应停用包括阿司匹林在内的 NSAID,因为这是这些患者最可能的病因。如果不能停用,或者患者需长期服用小剂量阿司匹林来预防心血管疾病,应长期进行预防性抑酸治疗。为了降低胃肠道毒性(包括溃疡)的风险,相对于使用非甾体抗炎药,可优先考虑使用环氧合酶-2 抑制剂。一项大型随机临床试验发现,对于关节炎患者,在心血管安全性方面,中等剂量的塞来昔布不劣效于布洛芬和萘普生。[33]Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016 Nov 13;375(26):2519-29.www.doi.org/10.1056/NEJMoa1611593http://www.ncbi.nlm.nih.gov/pubmed/27959716?tool=bestpractice.com
然后应该启动溃疡愈合治疗。通常来说,PPI 是使溃疡愈合的首选药物,因其给药方案且治疗有效。PPI 和 H2 受体拮抗剂均可抑制胃酸分泌,但是 PPI 可在更大程度的减少胃酸分泌,从而使溃疡更迅速的愈合。[34]Richardson C, Hawkey CJ, Stack WA. Proton pump inhibitors - pharmacology and rationale for use in gastrointestinal disorders. Drugs. 1998 Sep;56(3):307-35.http://www.ncbi.nlm.nih.gov/pubmed/9777309?tool=bestpractice.com 然而,如果患者对质子泵抑制剂无反应,可使用 H2 受体拮抗剂。
使用硫糖铝与使用 H2 受体拮抗剂的溃疡愈合率相似。然而,频繁的给药方案和大药片可能影响依从性;因而很少推荐该药。抗酸药疗效相对较差,促进溃疡愈合的速度缓慢,因此也不推荐使用。
对于需要长期服用 NSAID 的患者,为了预防由 NSAID 引起的胃溃疡,使用米索前列醇是另一种选择。[35]Rostom A, Dube C, Wells G, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2002;(4):CD002296.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002296/fullhttp://www.ncbi.nlm.nih.gov/pubmed/12519573?tool=bestpractice.com
如果存在幽门螺杆菌,则应该开始根除治疗。如果患者正在服用非甾体抗炎药(包括阿司匹林),应尽可能停用。
根除治疗可使溃疡愈合,并显著减少溃疡复发。[36]Ford AC, Gurusamy KS, Delaney B, et al. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people. Cochrane Database Syst Rev. 2016;(4):CD003840.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003840.pub5/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27092708?tool=bestpractice.com [
]Is there randomized controlled trial evidence to support the use of eradication therapy for healing peptic ulcer disease in Helicobacter pylori positive patients?https://cochranelibrary.com/cca/doi/10.1002/cca.1362/full显示答案 [
]Is there randomized controlled trial evidence to support the continuation of eradication therapy for preventing recurrence of peptic ulcer disease in previous Helicobacter pylori positive patients?https://cochranelibrary.com/cca/doi/10.1002/cca.1207/full显示答案 在临床实践中,大多数治疗方案的有效性在 70%-90% 之间,主要受到抗生素耐药和患者对治疗方案依从性的限制。如果没有明确感染,则不需要根除治疗。
对于经选择的患者,推荐将三联治疗(一种质子泵抑制剂+两种抗酸药)作为一线治疗。[25]Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.http://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com[37]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. November 2014 [internet publication].https://www.nice.org.uk/guidance/cg184
对于无大环内酯类抗生素暴露既往史的患者以及在已知克拉霉素耐药率低 (<15%) 的区域,基于克拉霉素的三联治疗(一种质子泵抑制剂+克拉霉素+阿莫西林或甲硝唑)是一种一线治疗选择。[25]Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.http://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com[37]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. November 2014 [internet publication].https://www.nice.org.uk/guidance/cg184 对于有青霉素过敏的患者,应使用甲硝唑替代阿莫西林。[25]Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.http://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com[37]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. November 2014 [internet publication].https://www.nice.org.uk/guidance/cg184
