程铋剂四联疗法在中国根治幽门螺杆菌感染疗效的Meta分析[J]. 第三军医大学学报, 2017, 39(10): 1044-1055.
Hu Jiali, Lan Chunhui, Zhang Haoxiang, Shen Caifei, Wang Pu, Feng Ji, Dai Jianhua, Yan Wu, Xia Yiju, He Jinlong, Chen Wensheng, Fang Dianchun. Efficacy of different durations of bismuth-based quadruple therapy for Helicobacter pylori infection in China: a meta-analysis[J]. Journal of Third Military Medical University, 2017, 39(10): 1044-1055.
不同疗程铋剂四联疗法在中国根治幽门螺杆菌感染疗效的Meta分析
1. 400038 重庆，第三军医大学西南医院全军消化病研究所;
2. 400042 重庆，第三军医大学大坪医院野战外科研究所消化内科
2. 400042 重庆，第三军医大学大坪医院野战外科研究所消化内科
[摘要] 目的
评价不同疗程(10 d或14 d)铋剂四联疗法在中国幽门螺杆菌感染的根除疗效及安全性。
方法
计算机检索2005年1月至2016年11月Pubmed、EMBASE、the Cochrane Central Register of Controlled Trials、中国知网、中国生物医学文献数据库、维普等数据库关于10 d或14 d铋剂四联疗法在中国根除幽门螺杆菌感染的随机对照试验，提取受试者的基本资料、观察指标(根除率及不良反应发生率)、研究质量等相关数据，使用RevMan 5.3软件分析相关指标，计算RR及95% CI，使用漏斗图行发表偏倚评价。
结果
纳入43篇文献，共7 686例患者。合并结果显示：据意向性分析，10 d或14 d铋剂四联疗法和三联疗法根除率分别是88.96%(95% CI:87.73%~90.19%)和74.11%(95% CI:72.53%~75.69%)，差异有统计学意义(RR=1.20，95% CI：1.16%~1.25%)；10 d或14 d铋剂四联疗法和7 d铋剂四联疗法相比，根除率分别是87.34%(95% CI：84.87% ~89.80%)、81.65%(95% CI:78.76% ~84.54%)(意向性分析)，差异有统计学意义(RR=1.07，95% CI：1.02%~1.12%)；10 d或14 d铋剂四联联疗法与序贯疗法(RR=1.02，95% CI：0.97%~1.07%)及与伴随疗法(RR=1.01，95% CI：0.95%~ 1.07%)差异无统计学意义。
结论
10 d或14 d铋剂四联疗法与序贯疗法及伴随疗法疗效相当，三联疗法及7 d铋剂四联疗法不作为首选治疗方案。
[关键词]
幽门螺杆菌
铋剂四联疗法
三联疗法
序贯疗法
伴随疗法
Efficacy of different durations of bismuth-based quadruple therapy for Helicobacter pylori infection in China: a meta-analysis
1.
Institute of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, 400038;
2. Department of Gastroenterology, Institute of Surgery Research, Daping hospital, Third Military Medical University, Chongqing, 400042, China
2. Department of Gastroenterology, Institute of Surgery Research, Daping hospital, Third Military Medical University, Chongqing, 400042, China
Corresponding author: Fang Dianchun, Tel:86-23-68754480, E-mail:fangdianchun@hotmail.com
[Abstract]
Objective
To assess the efficacy and safety of bismuth quadruple therapy for 10 or 14 days in eradicating Helicobacter pylori(H.pylori) infections in Chinese patients.
Methods
The databases including PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure Database, Chinese Biomedical Database and VIP database were searched for randomized controlled trials (RCTs) published from the year 2005 to 2016 describing bismuth-based quadruple therapy for 10 or 14 days in Chinese patients. The trails retrieved were examined for clinical features of patients, quality of study, eradication rate of H.pylori and incidence of adverse events. A meta-analysis of the included trials was performed using Revman 5.3 software, and the pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated; the publication bias was assessed with funnel plot.
