Clarithromycin Resistance, but Not CYP2C-19 Polymorphism, Has a Major Impact on Treatment Success in 7-Day Treatment Regimen for Cure of H. pylori Infection: A Multiple Logistic Regression Analysis

Mutations in the gene encoding the CYP2C-19 enzyme for PPI metabolism have been shown to enhance the chance for a cure in a H. pylori-positive patients using a two-week dual-therapy regimen involving omeprazole and amoxicillin. However, the impact of CYP2C-19 genetic polymorphism on eradication rates of a one-week triple-therapy regimen has not been examined. In this cohort study, 156 H. pylori-positive peptic ulcer or NUD patients who presented to our university hospital were recruited. They were treated by one-week omeprazole–amoxicillin–clarithromycin therapy. Host and bacterial predictive factors including H. pylori susceptibility and CYP2C-19 genotyping, as well as cure rate for H. pylori infection, were studied. Cure rate was 85.9% (95% CI: 79–91%) on an intent to treat (ITT) basis. By multiple logistic regression analysis, only clarithromycin resistance had a significant impact on treatment success (odds ratio 28.7: 95% CI: 6–172). CYP2C-19 genetic polymorphism was not associated with a significant change in cure rate. These observations indicate only clarithromycin susceptibility, not CYP2C-19 polymorphism, has a major impact on the treatment success when using a seven-day OAC H. pylori treatment regimen.     

A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism

BACKGROUND AND AIM: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. METHODS: One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [(13)C]-urea breath test at 1--2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56--75) and 62.4% (95% CI, 52--71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure. CONCLUSION: Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.     

香砂六君子汤治疗慢性萎缩性胃炎的Meta分析

目的：系统分析香砂六君子汤治疗慢性萎缩性胃炎的疗效和安全性。方法：通过检索PubMed、Cochrane Library、Medline、中国期刊全文数据库、中国学术期刊数据库、中文科技期刊数据库等数据库,收集2010年1月至2020年1月以香砂六君子汤为基础方治疗慢性萎缩性胃炎的随机对照试验,按Cochrane系统评价的方法评价纳入研究的质量,并用RevMan5.3软件对结局指标进行Meta分析。结果：纳入17篇文献研究,共1 621例患者。Meta分析结果：与对照组比较,香砂六君子汤组可以提高慢性萎缩性胃炎的总有效率、治愈率及幽门螺杆菌根除率,促进胃黏膜修复,降低复发率,差异有统计学意义（P<0.05）;但未能降低不良反应的发生率（P>0.05）。结论：相较于常规使用的中成药和西药,香砂六君子汤治疗慢性萎缩性胃炎更有效。     

海岛地区就医患者幽门螺杆菌对常用抗生素的耐药特点分析

目的　探讨幽门螺杆菌（IHelicobacter pylori/I， Hp）对海岛地区常用抗生素的耐药特点，并根据本地区特点指导选择最特异最合适的抗生素进行治疗。方法　将来自不同患者的胃镜活检标本分别涂布接种幽门螺杆菌培养基后37 ℃微需氧环境下培养96 h, 对188株Hp临床分离株采用Kirby-Bauer法行甲硝唑、克拉霉素、阿莫西林、呋喃唑酮和左氧氟沙星5种抗生素药敏试验,并分析其特点。结果　Hp临床分离株对甲硝唑、克拉霉素、阿莫西林、呋喃唑酮和左氧氟沙星5种抗生素的耐药率分别为98.9%, 18.1%, 0.1%，8.5%和7.8%。舟山各区县和城乡之间对常用抗生素耐药率比较差异无统计学意义。结论　甲硝唑耐药率均较高, 可用呋喃唑酮替代甲硝唑，左氧氟沙星也可以选择；应注意对本地克拉霉素耐药的监测；根据体外药敏试验有利于提高Hp的根除率。     

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??Objective??To understand the clinical eradication therapy for Helicobacter pylori infection in children and analyze the causes. Methods??H.pylori eradication therapy for 10 or 14 days was accepted by 301 cases of children??who were diagnosed with H.pyori infection??in the Children’s Hospital of Zhejiang University School of Medicine from January??2012 to October??2015. Finally??the eradication rate of H.pylori was judged. Results??In initial treatment??the eradication rate of OAC program??omeprazole??amoxicillin and clarithromycin?? was 42.3%??the eradication rate of non-OAC program was 56.7%??and there were statistically significant differences between the two groups??P??0.05??. The eradication rate of bismuth-based regimens was 50.0%??the eradication rate of standard triple therapy was 41.2%??and there were no statistically significant differences between the two groups??P??0.05??. In the rescue treatment??the eradication rate of bismuth-based quadruple therapy was 58.3%??the eradication rate of triple therapy with furaxone was 55.0%??and there were no statistically significant differences between the two groups??P??0.05??. Totally 119 strains of H.pylori were not resistant to amoxicillin??while the resistance rate to clarithromycin and metronidazole was 27.7% and 69.3%??respectively. Conclusion??In this study??the clinical eradication rate in children with Hp infection fails to achieve the goal eradication rate of 80%. Drug sensitivity test is still the first choice for treatment of Helicobacter pylori infection in children.     

质子泵抑制剂大剂量二联与铋剂四联在幽门螺杆菌根除治疗中的疗效比较

目的 比较质子泵抑制剂大剂量二联与铋剂四联对幽门螺杆菌(Helicobacter pylori,H.pylori)的根除率和不良反应的发生率.方法 选择2021年1月至2021年8月就诊于河北省人民医院消化内科门诊的H.pylori阳性患者208例,随机分为试验组(质子泵抑制剂大剂量二联)和对照组(铋剂四联),其中试验...     

