Serum Pepsinogen Levels Research Articles

Factors Predicting Effectiveness of Eradication Therapy for Helicobacter pylori-Associated Dyspepsia Symptoms.

Functional dyspepsia is distinguishable from Helicobacter pylori-associated dyspepsia. However, distinguishing H. pylori-associated dyspepsia from functional dyspepsia before H. pylori eradication is difficult. Therefore, in the present study, we aimed to investigate whether serum pepsinogen levels before H. pylori eradication are associated with the amelioration of dyspepsia after successful H. pylori eradication. Additionally, we examined the usefulness of serum pepsinogen levels and other factors in predicting dyspepsia outcomes. H. pylori eradication was effective in 14 patients (Responders) and ineffective in 19 patients (Non-responders). The pepsinogen I/II ratio in Responders (3.4 ± 1.2) and Non-responders (2.3 ± 1.0) differed significantly (p = 0.006). The optimal cut-off pepsinogen I/II value was 2.3. Multivariate logistic regression analysis showed that the adjusted odds ratio for Non-responders was 26.1 (95% confidence interval: 2.0-338.0, p = 0.012) for a pepsinogen I/II ratio ≤ 2.3 and 8.10 (95% confidence interval: 1.1-57.6, p = 0.037) for smoking habits. The pepsinogen I/II ratio and smoking habits were associated with the effects of H. pylori eradication on dyspeptic symptoms. Thus, the pepsinogen I/II ratio cut-off value can be used to identify patients likely to respond to H. pylori eradication after the resolution of dyspeptic symptoms.

A novel predictive formula for highly accurate discrimination between truly Helicobacter pylori-uninfected and currently infected/spontaneously eradicated individuals for gastric cancer screening.

The ABC classification, which categorizes gastric cancer risk based on serum Helicobacter pylori (H pylori) antibody and pepsinogen levels, has a limitation of potentially misclassifying high-risk individuals as low risk. To overcome the problem, we previously developed a 4-parameter predictive formula (age, serum H pylori antibody, PGI, and PGII) using logistic regression analysis to accurately identify low-risk truly H pylori-uninfected status. Our predictive formula demonstrated superior sensitivity and specificity in distinguishing between low-risk truly uninfected individuals and high-risk currently/spontaneously eradicated status individuals, compared to the modified ABC classification based on latex immunoassay kits (traditional 3-parameter model). This study aimed to revalidate the diagnostic accuracy of the predictive formula in a new and different study population. We applied the predictive formula to the target population and compared the sensitivity and specificity with those of the traditional 3-parameter model. A total of 788 enrollees were analyzed: 703 were classified as truly uninfected, 45 as currently infected, and 40 as spontaneously eradicated according to the results of stool antigen testing and endoscopic findings. The sensitivities and specificities of the predictive formula and the traditional 3-parameter model were 89.5% and 87.1% versus 89.8% and 80.0%, respectively. The specificity of the predictive formula was superior in the 70 to 89 age range and H pylori antibody < 3 U/mL groups. The predictive formula had higher specificity than the traditional 3-parameter model. The results should contribute to efficient gastric cancer screening by predicting H pylori infection status.

Probiotic Supplementation With Saccharomyces boulardii and Enterococcus faecium Improves Gastric Pain and Bloating in Airline Pilots With Chronic Non-atrophic Gastritis: An Open-Label Study.

