Helicobacter pylori cagA/vacAs1-m1 strain is associated with high risk of fibrosis in metabolic-dysfunction-associated steatotic liver disease.

INTRODUCTION AND OBJECTIVES: Recent studies have suggested an association between H. pylori and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of H. pylori virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects. PATIENTS AND METHODS: A total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and H. pylori virulence genes (cagA, vacA) were evaluated. RESULTS: A cohort comprised of 61 % women and 39 % men with a median age of 52 (40-60) years. MASLD was observed in 42 %, and H. pylori-positive in 45 %. No differences were observed regarding H. pylori status at co-morbid metabolic conditions. In MASLD cohort, H. pylori-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (≥8 kPa) with H. pylori-positive was 2.56 (95 % CI, 1.2-5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38-11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE ≥8 kPa with H. pylori-positive was 2.43 (95 % CI, 1.88-12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22-14.49). CONCLUSIONS: In our cohort of functional dyspepsia (FD) patients with MASLD, H. pylori was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE.

In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori.

BACKGROUND: Colonization with Helicobacter pylori (H. pylori) has a strong correlation with gastric cancer, and the virulence factor CagA is implicated in carcinogenesis. Studies have been conducted using medicinal plants with the aim of eliminating the pathogen; however, the possibility of blocking H. pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed. This type of study is expensive and time-consuming, requiring in vitro and/or in vivo tests, which can be solved using bioinformatics. Therefore, prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein. AIM: To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H. pylori. METHODS: In this in silico study, the structures of the phenolic compounds (ligands) kaempferol, myricetin, quercetin, ponciretin (flavonoids), and chlorogenic acid (phenolic acid) were selected from the PubChem database. These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H. pylori infection. The three-dimensional structure model of the CagA oncoprotein of H. pylori (receptor) was obtained through molecular modeling using computational tools from the I-Tasser platform, employing the threading methodology. The primary sequence of CagA was sourced from GenBank (BAK52797.1). A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands, utilizing the GRaSP online platform. Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4 (ADT) software, and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software. Two sets of simulations were performed: One involving the central region of CagA with phenolic compounds, and another involving the carboxy-terminus region of CagA with phenolic compounds. The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software. RESULTS: The structure model obtained for the CagA oncoprotein exhibited high quality (C-score = 0.09) and was validated using parameters from the MolProbity platform. The GRaSP online platform identified 24 residues (phenylalanine and leucine) as potential binding sites on the CagA oncoprotein. Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein. No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds; however, all phenolic compounds interacted with the central region of the oncoprotein. Phenolic compounds and CagA exhibited significant affinity energy (-7.9 to -9.1 kcal/mol): CagA/kaempferol formed 28 chemical bonds, CagA/myricetin formed 18 chemical bonds, CagA/quercetin formed 16 chemical bonds, CagA/ponciretin formed 13 chemical bonds, and CagA/chlorogenic acid formed 17 chemical bonds. Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif, all of them bound to residues, mostly positively or negatively charged, located near this region. CONCLUSION: In silico, the tested phenolic compounds formed stable complexes with CagA. Therefore, they could be tested in vitro and/or in vivo to validate the findings, and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.

Helicobacter pylori cagA, vacA, iceA and babA Genotypes from Peruvian Patients with Gastric Intestinal Metaplasia.

We explored the clinical-stage association of gastric intestinal metaplasia (IM) compared to cases of chronic non-atrophic gastritis (CNAG) and its relationship with virulence genotypes of Helicobacter pylori (H. pylori) clinical isolates from patients with dyspepsia in Peru. This study was cross-sectional and included 158 H. pylori clinical isolates; each isolate corresponded to a different Peruvian patient, genotyped by polymerase chain reaction to detect cagA gene and EPIYA motifs, the vacA gene (alleles s1, s2, i1, i2, d1, d2, m1, m2 and subtypes s1a, s1b and s1c), the iceA gene (alleles 1 and 2), and the babA gene (allele 2). We observed that 38.6% presented with IM and that all clinical isolates were CagA positive. The EPIYA-ABC motif was predominant (68.4%), and we observed a high frequency for the vacA gene alleles s1 (94.9%), m1 (81.7%), i1 (63.9%), and d1 (70.9%). Strains with both iceA alleles were also detected (69.6%) and 52.2% were babA2 positive. In addition, it was observed that the cagA+/vacAs1m1 (PR: 2.42, 1.14 to 5.13, p < 0.05) and cagA+/vacAs1am1 (PR: 1.67, 1.13 to 2.45, p < 0.01) genotypes were associated with IM. Our findings revealed the cagA and vacA risk genotypes predominance, and we provided clinically relevant associations between Peruvian patients with H. pylori infection and IM clinical stage.

