The incidence of cancer and its associated mortality have increased over the past several decades [...].

Previous published data have confirmed that the addition of a citric acid meal improves the accuracy of the 13C-urea breath test (13C-UBT). However, some studies have suggested that a citric acid test meal may not be necessary. Thus, the aim of this study was to evaluate the combination of a 13C-UBT with a citric acid meal for the diagnosis of Helicobacter pylori (Hp) infection in a Chinese population, particularly for patients with results in the gray zone. In this paired self-controlled study, all subjects had previously undergone 13C-UBTs without citric acid meals and were randomly divided into two groups based on different doses of citric acid (a low-dose citric acid group and a high-dose citric acid group, comprising meals with 0.68 g and 3.84 g citric acid powder, respectively). Positive rapid urease test (CLO) test and histology results were considered the 'gold standard'. The mean delta over baseline (DOB) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were compared between the two groups, particularly for patients with results in the gray zone. In total, 285 patients were tested. Of these patients, 189 were included in the low-dose citric acid group, and 96 were included in the high-dose citric acid group. Among patients with a positive 13C-UBT result without citric acid [delta over baseline (DOB) value ≥ 4‰, n = 174] and a negative 13C-UBT result without citric acid (DOB value < 4‰, n = 111), 8.0% (14/174) were false positive, and 0.9% (1/111) was false negative as determined by gold standard. Of 14 patients with false positive, 78.6% (11/14) false positive were in the gray zone of 4-10‰. However, there were no false positive 13C-UBT results with citric acid in the the gray zone of 4-10‰. In the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, NPV and accuracy at 15 min were as follows: 99.1% vs. 99.1%, 97.5% vs. 88.9%, 98.2% vs. 92.2%, 98.8% vs. 98.6% and 98.4% vs. 94.7%, respectively. In the the gray zone of 4.0-10.0‰, the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, and accuracy at 15 min were as follows: 94.4% vs. 100.0%, 100.0% vs. 0%, 100.0% vs. 75.0% and 95.8% vs. 75.0%, respectively. No significant difference was observed between the 15-min and 30-min measurement intervals in the low- and high-dose citric acid groups, including patients with results in the gray zone. The low-dose citric acid test, with an optimal measurement interval of 15 min, was highly accurate in the diagnosis of Hp infection in the Chinese population, especially for individuals with results in the gray zone.

Recently, a simple tailored therapy based on clarithromycin resistance has been implemented as Helicobacter pylori (H. pylori) eradication therapy. Nonetheless, despite the tailored therapy and frequent adverse events, studies on treatment period are lacking. This study aimed to compare the H. pylori eradication rates of 7-day and 14-day tailored therapy regimens according to clarithromycin resistance.

This multicenter, prospective, randomized, noninferiority trial enrolled H. pylori-positive patients who were randomly assigned to 7-day and 14-day regimen groups, depending on the presence or absence of clarithromycin resistance by 23S rRNA gene point mutations. Standard triple therapy (STT) (20 mg rabeprazole, 1 g amoxicillin, and 500 mg clarithromycin twice daily) or bismuth quadruple therapy (BQT) (20 mg rabeprazole twice daily, 500 mg metronidazole thrice daily, 120 mg bismuth four times daily, and 500 mg tetracycline four times daily) was assigned by clarithromycin resistance. Eradication rates and adverse events were evaluated.

A total of 314 and 278 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively; however, 31 patients were lost to follow-up, whereas five patients violated the protocol. Both the 7-day and 14-day regimens showed similar eradication rates in the ITT (7-day vs. 14-day: 78.3% vs. 78.3%, p > 0.99) and PP (87.9% vs. 89.1%, p = 0.851) analyses. Non-inferiority was confirmed (p < 0.025). A subgroup analysis according to clarithromycin resistance (clarithromycin resistance rate: 28.7%) revealed no significant difference in eradication rates between the 7-day and 14-day STT (90.0% vs. 90.1%, p > 0.99) and BQT (82.5% vs. 86.5%, p = 0.757). Furthermore, adverse events did not significantly differ between the two groups.

The 7-day triple and quadruple therapy according to clarithromycin resistance showed similar eradication rates, as compared to the 14-day therapy.