Background Commercial airline pilots (APs) are prone to upper gastrointestinal symptoms, such as epigastric pain and bloating. These issues are often linked to occupational risk factors like irregular diet, sleep disruption, and circadian rhythm disturbance. The use of probiotics to enhance intestinal health is well established, but their efficacy in treating upper gastrointestinal diseases is still debated. This is primarily due to the stomach's small resident microbiota and its low pH, which is inhospitable to most microbes. However, emerging research suggests that specific probiotic strains, such as Enterococcus faecium, can withstand acidic environments. Moreover, certain yeast species, including Saccharomyces boulardii, can survive at a low pH. Consequently, we conducted a preliminary, three-arm, randomized, open-label, dose-finding, four-week study to compare the effects of watchful waiting (WW) with the administration of an oral probiotic supplement containing S. boulardii and E. faecium in APs diagnosed with Helicobacter pylori-negative chronic non-atrophic gastritis (CNG). Methods The study included 39 APs with CNG who were randomized into three groups with a 1:1:1 ratio. The low-dose group (n = 13) received one capsule of the probiotic supplement twice daily, before meals, for four weeks. The high-dose group (n = 13) was administered two capsules of the supplement on the same schedule. The third group (n = 13) underwent WW and served as the control arm. Blinding was maintained for the examining physicians and laboratory staff, but not for the patients. All participants self-rated their experiences of gastric pain and bloating at the beginning and conclusion of the four-week treatment period. Additionally, serum levels of pepsinogen I (PGI) and pepsinogen II (PGII) were measured at these time points. Results Supplementation with probiotics significantly outperformed WW in reducing subjective gastric pain and bloating. This effect was consistent across both tested dosages, with no significant differences observed. However, only high-dose probiotics led to a statistically significant decrease in PGII levels and an increase in the PGI/PGII ratio after the four-week study period, a result not observed with low-dose probiotics. Conclusions Oral administration of S. boulardii and E. faecium demonstrated potential efficacy in reducing gastric pain and bloating symptoms in APs with CNG, as evidenced by statistically significant symptom improvement compared to the control group that did not receive the probiotic supplementation. Notably, high-dose probiotics resulted in a significant increase in the PGI/PGII ratio, indicating potential long-term cytoprotective effects on the gastric mucosa.

A population-based study of Helicobacter pylori: Does asymptomatic infection mean no gastroscopic lesions?

We determined the common clinical characteristics of patients infected with Helicobacter pylori (H. pylori) and investigated the relationship between H. pylori infection, and clinical symptoms, and gastroscopic manifestations. Our focus was specifically on the clinical manifestations in asymptomatic patients. We obtained the physical examination data of patients who underwent the 14C urea breath test between January 2018 and December 2020 at our Hospital. Basic demographic data, questionnaire data on clinical symptoms, and clinical examination data of the patients were also collected, and the correlation analysis was performed. A total of 2863 participants were included in the study. The overall H. pylori infection rate was 26.30%. The clinical symptoms between H. pylori-positive patients and H. pylori-negative patients did not differ significantly (P > .05). However, H. pylori-positive patients exhibited more severe gastroscopic manifestations (P < .001). The 14C urea breath test disintegrations per minute (DPM) values in H. pylori-positive patients correlated with their serum pepsinogen and gastrin-17 levels. With an increase in the DPM value, more combinations of clinical symptoms appeared in the patients. Among H. pylori-positive patients, DPM levels in asymptomatic patients were lower than those in symptomatic patients (P < .001). However, gastroscopic manifestations did not vary significantly between asymptomatic and symptomatic patients (P > .05). Patients infected with H. pylori showed no specific gastrointestinal symptoms. Patients with asymptomatic infection showed lower DPM levels, but their gastroscopic manifestations were similar to those of patients with symptomatic infection, and their lesions were more severe than H. pylori-negative people.

Characteristics of Helicobacter pylori-Seropositive Subjects According to: A) The Stool Antigen Test Findings. B) Serum Pepsinogen Level. C) Upper Endoscopic Findings

