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3rd BRAZILIAN CONSENSUS ON Helicobacter pylori

3º Consenso Brasileiro para Estudo do Helicobacter pylori

Abstracts

Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

Helicobacter pylori; Helicobacter infections; Dyspepsia; Consensus


Os avanços significativos ocorridos desde o Segundo Consenso Brasileiro sobre H. pylori realizado em 2004, em São Paulo, justificam este terceiro consenso. O evento foi organizado pelo Núcleo Brasileiro para Estudo do Helicobacter, departamento da Federação Brasileira de Gastroenterologia, tendo sido realizado em Bento Gonçalves, RS, nos dias 12 a 15 de abril de 2011. Contou com a participação de 30 delegados provenientes das cinco regiões brasileiras e um convidado internacional, incluindo gastroenterologistas, patologistas, epidemiologistas e pediatras. Os participantes foram alocados em um dos cinco subgrupos do evento, a saber: Helicobacter pylori, dispepsia funcional e diagnóstico; Helicobacter pylori e câncer gástrico; Helicobacter pylori e afecções não-gastroduodenais; Helicobacter pylori, tratamento e retratamento, e, epidemiologia da infecção por Helicobacter pylori no Brasil. Após extensa discussão, todas as recomendações e conclusões emanadas tinham definidas a força da recomendações e seu grau de evidência científica. As conclusões de cada subgrupo foram referendadas em votação final com todos os participantes. Foi adotado como consensual as decisões que atingissem 70% ou mais de concordância entre os participantes. Este artigo apresenta as principais recomendações e conclusões para orientação aos profissionais brasileiros envolvidos com a infecção por H. pylori.

Helicobacter pylori; Infecções por Helicobacter; Dispepsia; Consenso


INTRODUCTION

Since its foundation in 1994, the Brazilian Helicobacter Study Nucleus, now also a Department of the Brazilian Federation of Gastroenterology has held two consensus conferences on H pylori infection( 2424. Coelho LG, Barros CAS, Lima DCA, Barbosa AJA, Magalhães AFN, Oliveira CA, Queiroz DMM, Cordeiro F, Rezende JM, Castro LP, Tolentino MM, Haddad MT, Zaterka S. Consenso Nacional sobre H. pylori e afecções associadas. GED Gastroenterol Endosc Dig. 1996;15:53-8. , 3131. Coelho LG, Zaterka S; Representantes indicados pela Federação Brasileira de Gastroenterologia e Núcleo Brasileiro para o Estudo do Helicobacter II Consenso Brasileiro sobre Helicobacter pylori. Arq Gastroenterol. 2005;42:128-32. ). Almost 8 years after the 2nd Brazilian Consensus for Study of Helicobacter pylori, the Nucleus promoted its 3rd conference in Bento Gonçalves, RS, Brazil from 12 to 15 April 2012. Thirty-one delegates from all five Brazilian regions took part at the conference, including gastroenterologists, pathologists, epidemiologist, a pediatrician, and an international guest from the USA. Participants were invited for their knowledge and contribution to the study of H pylori infection. The meeting sought to re-examine the role of H pylori infection in dyspepsia, gastric cancer and extradigestive diseases, besides addressing therapeutic options for treating and retreating the infection in Brazil. Finally, it was sought to carry out a critical analysis of the epidemiological features of the infection in Brazil, with suggestions for possible interventions to reduce the prevalence of the infection and hence its clinical outcomes among us.

METHODOLOGY

The participants were divided into five groups according to their main area of interest/expertise, namely: H pylori and functional dyspepsia; H pylori and gastric cancer; H pylori and other associated disorders; H pylori, treatment and retreatment; and H pylori and epidemiological aspects. To each group was assigned a coordinator. Prior to the Consensus conference date, the coordinators held a meeting in São Paulo at which a questionnaire was drawn up with specific questions for each participant at the Consensus conference to answer. In Bento Gonçalves, participants were divided among the five groups. Each participant would make a 10 minute presentation to their group, containing in-depth analysis of the topic, citing the top 10 re ferences on it, followed by extensive discussion, with modifications, additions and deletions. The strength of recommendations and levels of evidence adopted were, wherever possible, those recommended by the Brazilian Medical Association( 55. Associação Médica Brasileira. Conselho Federal de Medicina. Projeto Diretrizes. São Paulo: AMB/CFM; 2000 [Internet]. [cited 2012 May 9]. Available from http://www.projetodiretrizes.org.br.
http://www.projetodiretrizes.org.br...
) (Figure 1). The conclusions and recommendations from each group were then prepared and edited for the final plenary meeting, and were then presented to all participants for final voting, and those on which at least 70% of all participants agreed upon were adopted as consensual. The recommendations from these proceedings are reported here.

