CYP2C19基因多态性对埃索美拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 研究CYP2C19(cytochrome P450 2C19)基因多态性对以埃索美拉唑为基础三联1周疗法的Hp根除率的影响.方法 选取101例Hp阳性的慢性胃炎或消化性溃疡患者,分成2组,分别进入埃索美拉唑联合阿莫西林与克拉霉素方案(EAC)或奥美拉唑联合阿莫西林与克拉霉素方案(OAC)进行1周根除治疗.治疗前采...     

细胞色素P450 2C19基因多态性对埃索美拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 前瞻性对比埃索美拉唑和奥美拉唑三联疗法根除幽门螺杆菌(Hp)的疗效,及细胞色素P450(CYP)2C19基因多态性对根除Hp疗效的影响.方法 240例Hp阳性消化性溃疡患者,随机分为EAC组(埃索美拉唑、阿莫西林和克拉霉素)和OAC组(奥美拉唑、阿莫西林和克拉霉素),每组120例,疗程7 d.继后埃索美拉唑或奥美拉唑巩固治疗3周.胃镜观察2周溃疡愈合情况,结束治疗4周后进行13C尿素呼气试验.利用聚合酶链反应(PCR)及限制片段长度多态性(RFLP)分析技术,测定所有患者的CYP2C19基因型,分为强代谢型(Ems)和弱代谢型(PMs),强代谢型包括纯合子(homEM)和杂合子(hetEM).结果 240例患者中225例完成疗效观察.Hp根除率按意向处理分析(ITT),EAC组为88.3%,OAC组为79.2%(P>0.05);按方案分析(PP)EAC组为91.4%,OAC组为87.2 oA(P>0.05).ITT分析显示,在CYP2C19 homEM基因型中,EAC和OAC组Hp根除率分别为91.9%和71.8%,两组间差异有统计学意义(P=0.037).PP分析显示,在homEM基因型中,EAC组和OAC组Hp根除率分别为97.1%和77.8%,两组间差异也有统计学意义(P=0.028).ITT分析显示,EAC组和OAC组2周溃疡愈合率分别为79.2%和69.2%(P>0.05);PP分析显示分别为81.9%和76.1%(P>0.05).EAC组和OAC组不良反应均较少(分别为3.3%和7.5%,P>0.05).结论 EAC方案Hp根除率较高,尤其在CYP2C19 homEM基因型患者,埃索美拉唑优于奥美拉唑.     

细胞色素P450 2C19基因多态性对埃索美拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 前瞻性对比埃索美拉唑和奥美拉唑三联疗法根除幽门螺杆菌(Hp)的疗效,及细胞色素P450(CYP)2C19基因多态性对根除Hp疗效的影响.方法 240例Hp阳性消化性溃疡患者,随机分为EAC组(埃索美拉唑、阿莫西林和克拉霉素)和OAC组(奥美拉唑、阿莫西林和克拉霉素),每组120例,疗程7 d.继后埃索美拉唑或奥美拉唑巩固治疗3周.胃镜观察2周溃疡愈合情况,结束治疗4周后进行13C尿素呼气试验.利用聚合酶链反应(PCR)及限制片段长度多态性(RFLP)分析技术,测定所有患者的CYP2C19基因型,分为强代谢型(Ems)和弱代谢型(PMs),强代谢型包括纯合子(homEM)和杂合子(hetEM).结果 240例患者中225例完成疗效观察.Hp根除率按意向处理分析(ITT),EAC组为88.3%,OAC组为79.2%(P>0.05);按方案分析(PP)EAC组为91.4%,OAC组为87.2 oA(P>0.05).ITT分析显示,在CYP2C19 homEM基因型中,EAC和OAC组Hp根除率分别为91.9%和71.8%,两组间差异有统计学意义(P=0.037).PP分析显示,在homEM基因型中,EAC组和OAC组Hp根除率分别为97.1%和77.8%,两组间差异也有统计学意义(P=0.028).ITT分析显示,EAC组和OAC组2周溃疡愈合率分别为79.2%和69.2%(P>0.05);PP分析显示分别为81.9%和76.1%(P>0.05).EAC组和OAC组不良反应均较少(分别为3.3%和7.5%,P>0.05).结论 EAC方案Hp根除率较高,尤其在CYP2C19 homEM基因型患者,埃索美拉唑优于奥美拉唑.     