Abstract Background Helicobacter pylori infection can be diagnosed by invasive methods using the gastric biopsied specimens or non-invasively by examining serum, urine, breath, or stool. Histological examination by Giemsa staining is usually recommended for the diagnosis, but it is difficult to visualize the bacterium when there is alow density of H.Pylori on the gastric mucosa with atrophic and metaplastic changes, Limitations of histological examination include increased false negative test findings due to various density of H. pylori at a different sites, high cost, long turn-around time, and inter observer variability. Therefore, in endemic countries like Egypt with s higher risk of chronic atrophic gastritis (CAG), intestinal metaplasia, and gastric cancer, noninvasive tests need to be added for a more reliable diagnosis of H.Pylori infection. Aim of the Work The aim of this study is to compare between the prevalence of chronic atrophic gastritis (CAG) and gastric corpus atrophy in Helicobacter pyloriseropositive subjects according to the stool antigen test, serum pepsinogen(PG) level and upper endoscopic findings. Patients and Methods The current study represents Cross- sectional study -Descriptive -Diagnostic study. This study had been carried at Ain Shams University and Abbasia fever hospital on 80 seropositive- patients attending to endoscopy ward for a regular check-up, All patients subjected to full history, clinical examination and investigation in the form of; complete blood count, serum antiH.Pylori immunoglobulin G (IgG), stool antigen test and serum pepsinogen. Results The current study showed that there was a significant difference between positive and negative H. pylori regarding pepsinogen I &amp; II and endoscopic finding regarding CAG and CSG. Conclusion In conclusion, there is a link between positive stool H. pylori antigen test findings and a serum PG assay and upper endoscopic findings in seropositive subjects. Positive stool H. pylori antigen test findings are common in seropositive subjects with increased serum PG I levels indicating an ongoing H. pylori infection. Our study findings further suggest that, to reduce the infected subjects with H. pylori in their fecal material, seropositive subjects with increased gastric secreting ability need to be treated.

Identification of serologically active Helicobacter pylori antigens related to alterations in serum pepsinogen levels

Gastric adenocarcinoma is associated with Helicobacter pylori infection. The transition to a carcinogenic process is preceded by glandular atrophy and serum levels of pepsinogen I and II (PGI and PGII) correlate with this type of gastric lesions. Possible associations of serum PG levels in relation to the frequency of serological activity against H. pylori antigens were studied. Serum samples from patients with gastric pathology associated with H. pylori (n=26) and asymptomatic individuals as controls (n=37) were used. Seroactive antigens were identified by immunoblot using a protein extract of H. pylori. The antibody titers anti-H. pylori and the concentration of PGs in serum was determined by ELISA. Thirty-one seroactive antigens were identified, nine of which exhibited a differential frequency between both groups (116.7, 68.8, 61.9, 54.9, 45.6, 38.3, 36.5, 33.8 and 30.1kDa) and only 3 were related to altered levels of PGs in serum. In the control group, the seropositivity of the 33.8kDa antigen was related to an increase in PGII, while the 68.8kDa antigen was related to normal PG values (decreased PGII and elevated PGI/PGII levels) indicating that seropositivity to this antigen could be a protective factor to gastric pathology. The seropositivity of the 54.9kDa antigen was related to altered values of PGs indicative of inflammation and gastric atrophy (increased in PGII and decreased in PGI/PGII). The identification of serum alterations in pepsinogen levels related to seropositivity to H. pylori 33.8, 54.9 and 68.8kDa antigens sets a precedent for further study as possible prognostic serological biomarkers.

Sex-specific disparities of serum pepsinogen I in relation to body mass index.

The clinical significance of serum pepsinogen (PG) for screening gastric cancer has been a controversial topic. Serum PG I levels have been demonstrated to be correlated with age, sex, and the Helicobacter pylori (HP) infection. However, the underlying factors that influence serum PG I variations remain to be fully elucidated. We aimed to evaluate the impacts of sex and body mass index (BMI) on PG I in Chinese population. The cross-sectional study recruited 4,299 apparently healthy participants in Fujian Province. Serum PG levels were automatically measured using ELISA method. Serum H.pylori-IgG antibody was detected by the colloidal gold immunoassay. Clinical characteristics were obtained by questionnaire. Totally, 2,263 participants who had tests of serum PG and anti-HP IgG antibody were enrolled. Increased BMI and serum uric acid were observed in males with low PG I value (<70 μg/L). Multiple logistic regression showed the presence of overweight was the independent risk factor for male participants with low PG I level (odds ratio [OR] 1.519; p=0.017). However, the association was not found in females. Sex-specific association of serum low PG I with overweight was observed in the southeast coastal areas of China. Thus, effects of sexual dimorphism should not be ignored during the clinical utilization of serum PG I.

Association between salt intake and gastric atrophy by Helicobacter pylori infection: first results from the Epidemiological Investigation of Gastric Malignancy (ENIGMA).

