Tratamiento de primera línea para erradicación de Helicobacter pylori: todavía una terapia eficaz / First-line treatment for eradication of Helicobacter pylori: Still an effective therapy

Resumen Objetivo: Este estudio tiene como objetivo principal determinar la respuesta al esquema de tratamiento de primera línea con triple terapia estándar (amoxicilina, claritromicina, omeprazol), para erradicación de Helicobacter pylori en una determinada población, para determinar si este esquema propuesto en guías internacionales es aún una opción adecuada para pacientes en una determinada región de Costa Rica. Métodos: Se realizó una búsqueda en el servicio de gastroenterología del Hospital San Francisco de Asís, Grecia, Alajuela, Costa Rica; de todos los pacientes con infección por Helicobacter pylori y que recibieron tratamiento de primera línea con triple terapia (amoxicilina, claritromicina y omeprazol) por 14 días, en el periodo comprendido entre febrero 2017 a febrero 2019, incluyendo para el análisis solamente en los que se contaba con una prueba confirmatoria posterior a tratamiento, ya fuera por antígeno fecal de H. pylori o biopsia convencional. Resultados: Se identificaron un total de 369 casos. El diagnóstico se realizó con biopsia en el 96,4% de los pacientes. La respuesta al tratamiento de primera línea se alcanzó en un 90.5% corroborada por antígeno fecal en el 92.1% de los casos. Conclusiones: Este estudio muestra que la terapia triple con amoxicilina, claritromicina e Inhibidor de bomba de protones por 14 días mantiene un adecuado nivel de eficacia. Sin embargo, hay que tomar en cuenta que estos datos son únicamente de un área de atracción determinada y puede que no reflejen la realidad de todo el país.

Abstract Aim: The main objective of this study is to determine the response to the firstline treatment regimen with triple standard therapy (amoxicillin, clarithromycin, omeprazole), to eradicate Helicobacter pylori in a certain population. The goal is to determine if the proposed regimen in international guidelines services is still a suitable option for patients in a certain region of Costa Rica. Methods: The study took place in San Francisco de Asís Hospital, Grecia, Alajuela, Costa Rica. All patients with a Helicobacter pylori infection that were given first- line treatment with triple therapy (amoxicillin, clarithromycin and omeprazole) for its eradication for 14 days, in the period between February of 2017 and February of 2019, were included in the study. Results: A total of 369 cases were identified. The diagnosis was made with biopsy in 96.4% of patients. Response to first-line treatment was achieved in 90.5% corroborated by fecal antigen in 92.1% of all cases. Conclusions: This study shows that triple therapy with amoxicillin, clarithromycin and omeprazole for 14 days maintains an adequate level of efficacy. However, it must be considered that these results are from a specific area and may not reflect the reality of the entire country.

Clinicopathological features of Helicobacter pylori-negative early gastric cancer / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features of Helicobacter pylori (Hp)-negative early gastric cancer.@*METHODS@#The clinicopathological data of 30 cases of Hp-negative early gastric cancer were collected retrospectively at Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, and Beijing Chaoyang Hospital, Capital Medical University, from 2009 to 2021, and the histomorphological characteristics and immunophenotype were observed, and combined with the literature to explore.@*RESULTS@#The median age of 30 patients was 58.5 years (range: 21-80 years), including 13 males and 17 females. The upper part of the stomach was 13 cases, the middle part of the sto-mach was 9 cases, and the lower part of the stomach was 8 cases. The median diameter of the tumor was 11 mm (range: 1-30 mm). According to the Paris classification, 9 cases were 0-Ⅱa, 7 cases were 0-Ⅱb, and 14 cases were 0-Ⅱc. Endoscopic examination showed that 18 cases of lesions were red, 12 cases of lesions were faded or white, and microvascular structures and microsurface structures were abnormal. In all the cases, collecting venules were regularly arranged in the gastric body and corner mucosa. There were 18 cases of well differentiated adenocarcinoma in the mucosa. The tumor presented glandular tubular-like and papillary structure, with dense glands and disordered arrangement; the cells were cuboidal or columnar, with increased nuclear chromatin and loss of nuclear polarity, and most of them expressed gastric mucin. Signet-ring cell carcinoma was found in 7 cases, all the cancer tissues were composed of signet-ring cells, and the cancer cells were mainly distributed in the middle layer to the surface layer of mucosa. Gastric oxyntic gland adenoma (gastric adenocarcinoma of the fundic gland type confined to mucosa) in 2 cases, gastric adenocarcinoma of the fundic gland type in 2 cases, and gastric adenocarcinoma of fundic gland mucosa type in 1 case. The tumor tissue was composed of branching tubular glands, except 1 case of mucosal surface epithelium was partially neoplastic, the other 4 cases of mucosal surface epi-thelium were all non-neoplastic; the cells were arranged in a single layer, and the nucleus was close to the basal side, and the nucleus was only slightly atypical. Pepsinogen I and H+/K+ ATPase were positive in 5 cases of gastric fundus gland type tumors, and 1 case of foveolar-type tumor cells at the surface and depth of mucosa showed MUC5AC positive. The gastric mucosa adjacent to cancer was generally normal in all cases, without atrophy, intestinal metaplasia and Hp.@*CONCLUSION@#Hp-negative early gastric cancer is a heterogeneous disease group with various histological types, and tubular adenocarcinoma and signet-ring cell carcinoma are common. Tubular adenocarcinoma mostly occurs in the elderly and the upper to middle part of the stomach, while signet-ring cell carcinoma mostly occurs in young and middle-aged people and the lower part of the stomach. Gastric neoplasm of the fundic gland type is relatively rare.

Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial / 中华内科杂志

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

Pathological features of early gastric cancer and its background mucosa after eradication of Helicobacter pylori and their implications for biopsy diagnosis / 中华病理学杂志

Objective: To investigate the clinicopathological changes of early gastric cancer, especially its background mucosa, after the eradication of Helicobacter pylori (H. pylori), and to investigate the causes of underdiagnosis in preoperative biopsy pathology. Methods: Ninety cases of early gastric cancer after H. pylori eradication and 120 cases of endoscopic submucosal dissection (ESD) specimens without H. pylori eradication and their corresponding biopsy specimens were collected from Beijing Friendship Hospital Affiliated to Capital Medical University during 2016-2021. The clinicopathological data of the patients were analyzed, and the histopathological characteristics and immunophenotypic results compared. Results: Compared with the early gastric cancer without H. pylori eradication history, the histopathological type of early gastric cancer after H. pylori eradication was differentiated adenocarcinoma, with staggered distribution of cancerous and non-cancerous epithelium in the tumor area. The morphologic characteristics of gastric mucosa in the background of early gastric cancer after H. pylori eradication, were distinctive, including widening of the opening of enterosylated glandular ducts, serrated change of luminal margin, eosinophilic and microvesicular cytoplasm of enterosylated epithelium. Low-grade atypia existed in gastric cancer epithelial cells after sterilization, which might lead to underdiagnosis or missed diagnosis in biopsy pathology. Conclusions: Early gastric cancer and its background mucosa after H. pylori eradication have unique morphological characteristics, which can be used as a clue for pathological diagnosis, improve the accuracy of biopsy pathology and reduce the underdiagnosis.

Research progress of Helicobacter pylori vaccine / 细胞与分子免疫学杂志

Helicobacter pylori (Hp) is one of most common pathogens causing gastrointestinal disorder including gastric ulcer, duodenal ulcer and gastric cancer, etc. It has been verified as class I carcinogen by WHO. Nowadays, combination antibiotics and proton pump inhibitor are mainly used to erase Hp in clinical application. However, with the increased resistance of Hp, the vaccine against Hp might become the best strategy to eradicate Hp. Elements including urease, virulence factor, outer membrane protein, flagella, play an important role in Hp infection, colonization and reproduction. They have become potential candidate antigens in the development of Hp vaccine, as reported in previous studies. Presently, these antigens-centric vaccines have been tested in animal models. Therefore, this article reviews the studies on Hp vaccine with urease, virulence genes, outer membrane protein and flagella as their candidate antigens, in an attempt to provide insights for research in this regard.

Helicobacter pylori promotes gastric cancer metastasis via up-regulating the expression of Bmi-1 / 细胞与分子免疫学杂志

Objective To clarify whether Helicobacter pylori (H. pylori) can promote metastasis of gastric cancer cells via the high-expression of induced B cell specific Moloney murine leukemia virus integration site 1 (Bmi-1). Methods The gastric cancer tissue specimens from 82 patients were collected for this study. The protein and gene expression level of Bmi-1 in gastric adenocarcinoma tissue were detected by immunohistochemistry and real time quantitative PCR, respectively. And meanwhile the correlation between Bmi-1 levels and pathological features, and prognosis of gastric cancer were analyzed retrospectively. Then, the GES-1 cells were transfected with pLPCX-Bmi-1 plasmid and infected with H. pylori respectively. After the Bmi-1 overexpression in GES-1 cells, the invasion ability of the GES-1 cells was detected by Transwell assay, and the cell cycle and apoptosis were detected by flow cytometry. Results The mRNA and protein of Bmi-1 expression in gastric cancer tissues were higher than tumor-adjacent tissue, and the high expression of Bmi-1 was positively correlated with tumor invasion, TNM stage, tumor differentiation, lymph node metastasis and H. pylori infection. When expression of Bmi-1 was up-regulated as a result of H.pylori infection or pLPCX-Bmi-1 transfection, the GES-1 cells had higher invasiveness and lower apoptosis rate with the above treatment respectively. Conclusion H. pylori infection can inhibit the apoptosis of gastric cancer cells and promote their invasion via up-regulating expression of Bmi-1.

The effect of Helicobacter pylori infection on duodenal bulbar microbiota in children with duodenal ulcer / 中华儿科杂志