Historical and Molecular Perspectives on the Presence of Helicobacter pylori in Latin America: A Niche to Improve Gastric Cancer Risk Assessment.

Helicobacter pylori (H. pylori) is responsible for causing chronic gastritis, which can cause peptic ulcer and premalignant lesions such as atrophic gastritis, intestinal metaplasia, and dysplasia, with the risk of developing gastric cancer. Recent data describe that H. pylori colonizes the gastric mucosa of more than 50% of the world's population; however, this bacterium has been described as infecting the human population since its prehistory. This review focuses on the populations and subpopulations of H. pylori, differentiated by the polymorphisms present in their constitutive and virulence genes. These genes have spread and associated with different human populations, showing variability depending on their geographical distribution, and have evolved together with the human being. The predominant genotypes worldwide, Latin America and Chile, are described to understand the genetic diversity and pathogenicity of H. pylori in different populations and geographic regions. The high similarity in the sequence of virulence genes between H. pylori strains present in Peruvian and Spanish natives in Latin America suggests a European influence. The presence of cagA-positive strains and vacA s1 m1 allelic variants is observed with greater prevalence in Chilean patients with more severe gastrointestinal diseases and is associated with its geographical distribution. These findings highlight the importance of understanding the genetic diversity of H. pylori in different regions of the world for a more accurate assessment of the risk of associated diseases and their potential impact on health.

Relationship between antibiotic resistance and the cagA and vacA genotypes among Helicobacter pylori strain isolates from patients in Xi'an.

The issue of drug resistance of Helicobacter pylori is becoming increasingly serious. To analyze the correlation between the cagA and vacA genotypes of H. pylori strains and their resistance to metronidazole, levofloxacin, and clarithromycin in patients in Xi'an, we studied 117 H. pylori strains isolated from patients in Xi'an. Antibiotic susceptibility testing of H. pylori was performed. The cagA and vacA genotypes were investigated using PCR. Among 117 strains of H. pylori, the rate of detection of cagA was 91.45% (107/117), among which the detection rate of East Asian-type cagA was 85.05% (91/107) and that of Western-type cagA was 14.95% (16/107). There were only two genotypes of vacA: s1m1 and s1m2. The detection rate of vacAs1m1 was 47.01% (55/117) and that of vacAs1m2 was 52.99% (62/117). The dominant strains in Xi'an were cagA + vacAs1m2 strains. The metronidazole resistance rate of vacAs1m2 H. pylori strains was significantly higher than that of vacAs1m1 H. pylori strains (91.94% vs. 69.09%, P = 0.002). The levofloxacin resistance rate of Western-type cagA strains was significantly higher than that of East Asian-type cagA strains (56.25% vs. 20.88%, P = 0.004). The metronidazole resistance rate of cagA + vacAs1m2 H. pylori strains was significantly higher than that of cagA + vacAs1m1 H. pylori strains (91.23% vs. 66.00%, P = 0.001). Our results showed that Western-type cagA strains were more likely to develop levofloxacin resistance than East Asian-type cagA strains. VacAs1m2 strains were more prone to metronidazole resistance than vacAs1m1 strains.

Helicobacter pylori virulence genotypes in Bogotá River and wastewater treatment plants in Colombia.

