Analyses of the association between Helicobacter pylori antibody titre and pathogenicity before and after eradication: results of the Kyushu and Okinawa population study, a retrospective observational cohort study.

OBJECTIVES: To assess the utility of Helicobacter pylori antibody testing, we evaluated the correlation between the H. pylori antibody titre and H. pylori-associated pathogenicity and the changes in antibody titre after H. pylori eradication therapy. DESIGN: A retrospective observational cohort study. SETTING AND PARTICIPANTS: From 2004 to 2016, medical check-ups were performed in different regions of Japan. In total, 324 subjects infected with H. pylori who received H. pylori eradication therapy were enrolled; H. pylori was eradicated in 266 of these subjects. We examined the associations between H. pylori antibody titre with pepsinogen and the presence or absence of H. pylori-associated pathogenic proteins, such as cytotoxin-associated gene A and vacuolating cytotoxin gene A, at baseline and after H. pylori eradication therapy. RESULTS: The H.pylori antibody titre showed a positive correlation with pepsinogen II and a negative correlation with the pepsinogen I/II ratio. Moreover, the H.pylori antibody titre significantly correlated with the positive rates of H. pylori-associated pathogenic protein before eradication therapy. Antibody titres decreased after eradication, the pepsinogen I/II ratio increased and the H. pylori-associated pathogenic protein-positive rate decreased in patients with successful eradication. The determination of eradication using the decline in antibody titre 6 months after eradication therapy was useful (area under the receiver operating characteristic curve: 0.98). CONCLUSIONS: Our data indicate that the H. pylori antibody titre may represent the degree of pathogenicity. The H. pylori antibody titre was associated with attenuation of pathogenicity in patients with H. pylori eradication, indicating the clinical utility of H. pylori antibody testing.

Effect of Gastrin G-17 Combined with Pepsinogen PGI and PGII on the Early Screening of Gastric Cancer in the Department of Gastroenterology.

Objective: To compare serum levels of pepsinogen I (PGI), pepsinogen II (PGII), and gastrin-17 (G-17) among patients with gastritis, gastric ulcer, and gastric cancer, and to assess the effectiveness of these biomarkers individually and in combination for screening gastric cancer. Methods: Serum levels of PGI, PGII, and G-17 were measured using enzyme-linked immunosorbent assay (ELISA) in 50 patients with gastric cancer, 60 with chronic gastritis, and 60 with gastric ulcer from February 2020 to June 2021. The diagnostic value of these biomarkers was analyzed through sensitivity, specificity, and ROC curve assessments. Results: Serum PGI levels were significantly lower in patients with advanced gastric cancer compared to those with early gastric cancer (P < .05), while PGII and G-17 levels were significantly higher in advanced-stage patients (P < .05). The combined ROC curve analysis of PGI, PGII, and G-17 yielded an area under the curve (AUC) of 0.933, indicating higher diagnostic accuracy than any of the markers alone. Statistically significant differences were noted between the combined and individual tests (Z = 2.376, P < .05). Patients with PGI levels lower than 17.21 ng/ml had a worse prognosis compared to those with higher levels. Similarly, patients with PGII levels greater than 74.65 ng/ml and G-17 levels greater than 17.03 pmol/L had poorer prognoses. Additionally, higher G-17 levels were associated with significantly lower serum PGI levels. Conclusions: Patients with low expression of PGI have a poorer prognosis, and those with high expression of PGII and G-17 also have a poor prognosis. Combining the three indicators has clear value for the screening and prognostic evaluation of gastric cancer, making it worthy of clinical promotion and application.

The role of gastrin 17 and pepsinogen I:pepsinogen II ratio in pathological diagnosis and endoscopic selection in gastritis patients.