Objective: To investigate the characteristics of duodenal bulbar microbiota in children with duodenal ulcer and Helicobacter pylori (Hp) infection. Methods: This prospective cohort study enrolled 23 children with duodenal ulcers diagnosed by gastroscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to abdominal pain, abdominal distension, and vomiting from January 2018 to August 2018. They were divided into Hp-positive and Hp-negative groups according to the presence or absence of Hp infection. Duodenal bulbar mucosa was sampled to detect the bacterial DNA by high-throughput sequencing. The statistical difference in α diversity and β diversity, and the relative abundance in taxonomic level between the two groups were compared. Microbial functions were predicted using the software PICRUSt. T-test, Rank sum test or χ2 test were used for comparison between the two groups. Results: A total of 23 children diagnosed with duodenal ulcer were enrolled in this study, including 15 cases with Hp infection ((11.2±3.3) years of age, 11 males and 4 females) and 8 cases without Hp infection ((10.1±4.4) years of age, 6 males and 2 females). Compared with Hp-negative group, the Hp-positive group had higher Helicobacter abundance (0.551% (0.258%, 5.368%) vs. 0.143% (0.039%, 0.762%), Z=2.00, P=0.045) and lower abundance of Fusobacterium, Streptococcus and unclassified- Comamonadaceae (0.010% (0.001%, 0.031%) vs. 0.049% (0.011%, 0.310%), Z=-2.24, P=0.025; 0.031% (0.015%, 0.092%) vs. 0.118% (0.046%, 0.410%), Z=-2.10, P=0.036; 0.046% (0.036%, 0.062%) vs. 0.110% (0.045%, 0.176%), Z=-2.01, P=0.045). Linear discriminant analysis (LDA) effect sized showed that at the genus level, only Helicobacter was significantly enriched in Hp-positive group (LDA=4.89, P=0.045), while Streptococcus and Fusobacterium significantly enriched in Hp-negative group (LDA=3.28, 3.11;P=0.036,0.025, respectively). PICRUSt microbial function prediction showed that the expression of oxidative phosphorylation and disease-related pathways (pathways in cancer, renal cell carcinoma, amoebiasis, type 1 diabetes mellitus) in Hp-positive group were significantly higher than that in Hp-negative group (all P<0.05), while the expression of pathways such as energy metabolism and phosphotransferase system pathways were significantly lower than that in Hp-negative group (all P<0.05). Conclusion: In children with Hp-infected duodenal ulcers, the mucosal microbiota of the duodenal bulb is altered, characterized by an increased abundance of Helicobacter and a decreased abundance of Clostridium and Streptococcus, and possibly alters the biological function of the commensal microbiota through specific metabolic pathways.

Dual therapy for Helicobacter pylori infection / 中华医学杂志(英文版)

Bismuth-containing quadruple therapy (BQT) has long been recommended for Helicobacter pylori ( H. pylori ) eradication in China. Meanwhile, in the latest national consensus in China, dual therapy (DT) comprising an acid suppressor and amoxicillin has also been recommended. In recent years, the eradication rate of H. pylori has reached >90% using DT, which has been used not only as a first-line treatment but also as a rescue treatment. Compared with BQT, DT has great potential for H. pylori eradication; however, it has some limitations. This review summarizes the development of DT and its application in H. pylori eradication. The H. pylori eradication rates of DT were comparable to or even higher than those of BQT or standard triple therapy, especially in the first-line treatment. The incidence of adverse events associated with DT was lower than that with other therapies. Furthermore, there were no significant differences in the effects of dual and quadruple therapies on gastrointestinal microecology. In the short term, H. pylori eradication causes certain fluctuations in the gastrointestinal microbiota; however, in the long term, the gastrointestinal microbiota eventually returns to its normal state. In the penicillin-naïve population, patients receiving DT have a high eradiation rate, better compliance, lower incidence of adverse reactions, and lower primary and secondary resistance to amoxicillin. These findings suggest the safety, efficacy, and potential of DT for H. pylori eradication.

Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori.@*METHODS@#This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed.@*RESULTS@#A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05).@*CONCLUSIONS@#The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.

Bismuth, esomeprazole, metronidazole, and minocycline or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens.@*METHODS@#This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables.@*RESULTS@#As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups.@*CONCLUSION@#The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance.@*TRIAL REGISTRATION@#ClinicalTrials.gov, ChiCTR 1900023646.

Helicobacter pylori infection and UBT-13C values are associated with changes in body mass index in children and adults / La infección por Helicobacter pylori y los valores de UBT-13C se asocian con el índice de masa corporal en niños y adultos

BACKGROUND: The urea breath test (UBT-13C) is a non-invasive technique that allows the diagnosis and confirmation of eradication of Helicobacter pylori infection. Aim: To evaluate H. pylori positivity and values of UBT-13C among infected Chilean children and adults, and to analyze its variation in relation to sex, nutritional status, and age of the patients. Material and Methods: Retrospective study of 1141 patients aged 6 to 94 years, with an indication for a UBT-13C either for diagnosis or for confirmation of eradication of H. pylori infection. 13C enrichment was measured using an infrared spectrometer calculating the delta 13C values before and after the ingestion of 13C marked urea. The clinical data of the patients were obtained at the time of the examination. Results: We included 241 children and 900 adults. Infected children obtained lower UBT-13C delta values than infected adults (16.1 ± 8.7 and 37 ± 52.9, respectively). The rates of infection were higher in males who were recruited for diagnosis. Significant differences were obtained between positivity for H. pylori in overweight and obese children but not adults. UBT-13C titers were significantly associated with the body mass index (BMI) only in adults. Conclusions: H. pylori infection rates are similar between sexes and are higher in children probably because of selection bias. In children, H. pylori positivity is associated with higher BMI and excess malnutrition although with similar UBT-13C values. In adults, H. pylori infection is not related with BMI, but a higher BMI impacts UBT-13C titers.