BACKGROUND: Helicobacter pylori is a bacterium that infects 70%-80% of the population in Colombia, causing chronic gastritis in all those infected and gastric cancer in 1%-2% of those infected. In Colombia, some studies have identified the presence of vacA and cagA genes in environmental samples such as treated, surface, and wastewater, but they have not been evaluated in the Bogotá River. For this, the aim of this study was to identify the virulence genotypes of H. pylori present in samples from the Bogotá River and domestic wastewater treatment plants (WWTPs). MATERIALS AND METHODS: A total of 75 water samples (51 from the Bogotá River and 24 from wastewater treatment plants) were collected. The presence of H. pylori DNA and its virulence genotypes was determined by polymerase chain reaction (PCR). RESULTS: The presence of H. pylori DNA was demonstrated in 44% (33/75) of the samples, obtaining 63.6% (21/33) from the Bogotá River and 36.4% (12/33) from the WWTPs. The most prevalent H. pylori genotype was cagA (-) and vacAm1/s1/i1 being the most virulent of the vacA gene. CONCLUSIONS: This is the first study in Colombia that determines the cagA and vacA genotypes in surface water and WWTPs, indicating the circulation of virulent genotypes in the population. The presence of this pathogen in the waters can be represent a risk to the health of the surrounding population since these waters are reused by the communities for different purposes.

Genotyping of Helicobacter pylori CagA/CagE strains in gastric mucosa and its association with gastric illness.

The aim of this work was associate the presence of the virulence factors of Helicobacter pylori, cagA/cagE, with gastric illness. We found evidence that indicate the contribution of these genotypes with the severity of gastric lesions in patients infected, principally in histological subtypes as atrophic gastritis, and metaplasia.

Association between genetic polymorphisms of NOD1, Interleukin-1B, and cagA strain with low-grade duodenal eosinophilia in Helicobacter pylori-related dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and host genetic polymorphism of innate and pro-inflammatory cascade, nucleotide-binding oligomerization domain 1 (NOD-1), and interleukin-1 beta (IL-1ß) in HpD was not explored. AIM: To evaluate the association of NOD1-796G>A and IL-1B-511C>T gene variants and low-grade duodenal eosinophilia in HpD. METHODS: A multicenter cross-sectional study was conducted. A total of 253 patients who met Rome-IV criteria were selected before upper endoscopy and 98 patients were included after unremarkable upper endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori cagA and duodenal histology, were evaluated. RESULTS: Sixty-four (65%) patients had epigastric pain syndrome (EPS), 24 (25%) postprandial distress syndrome (PDS), and 10 (10%) EPS/PDS overlap. FD subtypes were not associated with NOD1-796G>A and IL-1B-511C>T gene variants. Low-grade duodenal eosinophilia was significantly increased in NOD1-796 GG versus single A-allele, but not in IL-1B-511 single T-allele or CC-allele. This association is dependent of cagA infection, since harboring cagA strain was significantly associated with low-grade duodenal eosinophilia with isolated variants NOD1-796 GG and IL-1B-511 single T-allele, but not without cagA. When we performed combined polymorphism analysis with NOD1-796 GG/IL-1B-511 single T-allele, a synergistic effect on low-grade duodenal eosinophilia was found between these two loci irrespective of cagA strain status in HpD. CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is significantly associated with NOD1-796 GG allele specially in cagA strain and with allelic combination NOD1-796 GG/IL-1B-511 single T-allele independent of cagA strain infection in HpD patients.

IL-8 Secreted by Gastric Epithelial Cells Infected with Helicobacter pylori CagA Positive Strains Is a Chemoattractant for Epstein-Barr Virus Infected B Lymphocytes.

Helicobacter pylori and EBV are considered the main risk factors in developing gastric cancer. Both pathogens establish life-lasting infections and both are considered carcinogenic in humans. Different lines of evidence support that both pathogens cooperate to damage the gastric mucosa. Helicobacter pylori CagA positive virulent strains induce the gastric epithelial cells to secrete IL-8, which is a potent chemoattractant for neutrophils and one of the most important chemokines for the bacterium-induced chronic gastric inflammation. EBV is a lymphotropic virus that persists in memory B cells. The mechanism by which EBV reaches, infects and persists in the gastric epithelium is not presently understood. In this study, we assessed whether Helicobacter pylori infection would facilitate the chemoattraction of EBV-infected B lymphocytes. We identified IL-8 as a powerful chemoattractant for EBV-infected B lymphocytes, and CXCR2 as the main IL-8 receptor whose expression is induced by the EBV in infected B lymphocytes. The inhibition of expression and/or function of IL-8 and CXCR2 reduced the ERK1/2 and p38 MAPK signaling and the chemoattraction of EBV-infected B lymphocytes. We propose that IL-8 at least partially explains the arrival of EBV-infected B lymphocytes to the gastric mucosa, and that this illustrates a mechanism of interaction between Helicobacter pylori and EBV.