FIGURE 1
Recommendation grade and evidence level adopted at the 3rd Brazilian Consensus on Hpylori

GROUP 1. H PYLORI, FUNCTIONAL DYSPEPSIA AND DIAGNOSIS

  Statement 1:

The diagnosis of functional dyspepsia among us should be the one recommended by the Rome III Consensus, plus stool parasite testing or empiric use of antiparasitics Agreement level: 100%; Recommendation grade: D; Evidence level: C

In accordance with the Rome III Consensus( 4242. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006;130:1377-90. ) the following criteria are required for diagnosis of functional dyspepsia: 1) dyspeptic complaints during the last 3 months, beginning at least 6 months prior; 2) the presence of one or more of the following symptoms is fundamental: a) postprandial fullness, b) early satiety c) epigastric pain d) epigastric burning, 3) absence of structural lesions (necessary to perform upper endoscopy) that may justify the symptoms.

Although variable, the prevalence of intestinal parasites in Brazil is still considered high in some regions, especially those caused by Ascaris lumbricoides, Strongiloides stercoralis and Giardia lamblia. In this context, the World Health Organization has considered valid the use of antiparasitic drugs at regular intervals for populations at high risk of contracting intestinal parasites( 154154. Organização Mundial da Saúde. Schistosomiase et géohelminthiases: prevétion et lutte. Genève: OMS; 2004. 68p. (Série de Informes Técnicos v. 912). ). Thus, the Consensus opted to adopt the concept of functional dyspepsia issued by the Rome III Consensus in addition to the performing of stool parasite testing or the empiric use of antiparasitics.

  Statement 2:

When available, the urea breath test with 13 Carbon is the noninvasive method of choice for both diagnosis and confirmation of bacterial eradication Agreement level: 100%; Recommendation grade: A; Evidence level: 1A

The 13C-urea breath test is now universally accepted as the gold standard method for diagnosing and monitoring treatment of H pylori infection in adults and children over 6 years old, with sensitivity and specificity always higher than 95%( 7171. Gisbert JP, Pajares JM. 13C-urea breath test in the diagnosis of Helicobacter pylori infection - a critical review. Aliment Pharmacol Ther. 2004;20:1001-17. ). The test was validated for adults in Brazil on 1999( 2626. Coelho LG, Reber M, Passos MC, Aguiar RO, Casaes PE, Bueno ML, Yazaki FR, Castro FJ, Vieira WL, Franco JM, Castro LP. Application of isotopeselective non-dispersive infrared spectrometry for the evaluation of the 13C-urea breath test: comparison with three concordant methods. Braz J Med Biol Res. 1999;32:1493-7. ) and for adolescents and children on 2002( 106106. Kawakami E, Machado RS, Reber M, Patricio FR. 13C-urea breath test with infrared spectroscopy for diagnosing Helicobacter pylori infection in children and adolescents. J Pediatr Gastroenterol Nutr. 2002;35:39-43. ). Although highly accurate, simple and relatively cheap, the test has not yet been incorporated into daily gastroenterology practice, its use being restricted to large urban centers and for epidemiological studies. Difficulties in importing spectrometers and substrate(13C-urea), in contrast to relatively low costs of endoscopy and its histopathology in Brazil, compared to North America and Europe, are factors that have hindered the spread of their employment among us.