ANTECEDENTES: La prueba de aliento con urea (UBT-13C) es una técnica no invasiva que permite el diagnóstico y confirmación de erradicación de la infección por Helicobacter pylori. Objetivo: Evaluar los valores de UBT- 13C en niños y adultos chilenos infectados y analizar su variación en relación al sexo, diagnóstico nutricional y edad de los pacientes. Material y Métodos: Estudio retrospectivo de 1.141 pacientes de 6 a 94 años. El enriquecimiento de13C se midió usando un espectrómetro de infrarrojos, calculando el delta 13C antes y después de la ingesta de urea marcada con 13C. Los datos clínicos de los pacientes se obtuvieron al momento del examen. Resultados: Incluimos 241 niños y 900 adultos con valores delta de UBT-13C de 16,1 ± 8,7 frente a 37 ± 52,9, respectivamente. Las tasas de infección fueron mayores en los hombres reclutados para el diagnóstico. Se obtuvieron diferencias significativas entre la positividad para H. pylori en niños con sobrepeso y obesidad, pero no en adultos. Los títulos de UBT-13C se asociaron significativamente con el índice de masa corporal (IMC) solo en adultos. Conclusiones: Las tasas de infección por H. pylori son similares entre los sexos y aumentan en los niños probablemente debido al sesgo de selección. En niños, la positividad para H. pylori se asocia con un IMC más alto y malnutrición por exceso, aunque con valores similares de UBT-13C. En los adultos, la infección por H. pylori no se relaciona con el IMC ni con la obesidad, pero el aumento del IMC afecta los títulos de UBT-13C.

Relação entre a infecção por Helicobacter pylori e doenças hematológicas: uma revisão integrativa / The relationship between Helicobacter pylori infection and hematologic diseases: an integrative review

Helicobacter pylori, uma bactéria gram-negativa, desde 1984 vem sendo associada às doenças gástricas. A partir da década de 1990, surgiram crescentes relatos indicando a relação da infecção com manifestações extragástricas. Nesse sentido, o objetivo do estudo foi investigar, através de uma revisão integrativa, as evidências relacionadas à H. pylori e a presença de doenças hematológicas, focando na anemia por deficiência de ferro (ADF) e na púrpura trombocitopênica idiopática (PTI). Bases de dados foram consultadas com as palavras-chave e descritores Helicobacter pylori, Doenças extragástricas, Doenças hematológicas, Anemia ferropriva e Púrpura Trombocitopênica Idiopática, nos idiomas inglês, português e espanhol, combinados com o operador booleano "AND". Após a leitura de 1.964 títulos, 85 artigos atendiam aos critérios de inclusão. Com a exclusão dos artigos duplicados e pela análise dos resumos, 62 trabalhos foram selecionados e lidos na íntegra. Por fim, 27 estudos foram incluídos: 13 relacionados à ADF e 77% deles encontraram associação com H. pylori, e 14 relacionados à PTI, nos quais a relação com a bactéria foi encontrada em 93%. As evidências que associam essas doenças hematológicas com H. pylori são expressivas, portanto, mais estudos são necessários para elucidar os mecanismos relacionados e contribuir para prevenção, diagnóstico e tratamento mais eficazes.

Helicobacter pylori is a gram-negative bacterium that has been associated with gastric diseases since 1984. Since the 1990s, there have been increasing reports indicating that the infection may also be associated with extragastric manifestations. This integrative review aimed to investigate the evidence on the relationship between H. pylori and hematological diseases, specifically iron deficiency anemia (IDA) and idiopathic thrombocytopenic purpura (ITP). Databases were searched for the keywords "Helicobacter pylori," "extragastric diseases," "hematologic diseases," "iron deficiency anemia," and "idiopathic thrombocytopenic purpura" in English, Portuguese, and Spanish, combined with the boolean operator "AND." The search yielded 1,964 studies. After reading the titles, only 85 met the inclusion criteria. Sixty-two studies were selected for full-text reading after exclusion of duplicates and abstract analysis. Finally, 27 studies were included in this review. Thirteen studies addressed IDA, among which 77% found an association with H. pylori; whereas 14 studies addressed ITP, among which 93% found a relationship with H. pylori. There is strong evidence supporting the association between hematologic diseases and H. pylori. Further studies are needed to elucidate the mechanisms involved in this relationship, contributing to more effective prevention, diagnosis, and treatment.

Upper gastrointestinal ulcer in children: a clinical analysis of 173 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical manifestations and gastroscopic characteristics of upper gastrointestinal ulcer in children.@*METHODS@#A retrospective analysis was performed for the children who underwent gastroscopy and were found to have upper gastrointestinal ulcer for the first time at the Endoscopy Center of Shengjing Hospital, China Medical University, from January 2011 to May 2021. According to the cause of the disease, they were divided into primary ulcer group (primary group; n=148) and secondary ulcer group (secondary group; n=25). The clinical data were compared between the two groups.@*RESULTS@#A total of 173 children with upper gastrointestinal ulcer were enrolled, with a male/female ratio of 3.9:1. Compared with girls, boys had significantly higher proportions of duodenal ulcer and primary ulcer (P<0.05). Compared with the children aged below 6 years, the children aged 6-14 years had higher proportions of duodenal ulcer and primary ulcer and lower proportions of giant ulcer and multiple ulcers. Of the 148 children in the primary group, 95 (64.2%) had Helicobacter pylori infection. Abdominal pain was the most common clinical symptom and was observed in 101 children (68.2%). Duodenal ulcer was common and was observed in 115 children (77.7%), followed by gastric ulcer in 25 children (16.9%) and esophageal ulcer in 7 children (4.7%). Multiple ulcers were observed in 32 children (21.6%). Seventy children (47.3%) experienced complications, among which bleeding was the most common complication and was observed in 63 children (43.6%). Of the 25 children in the secondary group, abdominal pain was the most common clinical symptom and was observed in 9 children (36.0%), with a significantly lower incidence rate than the primary group (P<0.05); foreign body in the digestive tract was the most common cause of ulcer and was observed in 17 children (68%), followed by abdominal Henoch-Schönlein purpura in 5 children (20.0%) and Crohn's disease in 3 children (12.0%). The secondary group had a significantly higher proportion of multiple ulcer or giant ulcer than the primary group (P<0.05).@*CONCLUSIONS@#Upper gastrointestinal ulcer is more common in boys than girls, and duodenal ulcer and primary ulcer are more common in boys. Children aged 6-14 years often have duodenal ulcer and primary ulcer, and giant ulcer and multiple ulcers are relatively uncommon. Primary ulcer in children has a variety of clinical manifestations, mainly abdominal pain, and duodenal ulcer is relatively common, with bleeding as the main complication. The clinical symptoms and endoscopic manifestations of secondary ulcer are closely associated with the primary causes, and it is more likely to induce huge ulcers and multiple ulcers.