Results
Forty-three trials involving a total of 7 686 patients were eligible for inclusion in the analysis. Intention-to-treat analysis showed that the eradication rate of H.pylori was 88.96% (95% CI: 87.73%~90.19%) with bismuth quadruple therapy for 10 or 14 d and 74.11% (95% CI: 72.53%~75.69%) with triple therapy, showing a significant difference in the efficacy between the 2 therapies (RR=1.20, 95% CI:1.16%~1.25%). Analysis of 9 trials comparing bismuth quadruple therapy for 10 or 14 d and for 7 d showed that a treatment duration for 10 or 14 d resulted in an significantly higher eradication rate than a treatment duration of 7 days CI: 84.87%~89.80%) vs 81.65% (95% CI: 78.76%~84.54%), RR=1.07, 95% CI: 1.02%~1.12%]. The eradication rate produced by bismuth quadruple therapy for 10 or 14 d did not differ significantly from that by sequential therapy (RR=1.02, 95% CI: 0.97%~1.07%) or concomitant therapy (RR=1.01, 95% CI: 0.95%~1.07%).
Conclusion
Bismuth-based quadruple therapy for 10 or 14 d has a comparable efficacy in eradicating H.pylori with sequential therapy and concomitant therapy. Triple therapy and bismuth quadruple therapy for 7 d are not recommended as the primary options for treatment of H.pylori infection.
[Key words]
Helicobacter pylori
bismuth quadruple therapy
triple therapy
sequential therapy
concomitant therapy
幽门螺杆菌(Helicobacter pylori, H.pylori)感染是一种感染性疾病，是慢性胃炎、消化性溃疡及胃黏膜相关淋巴瘤的主要致病因素之一，多个研究表明，H.pylori还与很多胃肠外疾病的发病有关, 因此寻找有效H.pylori根治方案是亟须的。三联疗法是目前最常见的治疗方案，但近年来多种证据显示其根除率显著下降，主要与克拉霉素、甲硝唑等抗生素耐药有关[1-2]。为提高根除率，又提出了序贯疗法及伴随疗法，在近年的Meta分析中其根除率远优于三联疗法，但国内相关研究较少，疗效不确切[2-4]。许多研究显示，添加铋剂到三联疗法中可取得相对满意的疗效，在耐药情况下，甚至可提高30%~40%的成功率，因此在H.plori高耐药背景下，铋剂四联疗法得到重视[5]。Maastricht-4共识指出在克拉霉素高耐药地区(＞15%~20%)，铋剂四联疗法可作为首选治疗方案[6]。我国克拉霉素、甲硝唑及左氧氟沙星耐药率均较高，且耐药率呈上升趋势，而铋剂普遍可获得，共识推荐铋剂四联疗法在一二线治疗中均可选用，疗程为10 d或14 d[7]。但近年一些研究仍显示铋剂四联疗法根除率并不尽人意，一项关于4种含铋剂四联治疗方案的研究结果显示，雷贝拉唑与左氧氟沙星、泮托拉唑与左氧氟沙星组成的铋剂四联疗法根除率分别是83.3%、85.7%，而雷贝拉唑与替硝唑、泮托拉唑与替硝唑组成的铋剂四联疗法根除率仅有56.0%、58.8%[8]。为评价10 d或14 d铋剂四联疗法在中国幽门螺杆菌感染的根除疗效及安全性，本研究对该疗法的疗效行荟萃分析，希望为临床幽门螺杆菌治疗方案的选择提供依据。