BACKGROUND: The noninvasive serum markers pepsinogen I (PGI), pepsinogen II (PGII), gastrin-17 (G17), and PGI:PGII ratio (PGR) have recently been proposed as a new tool for predicting various gastric pathologies. METHODS: A total of 83 gastritis patients confirmed by gastroscopy were enrolled, with 78 undergoing concurrent colonoscopies. The control group included 99 healthy subjects. Enzyme-linked immunosorbent assay was used to detect PGI, PGII, G17, and PGR. The performance of serological analysis for detecting gastritis pathology was evaluated using receiver operating characteristic (ROC) curves. RESULTS: The G17 and PGII levels increased significantly (P < .001), whereas PGR levels decreased (P = .001) in the gastritis group. The ROC analysis revealed that PGR had a sensitivity and specificity of 70.83% and 86.67%, respectively, in predicting Helicobacter pylori-infected gastritis and a sensitivity and specificity of 88% and 65.52%, respectively, in predicting active gastritis. The G17 levels were significantly elevated in gastritis patients undergoing concurrent colonoscopies (P < .05). CONCLUSION: Pepsinogen I:pepsinogen II ratio was found to be a useful predictor of active gastritis and H pylori-infected gastritis. Furthermore, G17 was found to be closely related to pathological conditions found by colonoscopy and may provide recommendations for whether gastritis patients should undergo a concurrent colonoscopy.

Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft dysfunction.

BACKGROUND: Aspiration is a known risk factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration; however, they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs, while others, such as pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. METHODS: Expression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to preexisting markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after antireflux surgery were assessed in a third cohort of LTRs. RESULTS: PGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Antireflux surgery was associated with reduced airway PGA4. CONCLUSIONS: Airway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

Low serum pepsinogen II levels are closely linked with a risk of metabolic syndrome among healthy individuals with asymptomatic Helicobacter pylori infection: a cross-sectional study.

Aim:Helicobacter pylori (Hp) infection has a connection with metabolic syndrome (MetS). Pepsinogen II (PGII) is a marker for gastric epithelial function. The present research was aimed at determining the associations among serum PGII levels, Hp infection and MetS in healthy subjects. Methods: This cross-sectional study enrolled 1242 healthy people, including 545 subjects with asymptomatic Hp infection and 697 subjects without Hp infection. Based on the number of MetS components present, subjects with Hp infection were assigned to the following groups: group 1, no component (126 subjects); group 2, one or two components (260 subjects); and group 3, three or more components (159 subjects). Physical measurements and biochemical indices were recorded. Serum PGII levels were recorded using ELISA. SPSS and GraphPad Prism were used for statistical analyses. Results: Among subjects with Hp infection, serum PGII was evidently downregulated in group 3 compared with group 1 (14.95 ± 8.24 vs 17.97 ± 9.08 µg/l; p = 0.015). Serum PGII levels were correlated with an increased risk of MetS (odds ratio: 0.867; 95% CI: 0.772-0.974; p = 0.016), as indicated by the multivariate logistic regression analysis. Grouping subjects with Hp infection according to quartiles of serum PGII levels identified an evident difference in MetS prevalence among the four quartile-based groups (p = 0.047). Conclusions: Among healthy subjects with asymptomatic Hp infection, serum PGII levels were lower in those with MetS than in those without MetS. Serum PGII levels showed an independent and negative correlation with the risk of MetS in healthy subjects with Hp infection.

Gastric cancer detection using the serum pepsinogen test method.

BACKGROUND: Gastric cancer (GC) is the eighth most common cause of cancer deaths in Croatia and one of the most common causes of cancer deaths worldwide. A reliable diagnostic tool for the early detection of GC is essential. OBJECTIVE: We previously suggested a pepsinogen test method to reduce the mortality from GC by allowing early detection. Here, we report an updated analysis from a prospective single-center clinical study to evaluate the sensitivity and specificity of the pepsinogen test method and to determine whether this test can be used as a part of routine laboratory assessment of high-risk patients. METHODS: We present mature data of the pepsinogen test method in the Croatian population after a median follow-up of 36 months. Statistical analyses were performed using a Mann-Whitney U test, multiple logistic regression, and receiver operating characteristics (ROC) to evaluate the predictive power of the assayed biomarkers. RESULTS: Of the 116 patients, 25 patients had GC and 91 demonstrated a nonmalignant pathology based on tissue biopsy. Cutoff values were pepsinogen I ⩽70 and pepsinogen I/II ratio ⩽3.0. Using ROC curve analysis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were determined to be 87.22%, 78.12%, 90.10%, 71.43%, and 92.86%, respectively, for the diagnosis of GC. The area under the curve was 0.700 (95% confidence interval 0.57-0.83). CONCLUSION: Pepsinogen tests are valuable for screening a population in need of further diagnosis and could help to avoid unnecessary invasive endoscopic procedures.

