Host Genetic Determinants Associated With Helicobacter pylori Eradication Treatment Failure: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Helicobacter pylori infects approximately 50% of individuals worldwide. Successful H pylori eradication is associated with reduced risk of gastric cancer and peptic ulcer disease, among other conditions. We hypothesized that host genetic determinants, especially those affecting gastric pH, might contribute to eradication therapy failure, particularly when treatment adherence and antibiotic susceptibility are confirmed. We aimed to conduct a meta-analysis of host genetic variants associated with H pylori eradication failure. METHODS: We searched the literature for studies comparing posttreatment H pylori eradication failure vs success (outcome) according to host genetic polymorphisms (exposure). Reference groups were defined according to genotypes (or corresponding phenotypes) hypothesized to be associated with successful eradication. We pooled estimates using a random-effects model and performed comprehensive sensitivity analyses. RESULTS: We analyzed 57 studies from 11 countries; the vast majority analyzed CYP2C19 polymorphisms. Among individuals prescribed eradication regimens with proton pump inhibitors predominantly CYP2C19 metabolized, enhanced vs poor metabolizer phenotypes were associated with a 2.52-fold significantly higher likelihood of eradication failure and 4.44-fold significantly higher likelihood when treatment adherence and H pylori clarithromycin susceptibility (if relevant) were confirmed. There was no association between CYP2C19 variants and eradication failure if proton pump inhibitors less metabolized by or that bypass CYP2C19 metabolism were used. IL1B polymorphisms that are vs are not associated with less gastric acid suppression were associated with 1.72-fold significantly higher likelihood of eradication failure. There was no association between MDR1 polymorphisms and H pylori eradication failure. The certainty of evidence was moderate. CONCLUSION: Based on meta-analysis, we identified host genetic polymorphisms significantly associated with H pylori eradication failure; host genetics might underlie eradication failure among treatment-adherent individuals with confirmed H pylori antibiotic susceptibility.

Association Between Helicobacter pylori Exposure and Decreased Odds of Eosinophilic Esophagitis-A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Previous or current infection with Helicobacter pylori (exposure) has been reported to protect against eosinophilic esophagitis (EoE), perhaps owing to H pylori-induced immunomodulation. However, findings vary. We performed a systematic review and meta-analysis of comparative studies to define the association between H pylori exposure and EoE more clearly. METHODS: We searched 4 large databases to identify comparative clinical studies that included sufficient detail to determine the odds or risk of EoE (primary outcome) or esophageal eosinophilia (secondary outcome) among individuals exposed to H pylori (exposed) vs individuals who were tested and found to be unexposed. Estimates were pooled using a random-effects model. Meta-regression and sensitivity analyses were planned a priori. Studies were evaluated for quality, risk of bias, publication bias, and heterogeneity. RESULTS: We analyzed 11 observational studies comprising data on 377,795 individuals worldwide. H pylori exposure vs nonexposure was associated with a 37% reduction in odds of EoE (odds ratio, 0.63; 95% CI, 0.51-0.78) and a 38% reduction in odds of esophageal eosinophilia (odds ratio, 0.62; 95% CI, 0.52-0.76). Fewer prospective studies found a significant association between H pylori exposure and EoE (P = .06) than retrospective studies. Effect estimates were not affected by study location, whether the studies were performed in pediatric or adult populations, time period (before vs after 2007), or prevalence of H pylori in the study population. CONCLUSIONS: In a comprehensive meta-analysis, we found evidence for a significant association between H pylori exposure and reduced odds of EoE. Studies are needed to determine the mechanisms of this association.

Gender-Based Differences in Response to Tumor Necrosis Factor Inhibitor Therapies for Ulcerative Colitis: Individual Participant Data Meta-Analyses of Clinical Trials.

BACKGROUND: Gender-based differences are reported in inflammatory bowel diseases (IBD) pathogenesis, but their impacts on IBD outcomes are not well known. We determined gender-based differences in response to treatment with tumor necrosis factor inhibitor (TNFi) therapies in individuals with ulcerative colitis (UC). METHODS: We used the Yale University Open Data Access (YODA) platform to abstract individual participant data from randomized clinical trials to study infliximab and golimumab as induction and maintenance therapies in moderately to severely active UC. Using multivariable logistic regression, we examined associations between gender and the endpoints of clinical remission, mucosal healing, and clinical response for each study individually and in a meta-analysis. RESULTS: Of 1639 patients included in induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Subcutaneous [PURSUIT-SC], active ulcerative colitis trials [ACT] 1 and 2) and 1280 patients included in maintenance trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Maintenance [PURSUIT-IM], ACT 1 and 2), 696 (42.5%) and 534 (41.7%) were women, respectively. In a meta-analysis of induction trials, the adjusted odds ratios (aORs) of clinical remission (aOR, 0.55; 95% CI, 0.31-0.97), mucosal healing (aOR, 0.47; 95% CI, 0.27-0.83), and clinical response (aOR, 0.51; 95% CI, 0.29-0.90) in the treatment arm and of clinical remission in the placebo arm (aOR, 0.34; 95% CI, 0.15-0.82) were lower in men compared to women. There were no differences in outcomes by gender in the treatment and placebo arms in the meta-analysis of maintenance trials. CONCLUSIONS: Men are less likely to achieve clinical remission, mucosal healing, and clinical response compared to women during induction treatment with TNFi for UC, but not during the maintenance phase. Future studies delineating the mechanisms underlying these observations would be informative.