Helicobacter pylori Virulence Factors and Clarithromycin Resistance-Associated Mutations in Mexican Patients.

Persistent infection with Helicobacter pylori (H. pylori) is an important factor in gastric diseases. The vacA and cagA virulence factors of H. pylori contribute to the development of these diseases. Triple therapy containing clarithromycin has been used to eradicate this infection. Unfortunately, resistance to this antibiotic is the primary cause of treatment failure. This study aimed to determine the prevalence of clarithromycin resistance-associated mutations and to assess the relationship between virulence factors and Mexican patients infected with H. pylori. The cagA and vacA genotypes were determined by multiplex PCR. Furthermore, a qPCR was used to identify mutations of the 23S rRNA gene. This study reported a prevalence of 84.3% of H. pylori among patients with gastric diseases, and the vacA s1m1/cagA+ genotype was the most frequent (44.8%) in antrum and corpus. Analysis of the 23S rRNA gene revealed a 19.8% prevalence of clarithromycin resistance-associated mutations. The most prevalent mutations were A2143G (56%) and A2142C (25%). A significant association (p < 0.05) between the A2142G and the vacA s1m1/cagA+ genotype was detected. In conclusion, we report a high prevalence (>15%) of clarithromycin resistance-associated mutations, and we found an association between the genotypes of virulence factors and a mutation in the 23S rRNA gene.

Low-grade duodenal eosinophilia is associated with cagA in Helicobacter pylori-related dyspepsia.

BACKGROUND AND AIM: Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and H. pylori virulence genes in HpD was not explored. We aim to evaluate the association of H. pylori virulence genes and low-grade duodenal eosinophilia in HpD. METHODS: A multi-center cross-sectional study was conducted. A total of 301 patients who meet Rome-III criteria were selected before upper endoscopy, and 95 patients were included after normal endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori virulence genes (cagA, oipA, and vacA) and duodenal histology were evaluated. RESULTS: Sixty-nine (72%) patients had epigastric pain syndrome (EPS), 17 (18%) post-prandial distress syndrome (PDS) and 9 (10%) EPS/PDS overlap. FD syndromes were not associated with cagA or oipA strains. A significantly trend of vacA s1/m1 (78%) and s1/m2 (80%) positive strains in EPS was observed. Histological duodenal grading of chronic inflammation, low-grade duodenal eosinophilia and intra-epithelial lymphocytes showed no difference in oipA and vacA strains. Low-grade duodenal eosinophilia was significant in cagA positive strain, and the OR for low-grade duodenal eosinophilia with H. pylori cagA positive strain was 4.2 (95% CI, 1.78-9.93). Adjusting for age, gender, smoking, diabetes, alcohol, PPI, and NSAID, the OR was 5.44 (1.989-14.902). CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is significantly associated with cagA strain in HpD.

Influence of Helicobacter pylori oncoprotein CagA in gastric cancer: A critical-reflective analysis.

Gastric cancer is the fifth most common malignancy and third leading cancer-related cause of death worldwide. Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3% of the world's population and represents the main risk factor for the onset of gastric neoplasms. CagA is the most important virulence factor in H. pylori, and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions. Upon translocation and tyrosine phosphorylation, CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways, thereby disrupting cell proliferation, differentiation and apoptosis. All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes. In this sense, once gastric cancer sets in, its perpetuation is independent of the presence of the oncoprotein, characterizing a "hit-and-run" carcinogenic mechanism. Therefore, this review aims to describe H. pylori- and CagA-related oncogenic mechanisms, to update readers and discuss the novelties and perspectives in this field.