Effects of CYP2C19 and MDR1 genotype on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxycillin and clarithromycin

Backgrounds:  CYP2C19 polymorphism plays an important role in the metabolism of proton pump inhibitors. The multidrug resistance (MDR)1 genotype is associated with the successful eradication of Helicobacter pylori . The aim of the present study was to investigate the effects of CYP2C19 and MDR1 genotypes on the eradication rate of H. pylori using a pantoprazole-based triple therapy.
Methods:  A total of 210 patients infected with H. pylori were treated with 40 mg pantoprazole, 500 mg clarithromycin and 1000 mg amoxicillin twice daily for 7 days. The CYP2C19 genotype was determined with polymerase chain reaction (PCR)–restriction fragment length polymorphism analysis. The MDR1 C3435T polymorphism was identified by PCR-based allele-specific amplification (PCR-ASA).
Results:  Of the 210 patients who completed the study, 174 (82.9%, 95.0% confidence interval [CI], 77.8–88.0%) achieved successful eradication after the first cycle of therapy. The eradication rates for H. pylori were 86.7%, 81.1% and 82.1% in the homozygous extensive, heterozygous extensive and poor metabolizer groups, respectively ( P  = 0.65). Moreover, the cure rates in the CC, CT, and TT groups were 82.7%, 84.4% and 76.9%, respectively ( P  = 0.66). Multiple logistic regression analysis revealed that endoscopic diagnosis was a significant independent risk factor for treatment failure.
Conclusion:  The eradication rates of H. pylori by pantoprazole, amoxicillin and clarithromycin were not significantly different among the CYP2C19 and MDR1 genotypes. Hence, the cure rate of H. pylori in the Korean population was no different for the CYP2C19 and MDR1 genotypes.     

CYP2C19 polymorphism influences Helicobacter pylori eradication

The known factors that have contributed to the decline of Helicobacter pylori(H.pylori)eradication rate include antibiotic resistance,poor compliance,high gastric acidity,high bacterial load,and cytochrome P450 2C19(CYP2C19)polymorphism.Proton pump inhibitor(PPI)is important in the eradication regimen.The principal enzyme implicated in the metabolism of PPIs is CYP2C19.The effects of PPI depend on metabolic enzyme,cytochrome P450 enzymes,and CYP2C19 with genetic differences in the activity of this enzyme(the homozygous EM,heterozygous EM(Het EM),and poor metabolizer).The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations.The CYP2C19genotype is a cardinal factor of H.pylori eradication in patients taking omeprazole-based or lansoprazolebased triple therapies.In contrast,the CYP2C19 polymorphism has no significant effect on the rabeprazolebased or esomeprazole-based triple therapies.The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism,but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies.Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug.Other possible factors influencing gastric acid secretion(e.g.,IL-1β-511 polymorphism)would be also under consideration.     

High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin

BACKGROUND/AIMS: Some patients are refractory to the usual triple therapy for eradication of Helicobacter pylori, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, so there needs to be an alternative strategy for retreatment after failure to eradicate the infection. METHODOLOGY: The study group comprised 17 H. pylori-positive patients who had failed to clear H. pylori infection after 1 week of treatment with usual doses of proton pump inhibitor, amoxicillin and clarithromycin. The sensitivity of H. pylori to clarithromycin and amoxicillin, and the CYP2C19 genotype status of each patient were determined and treatment with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2 weeks was started. RESULTS: Eleven patients were infected with a clarithromycin-resistant strain of H. pylori. Twelve patients had the homozygous extensive metabolizer genotype, 5 had the heterozygous extensive metabolizer genotype and there were none with the poor metabolizer genotype of CYP2C19. All patients were successfully cleared of their H. pylori infection without any adverse effects, irrespective of CYP2C19 genotype status (100%, 95% confidence interval: 76-100%). CONCLUSIONS: High-dose dual therapy with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2 weeks appears useful treatment strategy after failure of eradication of H. pylori by the usual triple proton pump inhibitor/amoxicillin/clarithromycin therapy.     