Protective effect of the combination of essential oil from patchouli and tangerine peel against gastric ulcer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. AIM OF THE STUDY: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. MATERIALS AND METHODS: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. RESULTS: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). CONCLUSION: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.

Serological Biomarker Panel in Diagnosis of Atrophic Gastritis and Helicobacter pylori Infection in Gastroscopy Referral Patients: Clinical Validation of the New-Generation GastroPanel® Test.

BACKGROUND/AIM: Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel® test (GP: biomarker panel of PGI, PGII, G-17, Hp IgG ELISA) that was developed in the early 2000's, was recently updated to a new-generation (unified GP) test version. This clinical validation study evaluated the diagnostic accuracy of the new-generation GP test in detection of AG and Hp among gastroscopy referral patients in a University Clinic. PATIENTS AND METHODS: Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing. RESULTS: Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κw) of 0.861 (95%CI=0.834-0.883). In ROC analysis using moderate/severe AG of the corpus (AGC2+) as the endpoint, AUC=0.952 (95%CI=0.891-1.000) and AUC=0.998 (95%CI=0.996-1.000) for PGI and PGI/PGII, respectively. Hp IgG antibody ELISA detected biopsy-confirmed Hp-infection with AUC=0.993 (95%CI=0.987-0.999). CONCLUSION: The new generation GastroPanel® is a precise test for non-invasive diagnosis of atrophic gastritis and Hp-infection in dyspeptic patients referred for diagnostic gastroscopy.

Diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PGII and CA199 in early gastric cancer.

To explore the diagnostic value of MRI-DWI signal intensity value combined with serum PGI. PGII and CA199 in early gastric cancer. Sixty cases of gastric cancer patients admitted to our hospital from December 2019 to December 2020 were selected as the gastric cancer group and 80 cases of healthy volunteers who underwent physical examination in our hospital during the same period were selected as the healthy group. All the 60 patients underwent MRI-DWI examination, and the pathological diagnosis results were regarded as the gold standard. MRI-DWI images, MRI-DWI signal intensity values of patients with different degrees of gastric cancer differentiation. Serum PGI, PGII and CA199 levels of subjects in the two groups were compared. AUC was used to evaluate the diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PG II and CA199 for early gastric cancer. In the healthy group, T1W1 showed relatively uniform low signal intensity. While T2WI showed no significant increase in signal intensity. In the gastric cancer group. There was diffuse gastric wall thickening, local thickening or mass formation; T1WI and WATS showed slightly lower signal intensity in the lesion area. T2WI, FLAIR and B-TFE showed slightly uneven or moderately increased signal intensity. DWI showed limited diffusion, and the signal intensity increased uniformly or more uniformly, and the range of increase was clear. The signal intensity of MRI-DWI was 89.12 ± 8.14 in patients with low differentiation, 82.17 ± 6.35 in patients with moderate differentiation, and 74.52 ± 4.53 in patients with high differentiation. There were significant differences in the signal intensity of MRI-DWI among the three groups, and the difference was statistically significant (F=12.214, P <0.05). Serum PGI levels of subjects in the gastric cancer group were significantly lower than those in the healthy group, and the levels of PGII and CA199 were significantly higher than that in the healthy group, with statistical significance (P <0.05). The AUC, sensitivity and specificity of MRI-DWI signal intensity value and serum PGI, PGII and CA199 combined indexes in the diagnosis of gastric cancer were significantly higher than those of the independent indexes, with statistical significance (P <0.05). Conclusion: MRI-DWI signal strength value, serum PGI, PGII and CA199 levels are closely related to the occurrence and development of early gastric cancer. The combined detection and diagnosis efficiency is higher, which is helpful to improve the detection rate of early gastric cancer and is worthy of extensive clinical application.