Gastric atrophy (GA), usually linked to chronic infection with Helicobacter pylori (H. pylori), may over time evolve into gastric malignancy. Besides H. pylori, high salt intake may play a role in GA development. This study evaluates cross sectionally the association between salt intake and GA in Chilean adults. Population-based samples were recruited from two sites, Antofagasta and Valdivia, partaking in the Epidemiological Investigation of Gastric Malignancies. At recruitment, participants answered questionnaires and provided biospecimens. Salt intake (g/day) was estimated from casual spot urine samples using the Tanaka equation. GA was determined by serum pepsinogen levels. Only participants ≥ 40 to 70years of age were considered in this analysis, n = 565. For the association between salt intake (as sex-specific quartiles) and GA, odds ratios (ORs) and the corresponding 95% confidence intervals (CI) were estimated through multivariable logistic regression. In women, the multivariable-adjusted OR for GA comparing quartile 4 of the estimated salt intake (12.8g/day) to quartile 1 (6.6g/day) was 1.18 (95% CI 0.52-2.68, P-trend = 0.87). The corresponding OR in men was 0.49 (95% CI 0.19-1.27, P-trend = 0.17) with salt intakes of 12.8g/day and 7.1g/day for quartiles 4 and 1, respectively. There was little evidence for an association between salt intake estimated from spot urine and GA risk in our cross-sectional analysis of middle aged and older adults in Chile. Reverse causation bias cannot be ruled out and the sample size was limited to provide more precise estimates.

Association of serum pepsinogens and gastrin-17 with Helicobacter pylori infection assessed by urea breath test.

BackgroundAssociation of gastric atrophy or cancer with levels of serum pepsinogens, gastrin-17 and anti-Helicobacter pylori IgG antibody have been extensively studied. However, the association of serum pepsinogen and gastrin-17 with H. pylori infection has not been studied in a large population.AimTo investigate the impact of H. pylori infection on serum levels of pepsinogens and gastrin-17.MethodsA total of 354, 972 subjects who underwent health check-ups were included. Serum levels of pepsinogens and gastrin-17 were measured using the enzyme-linked immunosorbent assay. H. pylori infection was detected using 14C-urea breath test (UBT). Multivariable logistic regression analysis was used to investigate the association of serum pepsinogen and gastrin-17 with H. pylori infection.ResultsH. pylori prevalence was 33.18% in this study. The mean levels of pepsinogens and gastrin-17 were higher, while the mean pepsinogen-I/II ratio were lower among H. pylori-positive than -negative subjects. In H. pylori-positive subjects, pepsinogen and gastrin-17 levels correlated positively, whereas the pepsinogen-I/II ratio correlated negatively with UBT values (e.g., the mean serum level of pepsinogen-I in subjects with UBT values in the range of 100-499dpm, 500-1499dpm, and ≥1500dpm was 94.77 ± 38.99, 102.77 ± 43.59, and 111.53 ± 47.47 ng/mL, respectively). Compared with H. pylori-negative subjects, the adjusted odds ratio (aOR) of having pepsinogen-I ≤ 70 ng/mL in the three H. pylori-positive but with different UBT value groups was 0.31 (p<0.001), 0.16 (p<0.001), and 0.08 (p<0.001), respectively; while the aOR of having G-17>5.70 pmol/L was 4.56 (p<0.001), 7.43 (p<0.001), and 7.12 (p<0.001). This suggested that H. pylori-positive subjects with higher UBT values were less likely to have pepsinogen-I ≤70 ng/mL (a serum marker for gastric atrophy), but more likely to have gastrin-17 >5.70 pmol/L (a marker for peptic ulcer).ConclusionsH. pylori-positive subjects with higher UBT values are unlikely to have gastric atrophy, but may have greater risk of severe gastritis or peptic ulcers. Our study suggests that H. pylori-positive patients with high UBT values may benefit the most from H. pylori eradication.

SNP rs2920280 in PSCA Is Associated with Susceptibility to Gastric Mucosal Atrophy and Is a Promising Biomarker in Japanese Individuals with Helicobacter pylori Infection.

