Non-invasive diagnosis of gastroesophageal reflux disease using gastrin- and pepsinogen-based tests

Gastrin-17 (G-17), pepsinogen-1 (Pg1) and pepsinogen-2 (Pg2) reflect the functional state of gas-tric mucosa and are used for non-invasive diagnosis and screening of atrophic gastritis. The aimof the study was to clarify if erosive reflux disease (ERD) or non-ERD (NERD) can be distin-guished from other dyspeptic conditions in patients, in a non-invasive manner using specificbiomarkers. Levels of G-17, Pg1, and Pg2 were measured in 141 ERD patients (median age 48years, males — 68), 122 NERD patients (median age 45 years, males — 32) and 410 control pa-tients (median age 50 years, males — 97). Levels of biomarkers in ERD and NERD groups werecompared to controls. Median levels of G-17 (1.94 vs 2.92 pmol/L, p = 0.036) and Pg2 (6.70 vs7.79 μg/l,p= 0.046) were lower in the ERD group compared to control patients; no differencewith respect to the control was found for the NERD group. After exclusion of the patients havingat least one potential condition that might modify the levels of the biomarkers (gastric mucosa at-rophy, Helicobacter pylori colonisation), no difference in levels of biomarkers was observed withrespect to the control for both the ERD and NERD groups. G-17, Pg1, and Pg2 based tests can-not be used to distinguish ERD or NERD from other dyspeptic conditions in patients.publishersversionPeer reviewe

Association of Obesity with Proteasomal Gene Polymorphisms in Children

The aim of this study was to ascertain possible associations between childhood obesity, its anthropometric and clinical parameters, and three loci of proteasomal genes rs2277460 (PSMA6 c.-110C>A), rs1048990 (PSMA6 c.-8C>G), and rs2348071 (PSMA3 c. 543+138G>A) implicated in obesity-related diseases. Obese subjects included 94 otherwise healthy children in Latvia. Loci were genotyped and then analyzed using polymerase chain reactions, with results compared to those of 191 nonobese controls. PSMA3 SNP frequency differences between obese children and controls, while not reaching significance, suggested a trend. These differences, however, proved highly significant (PG SNP differences, while being nonsignificant, likewise suggested a trend in comparison to the nonobese controls. No PSMA6 c.-110C>A SNP differences were detected in the obese group or its subsets. Finally, PSMA3 SNP differences were significantly associated (P<0.05) with circulating low-density lipoprotein cholesterol (LDL) levels. Our results clearly implicate the PSMA3 gene locus as an obesity risk factor in those Latvian children with a family history of obesity. While being speculative, the clinical results are suggestive of altered circulatory LDL levels playing a possible role in the etiology of obesity in the young

Prevalence estimation of celiac disease in the general adult population of Latvia using serology and HLA genotyping

BACKGROUND: Prevalence estimates for celiac disease (CD) depend on the method used. The role of deamidated gliadin peptide (DGP) and genetic testing in epidemiological studies and diagnostic settings of celiac disease (CD) has still to be established. OBJECTIVES: The objective of this article is to assess the prevalence of CD in Latvia by combining serological tests with DQ2.5/DQ8 testing. METHODS: A total of 1444 adults from a randomly selected cross-sectional general population sample were tested by ELISA for tTG IgA, DGP IgA and IgG antibodies (QUANTA Lite®, Inova Diagnostics Inc). Samples with tTG IgA ≥20U were tested for EMA IgA by indirect immunofluorescence assay, and all specimens with tTG IgA ≥15U were tested by QUANTA-Flash® chemiluminescent assays (CIA) (Inova Diagnostics Inc) for tTG IgA, DGP IgA and IgG. DQ2.5/8 was detected in individuals with any positive ELISA test and a subgroup of controls. RESULTS: Forty-three individuals (2.98%; 95% CI: 2.10–3.86%) tested positive by at least one ELISA test; 41.86% of the serology-positive individuals (any test above the cutoff) were DQ positive. Six individuals (0.42%; 95% CI: 0.09–0.75%) were triple ELISA positive, and DQ2.5 or DQ8 was positive in all; 0.35% (95% CI: 0.05–0.65%) were tTG IgA and EMA positive. Two tTG IgA-negative cases were both DGP IgG and IgA positive, both being DQ positive; including them in the “serology-positive” group would increase the prevalence to 0.49% (95% CI: 0.13–0.85%). CIA tests revealed 2 tTG IgA-positive and EMA-negative cases with a positive genotype. DQ2.5 or DQ8 genotype was positive in 28.6% of the serology-negative population. CONCLUSIONS: Estimates of the prevalence of CD in Latvia based on the serogenetic testing approach range from 0.35% to 0.49% depending on the criteria used. There is a rationale for combining serological tests and DQ2.5/8 genotyping

Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection?

Funding Information: Acknowledgments: The study was funded in part by the Fundamental and Applied Research Project Program in Latvia, project No. lzp-2018/1-0135 “Research on implementation of a set of measures for prevention of gastric cancer mortality by eradication H. pylori and timely recognition of precancerous lesions”. We acknowledge the entire GISTAR study team as well as the infrastructure provided by the Digestive Diseases Centre GASTRO for endoscopy and the Academic Histology Laboratory for pathology infrastructures. Our acknowledgements also to Biohit Oyj, Finland, for their support with laboratory reagents. Funding Information: Funding: The work is funded by ERDF (European Regional Development Fund) within the frame-work of 2nd part of measure 1.1.1.1. ‘Practical Studies’, project ID Nr. 1.1.1.1/18/A/184. Funding Information: The work is funded by ERDF (European Regional Development Fund) within the framework of 2nd part of measure 1.1.1.1. ?Practical Studies?, project ID Nr. 1.1.1.1/18/A/184. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Background. Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case of a previous infection, since antibodies may be present in blood following recovery from the infection. Aims. To identify true H. pylori-positive individuals in discrepant cases by serology and histology using real time polymerase chain reaction (RT-PCR) as a gold standard. Methods. Study subjects with discrepant histology and serology results were selected from the GISTAR pilot study data base in Latvia. Subjects having received previous H. pylori eradication therapy or reporting use of proton pump inhibitors, antibacterial medications, or bismuth containing drugs one month prior to upper endoscopy were excluded. We compared the discrepant cases to the corresponding results of RT-PCR performed on gastric biopsies. Results. In total, 97 individuals with discrepant results were identified: 81 subjects were serology-positive/histology-negative, while 16 were serologynegative/histology-positive. Among the serology-positive/histology-negative cases, 64/81 (79.0%) were false-positives by serology and, for the majority, inflammation was absent in all biopsies, while, in the serology-negative/histology-positive group, only 6.2% were proven false-positives by histology. Conclusions. Among this high H. pylori prevalent, middle-aged population, the majority of discrepant cases between serology and histology were due to false positive-serology, rather than false-negative histology. This confirms the available evidence that the choice of treatment should not be based solely on the serological results, but also after excluding previous, self-reported eradication therapy.publishersversionPeer reviewe