In our meta-analysis of individual patient data from 4 ulcerative colitis clinical trials, the odds of clinical remission, mucosal healing, and clinical response with tumor necrosis factor inhibitors were lower among men compared to women during induction therapy, but not during maintenance therapy.

Intake of artificial sweeteners among adults is associated with reduced odds of gastrointestinal luminal cancers: a meta-analysis of cohort and case-control studies.

The association between artificial sweetener (AS) consumption and the risk of organ-specific cancers has been debated for decades. We hypothesized that AS consumption is associated with reduced risk of gastrointestinal (GI) cancers. We aimed to test this hypothesis by conducting a systematic review and meta-analysis of the association between AS and GI cancers. We searched 4 databases for comparative studies of AS consumption (exposed) versus no consumption (nonexposed) and the odds or risk of GI luminal or non-luminal cancer (primary outcome). Estimates were pooled using a random-effects model. Studies were evaluated for quality, bias, and heterogeneity. We analyzed 8 (4 prospective, 4 case-control) studies comprising data on 1,043,496 individuals, among whom 3271 pancreatic, 395 gastric, 304 esophageal, 3008 colorectal, and 598 oropharyngeal cancers occurred. While there was no significant association between AS consumption and odds of GI cancer overall, AS consumption was associated with 19% reduced likelihood of luminal GI cancer (OR 0.81, 95% CI:0.68-0.97). There was no association between AS consumption and non-luminal GI cancer. Meta-regression demonstrated no difference in effect estimates based on study type. Based on this first meta-analysis of AS and GI cancer, we demonstrated that AS consumption is associated with a significantly lower likelihood of luminal, but not non-luminal, GI cancer.

Admission Serum Bicarbonate Predicts Adverse Clinical Outcomes in Hospitalized Cirrhotic Patients.

A low serum bicarbonate (SB) level is predictive of adverse outcomes in kidney injury, infection, and aging. Because the liver plays an important role in acid-base homeostasis and lactic acid metabolism, we speculated that such a relationship would exist for patients with cirrhosis. To assess the prognostic value of admission SB on adverse hospital outcomes, clinical characteristics were extracted and analyzed from a large electronic health record system. Patients were categorized based on admission SB (mEq/L) into 7 groups based on the reference range (22-25) into mildly (18-21), moderately (14-17), and severely (<14) decreased groups and mildly (26-29), moderately (30-33), and severely (>30) increased groups, and the relationship of SB category with the frequency of complications (acute kidney injury/hepatorenal syndrome, portosystemic encephalopathy, gastrointestinal bleeding, ascites, and spontaneous bacterial peritonitis) and hospital metrics (length of stay [LOS], admission to an intensive care unit [ICU], and mortality) was assessed. A total of 2,693 patients were analyzed. Mean SB was 22.9 ± 4.5 mEq/L. SB was within the normal range (22-25 mEq/L) in 1,072 (39.8%) patients, and 955 patients (36%) had a low SB. As the SB category decreased, the incidence of complications progressively increased (p < 0.001). Increased MELD-Na score and low serum albumin also correlated with frequency of complications (p < 0.001). As the SB category decreased, LOS, ICU admission, and mortality progressively increased (p < 0.001). On multivariate analysis, the association of decreased SB with higher odds of complications, LOS, ICU admission, and mortality persisted. Conclusion. Low admission SB in patients with cirrhosis is associated with cirrhotic complications, longer LOS, increased ICU admissions, and increased hospital mortality.

Systematic review with meta-analysis: association between Helicobacter pylori CagA seropositivity and odds of inflammatory bowel disease.

BACKGROUND: Accumulating data support a protective role of Helicobacter pylori against inflammatory bowel diseases (IBD), which might be mediated by strain-specific constituents, specifically cagA expression. AIM: To perform a systematic review and meta-analysis to more clearly define the association between CagA seropositivity and IBD. METHODS: We identified comparative studies that included sufficient detail to determine the odds or risk of IBD, Crohn's disease (CD) or ulcerative colitis (UC) amongst individuals with vs without evidence of cagA expression (eg CagA seropositivity). Estimates were pooled using a random effects model. RESULTS: Three clinical studies met inclusion criteria. cagA expression was represented by CagA seropositivity in all studies. Compared to CagA seronegativity overall, CagA seropositivity was associated with lower odds of IBD (OR 0.31, 95% CI 0.21-0.44) and CD (OR 0.25, 95% CI 0.17-0.38), and statistically nonsignificant lower odds for UC (OR 0.68, 95% CI 0.35-1.32). Similarly, compared to H pylori non-exposed individuals, H pylori exposed, CagA seropositive individuals had lower odds of IBD (OR 0.26, 95% CI 0.16-0.41) and CD (OR 0.23, 95% CI 0.15-0.35), but not UC (OR 0.66, 0.34-1.27). However, there was no significant difference in the odds of IBD, CD or UC between H pylori exposed, CagA seronegative and H pylori non-exposed individuals. CONCLUSION: We found evidence for a significant association between CagA seropositive H pylori exposure and reduced odds of IBD, particularly CD, but not for CagA seronegative H pylori exposure. Additional studies are needed to confirm these findings and define underlying mechanisms.