Evaluation of the Gastric Microbiome in Patients with Chronic Superficial Gastritis and Intestinal Metaplasia / 中国医学科学杂志(英文版)

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis (CSG) and intestinal metaplasia (IM) and investigate the influence of Helicobacter pylori (H. pylori) on the gastric microbiome. Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM, and the patients were classified into the following four groups based on the state of H. pylori infection and histology: H. pylori-negative CSG (n=24), H. pylori-positive CSG (n=14), H. pylori-negative IM (n=11), and H. pylori-positive IM (n=5). The gastric microbiome was analyzed by 16S rRNA gene sequencing. Results H. pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM. In H. pylori-positive subjects, the bacterial abundance and diversity were significantly lower than in H. pylori-negative subjects. The H. pylori-negative groups had similar bacterial composition and bacterial abundance. The H. pylori-positive groups also had similar bacterial composition but different bacterial relative abundance. The relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella were richer in the I-HP group than in G-HP group, especially Neisseria (t=175.1, P<0.001). Conclusions The gastric microbial abundance and diversity are lower in H. pylori- infected patients regardless of CSG and IM. Compared to H. pylori-positive CSG group and H. pylori-positive IM, the relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella is higher in H. pylori-positive patients with IM than in H. pylori-positive patients with CSG, especially Neisseria.

Aberrant Expression and Glycosylation of Mucins in Gastric Mucosal Disease / 中国医学科学院学报

Mucins,a family of heavily glycosylated proteins,present mainly in epithelial cells.They function as essential barriers for epithelium and play important roles in cellular physiological processes.Aberrant expression and glycosylation of mucins in gastric epithelium occur at pathological conditions,such as Helicobacter pylori infection,chronic atrophic gastritis,intestinal metastasis,dysplasia,and gastric cancer.This review addresses the major roles played by mucins and associated O-glycan structures in normal gastric epithelium.Further,we expound the alterations of expression patterns and glycan signatures of mucins at those pathological conditions.

Helicobacter pylori may participate in the development of inflammatory bowel disease by modulating the intestinal microbiota / 中华医学杂志(英文版)

Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of the gastrointestinal (GI) tract that is generally accepted to be closely related to intestinal dysbiosis in the host. GI infections contribute a key role in the pathogenesis of IBD; however, although the results of recent clinical studies have revealed an inverse correlation between Helicobacter pylori (H. pylori) infection and IBD, the exact mechanism underlying the development of IBD remains unclear. H. pylori, as a star microorganism, has been a focus for decades, and recent preclinical and real-world studies have demonstrated that H. pylori not only affects the changes in the gastric microbiota and microenvironment but also influences the intestinal microbiota, indicating a potential correlation with IBD. Detailed analysis revealed that H. pylori infection increased the diversity of the intestinal microbiota, reduced the abundance of Bacteroidetes, augmented the abundance of Firmicutes, and produced short-chain fatty acid-producing bacteria such as Akkermansia. All these factors may decrease vulnerability to IBD. Further studies investigating the H. pylori-intestinal microbiota metabolite axis should be performed to understand the mechanism underlying the development of IBD.

Associação entre Infecção por Heicobacter Pylori e Hipertensão Arterial Sistêmica: Metanálise / Association between Helicobacter Pylori Infection and Systemic Arterial Hypertension: A Meta-Analysis