Serum pepsinogen II levels are doubled with Helicobacter pylori infection in an asymptomatic population of 40,383 Chinese subjects.

ABSTRACT: Pepsinogen (PG) I and II are crucial in the gastric digestive processes. This study is to examine the relationship of serum PGI, PGII, and PGI/PGII ratio with Helicobacter pylori (Hp) infection, age, sex, and body mass index (BMI) in subjects in Beijing, China.A total of 40,383 asymptomatic subjects, who underwent medical examination in Beijing Rehabilitation Hospital, were included in this study. Serum PG levels were measured using chemoluminescence techniques. The age, sex, and BMI data were collected, and Hp infection was identified with 13C-urea breath test. Statistical analysis was conducted with Python, Pandas and Seaborn software.Asymptomatic subjects with Hp infection (Hp+) had a significantly higher level of PGI in the serum (111 ng/mL [median]) than those without Hp infection (Hp-) (94 ng/mL, P < .001). The asymptomatic Hp+ subjects had 2-fold higher PGII levels (7.2 ng/mL) than Hp- subjects (3.2 ng/mL, P < .001). These changes produced significantly lower PGI/II ratio in Hp+ patients than in Hp- subjects (16:30, P < .001). The serum PGI and PGII levels were higher in males than in females (PGI: 104 ng/mL vs 95 ng/mL, PGII: 4.3 ng/mL vs 3.7 ng/mL, both P < .001), PGI/II ratio of males is at 95% of that in females (P < .001). PGI and PGII levels gradually increased in older people (P < .001), whereas the PGI/II ratio decreased significantly with age (P < .001). The levels of the two serum PGs were decreased and the ratio increased when BMI were higher than 28 kg/cm2 (P < .05).The levels of serum PGI, especial PGII, were increased by Hp infection, and also influenced by age, sex, and BMI. Therefore, these influencing factors should be considered during clinical practice.

Association between serum pepsinogen and atherosclerotic cardiovascular disease.

BACKGROUND AND AIM: Serum pepsinogens (PGs) are biomarkers for gastric mucosal damage and have been reported to be associated with atherosclerosis. Its correlation with atherosclerotic cardiovascular disease (ASCVD) is still unknown. This study aimed to explore the association between serum PGs and ASCVD for providing physicians with an integrative picture to make rational plans in the diagnosis and treatment of ASCVD. METHODS AND RESULTS: The concentrations of serum PGs and their distributions between ASCVD and non-ASCVD were compared by non-parametric test, Chi-squared test and Fisher exact test. The correlation between variables was analyzed by Spearman's correlation test. The association of serum PGs with ASCVD was analyzed by the binary logistic regression and two-piecewise linear regression. A total of 8355 recruited cases were eligible for the study. The concentrations of serum PGs were significantly different between the ASCVD and non-ASCVD groups (P = 0.025, P < 0.001). The lower PGI and PGR levels were significantly correlated with a high risk of ASCVD presence after adjustment for 26 potential covariates. Moreover, there was a linear relationship between the high level of PGII and the high risk of ASCVD [adjusted OR = 1.16 (1.00, 1.37), P = 0.07]. A nonlinear relationship of PGI/PGR and ASCVD (P = 0.08/<0.001) was also revealed. The risk of ASCVD increased with a range of log PGI ≥2.13 (PGI≥131 ng/mL) [adjusted OR = 4.67 (1.00, 23.17)], and decreased with a range of log PGR ≥0.22 (1.65) [adjusted OR = 0.59 (0.48, 0.74), P < 0.001]. CONCLUSIONS: Serum PGI and PGR are nonlinearly correlated with ASCVD, while PGII is linearly correlated with ASCVD. Among all PGs, PGR may serve as a reliable biomarker for ASCVD.