Helicobacter pylori infection results in gastric cancer (GC) with gastric mucosal atrophy (GMA). Some single-nucleotide polymorphisms (SNPs) in the prostate stem cell antigen gene (PSCA) are associated with GC and duodenal ulcers. However, the relationship of other identified SNPs in PSCA with these diseases remains unclear. Herein, the association between PSCA SNPs and GMA among 195 Japanese individuals with H. pylori infection was evaluated. The definition of GMA or non-GMA was based on serum pepsinogen levels or endoscopic findings. Five tag PSCA SNPs were analyzed using PCR high-resolution melting curve analysis with nonlabelled probes. The frequencies of alleles and the genotypes of each tag SNP were compared between the GMA and non-GMA groups. Subsequently, a genetic test was performed using associated SNPs as biomarkers to detect patients developing GMA. Two tag PSCA SNPs (rs2920280 and rs2294008) were related to GMA susceptibility. Individuals with the rs2920280 G/G genotype or the rs2294008 T/T genotype in PSCA had 3.5- and 2.1-fold susceptibility to GMA, respectively. In conclusion, SNP rs2920280 is a possible biomarker for detecting individuals developing GMA. PSCA polymorphisms may be useful biomarkers for predicting GMA linked to GC risk and a screening endoscopy strategy to detect GC related to early stage H. pylori associated GMA.

Identification of Helicobacterpylori-related gastric cancer risk using serological gastritis markers and endoscopic findings: a large-scale retrospective cohort study

BackgroundGastric cancer remains a severe public health problem worldwide, particularly in Japan. Recent studies have demonstrated that serum markers are beneficial for risk stratification in gastric cancer development. We aimed to evaluate the usefulness of serum markers either alone or in combination (serum markers plus endoscopy) for effective risk stratification of gastric cancer development.MethodsWe enrolled 22,736 patients aged 20–95 years who underwent blood sampling and endoscopic examination at Hiroshima University Hospital in Japan between 1990 and 2014. The serum pepsinogen (PG) levels and anti-Helicobacter pylori antibody (Hp-Ab) titers were evaluated in each patient. The enrolled patients were matched with the database of the Hiroshima Prefecture Regional Cancer Registry. We processed the medical records and excluded patients with possible confounding factors for PG levels, such as proton pump inhibitor use, prior successful eradication therapy, post-gastrectomy, severe hepatorenal dysfunction, Zollinger–Ellison syndrome, and autoimmune gastritis. Among the remaining 5131 patients, we reviewed records of endoscopic examinations and selected 1507 patients (mean age, 62.5 years; 985 men and 522 women) who underwent endoscopic examination more than three months after blood sampling.First, based on the ABC method, patients were classified as follows: High PG levels and negative Hp-Ab, group A, high PG levels and positive Hp-Ab, group B, low PG levels and positive Hp-Ab, group C, and low PG levels and negative Hp-Ab, group D. Group A was further classified into two subgroups using endoscopic findings: true A without atrophic gastritis and pseudo A with atrophic gastritis. All patients underwent annual endoscopy follow-up.ResultsAmong the 1,507 patients (mean age, 62.5 years; 985 men), 24 were diagnosed with newly developed gastric cancer. No significant difference in cancer development was found between group A (PG negative and Hp-Ab negative) and the other groups. Remarkably, no true A group subjects developed gastric cancer.ConclusionsThe combination of serum markers and endoscopic findings is essential for the risk evaluation of gastric cancer.

Serum Pepsinogen as a Biomarker for Gastric Cancer in the United States: A Nested Case-Control Study Using the PLCO Cancer Screening Trial Data.

Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed gastric cancer and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I ≤ 70 μg/L and pepsinogen I/II ratio ≤3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for gastric cancer are reported. Gastric cancer cases were more likely to be PG+ (31.4% vs. 5.5%, P < 0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for gastric cancer [95% confidence interval (CI) = 3.8-19.4]. This risk remained significant after adjusting for Helicobacter pylori, family history of gastric cancer, education, smoking, and BMI (aOR, 10.6; 95% CI, 4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia gastric cancer (OR, 11.1; 95% CI, 4.3-28.8); conversely, they were not significantly more likely to develop cardia gastric cancer (OR, 2.0; 95% CI = 0.3-14.2). PG+ status yielded low sensitivity but high specificity for both noncardia (44.3%; 93.6%) and cardia gastric cancer (5.7%; 97.2%). Prediagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of gastric cancer, particularly noncardia gastric cancer. PG status may identify individuals at higher risk of noncardia gastric cancer for targeted screening or interventions. See related commentary by Zhou and Huang, p. 1257.