Helicobacter pylori (H. pylori) infections can recur as either recrudescence or reinfection. At a time when the decline in the eradication rate is becoming evident, increases in the rate of recurrence are concerning. In addition, there are no guidelines for selecting an eradication regimen for H. pylori recurrence.

A total of 996 H. pylori-infected patients treated with proton-pump inhibitor-based triple eradication therapy between 2017 and 2022 were enrolled in the study, and successful eradication therapies were confirmed by the 13 C-urea breath test. When retested within 1 year after successful eradication, analysis related to recrudescence was performed, and when retested after 1 year, analysis related to reinfection was performed. We reviewed the medical records and treatment outcomes of patients with H. pylori reinfection after successful eradication.

The recrudescence rate was 3.9% (9/228), and the reinfection rate was 3.7% (36/970 person-year). The frequency of reinfection reached 5.9% per person-year within the first 24 months and 2.0%-2.4% per person-year thereafter. In multivariate factor analysis, reinfection was significantly higher in patients with non-ulcer dyspepsia (p < 0.01). At first-line therapy for reinfection, the eradication rate of standard triple therapy (STT) was 50.0% (16/32). The eradication rate of second-line bismuth quadruple therapy was 81.3% (13/16), and levofloxacin-based rescue therapy was 66.7% (2/3).

Re-treatment of patients with H. pylori reinfection with STT had limited efficacy. Prospective research is needed to determine whether patients with non-ulcer dyspepsia are vulnerable to reinfection.

The urea breath test is a non-invasive diagnostic method for Helicobacter pylori infections, which relies on the change in the proportion of 13CO2 in exhaled air. Nondispersive infrared sensors are commonly used for the urea breath test in laboratory equipment, but Raman spectroscopy demonstrated potential for more accurate measurements. The accuracy of the Helicobacter pylori detection via the urea breath test using 13CO2 as a biomarker is affected by measurement errors, including equipment error and δ13C measurement uncertainty. We present a Raman scattering-based gas analyzer capable of δ13C measurements in exhaled air. The technical details of the various measurement conditions have been discussed. Standard gas samples were measured. 12CO2 and 13CO2 calibration coefficients were determined. The Raman spectrum of the exhaled air was measured and the δ13C change (in the process of the urea breath test) was calculated. The total error measured was 6% and does not exceed the limit of 10% that was analytically calculated.

Failure of Helicobacter pylori (H. pylori) eradication is principally caused by antimicrobial resistance. Nowadays, multidrug resistance could be a major determinant of eradication failure. To assess minimal inhibitory concentration (MIC), antimicrobial resistance rates and trends in H. pylori isolated from patients with upper gastrointestinal disease with long-term period.

Patients who had H. pylori colonies isolated from culture were consecutively enrolled during the period of 2003-2022. From each patient, one to ten isolates were collected from culture of mucosal biopsy. MIC test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using agar dilution method. Trends in MIC distribution, prevalence of resistances with single and multiple were investigated which were suspected to be related to the failure of empirical H. pylori eradication treatment.

From 2003 to 2022, a total of 873 patients were enrolled and 2735 H. pylori isolates were successfully collected. Increase in the primary resistance rate was found in clarithromycin (16.1%-31.0%, p = .022), metronidazole (30.6%-38.1%, p < 0.001), and both of levofloxacin and moxifloxacin (7.3%-35.7%, p < 0.001). The prevalence of multidrug resistance to both clarithromycin and metronidazole (9.2%-37.9%, p < 0.001), clarithromycin and fluoroquinolone (2.8%-41.7%, p < 0.001), and clarithromycin, metronidazole, and fluoroquinolone (1.4%-28.2%, p < 0.001) was found to significantly increase.

The prevalence of multiple resistance against H. pylori in Korea is ongoing. Its trend should be considered when establishing an empirical treatment strategy (ClinicalTrials. gov: NCT05247112).

Our team previously reported the use of antofloxacin-based bismuth quadruple therapy for the eradication of Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy in the first-line treatment for H. pylori infection.

1174 patients with H. pylori infection were randomized into three groups: 10-days and 14-days antofloxacin (ANT10 and ANT14) groups who received 10 and 14 days of antofloxacin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and antofloxacin 200 mg q.d.), 14-days clarithromycin (CLA14) group who received 14 days of clarithromycin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.). Eradication rate, antibiotic resistance and adverse events were analyzed.

