ROLE OF HELICOBACTER PYLORI INFECTION AND LIFESTYLE HABITS IN THE DEVELOPMENT OF GASTRODUODENAL DISEASES IN A POPULATION FROM THE BRAZILIAN AMAZON

Context Although more than half of the world's population is colonized with Helicobacter pylori, it remains unknown why this organism is able to produce severe disease in some hosts and be innocuous in others. The clinical outcome of infection is determined by several factors, including differences in the host response to bacterial stimulation, specific virulence factors of the organism and environmental influences, or a combination of these factors. Objectives This study compared the prevalence of H. pylori infection and risk factors (infection with CagA+ strains, excessive alcohol consumption, smoking, and inadequate eating habits) between patients with different gastrointestinal disorders and associated these risk factors with the histopathological findings. Methods In a prospective study, samples were collected from 442 patients and a standardized questionnaire regarding lifestyle habits (excessive alcohol consumption, smoking, and eating habits) was applied. The presence of H. pylori and of the cagA gene was investigated by polymerase chain reaction (PCR). Gastric biopsies were obtained for histological assessment. Results The frequency of alcohol consumption, smoking, inadequate diet and infection with CagA+ H. pylori was higher among patients with peptic ulcer and adenocarcinoma when compared to those with gastritis. Gastric inflammation was more pronounced in patients infected with CagA+ strains. Conclusion We conclude that infection with CagA+ H. pylori strains, excessive alcohol consumption, smoking and inadequate eating habits increase the risk of developing peptic ulcer and gastric carcinoma

Infecção pelo Helicobacter pylori e perfil imunológico em pacientes com diferentes doenças gastroduodenais

The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. Objective: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. Methods: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. Results: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. Conclusion: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.A associação da infecção por Helicobacter pylori com diferentes doenças gastroduodenais pode estar associada a fatores bacterianos, do hospedeiro e do ambiente. Nesse contexto, estudos têm demonstrado que a diversidade genética do H. pylori, sobretudo nos genes vacA e cagA, está associada ao desenvolvimento de doenças gastroduodenais como a úlcera péptica e o câncer gástrico. Além disso, a natureza da resposta inflamatória do hospedeiro pode explicar essas diferentes manifestações da infecção por esse microrganismo. Portanto, fatores do hospedeiro que regulam as respostas imunológica e inflamatória, envolvendo a interação funcional da infecção por H. pylori com diferentes membros do compartimento imunológico, especialmente respostas imunes de células T nas doenças gastroduodenais, ainda precisam ser melhor estudados. Objetivo: Caracterizar a resposta imune, incluindo imunidade induzida por infecção pelo H. pylori, especialmente com cepas virulentas de H. pylori (alelos vacA e gene cagA), através da análise do perfil de citocinas e da caracterização da população de células T presentes em doenças gastroduodenais em nossa população. Métodos: Em um estudo prospectivo, foram coletadas biópsias gástricas de 554 pacientes portadores das diferentes doenças gastroduodenais. Nas amostras biológicas destes pacientes foi realizada a determinação do genótipo bacteriano e a detecção das citocinas IL-4, IL-10, INF-γ e IL-12 através do método Elisa. Foram obtidas biópsias gástricas para avaliação histológica. Resultados: Observamos que o genótipo predominante nas cepas de H. pylori isoladas dos pacientes estudados foi s1m1cagA positivo, sendo mais frequentes entre os pacientes com úlcera gástrica, úlcera duodenal e câncer gástrico. Houve associação significativa das cepas com o genótipo s1m1cagA positivo com maior grau de inflamação, atividade neutrofílica e desenvolvimento de metaplasia intestinal. As concentrações gástricas de INF-γ e IL-12 foram significativamente mais elevadas em pacientes infectados pelo H. pylori do que nos não infectados. Foram detectados níveis mais elevados dessas citocinas nos portadores de úlcera e câncer gástrico, sendo que nesses pacientes foram observados níveis mais baixos de IL-4 e IL-10 na mucosa gástrica. Além disso, as concentrações de INF-γ e IL-12 em biópsias gástricas, foram mais elevadas nos pacientes portadores das cepas bacterianas virulentas s1m1cagA+. Contrariamente, os níveis de IL-4 e IL-10 foram maiores em tecido infectado por cepas s2m2cagA. Pacientes com maior grau de inflamação, de atividade neutrofílica e presença de metaplasia intestinal, apresentaram níveis mais elevados de INF-γ e IL-12 e uma concentração mais baixa de IL-4 e IL-10 nas biópsias gástricas. Conclusão: Nosso estudo demonstra que a interação entre o tipo de cepa infectante e resposta imunológica com perfil Th1, podem influenciar e perpetuar a inflamação gástrica contribuindo para o desenvolvimento de diferentes manifestações clínicas na infecção pelo H. pylori.SILVA, A. V.; FECURY, A. A.; MARTINS, L. C. Universidade Federal do Par

HELICOBACTER PYLORI INFECTION AND IMMUNE PROFILE OF PATIENTS WITH DIFFERENT GASTRODUODENAL DISEASES

ABSTRACT BACKGROUND: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. OBJECTIVE: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. METHODS: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. RESULTS: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. CONCLUSION: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection

Análise do polimorfismo na região promotora do gene da interleucina 18 (-137 G/C e -607 C/A) em pacientes portadores do vírus da hepatite C na Amazônia Brasileira