  Statement 3:

To perform the 13C-urea breath test, antisecretory drugs and antimicrobials must be withdrawn at least 2 and 4 weeks, respectively, prior to examination date Agreement level: 100%; Recommendation grade: A; Evidence level: 1A

Proton pump inhibitors and H2 receptor antagonists, as well as antibiotics, may induce false-negative results, and it is recommended they be suspended 2 and 4 weeks, respectively, prior to testing( 8383. Graham DY, Opekun AR, Hammoud F, Yamaoka Y, Reddy R, Osato MS, El-Zimaity HM. Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors. Am J Gastroenterol. 2003;98:1005-9. ). False-positive results are seldom observed and may occur in patients undergoing surgery for gastric resection or individuals with oral flora rich in urease producing microorganisms retaining ingested urea in the oral cavity for a long time before swallowing( 7171. Gisbert JP, Pajares JM. 13C-urea breath test in the diagnosis of Helicobacter pylori infection - a critical review. Aliment Pharmacol Ther. 2004;20:1001-17. ).

  Statement 4:

If the breath test is not available, fecal antigen test is the noninvasive method of choice for both diagnosis and confirmation of H pylori eradication, provided a monoclonal antibody is used Agreement level: 100%; Recommendation grade: A; Evidence level: 1A

Although H pylori is seldom cultured in feces, the presence of antigens in fecal material can be determined by enzyme immunoassays using monoclonal antibodies in particular. The Maastricht IV Consensus acknowledged the role of testing for fecal antigens in diagnosing infection and their usefulness in cure control, but only in tests based on the ELISA format with a monoclonal antibody as reagent( 132132. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report. Gut. 2012; 61:646-64. ). A Brazilian study showed that the test using monoclonal antigens is accurate for diagnosing infection in children under 7 years of age, although local validation is needed to determine the optimal cutoff point( 163163. Raguza D, Machado RS, Ogata SK, Patrício FR, Kawakami E. Validation of a monoclonal stool antigen test for diagnosing Helicobacter pylori infection in young children. J Pediatr Gastroenterol Nutr. 2010;50:400-3. ).

Quick, easy to perform, tests using immunochromatography in fecal samples in studies conducted in Europe and Asia, showed limited accuracy, especially because of their low positive predictive values( 1616. Calvet X, Lario S, Ramírez-Lázaro MJ, Montserrat A, Quesada M, Reeves L, Masters H, Suárez-Lamas D, Gallach M, Miquel M, Martínez-Bauer E, Sanfeliu I, Segura F. Accuracy of monoclonal stool tests for determining cure of Helicobacter pylori infection after treatment. Helicobacter. 2010;15:201-5. , 184184. Schwarzer A, Lottspeich C, Rüssmann H, Ossiander G, Koletzko S. Evaluation of a novel rapid one-step monoclonal chromatographic immunoassay for detection of Helicobacter pylori in stool from children. Eur J Clin Microbiol Infect Dis. 2007;26:475-80. ). However, the predictive values of the tests depend on the sensitivity and specificity (inherent features of the tests), but also the prevalence of the disease in the population studied. A Brazilian study evaluating patients not undergoing treatment for H pylori infection found 88% (95% CI: 75.7 to 95.5) and positive predictive value of 87.5% (95% CI: 74.7 to 95.3) negative predictive value( 189189. Silva JMK, Villares CA, Monteiro MS, Colaúto C, Santos AF, Mattar R. Validation of a rapid stool antigen test for diagnosis of Helicobacter pylori infection. Rev Inst Med Trop Sao Paulo. 2010;52:125-8. ). Further studies using the immune-chromatographic method, before and after treatment of H pylori infection, are needed to define its real accuracy among us. Difficulties in testing and collecting feces, moderately high cost and questionable acceptability by patients have hampered fecal antigen research in our midst.