The intention-to-treat (ITT) and per-protocol (PP) analyses have showed statistically different eradication rates between ANT14 group and ANT10 group (ITT p = 0.001; PP p < 0.001), but no statistical difference between ANT10 group and CLA14 group (ITT p = 0.340; PP p = 0.092). Treatment regimen, drug resistance and therapy duration were important clinical factors related to H. pylori eradication rates in multivariate logistic analysis. Longer durations had significantly higher eradication rates in patients with antibiotic-resistant strains or antibiotic-susceptible strains. The incidences of nausea and bitter taste were significantly higher in CLA group compared with ANT group (p = 0.002 for nausea; p = 0.002 for bitter taste). The ANT10 and ANT14 group had similar adverse event rates of gastrointestinal reactions.

The study showed that the H. pylori eradication rate with ANT14 therapy was higher than that with ANT10 and CLA14 therapy without significantly increasing the rates of adverse event. 14 days of antofloxacin-based bismuth quadruple therapy may be a more effective way as the first-line treatment for H. pylori infection.

Underwater endoscopic mucosal resection (UW-EMR) has been recently introduced as an effective technique for rectal third layer subepithelial tumors. Therefore, we aimed to assess the safety, efficacy, and procedure time of UW-EMR for upper gastrointestinal subepithelial tumors (SETs) originating from the deep mucosal and/or submucosal layers.

Between August 2018 to July 2022, a total of 17 SETs (7 duodenal SETs, 6 gastric SETs, and 4 esophageal SETs) were included in this study. On endoscopic ultrasound examinations, the tumors were found to be embedded in the submucosa without muscularis propria invasion. All SETs were resected successfully using UW-EMR. The characteristics of the tumors and their R0 resection rate, adverse event rate, and recurrence rate were evaluated retrospectively.

The mean tumor size was 0.9 cm (range, 0.3-1.5 cm). En bloc resection and complete resection rates were 100%, respectively. The patients showed no complications such as perforation or bleeding. Histologic assessments of the resected tumors revealed 9 neuroendocrine tumors (7 on the duodenum, 2 on the stomach), 2 gastric cystica profunda, 1 gastric follicular lymphoma, 1 gastric fibromyxoma, 3 esophageal granular cell tumors, and 1 esophageal adenoid cystic carcinoma. The mean procedural time was 3.2 min (range, 1.3-8.7 minutes). The overall en bloc and complete resection rates were 100%, respectively. No recurrence was observed during the follow-up period.

UW-EMR is a safe and effective treatment for upper gastrointestinal SETs embedded in the submucosal layer. Further studies are needed to compare other endoscopic resection techniques.

The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON® Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard 13C-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients ≥18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naïve, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT < 0.90, positive ≥ 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON® Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection.

Increasing clarithromycin resistance has led to changes in several guidelines for treatment of Helicobacter pylori infections. We compared the H. pylori eradication rates of the empirical concomitant therapy (CoT) and a tailored therapy (TaT) using dual-priming oligonucleotide-based polymerase chain reaction to detect mutations in the 23S rRNA gene that are related to clarithromycin resistance.

Between June 2020 and May 2021, 290 patients were enrolled and randomly assigned to 2 groups. In the CoT group, the patients received rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 14 days. In the TaT group, point mutation-negative patients received rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 14 days and point mutation-positive patients received rabeprazole 20 mg twice daily, metronidazole 500 mg thrice daily, and bismuth 120 mg and tetracycline 500 mg 4 times daily for 14 days.

A total of 290 and 261 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. A2142G and/or A2143G point mutations were identified in 28.6% of the patients. No significant difference in eradication rates were observed between the 2 groups as per ITT (CoT, 82.8% and TaT, 85.5%, P = .520) and PP (CoT, 88.6% and TaT, 94.6%, P = .084) analyses. In point mutation-positive patients, the eradication rates in the CoT group were lower than those in the TaT group as per ITT (69.8% and 87.5%, respectively, P = .050) and PP (76.9% and 97.1%, respectively, P = .011) analyses.

CoT and TaT showed similar overall eradication rates for H. pylori. However, CoT eradication rate was suboptimal, especially in point mutation-positive patients.