Useful Serum Pepsinogen Levels for Detecting Ongoing Helicobacter pylori Infection in Asymptomatic Subjects: A Cross-Sectional Study Based on 13C-urea Breath Test Findings.

The serum pepsinogen (PG) assay is used to screen subjects at high risk for gastric cancer. Currently, there are few studies on the PG levels for the detection of Helicobacter pylori infection. This study aimed to determine the PG assay findings for detecting ongoing infection. Asymptomatic subjects who underwent a 13C-urea breath test (13C-UBT) on the day of gastroscopy and serum assay for cancer screening were included. Subjects with a recent intake of acid suppressants or antibiotics, gastrectomy, or renal failure were excluded. H. pylori infection was defined as a positive 13C-UBT result. Among the 500 included subjects, 167 (33.4%) had current infection. The serum PG II levels of > 12.95ng/mL (area under the curve [AUC] = 0.930, sensitivity 86.5%, specificity 90.7%) and PG I/II ratios of < 4.35 (AUC = 0.875, sensitivity 86.8%, specificity 79.6%) were related to infection. The PG I/II ratios were inversely correlated with age (r = -0.160, p = 0.039). The cutoff values of PG I/II ratios were lower in older subjects aged ≥ 50years (< 4.05; AUC = 0.875, sensitivity 80.7%, specificity 88.2%) than in younger subjects aged < 50years (< 4.35; AUC = 0.873, sensitivity 77.4%, specificity 88.9%). Serum PG II levels > 12.95ng/mL and PG I/II ratios < 4.35 suggest ongoing infection in asymptomatic subjects; therefore, H. pylori confirmation tests (i.e., 13C-UBT) should be considered under these conditions. Stricter criteria are required in older subjects aged ≥ 50years (PG I/II ratio < 4.05) to detect ongoing infection than younger subjects.

Gastric Corpus Hypertrophy with a Bleeding Hyperplastic Polyp in a Helicobacter pylori-naive Subject after Long-term Proton Pump Inhibitor Use

A 22-year-old man presented with recurrent dizziness and melena. He had no remarkable medical history except for the reflux symptoms for which 18 months of proton pump inhibitor (PPI) intake was required. Gastroscopy revealed a 1-cm, blood-tinged polyp within the gastric rugae. A thickened gastric corpus was observed with a regular arrangement of collecting venules on its surface. Hyperplastic foveolar epithelium was observed in the biopsied specimens from the fundus and gastric rugae. The diagnosis after polypectomy was gastric hyperplastic polyp. Abdominal CT revealed hypertrophy only in the gastric corpus without antral involvement. Increased levels of serum pepsinogen I (&gt;160 ng/mL), pepsinogen II (&gt;50 ng/mL), chromogranin A (&gt;1,800 ng/mL), and gastrin (534 pg/mL) were noted. Three months after PPI discontinuation, CT revealed improvement of the hypertrophic gastric corpus. Serum chromogranin A and gastrin levels decreased to 950.4 ng/mL and 517.0 pg/mL, respectively. Herein, we report a young, Helicobacter pylori-naive patient with prominent hyperplasia in the gastric corpus and a bleeding hyperplastic polyp after long-term PPI use.

Serum Gastrin and Pepsinogen Levels after Administration of Acid Secretion Inhibitors for Ulcers due to Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer.