Exploratory multigroup structural equation modeling approach to analyzing H. pylori infection, serological pepsinogen levels, and life style factors in an elderly population in Costa Rica / Enfoque exploratorio del modelo de ecuaciones estructurales multigrupo para el análisis de la infección con H. pylori, niveles de pepsinógenos séricos y factores asociados a estilo de vida en una población de adultos mayores en Costa Rica

Abstract The aim of this work is to describe and analyze the association of PGI/PGII ratio (indicator of gastric atrophy) with H. pylori-CagA and life style factors such as caloric intake, obesity, and harmful habits amongst H. pylori-positive elderly people infected in Costa Rica using an exploratory multigroup structural equations model (SEM). Using a sample of 1748 H. pylori-positive elderly people from CRELES first wave study, a SEM was employed analyze if the relationships between PGI/PGII ratio with levels of H. pylori-CagA, caloric intake, obesity, and harmful habits, differs by sex, age and risk areas subgroups. The proposed SEMs exhibited a good fit in males (RMSEA = 0.039), females (RMSEA = 0.000), low-risk area (RMSEA = 0.038), middle-risk area (RMSEA = 0.042), individuals under 80 years (RMSEA = 0.038) and individuals aged 80 and over (RMSEA = 0.042), while an acceptable fit was observed for the high-risk area (RMSEA = 0.061). Fitted SEMs showed that CagA predicted PG-ratio as expected, with effects increasing with the risk area, but similar between sex and age groups. All indicators measuring obesity (BMI, arms, and waist) showed significant standardized coefficients, with similar effects between sex, age and risk area groups. No other significant effects or differences between groups were identified. We propose a good-fitted SEM model for the possible relationships between CagA and PG ratio and the geographical risk area level for elderly people. No differences were observed on measured parameters between male and female population, or between under 80 years and older individuals.

Resumen El objetivo de este trabajo es describir y analizar la asociación entre PGI/PGII (indicador de atrofia gástrica con H. pylori-CagA y factores asociados a estilo de vida como ingesta calórica, obesidad y hábitos nocivos entre adultos mayores positivos por H. pylori en Costa Rica utilizando modelos de ecuaciones estructurales multigrupo (SEM). Con una muestra de 1748 adultos mayores del estudio CRELES, se utilizó un SEM para analizar las relaciones entre PGI/PGII, CagA, ingesta calórica, obesidad y hábitos nocivos difieren por sexo, edad y áreas de riesgo. Los SEMs propuestos exhibieron un buen ajuste en hombres (RMSEA = 0.039), mujeres (RMSEA = 0.000), área de bajo riesgo (RMSEA = 0.038), áreas de riesgo medio (RMSEA = 0.042), individuos menores de 80 años (RMSEA = 0.038) e individuos de 80 años o más (RMSEA = 0.042), mientras que hubo un ajuste aceptable en áreas de alto riesgo (RMSEA = 0.061). Los SEMs ajustados mostraron que CagA predice la relación PGI/II en la dirección esperada con efectos proporcionales al área de riesgo, pero no por sexo y edad. Todos los indicadores medibles de obesidad (IMC, brazos y cintura) mostraron coeficientes estandarizados significativos con efectos similares entre los grupos por sexo, edad y área de riesgo. No se encontraron otros efectos o diferencias significativas. Proponemos un modelo SEM bien ajustado para las posibles relaciones entre CagA y PGI/II y el nivel de riesgo del área geográfica en adultos mayores. No se encontraron diferencias en las variables analizadas entre hombres y mujeres ni entre los grupos de edad.

Identificación y evaluación de lesiones gástricas premalignas asociadas a la infección por Helicobacter pylori / Identification and evaluation of premalignant gastric lesions associated with Helicobacter pylori infection