The ¹³C-urea breath test (¹³C-UBT) is preferred for non-invasive detection of Helicobacter pylori (H. pylori); however, its accuracy drops when results fall between 2‰ and 6‰ (called the gray zone). This study aimed to evaluate the accuracy of ¹³C-UBT (cut-off point 4‰) between 2‰ and 6‰, find a more appropriate gray zone, and identify the factors influencing ¹³C-UBT.

Patients with ¹³C-UBT results 2‰-6‰, over an eight-year period, were studied. H. pylori infection was diagnosed if patients were positive for either Warthin-Starry staining or quantitative real-time polymerase chain reaction (real-time PCR), and excluded if both were negative. Accuracy of ¹³C-UBT under different cut-off points was calculated, and the factors affecting ¹³C-UBT were analyzed.

A total of 208 patients were included, of whom 129 were H. pylori-positive. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of ¹³C-UBT were 71.32%, 83.54%, 64.08%, and 87.62%, respectively. When the cut-off point was changed to 2.15‰, the NPV of ¹³C-UBT reached a maximum (76.47%); when the cut-off point was changed to 4.95‰, PPV reached its maximum (93.22%). Therefore, the original gray zone (2‰-6‰) was adjusted to 2‰-4.95‰. Gastric antral intestinal metaplasia (OR = 3.055, 95% CI: 1.003-9.309) was an independent risk factor for false-negative ¹³C-UBT.

Accuracy of ¹³C-UBT over 2‰-6‰ was poor, and the gray zone was changed to 2‰-4.95‰. ¹³C-UBT results over 2‰-4.95‰ should be interpreted with caution during mass screening of H. pylori, especially for patients with gastric antral intestinal metaplasia.

Tailored therapy based on dual priming oligonucleotide-based polymerase chain reaction (DPO-PCR) can be considered an alternative to overcome the low eradication rate in high clarithromycin-resistance areas. The triple therapy (TT) duration of the tailored approach in most studies was 7 days for patients without point mutation. However, recent western guidelines have recommended a treatment duration of 14 days. The aim of this study was to compare the success rate of 7 and 14 days of TT for eradicating Helicobacter pylori without point mutation, as determined by DPO-PCR.Between Feb 2016 and Feb 2019, medical records of patients who underwent DPO-PCR were reviewed. Patients without point mutation as determined by DPO-PCR were enrolled in this study. The eradication success rate and adverse events were evaluated.A total of 366 patients without A2142G and A2143G point mutation were enrolled. The success rates of 7-day and 14-day TT were 88.4% (168/190) and 85.9% (151/176) by intention to treat analysis (P = .453) and 90.8% (168/185) and 90.4% (151/167) by per-protocol analysis (P = .900), respectively. The adverse event rates showed no significant difference between the 2 groups.In patients without point mutation based on DPO-PCR results, 7-day TT is as effective as 14-day TT. Therefore, 7 days may be considered as a cost-effective treatment duration in Korea.

We evaluated the efficacy of tailored therapy based on point mutation presence identified with the dual-priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) method compared with concomitant therapy.

Subjects were randomly assigned concomitant therapy (amoxicillin 1 g, clarithromycin 500 mg, metronidazole 500 mg, and lansoprazole 30 mg twice/day for 14 days) or tailored therapy (amoxicillin 1 g, clarithromycin 500 mg, and lansoprazole 30 mg twice/day for 14 days in point mutation-negative subjects; and amoxicillin 1 g, metronidazole 500 mg, and lansoprazole 30 mg twice/day for 14 days in point mutation-positive subjects).

A total of 397 and 352 subjects were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. Point mutations were identified in 25.9% of the subjects. The overall eradication rate was not significantly different between the groups by ITT (86.2% vs 81.6%, P = .132) and PP analyses (90.2% vs 86.5%, P = .179). There was no significant difference in the eradication rates between the groups in both the point mutation-negative subjects (91.7% vs 87.3%, P = .154) and the point mutation-positive subjects (71.2% vs 64.7%, P = .312). The eradication rates were significantly lower in the point mutation-positive subjects than in the point mutation-negative subjects in both the concomitant and tailored therapy groups.

Tailored therapy based on point mutation presence identified with the DPO-based multiplex PCR method was as effective as concomitant therapy. The eradication rates of both therapy regimens were suboptimal in point mutation-positive subjects.