Resumo Fundamento: Estudos epidemiológicos recentes demonstraram que alterações na microbiota e seus metabólitos estão associadas à hipertensão arterial sistêmica. A Helicobacter pylori (H. pylori) é um dos patógenos bacterianos mais comuns, e a possível associação entre a infecção por H. pylori e a hipertensão é controversa. Objetivos: Este estudo teve o objetivo de esclarecer a associação entre eles e proporcionar uma nova base teórica para detectar a patogênese da hipertensão. Métodos: Foram selecionados estudos caso-controle e transversais sobre a associação entre H. pylori e hipertensão, publicados de 1996 a 2019 indexados nos bancos de dados PubMed, Google Scholar, Chinese Wan Fang Data, e Chinese National Knowledge Infrastructure (CNKI). As razões de chance (RC) combinadas e o intervalo de confiança (IC) 95% foram estimados. O I² foi realizado para avaliar a heterogeneidade estatística. O viés de publicação foi avaliado utilizando-se os testes de Beggs e de Egger. Os dados extraídos foram analisados no software Stata 12.0. A significância estatística foi definida com um p-valor < 0,05. Resultados: Foram cadastrados 17 estudos envolvendo 6376 casos de hipertensão e 10850 controles. A taxa de infecção por H. pylori em pacientes hipertensos e em controles foi de 64,9% e 56,3%, respectivamente. Foi demonstrada uma associação significativamente positiva entre a infecção por H. pylori e a hipertensão, com uma RC global de 2,07 (IC 95%: 1,46-2,94; p < 0,05). A análise de subgrupos revelou que a prevalência de infecção por H. pylori foi associada à hipertensão na região da Ásia e no grupo de caso-controle, as RC (IC 95%) foram 2,26 (1,51-3,38) e 2,53 (1,72-3,72), respectivamente. Depois de estratificar por métodos de detecção, ainda existiam diferenças entre os subgrupos (todos p < 0,05). Conclusão: Esta metanálise indicou que a infecção por H. pylori está associada positivamente à hipertensão.

Abstract Background: Recent epidemiological studies have shown that alterations in microbiota and its metabolites are associated with systemic arterial hypertension. Helicobacter pylori (H. pylori) is one of the most common bacterial pathogens, and the potential association between H. pylori infection and hypertension are controversial. Objective: This study aimed to clarify their association and provide a new theoretical basis for uncovering the pathogenesis of hypertension. Methods: Case-control and cross-sectional studies on the association between H. pylori and hypertension published from 1996 to 2019 indexed in PubMed, Google Scholar, Chinese Wan Fang Data, and Chinese National Knowledge Infrastructure (CNKI). The pooled odds ratios (OR) and 95% confidence interval (CI) were estimated. I2 was performed to evaluate the statistical heterogeneity. Publication bias was evaluated using Begg's and Egger's test. The extracted data was analyzed in Stata 12.0. Statistical significance was defined as p-value < 0.05. Results: A total of 17 studies involving 6,376 cases of hypertension and 10,850 controls were enrolled. H. pylori infection rate in hypertension patients and controls were 64.9% and 56.3%, respectively. A significantly positive association was shown between H. pylori infection and hypertension with an overall OR of 2.07 (95% CI: 1.46-2.94; p < 0.05). Subgroup analysis revealed that the prevalence of H. pylori infection was associated with hypertension in the region of Asia and the case-control group, ORs (95% CI) were 2.26 (1.51-3.38) and 2.53 (1.72-3.72), respectively. After stratifying by detection methods, differences still existed in subgroups (all p < 0.05). Conclusion: This meta-analysis indicated that H. pylori infection is positively associated with hypertension.

Soroprevalência e fatores associados a infecções crônicas entre idosos residentes na comunidade / Seroprevalence and factors associated with chronic infections among community-dwelling elderly individuals

Resumo Infecções crônicas podem contribuir com o processo de envelhecimento, mas isso ainda é pouco explorado na América Latina. O objetivo foi avaliar a prevalência e os fatores associados ao citomegalovírus (CMV), Herpes simples 1 (HSV-1), Chlamydia pneumoniae e Helicobacter pylori entre idosos. Participaram 1.320 indivíduos da linha de base da Coorte de Idosos de Bambuí. Foram avaliados anticorpos (IgG) para as infecções e variáveis exploratórias (sociodemográficas, comportamentos em saúde e condições de saúde). Utilizaram-se modelos de regressão de Poisson com variância robusta. A prevalência foi de 99,4% para CMV, 96,7% para HSV-1, 56,0% para C. pneumoniae e 70,5% para H. pylori. Os mais velhos, mulheres, fumantes, diabéticos, incapazes e com maiores níveis de IL-6 tinham maior prevalência de CMV. HSV-1 foi menos frequente entre as mulheres. Infecção por C. pneumoniae foi maior entre os mais velhos e diabéticos; e menor entre mulheres e os menos escolarizados. H. pylori foi menos frequente entre as mulheres e naqueles com maiores níveis de IL-1β, mas mais comuns entre os fumantes. Os achados mostram elevada prevalência de infecções crônicas e diferentes perfis epidemiológicos para cada patógeno, permitindo a detecção de grupos vulneráveis a essas infecções.

Abstract Chronic infections can contribute to the aging process, but this issue is less studied in Latin America. The aim was to assess the prevalence and factors associated with cytomegalovirus (CMV), Herpes Simplex 1 (HSV-1), Chlamydia pneumoniae and Helicobacter pylori among the elderly. A total of 1,320 individuals participated from the baseline of the Elderly Cohort of Bambuí. IgG antibodies against infections and explanatory variables (sociodemographic factors, health behaviors and health conditions) were evaluated. Poisson regression models with robust variance were used. Seroprevalence rates were 99.4% for CMV, 96.7% for HSV-1, 56% for C. pneumoniae and 70.5% for H. pylori. Elderly men, women, smokers, diabetics, the disabled and those with high levels of IL-6 had a higher prevalence of CMV. HSV-1 was less frequent among women. The prevalence of C. pneumoniae was higher at ages >75 and among diabetics; it was lower among women and individuals with less schooling. H. pylori was less frequent among women and those with detectable levels of IL-1β, but more common among smokers. The findings show a high prevalence of chronic infection and a different epidemiologic profile for each pathogen, making it possible to detect groups that are vulnerable to these infections.