CYP2C19基因多态性对雷贝拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 分析CYP2C19基因多态性在含雷贝拉唑的不同三联方案中对幽门螺杆菌(Hp)根除率的影响。方法 连续收集128例Hp培养阳性的病人随机进入雷贝拉唑联合克拉霉素与羟氨苄青霉素方案(RAC)或雷贝拉唑联合羟氨苄青霉素与甲硝唑方案(RAM)进行1周根除治疗。治疗前CYP2C19基因多态性通过PCR-限制性片段长度多态性进行鉴定,治疗结束至少4周后Hp的状态用”C-呼气试验进行检测。结果 在128例病人中纯合子强代谢型(hom-Ems)、杂合子强代谢型(het-Ems)、弱代谢型(PMs)分别为30．5％、50．0％、19．5％。在无克拉霉素、甲硝唑耐药菌株的情况下,RAC方案与RAM方案的Hp根除率分别为98．1％与91．3％(按治疗方案分析)。但是,甲硝唑的耐药率高达66．8％,降低了RAM方案的Hp根除率。logistic回归分析显示不同的CYP2C19基因型对Hp的根除率没有显著的影响。结论 以雷贝拉唑为基础的三联疗法根除Hp无明显个体差异,RAC的治疗方案值得推荐。     

Interleukin-1beta genetic polymorphism influences the effect of cytochrome P 2C19 genotype on the cure rate of 1-week triple therapy for Helicobacter pylori infection

OBJECTIVES: Genetic polymorphism of interleukin (IL)-1beta is associated with differences in gastric acid suppression in response to Helicobacter pylori (H. pylori) infection. Thus, the polymorphism might affect H. pylori eradication therapy, as antibiotics used in treatment regimens may be acid sensitive. In this study, we examined the impact of IL-1beta genetic polymorphism on the cure rate of triple therapy for H. pylori in relation to cytochrome P (CYP) 2C19 genotype and antibiotic resistance. METHODS: A total 249 patients with peptic ulcer disease were randomized to receive one of the following regimens: amoxicillin and clarithromycin together with omeprazole, lansoprazole, or rabeprazole. CYP2C19 and IL-1beta-511 genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The intention-to-treat-based overall cure rate was 74.3% (95% CI=68-79%). In the normal acid secretion IL-1beta genotype group, the cure rate among CYP2C19 poor metabolizers (93.3%, 95% CI=56-99%) was significantly higher than among subjects in the CYP2C19 homozygous (60.0%, 95% CI=38-78%) and heterozygous (63.6%, 95% CI=46-78%), i.e., extensive metabolizer, groups (p<0.05). In the low acid secretion IL-1beta genotype group, there was no difference in the cure rate among the CYP2C19 genotype groups. Multiple logistic regression analysis identified susceptibility to clarithromycin (p<0.0001) and CYP2C19 genotype status (p=0.03) as significant independent factors for treatment failure. CONCLUSION: IL-1beta genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of 1-wk triple therapy for H. pylori infection.     