The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan's demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication.

We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed.

We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies.

The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.

The impact of different Helicobacter pylori (H. pylori) status (H. pylori negative, H. pylori eradication and H. pylori persistence) on the development of metachronous gastric lesions after endoscopic resection of early gastric cancer is not well defined. Thus, a systematic review and meta-analysis was performed to investigate this relationship. Two authors independently searched the electronic databases (Pubmed, Embase, the Cochrane Library and Web of Science) through March 2018, without language restriction. Pooled risk ratio for metachronous gastric lesions with regard to H. pylori status was calculated using fixed- or random-effects models, and heterogeneity and publication bias were also measured. 20 eligible studies were finally identified in systematic review, and 17 out of 20 studies were further included in meta-analysis. H. pylori eradication was associated with overall 50% lower odds of metachronous events (RR = 0.50; 95 % CI 0.41-0.61). Pooled risk ratios for metachronous gastric neoplasm were 0.85 (95 % CI 0.43-1.68) between H. pylori-eradicated and -negative patients, and 0.63 (95 % CI 0.35-1.12) between H. pylori-negative and -persistent patients, respectively. In conclusion, based on the best available evidence, eradication of H. pylori can provide protection against secondary gastric neoplasm, and this quantitative benefit seemed greater than among asymptomatic individuals. Metachronous risk seems comparable between H. pylori-eradicated and -negative population, or between H. pylori-negative and -persistent patients.

The standard triple Helicobacter pylori regimen now shows unacceptably low treatment success in Korea. Administration of the concomitant therapy for 10 days, which has a high cure rate, is recommended as an alternative first-line treatment in areas of high clarithromycin resistance including Korea. Recently, modified bismuth-containing quadruple therapy with amoxicillin (PAM-B therapy) showed excellent results, regardless of dual clarithromycin and metronidazole resistance. This study compared the concomitant therapy with PAM-B therapy as a first-line treatment for H. pylori infection.

Subjects infected with H. pylori and naïve to treatment were performed a head-to-head comparison between 10-day concomitant therapy [rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily] and 14-day PAM-B therapy [rabeprazole 20 mg, amoxicillin 1 g, metronidazole 750 mg, and tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily]. Six weeks after treatment, H. pylori eradication was assessed.

Two hundred and seventy subjects were randomized. Both regimens achieved high cure rates: 83.0% (112/135) and 88.1% (119/135) by the intention-to-treat analysis and 95.5% (106/111) and 96.6% (114/118) by the per-protocol analysis, respectively. The intention-to-treat and per-protocol analyses revealed no statistically significant difference in the eradication rate (P = .299 and P = .743, respectively). Rates of adverse events were similar between groups (25.2% vs 23.0%, P -value: .776) Adverse events, which resulted in poor compliance, occurred in six patients of each group, but there were no serious complications.

PAM-B therapy is as effective as concomitant therapy for eradicating H. pylori with comparative safety. PAM-B therapy is regarded as a promising alternative to standard triple therapy for a first-line eradication in Korea.

Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori.

To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started.

We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively.

We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as 13C or 14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection.

Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities.

We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons.

In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.

The stomach contents contain of both acid and proteolytic enzymes. How the stomach digests food without damaging itself remained a topic of investigation for decades. One candidate was gastric urease, which neutralized acid by producing ammonia from urea diffusing from the blood and potentially could protect the stomach. Discovery that gastric urease was not mammalian resulted in a research hiatus until discovery that gastric urease was produce by Helicobacter pylori which caused gastritis, peptic ulcer and gastric cancer. Gastric urease allows the organism to colonize the acidic stomach and serves as a biomarker for the presence of H. pylori. Important clinical tests for H. pylori, the rapid urease test and urea breath test, are based on gastric urease. Rapid urease tests use gastric biopsies or mucus placed in a device containing urea and an indicator of pH change, typically phenol red. Urea breath tests measure the change in isotope enrichment of ¹³C- or ¹⁴CO₂ in breath following oral administration of labeled urea. The urea breath test is non-invasive, convenient and accurate and the most widely used test for non-invasive test for detection of active H. pylori infection and for confirmation of cure after eradication therapy.

Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.