1 资料与方法 1.1 数据来源参照Cochranehandbook 5.0.1版RCT检索策略，采用主题词+自由词方式，英文检索词：Helicobacter pylori、bismuth、quadruple therapy、random；中文检索词：幽门螺杆菌、铋剂四联疗法、铋、随机，限定词：核心期刊。计算机检索2005-2016年11月Pubmed、EMBASE、Cochrane Library、维普、中国知网、中国生物医学文献数据库关于10 d或14 d铋剂四联疗法在中国的随机对照试验。
1.2 纳入标准① 随机对照试验；② 至少包含10 d或14 d铋剂四联疗法在内的两种或以上治疗方案的试验，如三联疗法、序贯疗法、伴同疗法、混合疗法；③ 至少有一种标准检测方法证实幽门螺杆菌感染，如：尿素呼气试验、组织学检验、细菌培养、快速尿素酶法及粪便抗原学检测；④ 治疗结束至少4周以上行尿素呼气试验和或组织学检测验证幽门螺杆菌根除状态；⑤ 有明确的根除率(意向性分析：intention-to-treat，ITT)；⑥ 成年(年龄＞18岁)，不限定性别；⑦ 初次治疗；⑧ 中国内地居民；⑨ 发表在国内的研究必须是刊登于核心期刊。
1.3 排除标准① 摘要或全文没有报道幽门螺杆菌感染检测方法(治疗前后)；② 试验不是中国大陆进行；③ 试验组及对照组有不适当的治疗，包括：传统的中药、益生菌或H2受体阻滞剂等；④ 有严重并发症或儿童患者。
1.4 资料提取由2位研究者独立进行文献筛选和资料提取，意见不一致时通过讨论解决或由第3位研究者协助解决。资料提取内容包括：作者、发表年限、样本量、干预措施、随访周期、H.pylori感染诊断方法(治疗前后)、ITT及不良反应人数及失访人数等。
1.5 文献质量评价根据Jadad量表对纳入研究的方法学、质量进行评估，具体内容包括随机序列产生(2)、盲法(2)、分配隐匿、退出/失访(1)。分数范围为1~5分，得分＞3提示文献质量较高。
1.6 统计学分析采用Cochrane协作网的RevMan 5.3软件对数据进行分析，合并效应量选用相对危险度(RR)及其95% CI。纳入研究进行异质性检验即：Q检验和I2统计量(25%、50%、75%分别表示低、中等及高度异质性)，如P＞0.1或I2＜50%提示各研究间无异质性，采用固定效应模型进行合并分析；反之则存在异质性，采用随机效应模型，并找出异质性原因对其行亚组分析、Breslow.Day法和回归近似法。敏感性分析为依次排除单个文献后重新进行Meta分析，P＜0.05认为存在发表偏倚。估计综合效应大小。
2 结果 2.1 文献检索结果根据检索策略，初检出978篇文献(图 1)。通过阅读题目及摘要，837篇因重复、非中国大陆、非随机对照试验、主题不符、观察组及干预组不当、非初次治疗者、儿童或严重并发症等因素剔除。经阅读全文，排除重复、仅有摘要、实验设计不合理、H.pylori感染诊断指标不明，无明确根除率等因素，最终纳入43篇。纳入患者的性别、年龄等一般情况及不良反应发生率差异无统计学意义(表 1)。
表 1 纳入试验基本情况
| 姓名 | 年份 | 治疗组 | 对照组 | HP检测 | 随访周期(周) | 根除率 | 不良反应 | 失访 | Jadad评分 |
| 王波玲[9] | 2016 | PBCM-14 | PCM-14 | UBT/UBT | 4 | 90.0%(90/100)/80.0%(80/100) | 4/2 | 3/2/3/1 | 3 |
| PBCA-14 | PCA-14 | 93.0%(93/100)/86.0%(86/100) | 4/3 | ||||||
| Dai[10] | 2016 | RBAC-10 | RAC-10 | RUT or UBT/UBT | 4 | 86.5%(45/52)/69.8%(37/53) | 35/3 | 1/1 | 3 |
| 李锐强[11] | 2015 | OBAC-14 | OAC-14 | RUT/UBT | 83.33%(20/24)/54.17%(13/24) | 2/3 | 0/0 | 1 | |
| 马军霞[12] | 2015 | LBAC-14 | LAC-14 | RUT/UBT | 93.75%(30/32)/76.67%(23/30) | 6/5 | - | 2 | |
| 喻德林[13] | 2015 | ApBCA-14 | ApCA-14 | RUT/UBT | 4 | 98%(49/50)/80%(40/50) | 5/4 | - | 1 |
| 聂军[14] | 2015 | PBAC-10 | PAC-10 | RUT or UBT/RUT or UBT | 4 | 93.1%(134/144)/72.2%(104/144) | 9/13 | - | 1 |