Associations of Serum Pepsinogens and Helicobacter Pylori Infection with High-Sensitivity C-Reactive Protein in Medical Examination Population.

OBJECTIVE: This study aimed to clarify the distribution characteristics of serum pepsinogen (PG) and Helicobacter pylori in the medical examination population and to explore the relationships of PG level and H. pylori infection status with the high-sensitivity C-reactive protein (hsCRP) level and their significance in health examination. METHODS: We detected H. pylori infection by C13 urea breath test, the serum pepsinogen I (PGI) and pepsinogen II (PGII) contents were measured by chemiluminescence microparticle immunoassay, and the PGI/PGII ratio was calculated. In addition, the serum hsCRP level was determined by the Abbott C16000 automatic biochemical analyzer. RESULTS: The PGI and hsCRP levels were significantly higher in men than in women, and the PGII level was slightly higher in men than in women (both P <.05). The PGI, PGII, and hsCRP levels were positively correlated with age (r = 0.210, 0.287, and 0.133, respectively; P <.05), whereas the PGI/PGII ratio was negatively correlated with age (r = -0.190; P <.05). The positive H. pylori infection rate was 30.2% among the patients in this study; H. pylori infection was not related to sex (P >.05), and the difference in age stratification was not statistically significant (P >.05). The abnormal PGI/PGII ratio in the medical examination population was not correlated with sex (P >.05). In the H. pylori positive infection group, the proportion of PGI/PGII ratio <3, the PGI and PGII levels were significantly higher than those in the H. pylori negative infection group, and the PGI/PGII ratio was significantly lower than that in the negative group (both P <.05). The hsCRP level was not associated with H. pylori infection (P >.05), and it was significantly higher in the PGI/PGII ratio <3 group than in the PGI/PGII ratio ≥3 group (P <.05). CONCLUSION: The PGI and PGII levels and the PGI/PGII ratio are correlated with H. pylori infection. The abnormal PGI/PGII ratio is closely related to H. pylori infection and hsCRP level. Therefore, H. pylori infection status and hsCRP level should be considered when determining atrophic gastritis by the PGI/PGII ratio.

Immunostimulatory membrane proteins potentiate H. pylori-induced carcinogenesis by enabling CagA translocation.

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, depletion of Hp0305 and Hp1564 significantly reduced levels of gastric cell-associated bacteria and markedly impaired the ability of H. pylori to stimulate pro-inflammatory cytokine production. Remarkably, our studies revealed that Hp1564 is required for translocation of the oncoprotein CagA into gastric epithelial cells. Our data provide experimental insight into the molecular mechanisms governing novel H. pylori pathogenicity factors that are strongly associated with gastric disease and highlight the potential of Hp0305 and Hp1564 as robust molecular tools that can improve identification of individuals that are highly susceptible to gastric cancer. We demonstrate that Hp0305 and Hp1564 augment H. pylori-mediated inflammation and gastric cancer risk by promoting key bacteria-gastric cell interactions that facilitate delivery of oncogenic microbial cargo to target cells. Thus, therapeutically targeting microbial interactions driven by Hp0305/Hp1564 may enable focused H. pylori eradication strategies to prevent development of gastric malignancies in high-risk populations.

Helicobacter pylori, clinical, laboratory, and noninvasive biomarkers suggestive of gastric damage in healthy school-aged children: A case-control study.