PREX2 gene's expression in gastric antral epithelial cells of patients with H. pylori infection / Expressão do gene PREX2 em células epiteliais antrais gástricas em pacientes com infecção por H. pylori

ABSTRACT BACKGROUND: The Prex2 protein is a member of the Rac family proteins that belongs to small G proteins with a critical role in cell migration, cell proliferation, and apoptosis through its effects on PI3K cell signaling pathway and phosphatase activity of PTEN protein. The effect of PREX2 gene expression has been shown in some cancer cells. A survey of PREX2 gene expression in gastric antral epithelial cells of gastric cancer patients with Helicobacter pylori various genotypes infection can conduct to better understanding H. pylori infection's carcinogenesis. METHODS: In a case-control study, PREX2 gene expression was evaluated in gastric antral biopsy samples on four groups of patients referred to Sanandaj hospitals, including gastritis with (n=23) and without (n=27) H. pylori infection and gastric cancer with (n=21) and without (n=32) H. pylori infection. Each gastric biopsy sample's total RNA was extracted and cDNA synthesized by using Kits (Takara Company). The PREX2 gene expression was measured using the relative quantitative real-time RT-PCR method and ΔΔCt formula. RESULTS: The PREX2 gene expression increased in gastric antral biopsy samples of gastritis and gastric cancer patients with H. pylori infection (case groups) than patients without H. pylori infection (control groups) 2.38 and 2.27 times, respectively. The patients with H. pylori vacA s1m1 and sabB genotypes infection showed a significant increase of PREX2 gene expression in gastric cancer antral epithelial cells. CONCLUSION: H. pylori vacA s1m1 and sabB genotypes have the positive correlations with PREX2 gene expression in gastric antral epithelial cells of gastritis and gastric cancer patients.

RESUMO CONTEXTO: A proteína Prex2 é membro das proteínas da família Rac que pertencem a pequenas proteínas G com um papel crítico na migração celular, na proliferação celular e na apoptose através de seus efeitos na via de sinalização celular PI3K e atividade fosfatase da proteína PTEN. O efeito da expressão genética PREX2 tem sido mostrada em algumas células cancerosas. Um levantamento da expressão genética PREX2 em células epiteliais antrais gástricas de pacientes infectados com vários genótipos de Helicobacter pylori pode conduzir a um melhor entendimento da carcinogênese da infecção por H. pylori. MÉTODOS: Em estudo de caso-controle, a expressão genética PREX2 foi avaliada em amostras de biópsia antral gástrica em quatro grupos de pacientes encaminhados aos hospitais de Sanandaj, incluindo gastrite com (n=23) e sem (n=27) infecção por H. pylori e de câncer gástrico com (n=21) e sem (n=32) infecção por H. pylori. O RNA total de cada amostra de biópsia gástrica foi extraído e cDNA sintetizado por meio de kits (Takara Company). A expressão genética PREX2 foi medida utilizando-se o método RT-PCR em tempo real quantitativo relativo e a fórmula ΔΔCt. RESULTADOS: A expressão genética PREX2 aumentou em amostras de biópsia antral gástrica de pacientes com gastrite e câncer gástrico com infecção por H. pylori (grupos de casos) em relação aos sem infecção por H. pylori (grupos de controle) 2,38 e 2,27 vezes, respectivamente. Os pacientes com infecção por genótipos H. pylori vacA s1m1 e sabB apresentaram um aumento significativo da expressão genética PREX2 em células epiteliais antrais de câncer gástrico. CONCLUSÃO: Os genótipos H. pylori vacA s1m1 e sabB têm correlações positivas com a expressão genética PREX2 em células epiteliais antrais gástricas de pacientes com câncer gástrico e gastrites.

Gastrite crônica por Helicobacter pylori em pacientes com condições pré-malignas: avaliação dos sistemas OLGA e OLGIM e desempenho de biomarcadores séricos / Helicobacter pylori chronic gastritis on patients with premalignant conditions: olga and olgim evaluation and serum biomarkers performance