  Statement 5:

Serologic testing is reserved for epidemiological studies and in special situations and should always be locally validated Agreement level: 100%; Recommendation grade: A; Evidence level: 2

Individuals infected by H pylori develop specific antibodies in the serum against this microorganism. In general, testing by ELISA is used the most. Although useful in epidemiological studies they are not useful for diagnosing an active infection, because patients who had the bacteria eradicated may remain seropositive for years. In a Brazilian study, 83/130 (64%) patients with a peptic ulcer were still seropositive 6.4 years after eradication of the microorganism( 2525. Coelho LG, Passos MCF, Cunha FAF, Galizzi HO, Araújo Jr AR, Fernandes MLM, Borges JM, Albuquerque DL, Lustosa-Cabral G, Castro LP. Helicobacter pylori reinfection rates and serological evaluation in a 6.4 years follow-up study from an emerging country. Gut. 1999;45(Suppl 111):A110. ). In addition to epidemiological studies, serologic tests are recommended in situations where other tests have dubious results, such as recent use of antisecretors or antimicrobials, digestive bleeding, atrophy and gastric cancer( 132132. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report. Gut. 2012; 61:646-64. ). The presence of specific anti-H pylori antibodies can also be demonstrated in other organic fluids such as urine and saliva.

The specificity of most serological tests is greater than 90%, but their sensitivity ranges from 60 to 90%, with accuracy being 80-84%. All serological tests must be locally validated( 137137. Mégraud F, Lehours P. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev. 2007;20:280-322. , 186186. Selgrad M, Kandulski A, Malfertheiner P. Helicobacter pylori: diagnosis and treatment. Curr Opin Gastroenterol. 2009;25:549-56. ). In Brazil, validation studies have been performed in Campinas and Belo Horizonte( 146146. Monici LT, Nishimura NF, Hara NH, Zeitune JMR. Validação de um método imunoenzimático para detecção da infecção pelo Helicobacter pylori. J etr Patol. 1999;35:65-70. , 169169. Rocha GA, Oliveira AM, Queiroz DM, Mendes EM, Moura SB, Oliveira CA, Ferrari TC. Serodiagnosis of Helicobacter pylori intection by Cobas Core ELISA in adults from Minas Gerais, Brazil. Braz J et Biol Res. 1998;31:1263-8. ). Less used in daily practice, research on serum antibodies reactive to CagA protein can be used to detect samples of bacteria carrying the CagA gene. Commercially available in the early 2000, it was validated in Brazil in 2004( 168168. Rocha AM, Rocha GA, Leite JL, Lisboa RLL, Silva PVO, Queiroz DMM. Inmunoblotting for the serodiagnosis of Helicobacter pylori infection in Brazilian patients with and without gastric carcinoma. Mem Inst Oswaldo Cruz. 2004;99:189-93. ) . As anti-H pylori detected by immunoblotting, especially anti-CagA, can remain in plasma longer (even years after H pylori eradication) than those identified immunoenzymatically, they seem to be the most sensitive method for detecting past infection by H pylori ( 9393. Ho B, Marshall BJ. Accurate diagnosis of Helicobacter pylori. Serologic testing. Gastroenterol Clin North Am. 2000;29:853-62. ).

  Statement 6:

Upper endoscopy in dyspeptic patients, when indicated, should be accompanied by a collection of fragments for study. It is recommended that at least one sample of gastric antrum and corpus should be collected, and the urease test and/or histological examination be performed using H&E staining, and another, to better identify H pylori (Giemsa, for example). Wherever possible, antisecretory drugs (proton pump inhibitors and H2 receptor antagonists) and antimicrobials must be suspended for two and four weeks, respectively. Level of concordance: 93%-100%; Recommendation grade: A; Evidence level: 1A-1B