影响慢性胃炎患者幽门螺杆菌根除的临床因素分析

背景:幽门螺杆菌(H.pylori)感染与慢性胃炎和消化性溃疡密切相关,然而,目前临床普遍采用的三联疗法对相当一部分患者的H.pylori根除无效。目的:探讨影响慢性胃炎患者H.Pylori根除的主要临床因素。方法:取128例H.pylori阳性的慢性胃炎患者的内镜活检标本行H.pylori培养和药敏试验,以奥美拉唑+克拉霉素+甲硝唑的7 d三联疗法行H.pylori根除治疗,以PCR-RFLP法检测CYP2C19基因型。分析不同因素对H.pylori根除率的影响。结果:共123例完成治疗,H.pylori根除率按ITT和按PP分析分别为66.4%和69.1%。H.pylori对甲硝唑和克拉霉素的耐药率分别为48.4%和14.1%。有吸烟史者的H.pylori根除率显著低于无吸烟史者(37.0%对88.3%,P0.01)。甲硝唑敏感菌株和克拉霉素敏感菌株的根除率均显著高于相应的耐药菌株(90.5%对46.7%,P0.01;76.6%对18.8%,P0.01)。CYP2C19强代谢型的根除率显著低于弱代谢型(63.4%对 86.7%,P0.05)。不同性别、年龄以及是否饮酒的患者之间H.pylori根除率差异均无统计学意义(P0.05)。结论:H.pylori对抗生素耐药和宿主CYP2C19强代谢型是导致H.pylori根除失败的主要原因,吸烟史对根除失败亦具有一定的意义。     

Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype

BACKGROUND AND AIMS: Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1-week triple regimen were compared in relation to CYP2C19 polymorphism. METHOD: One hundred and eighty-three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. CYP2C19 polymorphism was analyzed by PCR restriction fragment length polymorphism. RESULTS: Intention-to-treat-based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69-89%), 86.7% (CI: 75-93%), and 76.6% (CI: 64-85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with CYP2C19 genotypes (P = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol-based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%; P = 0.038). CONCLUSION: The overall cure rate of 1-week triple therapy for H. pylori eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of CYP2C19 genetic polymorphism on the cure rate appeared to differ between these PPI.     

细胞色素P450 2C19基因多态性对以质子泵抑制剂为基础的三联疗法根除幽门螺杆菌疗效的影响

目的 研究以质子泵抑制剂(PPI)、左氧氟沙星、羟氨苄青霉素作为一线疗法对幽门螺杆菌(Hp)根除的影响,以及Hp根除率与CYP2C19基因多态性的相关性.方法 205例Hp阳性的患者被分为4组:埃索美拉唑20 mg 2次/d(E_(20)组),埃索美拉唑40 mg 2次/d(E_(40)组),雷贝拉唑10 mg 2次/d(R组),兰索拉唑30 mg 2次/d(L组),4组均加左氧氟沙星500 mg 1次/d和羟氨苄青霉素1000 mg 2次/d,疗程1周.其中有161例患者进行了CYP2C19基因型的检测,对Hp根除率分别按意愿治疗(intention-to-treat,ITT)分析和按方案(per protocol,PP)分析进行评估.结果 Hp总根除率为83.4%(PP)和79.0%(ITT).各组的根除率为:E_(20)组86.7%,E_(40)组88.5%,R组73.5%,L组78.1%.其中完成基因型检测的161例患者中,各基因型的根除率分别为:纯合子弱代谢型(PM)90%,杂合子强代谢型(HetEM)81.5%,纯合子强代谢型(HomEM)82.1%.CYP2C19各基因型间Hp根除率、各治疗方案间的根除率及各方案内各基因型间的根除率差异均无统计学意义(P>0.05).结论 以PPI为基础包含左氧氟沙星的三联疗法是目前根除Hp的有效方案,且该方案对Hp的根除率不受CYP2C19基因多态性的影响.     