| 唐捷[15] | 2015 | RBAF-14 | RAC-14 | RUT.UBT/RUT or UBT | 4 | 93.33%(56/60)/61.67%(37/60) | 23/18/21 | - | 1 |
| RAL-14 | 63.33%(38/60) | ||||||||
| 徐娴[16] | 2015 | PBAF-10 | PAF-7 | RUB.UBT/UBT | 4 | 85.30%(93/109)/71.2%(79/111) | 2/1/2/2 | 7/6/8/9 | 3 |
| PAF-10 | 80.90%(89/110) | / | |||||||
| PBAF-7 | 83.10%(88/106) | ||||||||
| 郭义茹[17] | 2015 | EBAC-10 | EAC-10 | RUT or UBT/UBT | 4 | 90.32% (56/62)/72.58%(45/62) | 21/14 | - | 2 |
| 王丽昆[18] | 2015 | PBAC-14 | PAC-14 | RUT.UBT.G/UBT | 5 | 81.7%(49/60)/77.8%(49/63) | 32/39 | - | 1 |
| 韩思静[19] | 2014 | RBAC-14 | RAC-14 | RUT/RUT or UBT | 4 | 85.37(35/41)/65.85%(27/41) | 4/6 | - | 2 |
| 李丙生[20] | 2014 | EBAC-14 | EMoF-14 | RUT.UBT/UBT | 4 | 88.3%(53/60)/89.4%(59/66) | 22/11 | - | 1 |
| 吴改玲[21] | 2014 | EBCTi-14 | EAC-14 | RUT or BUT or H/BUT | 4 | 75%(21/28)/90%(27/30) | 9/7/5/9 | - | 2 |
| EATi-14 | 86.21%(25/29) | ||||||||
| ECTi-14 | 56.67%(17/30) | ||||||||
| 张健[22] | 2014 | OBAL-10 | OAC-14 | RUT or BUT or H/BUT | 4 | 87.50(91/104)/76.19%(80/105) | - | 4/3/3 | 2 |
| OBAL-7 | 83.33%(90/108) | ||||||||
| 曾丽妮[23] | 2014 | RBAC-10 | RAC-10 | RUT or UBT/UBT | 4 | 90%(45/50)/72%(36/50) | 16/15 | - | 1 |
| Xie[24] | 2014 | RBAF-10 | RAF-7 | RUT/UBT | 4 | 86.1%(155/180)/74.4% (134/180) | 17/16/16/15 | 12/15/13/14 | 2 |
| RBAF-7 | 82.8% (149/180) | ||||||||
| RAF-14 | 78.9% (142/180) | ||||||||
| 金浩淼[25] | 2013 | RBCM-14 | OAC-14 | RUT/RUT or UBT | 4 | 86%(43/50)/64%(32/50) | 7/26 | - | 1 |
| 严剑峰[26] | 2013 | RBATi-14 | OAC-7 | H or UBT/UBT | 4 | 97.22%(35/36)/85.71%(30/35) | 0/0/2/0 | - | 1 |
| OAC-14 | 88.23%(30/34) | ||||||||
| RBATi-7 | 97.14%(34/35) | ||||||||
| Liao[27] | 2013 | LBAL-14 | LAL-14 | RUT.C.H/UBT | 4 | 87.5% (70/80)/82.7% (67/81) | 4/6 | 6/3 | 3 |
| 程桂莲[28] | 2013 | LBAC-10 | LAC-10 | RUT or UBT or H/UBT | 4 | 90.3%(28/31)/63.3%(19/30) | 13/12 | - | 1 |
| 谢静[29] | 2012 | LBAC-10 | LAC10 | UBT/UBT | 6 | 90.1%(73/81)/53.6%(45/84) | 11/7 | - | 2 |
| 赵春明[30] | 2012 | RBAF-10 | RAC-10 | UBT/UBT | 4 | 90.57%(96/106)/79.69%(50/64) | - | 5/5 | 2 |