Introducción: La infección por Helicobacter pylori es la causa principal de enfermedades gastroduodenales (gastritis crónica, úlceras pépticas y cáncer gástrico). En Guatemala existen pocos estudios sobre la prevalencia de H. pylori y su relación con enfermedades gastrointestinales, particularmente con cáncer. Objetivos: Identificar la presencia de lesiones premalignas (atrofia gástrica, metaplasia intestinal y displasia) y su relación con la infección por H. pylori en pacientes de consulta externa en unidades de gastroenterología de dos hospitales nacionales de la ciudad de Guatemala. Métodos: El diagnóstico histopatológico y bacteriológico se realizó por medio de las tinciones de H & E y Giemsa, cultivo e identificación bioquímica, detección de anticuerpos específicos mediante la prueba ELISA, diagnóstico molecular por la amplificación del gen glmM y genotipificación por PCR para identificar los genes VacA y CagA. Se analizaron datos clínico-epidemiológicos de los pacientes, la prevalencia de la infección por H. pylori y la genotipificación de la bacteria. Resultados: En 293 de los pacientes estudiados (83 por ciento) se encontró algún tipo de lesión premaligna; las más frecuentes fueron la atrofia gástrica (70 por ciento), metaplasia intestinal (11 por ciento) y displasia gástrica (2 por ciento). El 17 por ciento de los pacientes no presentó lesiones premalignas. Se halló una prevalencia de infección por H. pylori del 58 por ciento, y el gen cagA se detectó en 118 (57 por ciento) de los pacientes infectados. Conclusiones: La mayoría de los pacientes presentó atrofia gástrica (70 por ciento) y el 43,5 por ciento estaba infectado por H. pylori, principalmente con cepas CagA positivo. Este hecho confirma la importancia del estudio de H. pylori y su relación con cáncer gástrico(AU)

Introduction: Helicobacter pylori infection is the main cause of gastroduodenal diseases (chronic gastritis, peptic ulcer and gastric cancer). In Guatemala few studies have been carried out on the prevalence of H. pylori and its relationship with gastrointestinal diseases, particularly with cancer. Objective: To identify the presence of premalignant lesions (gastric atrophy, intestinal metaplasia and dysplasia) and their relationship with H. pylori infection in outpatients in gastroenterology units in two national hospitals in Guatemala City. Methods: Histopathological and bacteriological diagnostic testings were performed by H & E and Giemsa stain, culture and biochemical identification, detection of specific antibodies by ELISA, molecular diagnosis by glmM gene amplification, and genotypification by PCR to identify vacA and cagA genes. Clinical and epidemiological data from patients, prevalence of H. pylori infection, and bacterium genotypification were analyzed. Results: Among the studied patients, 293 (83 percent) presented some type of premalignant lesion. The most prevalent were gastric atrophy (70 percent), intestinal metaplasia (11 percent), and gastric dysplasia (2 percent). Seventeen percent of the patients did not have any premalignant lesions. The prevalence of H. pylori infection was 58 percent, and cagA gene was identified in 118 (57 percent) of the infected patients. Conclusions: The majority of the patients presented gastric atrophy (70 percent), and 43.5 percent were infected by H. pylori, mainly with positive cagA strains. This finding confirms the importance of studying H. pylori and its relationship with gastric cancer(AU)

Helicobacter pylori: an up-to-date overview on the virulence and pathogenesis mechanisms.

Helicobacter pylori is an organism associated with ulcer disease and gastric cancer. The latter is one of the most prevalent malignancies and currently the fourth major cause of cancer-related deaths globally. The pathogen infects about 50% of the world population, and currently, no treatment ensures its total elimination. There has been an increase in our understanding of the pathophysiology and pathogenesis mechanisms of H. pylori over the years. H. pylori can induce several genetic alterations, express numerous virulence factors, and trigger diverse adaptive mechanisms during its adherence and colonization. For successful colonization and infection establishment, several effector proteins/toxins are released by the organism. Evidence is also available reporting spiral to coccoid transition as a unique tactic H. pylori uses to survive in the host's gastrointestinal tract (GIT). Thus, the virulence and pathogenicity of H. pylori are under the control of complex interplay between the virulence factors, host, and environmental factors. Expounding the role of the various virulence factors in H. pylori pathogenesis and clinical outcomes is crucial for vaccine development and in providing and developing a more effective therapeutic intervention. Here we critically reflect on H. pylori infection and delineate what is currently known about the virulence and pathogenesis mechanisms of H. pylori.

Helicobacter pylori genotypes associated with gastric cancer and dysplasia in Colombian patients.