CYP2C19基因多态性对亚洲人群中含质子泵抑制剂三联疗法幽门螺杆菌根除率影响的荟萃分析

以质子泵抑制剂（PPI）为基础的三联疗法的幽门螺杆菌（H．pylori）根除率不尽相同，可能与细胞色素P450（CYP）2C19基因多态性有部分关联。目的：研究CYP2C19基因多态性对亚洲人群中以PPI为基础的三联疗法H．pylori根除率的影响。方法：在PubMed、EMBASE、CNKI和万方数据中进行系统文献检索，以RevMan4．2．8软件行荟萃分析。结果：共17篇文献纳入荟萃分析。不考虑PPI类型，CYP2C19弱代谢型（PM）与杂合子强代谢型（HetEM）之间、PM与纯合子强代谢型（HomEM）之间、HetEM与HomEM之间H．pylori根除率均有显著差异（PM对HetEM：OR=1．75，95％CI1．24—2．47．舟0．002；PM对HomEM：OR=2．82，95％CI1．73～4．60，P〈0．0001；HetEM对HomEM：OR=1．84，95％CI1．33-2．57，P=-0．0003）。在以奥美拉唑或兰索拉唑为基础的三联疗法中，PM与HomEM之间、HetEM与HomEM之间且pylori根除率均有显著差异（含奥美拉唑方案PM对HomEM：OR=4．37，95％CI1．86—10．26．P=0．0007，HetEM对HomEM：OR=3．15,95％CI1．75—5．66，P=0．0001；含兰索拉唑方案PM对HomEM：OR=3．06．95％CI1．56-6．00。P=0．001。HetEM对HomEM：OR=1．95，95％CI1．03～3．70，P=0．04）。在以雷贝拉唑为基础的三联疗法中，PM、HetEM、HomEM三组间H．pylori根除率均无明显差异。结论：在亚洲人群中，以奥美拉唑和兰索拉唑为基础的三联疗法．其H．pylori根除率受CYP2C19基因多态性影响，以雷贝拉唑为基础的三联疗法则否。     

First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype

AIM: To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication.METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or ¹³C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642).RESULTS: The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population.CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs.     

以泮托拉唑为基础的三联和四联疗法根除幽门螺杆菌疗效比较——一项单中心、随机、开放、平行对照研究

背景：近年质子泵抑制剂（PPI）＋阿莫西林＋克拉霉素标准三联疗法对幽门螺杆菌（H.pylori）的根除率有所降低,PPI＋铋剂＋甲硝唑＋四环素的四联疗法能否成为一线治疗的首选以及适当延长疗程能否提高根除率尚有待明确。目的：比较以泮托拉唑为基础的7d标准三联疗法与7d、10d四联疗法根除H.pylori的疗效。方法：133例非溃疡性消化不良的H.pylori感染患者随机分配至7d三联组（45例,泮托拉唑40mgbid＋阿莫西林1.0gbid＋克拉霉素500mgbid,PAC方案）以及7d、10d四联组（43例和45例,泮托拉唑40mgbid＋枸橼酸铋钾220mgbid＋甲硝唑400mgtid＋四环素750mgbid,PBMT方案）。治疗结束后至少间隔4周行13C-尿素呼气试验复查H.pylori,评估治疗结果。结果：共129例患者按方案完成治疗。三组H.pylori根除率按意图治疗（ITT）分析分别为73.3%、79.1%和88.9%,按方案（PP）分析分别为75.0%、82.9%和90.9%。7dPAC方案的PP根除率显著低于10dPBMT方案（P〈0.05）。除四联组中有2例患者分别因头晕和腹泻而未完成治疗外,其余患者的不良反应相似且均能耐受。结论：在7d标准三联疗法H.pylori根除疗效降低的情况下,含泮托拉唑、铋剂、甲硝唑和四环素的10d四联疗法可考虑作为根除治疗的首选方案。     

Cure of Helicobacter pylori infection and healing of duodenal ulcer: comparison of pantoprazole-based one-week modified triple therapy versus two-week dual therapy