Vonoprazan is a potassium-competitive acid blocker, a new type of acid-suppressing drug, and has recently become available for peptic ulcers, gastroesophageal reflux disease, and Helicobacter pylori (H. pylori) eradication. Its efficacy for H. pylori eradication has been reported. However, the evidence for its efficacy and feasibility remains limited. We aimed to compare the feasibility, effectiveness and safety of vonoprazan-based triple therapy with conventional proton pump inhibitor (PPI)-based triple therapy in multicenter clinical practice.

We performed a multicenter retrospective study on patients receiving first-line H. pylori eradication therapy between March 2013 and November 2015 with either vonoprazan-based triple therapy or conventional PPI-based triple therapy.

A total of 2715 patients aged 63.0 ± 12.1 years (1412 [52.0%] males) were analyzed. Eradication rates were 87.2% (368/422) for vonoprazan-based therapy and 72.4% (1661/2293) for conventional PPI-based therapy (P < 0.01). Among the former group, there were 10 cases of diarrhea, six of nausea/vomiting, and five of rash, but the rates of these adverse events were similar to those in the conventional PPI group.

Vonoprazan-based triple therapy is feasible, and has a higher rate for H. pylori eradication than conventional PPI as a first-line regimen.

There is progress in endoscopy techniques. While it is not yet possible to detect Helicobacter pylori directly in the stomach, it becomes easier to detect the mucosal changes induced by the bacteria. Some small changes can also increase the sensitivity of the invasive tests, for example culture or histology, but the wide use of proton-pump inhibitors has a negative impact on these tests. Only molecular methods are able to detect a limited load of bacteria, especially by using real-time PCR but also with new methods, for example dual-priming oligonucleotide-based PCR, loop-medicated isothermal amplification, droplet-digital PCR or a multiple genetic analysis system. Among the noninvasive tests, urea breath test remains a test of major interest, while there are attempts to develop an ammonia breath test and other nanosensor devices. A new antigen stool test, a chemoluminescence immunoassay using the LIAISON apparatus has also been tested for the first time with success. Despite its limitations, serology remains the most popular test to detect H. pylori antibodies. It also allows pepsinogen dosage which is of interest for detecting atrophy.

Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.

Proton pump inhibitors (PPI) are a major cause of false-negative Helicobacter pylori test results. Detecting PPI use and stopping it 2 weeks before testing is the preferred approach to improve the reliability of H pylori diagnostic tests. Immunoblot and molecular methods may be useful for the detection of H pylori infection in difficult cases. When conventional tests are negative and eradication is strongly indicated, empirical H pylori treatment should be considered. In this article, an updated critical review of the usefulness of the various invasive and noninvasive tests in the context of extensive PPI use is provided.

Helicobacter pylori infection contributes to the development of diverse gastric and extragastric diseases. The infection is necessary but not sufficient for the development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, therefore there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to the development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk-these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma. When tested, these hypotheses have not been confirmed and are therefore most likely false.

This study was conducted to evaluate the diagnostic validity of the (13)C-urea breath test ((13)C-UBT) in the remnant stomach after partial gastrectomy for gastric cancer.

The (13)C-UBT results after Helicobacter pylori eradication therapy was compared with the results of endoscopic biopsy-based methods in the patients who have received partial gastrectomy for the gastric cancer.

Among the gastrectomized patients who showed the positive (13)C-UBT results (≥ 2.5‰, n = 47) and negative (13)C-UBT results (< 2.5‰, n = 114) after H. pylori eradication, 26 patients (16.1%) and 4 patients (2.5%) were found to show false positive and false negative results based on biopsy-based methods, respectively. The sensitivity, specificity, false positive rate, and false negative rate for the cut-off value of 2.5‰ were 84.0%, 80.9%, 19.1%, and 16.0%, respectively. The positive and negative predictive values were 44.7% and 96.5%, respectively. In the multivariate analysis, two or more H. pylori eradication therapies (odds ratio = 3.248, 95% confidence interval= 1.088-9.695, P = 0.035) was associated with a false positive result of the (13)C-UBT.

After partial gastrectomy, a discordant result was shown in the positive (13)C-UBT results compared to the endoscopic biopsy methods for confirming the H. pylori status after eradication. Additional endoscopic biopsy-based H. pylori tests would be helpful to avoid unnecessary treatment for H. pylori eradication in these cases.