Role of band ligation for secondary prophylaxis of variceal bleeding

AIM To summarize and critically examine the role of band ligation in secondary prophylaxis of variceal bleeding in patients with cirrhosis. METHODS A literature review was performed using the MEDLINE and PubM ed databases. The search terms consisted of the words "endoscopic band ligation" OR "variceal band ligation" OR "ligation" AND "secondary prophylaxis" OR "secondary prevention" AND "variceal bleeding" OR "variceal hemorrhage" AND "liver cirrhosis". The data collected from relevant meta-analyses and from the most recent randomized studies that were not included in these meta-analyses were used to evaluate the role of endoscopic band ligation in an effort to demonstrate the most recent advances in the treatment of esophageal varices. RESULTS This study included 11 meta-analyses published from 2002 to 2017 and 10 randomized trials published from 2010 to 2017 that evaluated the efficacy of band ligation in the secondary prophylaxis of variceal bleeding. Overall, the results proved that band ligation was superior to endoscopic sclerotherapy. Moreover, the use of β-blockers in combination with band ligation increased the treatment effectiveness, supporting the current recommendations for secondary prophylaxis of variceal bleeding. The use of transjugular intrahepatic portosystemic shunt was superior to combination therapy regarding rebleeding prophylaxis, with no difference in the survival rates; however, the results concerning the hepatic encephalopathy incidence were conflicting. Recent advances in the management of secondary prophylaxis of variceal bleeding have targeted a decrease in portal pressure based on the pathophysiological mechanisms of portal hypertension.CONCLUSION This review suggests that future research should be conducted to enhance current interventions and/or to develop innovative treatment options with improved clinical endpoints.     

Nonbismuth concomitant quadruple therapy for Helicobacter pylori eradication in Chinese regions: A meta-analysis of randomized controlled trials

AIM: To evaluate the applicability of nonbismuth concomitant quadruple therapy for Helicobacter pylori (H. pylori) eradication in Chinese regions.METHODS: A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the efficacy of nonbismuth concomitant quadruple therapy between sequential therapy or triple therapy for H. pylori eradication in Chinese regions. The defined Chinese regions include China, Hong Kong, Taiwan, and Singapore. The primary outcome was the H. pylori eradication rate; the secondary outcome was the compliance with therapy. The PubMed, Embase, Scopus, and Cochrane databases were searched for studies published in the period up to March 2016 with no language restriction.RESULTS: We reviewed six randomized controlled trials and 1616 patients. In 3 trials comparing concomitant quadruple therapy with triple therapy, the H. pylori eradication rate was significantly higher for 7-d nonbismuth concomitant quadruple therapy than for 7-d triple therapy (91.2% vs 77.9%, risk ratio = 1.17, 95%CI: 1.09-1.25). In 3 trials comparing quadruple therapy with sequential therapy, the eradication rate was not significant between groups (86.9% vs 86.0%). However, higher compliance was achieved with concomitant therapy than with sequential therapy.CONCLUSION: The H. pylori eradication rate was higher for nonbismuth concomitant quadruple therapy than for triple therapy. Moreover, higher compliance was achieved with nonbismuth concomitant quadruple therapy than with sequential therapy. Thus, nonbismuth concomitant quadruple therapy should be the first-line treatment in Chinese regions.     

Optimal treatment strategy for Helicobacter pylori:Era of antibiotic resistance

Standard triple therapy,consisting of a proton pump inhibitor,plus amoxicillin and clarithromycin,has been the most commonly used first-line treatment regimen for Helicobacter pylori(H.pylori)eradication for many years worldwide.However,as a result of increased resistance to antibiotics,H.pylori eradication rates with use of standard triple therapy have been declining and recently reached<80%in many countries.Several new strategies to enhance the eradication rate of H.pylori have been studied.Currently,among the alternative first-line eradication regimens,concomitant and hybrid regimens have shown excellent results and could be the optimal treatment option.Although clinical usefulness of rescue therapy for patients in whom eradication of H.pylori with non-bismuth quadruple regimen has failed is unclear,levofloxacin-based quadruple therapy has shown promise as a rescue treatment.The choice of third-line therapy depends on factors such as the local pattern of antibiotic resistance,drug availability,and previous treatment.We hope that a simple method for detection of antibiotic susceptibility using polymerase chain reaction would be a possible alternative to administration of"tailored treatment"in the era of increasing prevalence of antimicrobial resistance.     

Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype

The cure rates of Helicobacter pylori(H.pylori)eradication therapy using a proton pump inhibitor(PPI)and antimicrobial agents such as amoxicillin,clarithromycin,and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion.Annual cure rates have gradually decreased because of the increased prevalence of H.pylori strains resistant to antimicrobial agents,especially to clarithromycin.Alternative regimens have therefore been developed incorporating different antimicrobial agents.Further,standard PPI therapy(twice-daily dosing)often fails to induce a long-term increase in intragastric pH>4.0.Increasing the eradication rate requires more frequent and higher doses of PPIs.Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes(e.g.,cytochrome P450 2C19,CYP2C19),drug transporters(e.g.,multidrug resistance protein-1;ABCB1),and inflammatory cytokines(e.g.,interleukin-1β).For example,quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h,irrespective of CYP2C19 genotype.Therefore,tailored H.pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.