Objective: Eradication of Helicobacter pylori ( H. pylori ) is recommended as the first-line therapeutic concept for reliable long-term prevention of duodenal ulcer (DU) relapse. Current treatment regimens vary in efficacy, complexity, and compliance. To assess the efficacy of pantoprazole in H. pylori eradication in parallel groups of patients using two eradication regimens.
Methods: Patients, (18–85 yr old; intention-to-treat,  n = 286  ) with proven DU, positive rapid urease test (biopsy), and ¹³C-urea breath test (UBT) were included in a prospective, randomized, multicenter study. Modified triple therapy consisted of 40 mg pantoprazole b.i.d ., 500 mg clarithromycin t.i.d ., and 500 mg metronidazole t.i.d . for 7 days (PCM therapy); dual therapy consisted of 40 mg pantoprazole b.i.d . and 500 mg clarithromycin t.i.d . for 14 days (PC therapy). In both groups 40 mg pantoprazole o.d . was given until day 28 when healing of DU was evaluated endoscopically; H. pylori status was assessed by UBT on day 56.
Results: H. pylori eradication rate was 95% in PCM versus 60% in PC therapy groups (per-protocol population,   p < 0.001  ), and 82% in PCM versus 50% in PC therapy in the intention-to-treat patient population (   p < 0.001  ). The DU healing rate was 98% in the PCM and 95% in the PC therapy groups (per-protocol population). Both regimens were similarly well tolerated. Adverse events in both regimens included taste disturbance, diarrhea, and increased serum concentration of liver enzymes, at an incidence of < 10%.
Conclusions: Compared to 2-wk PC therapy (pantoprazole and clarithromycin), the 1-wk PCM therapy (pantoprazole, clarithromycin, and metronidazole) is a significantly superior and highly promising strategy for eradication of H. pylori .     

The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole

Background/Aims

The CYP2C19 polymorphism plays an important role in the metabolism of various proton-pump inhibitors. Several trials have produced conflicting data on eradication rates of Helicobacter pylori (H. pylori) among CYP2C19 genotypes. We investigated whether the CYP2C19 genotype affects the eradication rate of H. pylori by direct comparing the effects of lansoprazole- and rabeprazole-based triple therapies.

Methods

A total of 492 patients infected with H. pylori was randomly treated with either 30 mg of lansoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin and 1,000 mg of amoxicillin twice daily for 1 week. CYP2C19 genotype status was determined by a PCR-restriction-fragment-length polymorphism method. After 7 to 8 weeks, H. pylori status was evaluated by a C¹³-urea breath test.

Results

Four hundred and sixty-three patients were analyzed, and the eradication rate was 75.2% in a per-protocol analysis. Eradication rates for the lansoprazole regimen (n=234) were 73.8%, 80.7%, and 85.4% in the homozygous extensive (HomEM), heterozygous extensive (HetEM), and poor metabolizers (PM) groups, respectively (p=0.303). In the case of the rabeprazole regimen (n=229), the eradication rates were 68.6%, 73.0%, and 71.9% in the HomEM, HetEM, and PM groups, respectively (p=0.795).

Conclusions

The efficacies of triple therapies that include lansoprazole or rabeprazole are not affected by CYP2C19 genetic polymorphisms.     

CYP2C19 genotypes determine the efficacy of on-demand therapy of pantoprazole for reflux esophagitis as Los-Angeles grades C and D

Backgrounds and Aim: The present study determined whether the genotypes of S‐mephenytoin 4′‐hydroxylase (CYP2C19) could serve as an indicator to assess the success of long‐term on‐demand therapy (ODT) with pantoprazole for the patients with severe reflux esophagitis as Los Angles grade C or D (RE‐CD). Methods: A total of 240 patients with RE‐CD were prospectively enrolled to receive continuous pantoprazole, 40 mg daily for 6 months. The patients, who achieved complete healing and were free from acid reflux‐related symptoms during follow up, were included to receive ODT with a 40 mg pantoprazole tablet up to 1 year. Each patient was followed to assess the monthly tablet number of 40 mg pantoprazole and the cumulative rate of failure of ODT. The CYP2C19 genotype of each included patient was defined as homologous extensive metabolizer (HomoEM), heterologous extensive metabolizer (HeteroEM), and poor metabolizer (PM). Results: Two‐hundred patients were included to receive ODT, including 51 as HomoEM, 108 as HeteroEM, and 41 as PM. There were no differences in demographic and endoscopic features among patients with different CYP2C19 genotypes (P > 0.05). The 1‐year cumulative failure rate of ODT was significantly higher in HomoEM than in HeteroEM and PM (P < 0.05, by log–rank test). For those with successful ODT during the 1‐year follow up, the mean monthly tablet number of pantoprazole was lower in PM than in HeteroEM and HomoEM (11.5 vs 16.3 and 18.6, P < 0.05). Conclusion: For RE‐CD with complete healing after continuous pantoprazole, the successful shift to ODT is determined by the CYP2C19 genotypes of the patients.     