Background - The hepatitis C virus has been recognized as the leading cause of chronic liver disease in the world. Host genetic factors have been implicated in the persistence of hepatitis C virus infection. Single nucleotide polymorphisms at positions -607 C/A (rs1946518) and -137 G/C (rs187238) in the IL-18 gene promoter have been suggested to be associated with delayed hepatitis C virus clearance and persistence of the disease. Objective - Identify these polymorphisms in a population infected with hepatitis C virus from the Brazilian Amazon region. Methods - In a cross-sectional analytical study conducted in Belém, Pará, Brazil, 304 patients infected with hepatitis C virus were divided into two groups: group A, patients with persistent infection; group B, patients with spontaneous clearance. The control group consisted of 376 volunteers not infected with hepatitis C virus. Samples were analyzed by RT-PCR for the detection of viral RNA and by RFLP-PCR to evaluate the presence of the -137 G/C and -607 C/A IL-18 gene promoter polymorphisms. Results - Comparison of polymorphism allele frequencies between the patient and control groups showed a higher frequency of allele C at position -607 among patients (P=0.02). When the association between the polymorphisms and viral infection was analyzed, patients carrying genotype C/A at position -607 were found to be at higher risk of persistent hepatitis C virus infection (P=0.03). Conclusion - the present results suggest a possible role of the -607 IL-18 gene promoter polymorphism in the pathogenesis of hepatitis C virus infection

Prevalence of hepatitis C virus genotypes in the State of Pará, Brazil

Abstract INTRODUCTION This study reports the genotype prevalence of hepatitis C virus (HCV) in Pará, Brazil. METHODS: A retrospective cross-sectional study was conducted on 344 plasma samples sent to the Lacen-Pará for diagnostics by molecular techniques. RESULTS: HCV genotypes identified in the different regions of Pará were 1b (47.7%), 3 (23.3%), 1a (18%), and 2 (4.4%). Genotype 1 occurred in 41.6% of men and 30.8% of women in the 18-86-year-old group. CONCLUSIONS: Genotype 1 is the most predominant in Pará, which reinforces the idea of its relationship with late-diagnosed chronic infection

Helicobacter pylori infection in patients with different gastrointestinal diseases from northern brazil

Background - The mechanisms whereby Helicobacter pylori produces different pathological manifestations in the stomach and duodenum are not fully understood. Considering the geographic diversity in the prevalence of virulence factors of this microorganism and their association with the development of different diseases, the search for pathogenicity markers such as CagA and VacA alleles by molecular techniques has intensified. Objectives - To investigate the presence of H. pylori infection and the frequency of different genotypes of this bacterium in patients with gastrointestinal diseases from Northern Brazil, and to establish their association with the histopathological findings. Methods - In a prospective study, samples were collected from 554 patients with different gastrointestinal diseases (gastritis, duodenal ulcer, gastric ulcer, and gastric cancer) seen at a referral hospital attending the entire State of Pará, located in the metropolitan region of Belém. Data such as gender and age obtained with an epidemiological questionnaire were analyzed. The presence of H. pylori and the bacterial genotype were investigated by PCR. Gastric biopsies were assessed histologically. Results - The prevalence of H. pylori infection was 91%. Infection was more frequent among patients with gastric ulcer and gastric cancer. In these groups, there was a predominance of men and older patients when compared to the other two groups studied. The predominant bacterial genotype was s1m1cagA+, which was more frequent among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between s1m1cagA+ strains and a higher degree of inflammation, neutrophil activity and development of intestinal metaplasia. Conclusion - The present study demonstrates a high incidence of H. pylori infection in the patients analyzed, especially among those with gastric ulcer and gastric cancer. Virulent s1m- 1cagA+ strains predominated and were associated with more severe lesions.Contexto - Os mecanismos pelos quais o H. pylori produz diferentes quadros patológicos no estômago e no duodeno não são totalmente conhecidos. Considerando a diversidade geográfica relacionada à prevalência dos fatores de virulência desse microrganismo e sua associação com o desenvolvimento de diferentes doenças, vem se intensificando a pesquisa de marcadores de patogenicidade, como o CagA e os alelos do VacA por técnicas moleculares. Objetivos - O objetivo desse estudo foi investigar a presença da infecção por H. pylori, e a frequência dos diferentes genótipos dessa bactéria em pacientes com doenças gastrointestinais da nossa região, procurando estabelecer sua associação com os achados histopatológicos. Métodos - Em estudo prospectivo, foram coletadas amostras de 554 pacientes com diferentes doenças gastrointestinais (gastrite, úlcera duodenal, úlcera gástrica e câncer gástrico), atendidos em hospital de referência para todo o Estado do Pará, localizado na região metropolitana de Belém. Foram analisados dados obtidos através de questionário epidemiológico, relacionados ao sexo e faixa etária desses pacientes. A presença do H. pylori e do genótipo bacteriano foi detectada utilizando a PCR. As biopsias gástricas foram avaliadas histologicamente. Resultados - Observou-se uma prevalência de 91% da infecção pelo H. pylori, sendo mais frequente nos portadores de úlcera gástrica e câncer gástrico, nos quais houve predomínio do sexo masculino e a idade foi maior que a dos outros dois grupos estudados. O genótipo bacteriano predominante foi o s1m1cagA positivo, sendo mais frequentes entre os pacientes com úlcera gástrica, úlcera duodenal e câncer gástrico. Houve associação significante das cepas com o genótipo s1m1cagA positivo com maior grau de inflamação, atividade neutrofílica e desenvolvimento de metaplasia intestinal. Conclusão - Nosso estudo demonstra a alta incidência da infecção pelo H. pylori nos pacientes analisados em nosso meio, especialmente em portadores de úlcera e câncer gástricos. As cepas virulentas s1m1cagA+ foram predominantes e estavam associadas a lesões mais graves.VINAGRE, I. D. F.; MARTINS, L. C. Universidade Federal do Par

Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a Brazilian Amazon population

AIM: To study the association between Interleukin-1 (IL-1) and tumor necrosis factor (TNF)-α polymorphisms, infection by Helicobacter pylori (H pylori) and the development of gastrointestinal diseases