| 彭美玲[31] | 2012 | RBAF-10 | RAF-10 | RUT/UBT | 4 | 91.2%(73/80)/71.3%(57/80) | 8/8 | 0/0 | 1 |
| 赵蕊[32] | 2012 | EBAF-10 | EAF-7 | RUT or UBT/UBT6 | 4 | 86%(43/50)/74%(37/50) | 2/2/2/3 | 1/2/2/3 | 3 |
| EAF-10 | 78%(39/50) | ||||||||
| EBAF-7 | 82%(41/50) | ||||||||
| 杨秀英[33] | 2012 | RBAF-10 | RAC-10 | RUT/UBT | 4 | 93.2%(41/44)/73.8%(31/42) | 6/5 | 0/0 | 1 |
| 章金艳[34] | 2012 | EBAC-10 | EAC-7 | RUT or UBT/UBT | 6 | 88.6%(62/70)/74.3%(52/70) | 5/4 | 3/2 | 2 |
| Xu[35] | 2012 | OBAC-14 | OAC-7 | RUT or C/BUT | 4 | 90.0%(36/40)/70%(28/40) | 6/4/5 | 1/2/1 | 2 |
| OBAC-7 | 75%(30/40) | ||||||||
| 陈婉珺[36] | 2011 | PBMT-10 | PAC-7 | RUT.G/UBT | 4 | 89.41%(76/85)/63.53%(54/85) | 36/51 | 1/1 | 2 |
| 丛春莉[37] | 2010 | OBLF-10 | OLF-10 | RUT.UBT/UBT | 4 | 90%(45/50)/74%(37/50) | 5/5 | 1/2 | 2 |
| Gao[38] | 2010 | RBAL-10 | OA/OTiC-10 | RUT or H/UBT | 4~6 | 83.33% (60/72) /88.89%(64/72) | 6/14/11 | 0/0/0 | 3 |
| OAC-7 | 80.56%(58/71) | ||||||||
| Zheng[39] | 2010 | PBMT-10 | PAC-7 | UBT.G/UBT | 4 | 89.4% (76/85)/63.5%(54/85) | 35/45 | 2/2 | 2 |
| 郑青[40] | 2009 | PBMT-10 | PAC-7 | RUT.G/UBT | 4 | 88.9%(40/45)/73.3%(33/45) | - | 1/2/1 | 2 |
| PBMT-7 | 79.1%(34/43) | ||||||||
| 方建武[41] | 2006 | RBAC-14 | OAC-14 | H.RUT/ H.RUT | 2 | 85.7%(36/42)/63.2%(24/38) | 17/9 | - | 1 |
| 邹夏慧[42] | 2016 | RBAC-10 | RA/RCF-10 | RUT or UBT/UBT | 4 | 81.67%(49/60)/88.33%(53/60) | 8/6/7/5 | 4/3/5/4 | 1 |
| RACF-7 | 83.33%(50/60) | ||||||||
| RBAC-7 | 73.33%(44/60) | ||||||||
| 卫金歧[43] | 2014 | ApBAL-10 | ApA/ApLF-10 | RUT/UBT | 4~6 | 85.00%(85/100)/82%(82/100) | 6/7 | 2/2 | 2 |
| 张志宏[47] | 2014 | OBAC-10 | OA/OCM-10 | RUT.UBT/RUT.UBT | 4 | 90.56%(48/53)/88.46%(46/52) | 1/7/8 | 0/0/0 | 2 |
| OACM-10 | 90.38%(47/52) | ||||||||
| 李月月[45] | 2014 | OBAC-10 | OA/OCTi-10 | RUT/UBT | 6 | 85.3%(64/75)/70.7%(53/75) | 11/8/10 | 3/11/2 | 2 |
| OACTi-10 | 85.6%(65/76) | ||||||||
| 孙丽玲[46] | 2012 | RBAC-10 | RA/RCTi10 | RUT.BUT/RUT.BUT | 4 | 86.1%(31/36)/88.6%(31/35) | 4/5/3 | 1/1/0 | 3 |
| RCA-7 | 64.7%(22/34) | ||||||||