INTRODUCTION AND AIMS: Colombia has high incidence levels of gastric cancer that can be explained by the genetic variability of Helicobacter pylori (H. pylori). Our aim was to establish the relation of the H. pylori CagA and VacA genotypes to dysplasia and gastric cancer, in a high-risk population. MATERIAL AND METHODS: A case-control study was conducted on 202 patients from a high-risk cancer zone. Patients with dysplasia and gastric cancer (cases) and patients with nonatrophic gastritis (controls) were included. Endoscopic sampling and histologic classification were carried out according to the Sydney system and the Lauren classification. Genetic information was obtained through polymerase chain reaction on paraffin blocks. The measures of association of the variables of interest were evaluated in bivariate and multivariate models. A P<0.05 was considered statistically significant and the SPSS version 25 program was employed. RESULTS: Age above 50 years (OR: 23.76; CI: 8.40-67.17; P=0.000) and the VacA s1m1 genotype (OR: 6.18; CI: 1.25-30.51; P=0.025) were associated with higher risk for developing dysplasia and gastric cancer. The CagA+ genotype was not found to be a risk factor for developing those pathologies (OR: 1.02; CI: 0.39-2.62; P=0.965). CONCLUSIONS: The H. pylori VacA genotypes are markers for the development of gastric cancer. That information could be used to create a risk index in a predictive model to optimize the healthcare of higher-risk patients.

Helicobacter pylori genotypes associated with gastric cancer and dysplasia in Colombian patients. / Genotipos de Helicobacter pylori asociados con cáncer gástrico y displasia en pacientes de Colombia.

INTRODUCTION AND AIMS: Colombia has high incidence levels of gastric cancer that can be explained by the genetic variability of Helicobacter pylori (H. pylori). Our aim was to establish the relation of the H. pylori CagA and VacA genotypes to dysplasia and gastric cancer, in a high-risk population. MATERIAL AND METHODS: A case-control study was conducted on 202 patients from a high-risk cancer zone. Patients with dysplasia and gastric cancer (cases) and patients with nonatrophic gastritis (controls) were included. Endoscopic sampling and histologic classification were carried out according to the Sydney system and the Lauren classification. Genetic information was obtained through polymerase chain reaction on paraffin blocks. The measures of association of the variables of interest were evaluated in bivariate and multivariate models. A P<0.05 was considered statistically significant and the SPSS version 25 program was employed. RESULTS: Age above 50 years (OR: 23.76; CI: 8.40-67.17; P=0.000) and the VacA s1m1 genotype (OR: 6.18; CI: 1.25-30.51; P=0.025) were associated with higher risk for developing dysplasia and gastric cancer. The CagA+ genotype was not found to be a risk factor for developing those pathologies (OR: 1.02; CI: 0.39-2.62; P=0.965). CONCLUSIONS: The H. pylori VacA genotypes are markers for the development of gastric cancer. That information could be used to create a risk index in a predictive model to optimize the healthcare of higher-risk patients.

Relación de los genotipos CagA/VacA del Helicobacter pylori con lesiones precursoras de cáncer gástrico / Relationship of CagA/VacA genotypes of Helicobacter pylori with precursor lesions of gastric cancer

Introducción: El Helicobacter pylori predispone al cáncer gástrico. Los individuos con cepas CagA y VacA s1m1 desarrollan lesiones de la mucosa más graves. El sistema Operative Link on Gastritis Assessment permite determinar el riesgo de cáncer y define la atrofia como la lesión típica de progresión de la gastritis crónica. Objetivo: Relacionar los genotipos CagA y VacA del Helicobacter pylori con lesiones precursoras de cáncer gástrico. Métodos: Se realizó un estudio descriptivo en 62 pacientes. Las variables incluidas fueron los genotipos CagA y VacA del Helicobacter pylori y los estadios de OLGA (0, I, II, III, IV), las cuales se relacionaron. Se emplearon como medidas de resumen para variables cualitativas la frecuencia absoluta y el porcentaje. Para evaluar la asociación entre variables cualitativas se aplicó el test X2 (ji cuadrado). Se aceptó un nivel de significación estadística p ≤ 0,05. Para explorar la relación entre dos variables dicotómicas se utilizó el riesgo relativo. Se trabajó con un nivel de confiabilidad del 95 por ciento. Resultados: El 68 por ciento de los pacientes con atrofia presentaron genotipo CagA y el 55 por ciento genotipo VacA s1m1. El 6 por ciento de los pacientes con CagA se encontraban en estadio 0; 11 por ciento en estadio I; 40 por ciento en estadio II y 16 por ciento en estadio III. El 37 por ciento de los pacientes con VacA s1m1 estaban en estadio II. Conclusiones: Los genotipos CagA y VacA s1m1 fueron los más frecuentes y se relacionaron con la presencia de atrofia gástrica(AU)