Acid secretion inhibitors, such as proton pump inhibitors (PPIs) and potassium competitive acid blockers (PCABs), are used to treat ulcers after endoscopic submucosal dissection (ESD) for early gastric cancer. These drugs can influence serum gastrin and pepsinogen (PG) levels; however, their definite effects remain unclear. This open-label, randomized study investigated the effect of acid secretion inhibitors on the serum gastrin and pepsinogen levels. In total, 76 patients were enrolled in the study. They underwent gastric ESD and received a PPI (n = 21) or PCAB (n = 55). Changes in the serum gastrin and PG levels before and 4 weeks after administration were examined. Patient factors associated with the alteration of serum PG or gastrin levels were identified. The median serum levels of gastrin, PGI, and PGII before the administration of the acid secretion inhibitors were 110.5 pg/mL, 36.4 ng/mL, and 8.9 ng/mL, respectively; after administration, the levels increased to 300 pg/mL, 64.7 ng/mL, and 15.8 ng/mL, respectively (P < 0.01). Univariate analysis revealed that PCABs led to a more significant increase in the serum gastrin and PG levels as compared to PPIs. Furthermore, the PG levels were significantly increased in patients with previous Helicobacter pylori infections than in those with current infections. In conclusion, the serum gastrin and PG levels increased after the use of acid secretion inhibitors. This elevation was affected by the type of drug used, whereas the elevation in PGs was affected by the patient's background as well.

Development of plasma ghrelin level as a novel marker for gastric mucosal atrophy after Helicobacter pylori eradication

Background and aim The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication. Methods Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). Results Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication. Conclusion Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication. KEY MESSAGES Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication. Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication. Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.

Serum pepsinogen level as a biomarker for atrophy, reflux esophagitis, and gastric cancer screening in Indonesia.

Chronic dyspepsia's symptoms are frequently seen in primary to tertiary healthcare in Indonesia. This study aimed to describe the potential usability of pepsinogen (PG) values in determining gastric mucosal conditions, including superficial gastritis and atrophic gastritis. We recruited 646 adult dyspeptic patients and then analyzed PG values (including PGI, PGII, and PGI/II ratio) with endoscopic findings, gastric mucosal damages, and Helicobacter pylori infection. The gastric mucosal damage and H. pylori infection were evaluated using histological examination based on the updated Sydney system. Among 646 enrolled patients, 308 (47.2%), 212 (32.8%), 91 (14.1%), 34 (5.2%), and 1 (0.2%) patient were diagnosed with normal mucosa, gastritis, reflux esophagitis, peptic ulcer disease, and gastric cancer, respectively. Significant differences in PGI, PGII, and PGI/II ratio values were observed among ethnic groups (all P < 0.01). The PGI and PGII levels were significantly higher and PGI/II was significantly lower in H. pylori-infected patients than in uninfected ones (all P < 0.001). The optimal cutoff value for PGII and PGI/II was 12.45 ng/mL with an area under the curve (AUC) value of 0.755 (0.702-0.811), sensitivity 59.3%, and specificity 77.1%; and 4.75 with AUC value of 0.821 (0.763-0.855), sensitivity 81.5%, and specificity 78.7%, respectively, to determine moderate-severe atrophy. Serum PG levels, a useful biomarker, represent the endoscopic findings, especially for reflux esophagitis. In addition, the benefits of PG values detecting atrophic gastritis were limited to moderate-severe atrophic gastritis. This usefulness requires careful attention for several ethnic groups in Indonesia.

Association of serum pepsinogen with degree of gastric mucosal atrophy in an asymptomatic population.

BACKGROUNDAtrophic gastritis is a precancerous lesion of the stomach. It has been reported that pepsinogen (PG) can reflect the morphology and function of the gastric mucosa, and it is therefore used as a marker for the early diagnosis of atrophic gastritis.AIMTo evaluate the diagnostic value of serum PG for degree of gastric mucosal atrophy in asymptomatic Chinese upon physical examination.METHODSMedical data were collected from subjects who underwent transnasal gastroscopy between October 2016 and October 2018. For each study subject, serum PG levels and presence of Helicobacter pylori (H. pylori) infection were investigated. Pathology was evaluated using the Operative Link for Gastritis Assessment (OLGA) classification and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) systems. All statistical analyses were carried out using SPSS statistical software.RESULTSA total of 2256 subjects were enrolled and 1922 cases were finally included in the study. Based on the OLGA grading system, the levels of PGI were slightly decreased, while those of PGII were slightly increased. The PGI/PGII ratio (PGR) was reduced with increasing atrophy. The association between PG and OLGA grading was higher compared with that between PG and the OLGIM grading system. Compared with the OLGA-0 group, a statistically significant difference was observed in the mean age of OLGA-I, III, and IV groups (P < 0.05). In the H. pylori-positive subjects, the PGR levels were notably lower in the OLGA-I, II, and III groups compared with the OLGA-0 group (P < 0.05). H. pylori-positive subjects exhibited significantly higher PGI and PGII serum levels and a significantly lower PGR compared with H. pylori-negative patients in different OLGA groups (P < 0.05). CONCLUSIONSerum PG levels may represent a non-invasive screening marker for gastric mucosal atrophy in asymptomatic subjects.