| 张杰[47] | 2012 | RBAC-10 | RA/RCTi-8 | RUT or UBT/UBT | 4 | 91.1%(102/112)/90.2%(101/112) | 7/6/10 | 3/3/5 | 2 |
| RAC10 | 89/111 | ||||||||
| 邹国辉[48] | 2012 | RBAC-10 | RA/RCF-10 | RUT.G or UBT/UBT | 4 | 87.5%(35/40)/87.5%(35/40) | 9/10/6 | 3/2/2 | 3 |
| RAC7 | 72.5(29/40) | ||||||||
| Liao[49] | 2015 | IBAL-10 | IA/IFL-10 | RUT/BUT | 4~6 | 85.15%(86/101)/81.82%(81/99) | 6/7 | 2/2 | 2 |
| 杨雷[50] | 2015 | EBAC-14 | EACM-7 | UBT/UBT | 4 | 91.55%(65/71)/80.56%(58/72) | 3/4/3/3 | 3 | 3 |
| EACM-14 | 92.96%(66/71) | ||||||||
| EBAC-7 | 78.57%(55/70) | ||||||||
| 陈晓琴[51] | 2011 | OBAC-14 | OATF-14 | UBT/UBT | 4 | 90% (54/60)/91.67% (55/60) | 8/7 | - | |
| R：雷贝拉唑；P：泮托拉唑；O：奥美拉唑；E：埃索美拉唑：Ap:艾普拉唑；RUT：快速尿素酶法；UBT：尿素呼气试验；C：细菌培养；H：组织学检验；B：铋剂：C:克拉霉素；A:阿莫西林；F：呋喃唑酮；T：四环素；Ti:替硝唑；M：甲硝唑；Mo:莫西沙星 | |||||||||
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| 图 1 关于实验纳入及排除的流程 |
2.2 Meta分析结果 2.2.1 10 d或14 d铋剂四联疗法与三联疗法比较
共36篇研究进行关于10 d或14 d铋剂四联疗法与三联疗法的比较。如图 2所示，据ITT分析，铋剂四联疗法及三联疗法的根除率分别是88.96%(95%CI:87.73%~90.19%)和74.11%(95%CI:72.53%~75.69%), 两者相比，差异有统计学意义(RR=1.20，95%CI：1.16%~1.25%)。因为异质性存在(I2= 49%, P=0.000 7)，因此使用随机效应模型进行累积分析。图 3漏斗图基本对称，无明显发表偏倚。二者的不良反应发生率差异无统计学意义(RR=1.04，95% CI：0.92%~1.17%)。
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| 图 2 10 d或14 d铋剂四联疗法与三联疗法比较的Meta分析森林图 |
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| 图 3 10 d或14 d铋剂四联疗法与三联疗法比较的漏斗分析 |
2.2.2 10 d或14 d铋剂四联疗法与序贯疗法相比
共有9篇行10 d或14 d铋剂四联疗法与序贯疗法比较的研究。如图 4示，据ITT分析，铋剂四联疗法及序贯疗法的根除率分别是86.29%(95% CI：83.64%~88.94%)及84.65%(95% CI：87.43%~81.87%)，差异没有统计学意义(RR=1.02，95% CI：0.97%~1.07%)，使用固定效应模型进行累积分析(I2=0%, P=0.50)；两组不良反应发生率差异无统计学意义(RR=0.82，95% CI：0.59%~1.14%)。
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| 图 4 10 d或14 d铋剂四联疗法与序贯疗法比较的Meta分析森林图 |
2.2.3 10 d或14 d铋剂四联疗法与伴随疗法的比较
关于10 d或14 d铋剂四联疗法与伴随疗法比较的研究有5篇(图 5)。两组的根除率(ITT分析)分别是87.77%(95% CI：84.18%~91.37%)、87.21%(95% CI：83.90%~90.52%)，差异无统计学意义(RR=1.01，95% CI：0.95%~1.07%)，行固定效应模型分析(I2=0%, P=0.87)；两组不良反应发生率差异无统计学意义(RR=0.87，95% CI：0.56%~1.37%)。
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| 图 5 10 d或14 d铋剂四联疗法与伴随疗法比较的Meta分析森林图 |
2.2.4 10 d或14 d铋剂四联疗法与7 d铋剂四联疗法比较