One week of treatment with esomeprazole-based triple therapy eradicates Helicobacter pylori and heals patients with duodenal ulcer disease.

BACKGROUND: Proton pump inhibitor (PPI) monotherapy is commonly continued for 3 weeks after Helicobacter pylori eradication with PPI-based triple therapy regimens to ensure duodenal ulcer (DU) healing. This randomized, double-blind, multicentre study evaluated whether only 1 week of triple therapy with the new PPI esomeprazole was sufficient to ensure high rates of ulcer healing and H. pylori eradication. METHODS: A total of 446 H. pylori-positive patients with active DU received twice daily treatment with esomeprazole 20 mg (n = 222) or omeprazole 20 mg (n = 224) in combination with amoxicillin 1 g and clarithromycin 500 mg for 1 week (EAC and OAC, respectively). Patients in the OAC group then received 3 weeks' monotherapy with omeprazole 20 mg once daily; those treated with EAC received placebo. Ulcer healing was assessed by endoscopy on completion of therapy and H. pylori status was assessed by (13)C-urea breath testing and histology 4-6 weeks later. RESULTS: Ulcer healing rates (95% CI) for intention-to-treat and per-protocol populations were: EAC + placebo 91% (87-95%) and 94% (90-97%); OAC + omeprazole 92% (88-95%) and 96% (92-98%). Corresponding H. pylori eradication rates were: EAC + placebo 86% (81-90%) and 89% (84-93%); OAC + omeprazole 88% (83-92%) and 90% (85-93%). Both eradication regimens were well tolerated, and patient compliance was high. CONCLUSIONS: A 1-week regimen of esomeprazole-based triple therapy is sufficient for DU healing and H. pylori eradication in patients with DU disease.     

The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis

PREMISE: It has been suggested that proton pump inhibitor (PPI)-related differences in Helicobacter pylori eradication rates are partly because of CYP2C19 polymorphisms and there have been conflicting data in this area. We conducted a meta-analysis to investigate the evidence relating CYP2C19 to first-line H. pylori eradication rates. METHODS: A search of the literature was conducted up to June 2005 using Medline, EMBase, and Cochrane Register of Controlled Trials (CENTRAL). Twenty-eight arms from 17 papers were extracted for omeprazole, lansoprazole, and rabeprazole, collectively. Review Manager 4.2.8 was used for analysis. RESULTS: When all eradication rates, regardless of PPI used, were combined there was no significant difference between poor metabolizers (PM) and heterozygous extensive metabolizers (HetEMs) (odds ratio [OR]= 1.35, 95% confidence interval [CI] 0.89-2.07, p = 0.15); however, there was a significant difference between HetEM and homozygous extensive metabolizers (HomEMs) (OR = 1.90, 95% CI 1.38-2.60, p < 0.0001). Significant heterogeneity was observed in a HomEM and PM comparison, hence additional subanalysis of individual PPIs revealed that dual and triple omeprazole therapies significantly favored higher H. pylori eradication rates in PM over HomEM (OR = 4.03, 95% CI 1.97-8.28, p = 0.0001), and also over HetEM (OR = 2.24, 95% CI 1.09-4.61, p = 0.03). Dual and triple rabeprazole and triple lansoprazole therapies did not show significantly different H. pylori eradication rates between PM and HomEM (OR = 1.04, 95% CI 0.44-2.46, p = 0.25) and (OR = 1.80, 95% CI 0.67-4.85, p = 0.93), respectively. CONCLUSIONS: The impact of CYP2C19 polymorphisms on H. pylori eradication rates in studied populations appears clinically relevant in patients prescribed omeprazole as a component of their dual- or triple-drug therapy, whereas regimens that include lansoprazole or rabeprazole are unaffected. The choice of PPI and/or dose rather than CYP2C19 genotyping could be a more practical approach to assure the highest H. pylori eradication rates in clinical settings.     