BACKGROUND: Helicobacter pylori is acquired largely in early childhood, but its association with symptoms and indirect biomarkers of gastric damage in apparently healthy children remains controversial. We aimed to relate persistent H. pylori infection in apparently healthy school-aged children with clinical, laboratory, and noninvasive biomarkers suggestive of gastric damage using a case-control design. MATERIALS AND METHODS: We followed up 83 children aged 4-5 years with persistent H. pylori infection determined by stool antigen detection and/or a urea breath test and 80 noninfected matched controls from a low-income to middle-income, periurban city in Chile for at least 3 years. Monitoring included clinical visits every 4 months and annual assessment by a pediatric gastroenterologist. A blood sample was obtained to determine laboratory parameters potentially associated with gastric damage (hemogram and serum iron and ferritin levels), biomarkers of inflammation (cytokines, pepsinogens I and II, and tissue inhibitor metalloproteinase 1), and expression of cancer-related genes KLK1, BTG3, and SLC5A8. RESULTS: Persistently infected children had higher frequency of epigastric pain on physical examination (40% versus 16%; P = 0.001), especially from 8 to 10 years of age. No differences in anthropometric measurements or iron-deficiency parameters were found. Persistent infection was associated with higher levels of pepsinogen II (median 12.7 ng/mL versus 9.0 ng/mL; P < 0.001); no difference was observed in other biomarkers or gene expression profiles. CONCLUSIONS: H. pylori infection in apparently asymptomatic school-aged children is associated with an increase in clinical symptoms and in the level of one significant biomarker, pepsinogen II, suggesting early gastric involvement.

Serum Gastrin Predicts Hydrogen-Producing Small Intestinal Bacterial Overgrowth in Patients With Abdominal Surgery: A Prospective Study.

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) might be associated with a history of abdominal surgery. We aimed to evaluate the prevalence of SIBO and to investigate serum gastrin and pepsinogen as predictors of SIBO in patients with a history of hysterectomy, gastrectomy, or cholecystectomy. METHODS: This prospective study surveyed 146 patients with a history of hysterectomy, gastrectomy, or cholecystectomy, and 30 healthy controls, who underwent a hydrogen (H2)-methane (CH4) glucose breath test (GBT) for SIBO. Serum pepsinogen I and II and gastrin levels were reviewed. RESULTS: GBT positivity (+) was significantly higher in patients with histories of abdominal surgery than that in in controls (37.6% vs 13.3%, P < 0.01). Among GBT+ patients, 36.0% (18/50), 96.2% (25/26), and 17.1% (12/70) were in the hysterectomy, gastrectomy, and cholecystectomy groups, respectively. Among the GBT subtypes, 43.6% (24/55), 10.9% (6/55), and 45.5% (25/55) of patients were in the GBT(H2)+, GBT(CH4)+, and GBT(mixed)+ groups, respectively. The gastrectomy group had significantly more GBT+ or GBT(H2)+ patients than the other surgical groups. Gastrin levels were higher in GBT(H2)+ patients and lower in GBT(CH4)+ patients than those in GBT- patients. Previous gastrectomy and elevated gastrin levels were independent predictive factors of GBT(H2)+. DISCUSSION: SIBO is not uncommon in patients with histories of abdominal surgeries, but it is more common in patients who have undergone gastrectomy. Serum gastrin level could be a serologic predictor of H2-producing SIBO. The relationship between serum gastrin and SIBO requires further research.

Low Pepsinogen I/II Ratio and High Gastrin-17 Levels Typify Chronic Atrophic Autoimmune Gastritis Patients With Gastric Neuroendocrine Tumors.