Introduction: Helicobacter pylori predisposes to gastric cancer. Individuals with CagA and VacA s1m1 strains develop more severe mucosal lesions. The Operative Link on Gastritis Assessment system allows determining the risk of cancer and defines atrophy as the typical lesion in the progression of chronic gastritis. Objective: Relate the CagA and VacA genotypes of Helicobacter pylori with precursor lesions of gastric cancer. Methods: A descriptive study was carried out in 62 patients. The variables included were the CagA and VacA genotypes of Helicobacter pylori and the OLGA stages (0, I, II, III, IV), which were related. The absolute frequency and the percentage were used as summary measures for qualitative variables. To evaluate the association between qualitative variables, the X2 test (chi-square) was applied. A level of statistical significance p≤0.05 was accepted. To explore the relationship between two dichotomous variables, the relative risk was used. We worked with a confidence level of 95 percent. Development: 68 percent of the patients with atrophy had a CagA genotype and 55 percent had a VacA s1m1 genotype. 6 percent of the patients with CagA were in stage 0; 11 percent in stage I; 40 percent in stage II and 16 percent in stage III. 37 % of the patients with VacA s1m1 were stage II. Conclusions: The CagA and VacA s1m1 genotypes were the most frequent and were related to the presence of gastric atrophy(AU)

Discovery of unique African Helicobacter pylori CagA-multimerization motif in the Dominican Republic.

BACKGROUND: Helicobacter pylori (H. pylori) colonizes the human stomach and is a major cause of peptic ulcer disease and gastric cancer. However, although the prevalence of H. pylori is high in Africa, the incidence of gastric cancer is low, and this phenomenon is called to be African enigma. The CagA protein produced by H. pylori is the most studied virulence factor. The carcinogenic potential of CagA is associated with the Glu-Pro-Ile-Tyr-Ala (EPIYA) patterns and CagA-multimerization (CM) motifs. AIM: To better understand the EPIYA patterns and CM motifs of the cagA gene. METHODS: Gastric mucosal biopsy specimens were obtained from 258 patients with dyspepsia living in the Dominican Republic, from which 120 H. pylori strains were cultured. After the bacterial DNA extraction, the EPIYA pattern and CM motif genotypes were determined using a polymerase chain reaction-based sequencing. The population structure of the Dominican Republic strains was analyzed using multilocus sequence typing (MLST). Peptic ulcer disease and gastric cancer were identified via endoscopy, and gastric cancer was confirmed by histopathology. Histological scores of the gastric mucosa were evaluated using the updated Sydney system. RESULTS: All CagA-positive strains carried the Western-type CagA according to the identified EPIYA patterns. Twenty-seven kinds of CM motifs were observed. Although the typical Western CM motif (FPLKRHDKVDDLSKVG) was observed most frequently, the typical East Asian CM motif (FPLRRSAAVNDLSKVG) was not observed. However, "FPLRRSAKVEDLSKVG", similar to the typical East Asian CM motif, was found in 21 strains. Since this type was significantly more frequent in strains classified as hpAfrica1 using MLST analysis (P = 0.034), we termed it Africa1-CM (Af1-CM). A few hpEurope strains carried the Af1-CM motif, but they had a significantly higher ancestral Africa1 component than that of those without the Af1-CM motif (P = 0.030). In 30 cagA-positive strains, the "GKDKGPE" motif was observed immediately upstream of the EPIYA motif in the EPIYA-A segment, and there was a significant association between strains with the hpAfrica1 population and those containing the "GKDKGPE" motif (P = 0.018). In contrast, there was no significant association between the CM motif patterns and histological scores and clinical outcomes. CONCLUSION: We found the unique African CM motif in Western-type CagA and termed it Africa1-CM. The less toxicity of this motif could be one reason to explain the African enigma.