对于有既往大环内酯类抗生素暴露的患者,推荐使用四联治疗(一种质子泵抑制剂+铋剂+四环素+硝基咪唑 [例如甲硝唑或替硝唑])。[25]Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.http://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com[37]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. November 2014 [internet publication].https://www.nice.org.uk/guidance/cg184 对于有青霉素过敏的患者,四联治疗也是一种选择。
基于铋剂的方案和序贯治疗(即,先使用 5 天质子泵抑制剂+阿莫西林,然后使用 5 天质子泵抑制剂+克拉霉素和一种硝基咪唑 )可能与标准的三联一线治疗有相当的根除率。[38]Luther J, Higgins PD, Schoenfeld PS, et al. Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol. 2009 Sep 15;105(1):65-73.http://www.ncbi.nlm.nih.gov/pubmed/19755966?tool=bestpractice.com[39]Venerito M, Krieger T, Ecker T, et al. Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection. Digestion. 2013 Jul 19;88(1):33-45.www.doi.org/10.1159/000350719http://www.ncbi.nlm.nih.gov/pubmed/23880479?tool=bestpractice.com[40]Nyssen OP, McNicholl AG, Megraud F, et al. Sequential versus standard triple first-line therapy for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2016;(6):CD009034.www.doi.org/10.1002/14651858.CD009034.pub2http://www.ncbi.nlm.nih.gov/pubmed/27351542?tool=bestpractice.com
同步治疗(质子泵抑制剂、克拉霉素、阿莫西林和硝基咪唑)、混合治疗(质子泵抑制剂和阿莫西林使用 7 天,然后质子泵抑制剂、阿莫西林、克拉霉素和硝基咪唑使用 7 天)、左氧氟沙星三联治疗(质子泵抑制剂、左氧氟沙星和阿莫西林)以及氟喹诺酮序贯治疗(质子泵抑制剂和阿莫西林使用 5-7 天,之后质子泵抑制剂、氟喹诺酮和硝基咪唑使用 5-7 天)为替代一线治疗方案。[25]Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.http://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com 然而,评估其证据质量发现质量非常低。[25]Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.http://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
所有方案都含有抗生素,所以可能造成腹泻、促发机会性感染以及影响包括口服避孕药在内的许多其他药物的吸收。
治疗结束后一个月复查幽门螺杆菌是否被清除。[27]Best LM, Takwoingi Y, Siddique S, et al. Non-invasive diagnostic tests for Helicobacter pylori infection. Cochrane Database Syst Rev. 2018;(3):CD012080.www.doi.org/10.1002/14651858.CD012080.pub2http://www.ncbi.nlm.nih.gov/pubmed/29543326?tool=bestpractice.com 对于多数患者,治疗感染后,没有必要继续使用抑酸治疗。
如果初次治疗失败,需要尝试至少一种其他治疗方案。二线治疗应避免使用一线治疗中包含的抗生素。[25]Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.http://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com[37]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. November 2014 [internet publication].https://www.nice.org.uk/guidance/cg184 如果多次治疗仍不能根除幽门螺杆菌,那么可能应长期服用抑酸药来控制症状。
在多药耐药性发生率高的地区,与单独应用以克拉霉素为基础的三联治疗相比,在治疗前进行抗微生物药物敏感性检测,并以此为指导选择的治疗能够更有效地清除幽门螺杆菌。然而,幽门螺杆菌和分子检测未在所有国家普及。[41]Park CS, Lee SM, Park CH, et al. Pretreatment antimicrobial susceptibility-guided vs. clarithromycin-based triple therapy for Helicobacter pylori eradication in a region with high rates of multiple drug resistance. Am J Gastroenterol. 2014 Oct;109(10):1595-602.http://www.ncbi.nlm.nih.gov/pubmed/25091062?tool=bestpractice.com