Serum Assay Findings after Successful Helicobacter pylori Eradication

Serum pepsinogen (PG), anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG), and gastrin-17 (G-17) are plasma biomarkers for gastritis. H. pylori serology titers and PG levels increase during active H. pylori infection; moreover, elevated PG II levels indicate a high risk for diffuse-type gastric cancer in East Asian populations. Serum PG I/II ratios and PG I levels decrease with the progression of gastric corpus atrophy; thus, a combination of serum PG I levels ≤70 ng/mL and a PG I/II ratio ≤3 (serologic atrophy) indicates a high risk of intestinal-type gastric cancer. Serum G-17 is often not used as an indicator in H. pylori-seroprevalent populations because it is usually elevated in subjects with H. pylori infections. When H. pylori is eradicated, most patients show a rapid decrease in serum PG II levels and anti-H. pylori IgG titers within a few months. Seroreversion is required for several months to years after regression of H. pylori. Moreover, seroreversion may not always be achieved in all eradicated cases. The serum PG I/II ratio starts to increase after eradication; therefore, serologic atrophy improves accordingly, unless severe atrophy is present. Thus, some eradicated patients may show normal serum assay findings but have a higher risk for developing gastric cancer than H. pylori-naive subjects. Furthermore, serum PG levels decrease after gastrectomy and increase with the intake of certain drugs (e.g., aspirin or acid suppressants) or in renal failure patients. Due to such wide variations, serum assays are inadequate for the confirmation of H. pylori eradication. It is useful when interpreted with gastroscopy and other H. pylori test findings.

Study on the Value of miR6503-5p Combined with PGR in the Diagnosis of Early Gastric Cancer

Objective To investigate the value of serum miRNA 6503-5p (miR6503-5p) combined with pepsinogen ratio (PGR) in the diagnosis of early gastric cancer. Methods: 94 patients (gastric cancer group) with gastric cancer confirmed by pathological examination and 90 patients with chronic atrophic gastritis collected by Department of Pathology in our hospital were selected as the control group, the serum levels of pepsinogen (PG I, PG II) and miR6503-5p were measured in the two groups, and the value of the two indexes in the diagnosis of gastric cancer was analyzed by ROC. Results: The serum levels of miR6503-5p in gastric cancer group were significantly higher than those in control group (P&lt;0.05), the serum levels of PG I and PGR in gastric cancer group were significantly lower than those in control group (P&lt;0.05), the serum levels of miR6503-5p in stage II gastric cancer group were significantly higher than those in stage I patients with statistically significant difference (P&lt;0.05), and the serum levels of PG I and PGR in stage II gastric cancer group were significantly lower than those in stage I patients with statistically significant difference (P&lt;0.05). The serum levels of PG I, PG II and PGR in the patients with highly and moderately differentiated gastric cancer were not significantly different from those in the patients with poorly and undifferentiated gastric cancer, with no statistically significant different (P&gt;0.05); the serum levels of miR6503-5p in the patients with highly and moderately differentiated gastric cancer were significantly lower than those in the patients with poorly and undifferentiated gastric cancer, with statistically significant difference (P&lt;0.05); the sensitivity of miR6503-5p in diagnosing gastric cancer was 81.33%, the specificity was 71.09%, the area under the ROC curve was 0.767; the sensitivity of PGR in diagnosing gastric cancer was 85.81%, the specificity was 78.40%, and the area under the ROC curve was 0.827. The sensitivity of serum miR6503-5p combined with PGR was 96.40%, the specificity was 85.44%, and the area under the ROC curve was 0.920. Conclusion The miR 6503-5p combined with PGR has high sensitivity and specificity in the diagnosis of gastric cancer and is worthy of clinical application in the screenof patient with early gastric cancer.