ABSTRACT BACKGROUND: H. pylori chronic atrophic gastritis is a premalignant lesion, and its staging, according to OLGA and OLGIM systems aims to identify patients at increased risk of developing gastric cancer and optimize their follow-up. GastroPanel®, serum biomarkers panel including pepsinogen I (PGI), pepsinogen II (PGII), Gastrin 17 (G17) and anti- H. pylori antibodies is a noninvasive test for adenocarcinoma risk assessment in chronic H. pylori gastritis patients. OBJECTIVE: Prospective study to evaluate the concordance between OLGA and OLGIM grading systems, as well as to evaluate GastroPanel´s performance in patients with premalignant lesions secondary to H. pylori chronic gastritis in Brazil. METHODS: Patients with H. pylori chronic gastritis with premalignant lesions confirmed by histology were recruited from the gastrointestinal clinic of a University Hospital. All participants underwent endoscopic examination with biopsies which were reported according to updated Sydney system and premalignant lesions grading systems (OLGA and OLGIM). Blood samples were collected for biomarkers serological analysis (GastroPanel®, Biohit, Helsinki, Finland). The cut off values used to define high risk patients were those recommended by the manufacturer: PGI ≤30 µm/L and PGI/PGII ≤3. RESULTS: 41 patients were recruited: 28 women, 13 men, mean age 67.3 (47-89, SD: 9.6) years. By OLGA system, were obtained: OLGA 0 (n=1), OLGA I (n=7), OLGA II (n=17), OLGA III (n=9), and OLGA IV (n=7). By OLGIM system, were obtained: OLGIM 0 (n=14), OLGIM I (n=5), OLGIM II (n=10), OLGIM III (n=10), and OLGIM IV (n=2). Regarding histological staging among patients staged as low risk (OLGA/OLGIM 0, I and II) and high risk (OLGA/OLGIM III and IV) for gastric cancer development, the concordance rate found between both classifications was 85.4%. Considering high risk patients, those patients thus included in at least one of the systems the final distribution of our sample considered 24 low-risk and 17 high-risk patients for the development of gastric cancer. To determine by GastroPanel® whether the patient would be at low or high risk of developing gastric cancer, PGI showed a sensitivity, specificity and accuracy of 0.47 (95%CI: 0.26-0.69), 0.67 (95%CI: 0.47-0.82), and 0.58 (95%CI: 0.43-0.72), respectively, while PGI/PGII showed sensitivity, specificity and accuracy of 0.06 (95%CI: 0.01-0.27), 0.83 (95%CI: 0.64-0.93) and 0.51 (95%CI: 0.36-0.66), respectively. CONCLUSION: The histological classifications OLGA and OLGIM presented a substantial concordance rate among themselves. Simultaneous use of both histological classification systems increased the identification's rate of high-risk patients. Biomarker analysis was not effective to distinguish low to high risk patients in the studied population. Further studies are needed to validate its use in clinical practice in Brazil.

RESUMO CONTEXTO: Gastrite atrófica crônica por H. pylori constitui lesão pré-maligna e seu estadiamento de acordo com os sistemas OLGA e OLGIM, visa identificar pacientes com maior risco de desenvolver câncer gástrico e otimizar seu acompanhamento. GastroPanel® é um teste não invasivo composto por painel de biomarcadores séricos incluindo pepsinogênio I (PGI), pepsinogênio II (PGII), gastrina 17 (G17) e anticorpos anti- H. pylori para avaliação de risco de adenocarcinoma gástrico em pacientes com gastrite crônica por H. pylori. OBJETIVO: Estudo prospectivo para avaliar a concordância entre os sistemas de classificação OLGA e OLGIM, bem como avaliar o desempenho do GastroPanel® em pacientes com lesões pré-malignas secundárias à gastrite crônica por H. pylori no Brasil. MÉTODOS: Pacientes com gastrite crônica por H. pylori portadores de lesões pré-malignas confirmadas por histologia (gastrite atrófica e metaplasia intestinal) foram recrutados no ambulatório de gastroenterologia de um hospital universitário. Todos os participantes foram submetidos a exame endoscópico com biópsias de antro e corpo gástricos analisadas de acordo com o Sistema Sydney atualizado e estadiadas pelos Sistemas OLGA e OLGIM de classificação das gastrites. Amostras de sangue foram coletadas para análise sorológica de biomarcadores (GastroPanel®, Biohit, Helsinki, Finlândia). Os valores de corte utilizados para definir pacientes de alto risco para desenvolvimento de câncer gástrico foram os recomendados pelo fabricante: PGI ≤30 µm e PGI/PGII ≤3. RESULTADOS: Foram recrutados 41 pacientes: 28 mulheres, 13 homens, idade média 67,3 (47-89, DP: 9,6) anos. Pelo sistema OLGA, foram obtidos: OLGA 0 (n=1), OLGA I (n=7), OLGA II (n=17), OLGA III (n=9) e OLGA IV (n=7). Pelo sistema OLGIM, foram obtidos: OLGIM 0 (n=14), OLGIM I (n=5), OLGIM II (n=10), OLGIM III (n=10) e OLGIM IV (n=2). Em relação ao estadiamento histológico entre os pacientes de baixo risco (OLGA/OLGIM 0, I e II) e alto risco (OLGA/OLGIM III e IV) para o desenvolvimento de câncer gástrico, a taxa de concordância encontrada entre as duas classificações foi de 85,4%, com valor kappa=0,678 (IC95%: 0,440-0,916). Considerando como pacientes de alto risco, aqueles assim estadiados em pelo menos um dos sistemas, a distribuição final de nossa amostra encontrou 24 pacientes de baixo risco e 17 de alto risco para o desenvolvimento de câncer gástrico. Na determinação pelo GastroPanel® para classificação do paciente como de baixo ou alto risco para desenvolvimento de câncer gástrico, PGI mostrou sensibilidade, especificidade e acurácia de 0,47 (IC95%: 0,26-0,69), 0,67 (IC95%: 0,47-0,82) e 0,58 (IC95%: 0,43-0,72), respectivamente, enquanto a razão PGI/PGII mostrou sensibilidade, especificidade e acurácia de 0,06 (IC95%: 0,01-0,27), 0,83 (IC95%: 0,64-0,93) e 0,51 (IC95%: 0,36-0,66), respectivamente. CONCLUSÃO: As classificações histológicas OLGA e OLGIM apresentaram taxa de concordância substancial entre si. O uso simultâneo de ambos os sistemas de classificação histológica aumentou a taxa de identificação de pacientes de alto risco para desenvolvimento de câncer gástrico. Os resultados do GastroPanel® não foram eficazes para distinguir pacientes de baixo e alto risco para desenvolvimento de câncer gástrico na população estudada. Mais estudos são necessários para validar seu uso na prática clínica no Brasil.