The effect of <i>CYP2C19</i> gene polymorphism on the eradication rate of <i>Helicobacter pylori</i> by proton pump inhibitors-containing regimens in Asian populations: a meta-analysis

Fu, Juan; Sun, Changfeng; He, Hui; Ojha, Suvash Chandra; Shi, Han; Deng, Chuiwen; Sheng, Yun-Jian

doi:10.2217/pgs-2020-0127

Cited by 10 publications

(10 citation statements)

References 58 publications

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“…To date, the published data showed inconsistent results on the effects of the CYP2C19 genotype on the cure rates of H. pylori infections. Our pooled result showed that the CYP2C19 genotype could affect the cure rate of H. pylori, and the cure rate of EM genotype was significantly lower than that of the IM or PM genotype, consistent with the results reported by Ormeci et al (2016) and Fu et al (2021). Actually, the relative enzyme activity of the EM was roughly 2-fold higher than that of the IM (0.15 vs. 0.08, respectively), which in turn was double as that of the PM (0.08 vs. 0.04) (Kuo et al, 2014), indicating a gene-dosage effect.…”

Section: Discussionsupporting

confidence: 92%

“…However, our study showed a significant difference only in EM vs. IM in lansoprazole-based therapy, but not in EM vs. PM or IM vs. PM, a significant difference was observed only in EM vs. PM in esomeprazole-based therapy, but not in EM vs. IM or IM vs. PM. Previous reports suggested that the efficacy of lansoprazole is dependent on the CYP2C19 gene status (Fu et al, 2021), but Padol et al (2006) showed that H. pylori therapies with omeprazole are dependent on the CYP2C19 genotype while therapies with lansoprazole and rabeprazole are not. Thus, the conclusion drawn is ambiguous and requires further research.…”

Section: Discussionmentioning

confidence: 99%

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Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis

et al. 2022

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Background: The cure rates of Helicobacter pylori (H. pylori) treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and cytochrome P450 2C19 (CYP2C19) polymorphism, and the effects of PPI depend on metabolic enzymes, cytochrome P450 enzymes. The aim of this meta-analysis was to determine whether CYP2C19 polymorphisms affect H. pylori cure rates in patients treated with different proton pump inhibitors (PPIs) according to stratified analysis.Materials and methods: The literature was searched with the key words “H. pylori” and “CYP2C19” in PubMed, CNKI, and Wanfang up to 31 May 2022, and the studies were limited to clinical observational or randomized controlled trials (RCTs). Finally, seven RCTs and 29 clinical observational studies met the inclusion criteria and were used for the meta-analysis via STATA version 16.Results: The cure rates were significantly different between genotypes of homozygous extensive metabolizers (EM) and poor metabolizers (PM) (OR = 0.58, 95% CI: 0.47–0.71) and between EM and heterozygous extensive metabolizers (IM) (OR = 0.71, 95% CI: 0.59–0.86), but not between IM and PM. Moreover, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with omeprazole (66.4% vs. 84.1%), lansoprazole (76.1% vs. 85.6%), but not rabeprazole, esomeprazole, or pantoprazole. In addition, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with a PPIs for 7 days (77.4% vs. 82.1%), but not 14 days (85.4% vs. 90.0%).Conclusion: Carriers of CYP2C19 loss-of-function variant alleles (IM and PM) exhibit a significantly greater cure rate of H. pylori than noncarriers (EM) regardless of other factors (84.7% vs. 79.2%). In addition, pantoprazole- and rabeprazole-based quadruple therapy for H. pylori treatment is less dependent on the CYP2C19 genotype and should be prioritized in Asian populations with H. pylori.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis

et al. 2022

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“…The frequency of CYP 2C19 genotypes differs amongst different ethnic populations 21 . Although the effects of CYP 2C19 polymorphisms are mainly associated with CYP 2C19 extensive metaboliser (EM) phenotypes who receive first‐generation PPIs, namely omeprazole and lansoprazole, 22 this effect was only observed in mainland China and Japan 23 . Genotyping of CYP 2C19 amongst patients who receive PPIs within the local population and evaluating the treatment outcomes may provide further clarity on the effects of CYP 2C19 polymorphisms on H. pylori eradication.…”