INTRODUCTION: Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases. This study aimed to determine, in CAAG patients, the association of gNET development, the prevalence of autoimmune diseases other than CAAG, the association of autoimmunity, and gNET development with pepsinogen I, II, gastrin-17, and Helicobacter pylori infection analysis. METHODS: We determined the prevalence of gNETs and other autoimmune diseases and analyzed pepsinogen I and II, gastrin-17 serum levels, and H. pylori infection in all patients diagnosed with CAAG at our hospital between 2013 and 2017. RESULTS: A total of 156 patients were studied and in 15.4% was observed concomitant gNET. Approximately 68.6% had at least 1 other autoimmune disease at diagnosis of CAAG. Approximately 60.9% had autoimmune thyroiditis, followed by diabetes (19.9%) and autoimmune polyendocrine syndrome (12.8%). CAAG patients with and without gNET had similar rates of comorbidity with other autoimmune diseases, but the pepsinogen I/II ratio was lower in patients with gNET (1.6 vs 4.5, P = 0.018). Receiver operating characteristic curve analyses identified a pepsinogen I/II ratio <2.3 and gastrin-17 levels >29.6 pmol/L as cutoffs distinguishing CAAG patients with gNET from those without. The combined use of these cutoff correctly identified 16 of the 18 CAAG patients with gNET (P = 0.007). H. pylori infection was observed in 28.7% of cases tested but did not associate with gNET. DISCUSSION: This study suggests that a low pepsinogen I/II ratio and high gastrin-17 levels characterize patients with CAAG and gNET and confirms the frequent coexistence of CAAG with other autoimmune diseases.

A panel of stomach-specific biomarkers (GastroPanel®) for the diagnosis of atrophic gastritis: A prospective, multicenter study in a low gastric cancer incidence area.

BACKGROUND: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. MATERIAL AND METHODS: In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. RESULTS: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P = .015] and corpus AG [61.0% (95% CI 49.2; 72.0), P = .004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068). CONCLUSION: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.

LncRNAs adjacent to pepsinogen C in gastric diseases and diagnostic efficiencies of joint detection in gastric diseases.

Aims: We aimed to explore diagnostic efficiencies of long noncoding RNAs (lncRNAs) adjacent to PGC combining with sPGC and anti-Helicobacter pylori IgG in identifying GC (gastric cancer) and precancerous disease. Patients & methods: A total of 265 patients with different gastric diseases were collected. ELISA was to detect sPGC and anti-H. pylori IgG. LncRNAs was determined by qRT-PCR. Results: The area under receiver operating characteristic curve of lncRNAs in discriminating GC+AG (atrophic gastritis) and superficial gastritis (SG) were 79.0, 68.1 and 75.9%. The diagnostic performance of lncRNAs with sPGC had increasing trends in distinguishing GC from non-GC, SG from GC+AG comparing with lncRNAs, with no statistic difference. Diagnosis efficacies of lncRNAs with anti-H. pylori IgG improved dramatically. Conclusions: Serum lncRNAs could distinguish GC, AG and SG. Diagnosis efficiencies of lncRNAs with sPGC and anti-H. pylori-IgG could be improved.

Serum pepsinogens as a gastric cancer and gastritis biomarker in South and Southeast Asian populations.

Serum pepsinogens have been widely acknowledged as gastric mucosal biomarkers; however, a multicountry report on the benefits of pepsinogens as biomarkers has not yet been published. We analyzed 1,206 sera and gastric mucosal samples collected from Bangladesh, Bhutan, Indonesia, Myanmar, Nepal and Thailand then assessed the association between gastric mucosal changes and Helicobacter pylori infection. The new cutoff values for serum pepsinogen values were evaluated using a receiver operating characteristic analysis. The participants with H. pylori infection had significantly lower pepsinogen I and higher pepsinogen II values, but a lower pepsinogen I/II ratio than participants without the infection (all P < .001). The pepsinogen I and pepsinogen I/II values were significantly higher and lower, respectively, in individuals with atrophic gastritis than in those without (both P < .001). Among uninfected individuals, only the pepsinogen I/II ratio was significantly lower in atrophic individuals. Pepsinogen I/II ratio also were significantly different between disease among H. pylori-positive and H. pylori-negative individuals, suggesting the pepsinogen I/II ratio is a robust biomarker for determining both chronic and atrophic gastritis. The cutoffs for detecting chronic and atrophic gastritis for the pepsinogen I/II ratio were 4.65 and 4.95, respectively. In conclusion, pepsinogen levels are useful biomarker for both chronic gastritis and atrophic gastritis, but they should be used with caution. Population-based validation is necessary to determine the best cutoff values. Among all pepsinogen values, the pepsinogen I/II ratio was the most reliable gastric mucosal-change biomarker.