评估以泮托拉唑为基础的三联和四联疗法根除幽门螺杆菌的疗效

目的 比较以泮托拉唑为基础的7d标准三联疗法与泮托拉唑+铋剂+甲硝唑+四环素的10 d四联疗法根除Hp的疗效和安全性.方法 170例非溃疡性消化不良的Hp感染者随机入选三联、四联治疗组.三联治疗组实行PAC方案:泮托拉唑40 mg(2次/d)+阿莫西林1.0 g(2次/d)+克拉霉素500 mg(2次/d),口服7 d.四联治疗组实行PBMT方案:泮托拉唑40 mg(2次/d)+胶体次枸橼酸铋220 mg(2次/d)+四环素750 mg(2次/d)+甲硝唑400 mg(2次/d),口服10 d.治疗结束后至少停药4周后复查13C-尿素呼气试验,结果≤4%.为Hp阴性,表示根除成功.同时评估疗效及安全性.结果 166例患者按方案完成治疗.三联治疗组按意图治疗分析(ITT)根除率为63.53%(54/85),较四联治疗组低[89.41%(76/85),x2=17.168,P=0.000].三联治疗组按实验方案分析(PP)根除率为65.06%(54/83),亦较四联治疗组低[91.57%(76/83),x2=13.588,P=0.000].从年龄段分析,年龄＞30岁者三联治疗组根除失败率为22.22%(4/18),较四联治疗组高[3.84%(1/26),x2=19.884,P=0.000].三联和四联治疗组不良反应发生率分别为60.00%(51/85)和42.35%(36/85).结论 在7 d标准三联疗法Hp根除疗效降低的情况下,含泮托拉唑、铋剂、四环素和甲硝唑的10 d四联方案可考虑为首选方案.

Abstract：

Objective Compare the efficacy and safety of pantoprazole-based 7-day standard triple therapy with 10-day quadruple therapy including pantoprazole, bismuth, metronidazole and tetracycline in Helicobacter pylori (H.pylori) eradication.Methods A total of 170 H.pylori positive patients with non-ulcer dyspepsia were recruited and randomly assigned into triple and quadruple therapy groups.The triple therapy group was implemented with PAC program which included orally taking pantoprazole 40 mg twice per day, amoxicillin 1.0 g twice per day and clarithromycin 500 mg twice per day for seven days.The quadruple therapy group was implemented with PBMT program which consisted of orally taking pantoprazole 40 mg twice per day, colloidal bismuth subcitrate 220 mg twice per day, metronidazole 400 mg three times per day and tetracycline 750 mg twice per day for ten days.The 13C -urea breathe test was re-examined at least 4 weeks after the completion of treatment, the result lower than 4%.was H.pylori negative which indicated the success of H.pylori eradication.The efficacy and safety were also evaluated.Results A total of 166 patients completed the treatment.With intention-to-treat (ITT) analysis, the H.pylori eradication rate in the triple therapy group was 63.5% (54/85), lower than that of the quadruple therapy group (89.41%(76/85) ,x2= 17.168,P=0.000).With per protocol (PP) analysis, the eradication rate in the triple therapy group was 65.06% (54/83), also lower than that of the quadruple therapy group (91.57 % (76/83) ,x2 = 13.588 ,P=0.000).Through the age analysis, in patients over 30 years old,the eradication failed rate in the triple therapy group was 22.22% (4/18), higher than that of the quadruple therapy group (3.84% (1 / 26), x2 = 19.884, P=0.000).The incidence of adverse reaction rates of the triple and quadruple therapy group were 60.00% (51/85) and 42.35 % (36/85) respectively.Conclusion Since the reduction of eradication rate with seven day standard triple therapy,the 10-day pantoprazole, bismuth, metronidazole and tetracycline quadruple therapy may be considered as the first choice.