Helicobacter pylori infection among children in Riga, Latvia

Aims To identify the prevalence of H.pylori among asymptomatic children and their parents in Riga, Latvia. To study the age of acquisition for H.pylori and the risk factors and symptoms associated with H.pylori infection. To identify the prevalence of H.pylori and infection with cagA-positive and cagA-negative strains among dyspeptic children. Materials and methods H.pylori infection was detected by 13C-urea breath test (UBT) in 142 consecutive asymptomatic children (aged 112 years) and parents of 40 children and by monoclonal stool antigen test in 146 asymptomatiechildren (aged 0.5-5 years). The parents were asked to fill out a standardised questionnaire about possible risk factors. In 130 consecutive children (aged 8-18 years) with upper gastrointestinal symptoms coming for upper gastrointestinal endoscopy H.pylori infection was detected by rapid urease test and/or culture. Endoscopic changes were evaluated. In 56 consecutive H.pylori positive patients presence of cagA and vacA was detected by PCR. In culture positive patients (n=31) H.pylori-DNA was extracted from 10 different colonies of primary cultures and from a mixture of colonies and tested for the presence of cagA. Anti- CagA and VacA antibodies were assessed by immunoblot. The prevalence of H.pylori was compared between 55 consecutive asymptomatic children and 40 consecutive symptomatic children with symptoms from upper gastrointestinal tract of the same age. Statistical analysis: 72 or Ficher's test, and logistic regression analysis. Results The overall prevalence of H.pylori infection among asymptomatic children by UBT was 19%; by stool antigen test - 18 %. The age of the youngest H.pylori positive children was 4 and 6 months. The presence of infection was independently inversely related to previous antibiotic treatment (p=0.01) and higher educational status of a mother (p=0.04) and significantly associated with parental H.pylori status (p-0.003). Among symptomatic children the prevalence of infection was 54%(70/130) and it was significantly higher among patients with reflux oesophagitis (OR = 5.5, p=0.03) and a duodenal ulcer or erosions in duodenum or oesophagus (OR =5.5; p=0.01) compared to patients with hyperemic gastropathy alone. Previous or current infection with cagA-positive strains was observed in 50/56 patients. The presence of both cagA-positive and cagA-negative genotypes in the same individual was identified in 11 of the 31 culture-positive patients. In logistic regression analysis no significant difference between the prevalence of H.pylori in asymptomatic and symptomatic children could be shown. Conclusions The prevalence of H.pylori infection among asymptomatic children in Riga is higher than in Western countries, but it is similar to the prevalence rate in some Eastern European countries. H.pylori infection is present already during the first year of life. Infection with H.pylori is independently inversely related to previous antibiotic treatment and is significantly associated with parental H.pylori status and educational status of mother. Among symptomatic children H.pylori prevalence was significantly higher among patients with reflux oesophagitis and patients with an ulcer or erosions were more likely to have H.pylori infection. Both cagA+and cagA- strains could be identified in a large proportion of samples from dyspeptic children and previous or current infection with cagA' strains was observed in 89% of patients. The prevalence of H.pylori infection was not higher among children with gastrointestinal symptoms compared to the prevalence among asymptomatic children of the same age

The Dynamics of Pepsinogen Levels in a Caucasian Population within a 3-year Period

Our data show that initially PgI or PgI/PgII levels are relatively stable and do not changesubstantially during a 3 year period neither in the entire patient sample nor in patients with corpus atrophy

Factors Associated with False Negative Results in Serum Pepsinogen Testing for Precancerous Gastric Lesions in a European Population in the GISTAR Study

The accuracy of plasma pepsinogen (Pg) as a marker for precancerous gastric lesions (PGL) has shown variable results. We aimed to identify factors associated with false negative (FN) cases in Pg testing and to adjust cut-off values for these factors in order to improve Pg yield. Plasma Pg was measured and upper endoscopy with biopsy was performed within the “Multicentric randomized study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study”. A multivariable logistic model was built for FN and multiple factors. Values of Pg were compared and sensitivity and specificity were calculated using pre-existing Pg cut-offs for factors showing strong associations with FN. New cut-offs were calculated for factors that showed substantially lower sensitivity. Of 1210 participants, 364 (30.1%) had histologically confirmed PGL, of which 160 (44.0%) were FN. Current smokers, men, and H. pylori positives were more likely FN. Smoking in H. pylori negatives was associated with a higher Pg I/II ratio and substantially lower sensitivity of Pg testing than in other groups. Adjusting Pg cut-offs for current smokers by H. pylori presence improved sensitivity for detecting PGL in this group. Our study suggests that adjusting Pg cut-offs for current smokers by H. pylori status could improve Pg test performance