共有9篇研究涉及铋剂四联疗法10 d或14 d与7 d疗效比较。如图 6所示：据意向性分析，两组的根除率分别是87.34%(95% CI：84.87%~89.80%)、81.65%(95% CI:78.76%~84.54%)，差异具有统计学意义(RR=1.07，95% CI：1.02%~1.12%)，无异质性存在(I2=0%, P=0.57)，使用固定效应模型；两组不良反应发生率差异无统计学意义(RR=1.11，95% CI：0.72%~1.73%)。
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| 图 6 10 d或14 d铋剂四联疗法与7 d铋剂四联疗法比较的Meta分析森林图 |
3 讨论
京都共识明确将H.pylori性胃炎定义为感染性疾病，有效根除H.pylori可减少传染源、治疗或缓解H.pylori相关疾病及其并发症，较大程度预防胃癌的发生，根除其利远大于弊[52-53]。抗生素高耐药是H.pylori根除治疗面临的最大难题，黄继平等[54]关于深圳东部地区H.pylori耐药状况调查显示，H.pylori对阿莫西林、克拉霉素、甲硝唑、呋喃唑酮及左氧氟沙星的耐药率分别是2.1%、24%、82.3%、1.0%及47.9%；关于北京地区H.pylori对抗生素耐药情况调查显示，克拉霉素、甲硝唑及氟喹诺酮耐药率自2000-2009年分别由14.8%上升至65.4%，38.9%~78.8%，27.1%~63.5%。面对抗生素耐药率逐年增高，经典三联疗法根除率急剧下降，个体化治疗(依赖抗生素药敏试验及基因多态性检测)还未全面展开的局面，寻找有效安全的经验性治疗方案非常必要。
在本研究中，我们对含有铋剂的四联疗法与三联疗法、序贯疗法、伴随疗法及7 d铋剂四联疗法随机对照试验进行比较分析，结果表明，铋剂四联疗法及三联疗法的根除率分别是88.96%(95% CI:87.73%~90.19%)和74.11%(95% CI:72.53%~75.69%)，可看出10 d或14 d铋剂四联疗法明显优于三联疗法，其机制可能与幽门螺杆菌对克拉霉素及甲硝唑耐药，铋剂能抑制幽门螺杆菌细胞壁及蛋白合成、抑制细胞膜功能有关，与抗生素发挥协同作用，从而提高H.pylori的根除率[55]。一项研究示7 d三联疗法加入铋剂，根除率从66.67%提高至82.09%(ITT分析)[56]；而将7 d疗程延长至14 d，根除率可从80%提高至93.7%(ITT分析)[57]。我国含铋剂-呋喃唑酮四联疗法或含铋剂-四环素四联治疗方案均可取的满意疗效，甚至在补救治疗中可发挥更好疗效。一项关于阿莫西林、四环素、呋喃唑酮中任选两种抗生素的铋剂四联疗法研究中，铋剂四联疗法根除率可达90%以上，其中含呋喃唑酮及阿莫西林方案的根除率可达95%。但关于左氧氟沙星/替硝唑的铋剂四联疗法研究中，包含泮托拉唑及替硝唑的铋剂四联疗法根除率不到60%[8]，另一三联疗法与铋剂四联疗法相比的实验，铋剂四联疗法疗效甚至低于三联疗法[21]，原因可能都与幽门螺杆菌对抗生素如替硝唑等高耐药率有关，因此在临床治疗中，可选择四环素、阿莫西林、呋喃唑酮等耐药率相对低的抗生素，或给予足够的剂量及疗程，来提高铋剂四联疗法根除率。
与序贯疗法及伴随疗法相比，10 d或14 d铋剂四联疗法差异无统计学意义。伴随疗法及序贯疗法在我国相关研究较少。一项关于伴随疗法在我国的Meta分析表明，伴随疗法疗效明显优于三联疗法，而与序贯疗法无显著差异，但其依从性较序贯疗法好[58]。另一项Meta分析也同样显示序贯疗法与伴随疗法根除率差异无统计学意义[59]。Yeo等[4]对克拉霉素高耐药或低耐药地区H.pylori一线治疗进行荟萃分析，表明序贯疗法具有明显优势，可用于克拉霉素高耐药或低耐药地区。本研究中序贯疗法及伴随疗法疗效与铋剂四联疗法的对照研究纳入数量均较少，需要更多的数据行序贯疗法及伴随疗法与铋剂四联疗法的Meta分析。在10 d或14 d铋剂四联疗法与7 d铋剂四联疗法的比较中，前者稍优于后者，这与以往经验一致，即延长铋剂治疗方案疗程，可一定程度上提高根除率。
10 d或14 d铋剂四联疗法优于三联疗法及7 d铋剂四联疗法，可用于幽门螺杆菌根除治疗的首选。但本研究存在以下不足:① 所纳入的研究对象均是18岁以上成人，未行18岁以下人群对比研究；② 许多研究未评价幽门螺杆菌对抗生素的耐药情况；③ 纳入的43项研究均为随机对照研究，许多研究未提及盲法、分配隐匿、失访及其原因，研究样本量小等局限，对研究结果可能会有一定影响。因此，关于铋剂四联疗法、序贯疗法及伴随疗法的疗效评估还需要更多高质量的随机对照试验进行Meta分析。
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