Section: Introductionmentioning

confidence: 99%

“…PM). Unlike PPIs, the pharmacokinetics of vonoprazan are not affected by CYP 2C19 polymorphisms,26,28 and this may be useful in populations where EM phenotypes are predominant.Although the effects of CYP 2C19 polymorphisms are mainly related to EM phenotypes who receive omeprazole or lansoprazole,[19][20][21] its influence on H. pylori eradication remains controversial 23. We studied the effects of different polymorphisms of CYP 2C19 genotype (EM/IM/PM) on treatment outcomes.…”

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confidence: 99%

Clinical trial: seven‐day vonoprazan‐ versus 14‐day proton pump inhibitor‐based triple therapy for first‐line Helicobacter pylori eradication

Ang

Koo

Chan

et al. 2022

Aliment Pharmacol Ther

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Summary Background One‐week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)‐based triple therapy for first‐line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2‐week PPI‐based triple therapy. Aim To verify the non‐inferiority of 1‐week vonoprazan‐based triple therapy versus 2‐week PPI‐based triple therapy as first‐line H. pylori eradication in a multiracial Asian cohort. Methods Randomised controlled trial of treatment‐naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups. Results Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan‐ (n = 119) or PPI‐based (n = 125) triple therapy. Eradication rates by intention‐to‐treat analysis were 87.4% (vonoprazan‐based triple therapy) versus 88.0% (PPI‐based triple therapy. By per protocol analysis: 96.3% (vonoprazan‐based triple therapy) versus 94.0% (PPI‐based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4–96.3], p = 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups. Conclusion One‐week vonoprazan‐based triple therapy achieved comparable efficacy to 2‐week PPI‐based triple therapy and was well tolerated.

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“…Genetic polymorphisms are receiving increasing attention for their potential role in treatment outcomes. A few studies to date have shown that eradication rates may be higher in slower CYP metabolizers [ 99 , 155 , 156 ], although this association has not always been statistically significant. Polymorphisms in immune response genes can similarly impact disease severity and predispose to complications [ 157 , 158 , 159 ].…”

Section: Recent Advancesmentioning

confidence: 99%

Current and Future Perspectives in the Diagnosis and Management of Helicobacter pylori Infection

Shatila

Thomas

2022

JCM

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Helicobacter pylori (Hp) is a prevalent organism infecting almost half the global population. It is a significant concern, given its associated risk of gastric cancer, which is the third leading cause of cancer death globally. Infection can be asymptomatic or present with dyspeptic symptoms. It may also present with alarm symptoms in the case of progression to cancer. Diagnosis can be achieved non-invasively (breath tests, stool studies, or serology) or invasively (rapid urease test, biopsy, or culture). Treatment involves acid suppression and regimens containing several antibiotics and is guided by resistance rates. Eradication is essential, as it lowers the risk of complications and progression to cancer. Follow-up after eradication is similarly important, as the risk of cancer progression remains. There have been many recent advances in both diagnosis and treatment of Hp. In particular, biosensors may be effective diagnostic tools, and nanotechnology, vaccines, and potassium-competitive acid blockers may prove effective in enhancing eradication rates.

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The effect of CYP2C19 gene polymorphism on the eradication rate of Helicobacter pylori by proton pump inhibitors-containing regimens in Asian populations: a meta-analysis

Cited by 10 publications

References 58 publications

Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis

Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis

Clinical trial: seven‐day vonoprazan‐ versus 14‐day proton pump inhibitor‐based triple therapy for first‐line Helicobacter pylori eradication

Current and Future Perspectives in the Diagnosis and Management of Helicobacter pylori Infection

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