Digestive endoscopy in patients with dyspeptic complaints is usually indicated in those over 40 years of age or in the presence of alarm symptoms (weight loss, anemia, bleeding, dysphagia, visceral or abdominal masses, etc.). Endoscopy should always be accompanied by gastric biopsies. Although histological evaluation is ideally as that advocated by the updated Sydney system( 4141. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International Workshop on the Histopathology of Gastritis, Houston, 1994. Am J Surg Pathol. 1996;20:1161-81. ), the Consensus agrees that in order to identify H pylori in dyspeptic patients under practical circumstances, collecting at least one antrum and one gastric corpus sample is accepted. There is no specific staining for histological diagnosis for the presence of H pylori. Classical hematoxylin and eosin (H-E) staining used for the gastric histology study does not provide a good contrast between the bacterium and the gastric mucus. Therefore, using additional staining with acidophilic features capable of coloring the organism and not primarily the gastric mucus where it is found is recommended. Among the various existing stains, one of the most recommended because of its simplicity and low cost is Giemsa staining( 5252. Fallone CA, Loo VG, Lough L, Barkun AN. Hematoxylin and eosin staining of gastric tissue for the detection of Helicobacter pylori. Helicobacter. 1997;2:32-5. , 115115. Laine L, Lewin DN, Naritoku W, Cohen H. Prospective comparison of the H&E, Giemsa and Genta stains for the diagnosis of Helicobacter pylori. Gastrointest Endosc. 1997;45:463-7. , 169169. Rocha GA, Oliveira AM, Queiroz DM, Mendes EM, Moura SB, Oliveira CA, Ferrari TC. Serodiagnosis of Helicobacter pylori intection by Cobas Core ELISA in adults from Minas Gerais, Brazil. Braz J et Biol Res. 1998;31:1263-8. , 175175. Rotimi O, Cairns A, Gray S, Moayyedi P, Dixon MF. Histological identification of Helicobacter pylori: comparison of staining methods. J Clin Pathol. 2000;53:756-9. ). Histological diagnosis and the urease test may show up to 95% sensitivity depending on the quality of material and expertise of the examiner( 137137. Mégraud F, Lehours P. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev. 2007;20:280-322. , 197197. Tseng CA,Wang WM, Wu DC. Comparison of the clinical feasibility of three rapid urease tests in the diagnosis of Helicobacter pylori infection. Dig Dis Sci. 2005;50:449-52. ). Antisecretory drugs (H2 receptor antagonists of histamine and proton pump inhibitors) and/or previous use of bismuth or antibiotics, by reducing the bacterial load, affect the accuracy of the urease test, so, whenever possible, an interval of two and 4 weeks respectively between suspending the drugs and the test is recommended( 8383. Graham DY, Opekun AR, Hammoud F, Yamaoka Y, Reddy R, Osato MS, El-Zimaity HM. Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors. Am J Gastroenterol. 2003;98:1005-9. , 132132. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report. Gut. 2012; 61:646-64. ). Consensus held that with naïve anti-H pylori patients, where the use of antimicrobials and antisecretors can safely be discarded, a positive urease test is sufficient to diagnose infection. Meta-analysis and systematic review have shown that the presence of active or recent gastrointestinal bleeding may interfere with the urease test, reducing its sensitivity( 7575. Gisbert JP, Gisbert JL, Marcos S, Jimenez-Alonso I, Moreno-Otero R, Pajares JM. Empirical rescue therapy after Helicobacter pylori treatment failure: a 10-year single-centre study of 500 patients. Aliment Pharmacol Ther. 2008;27:346-54. ).

  Statement 7:

H pylori eradication is indicated for functional dyspepsia patients Agreement level: 93%; Recommendation grade: A; Evidence level: 1A

The benefits of eradicating H pylori for patients with functional dyspepsia symptoms are modest, with 60% to 80% of patients remaining symptomatic after treatment( 8787. Gwee KA, Teng L, Wong RK, Ho KY, Sutedja DS, Yeoh KG. The response of Asian patients with functional dyspepsia to eradication of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 2009;21:417-24. , 105105. Jin X, Li YM. Systematic review and meta-analysis from Chinese literature: the association between Helicobacter pylori eradication and improvement of functional dyspepsia. Helicobacter. 2007;12:541-6. , 145145. Moayyedi P. The health economics of Helicobacter pylori infection. Best Pract Res Clin Gastroenterol. 2007;21:347-61. ). The most recent Cochrane meta-analysis on the subject examined 21 randomized controlled studies on the role of H pylori eradication in the development of dyspeptic symptoms. It was observed a 6% to 14% therapeutic gain, suggesting that eradication of the bacteria may be useful in patients with functional dyspepsia( 143143. Moayyedi P, Soo S, Deeks J. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006;9;CD002096. ). Among us, Mazzolene et al.( 134134. Mazzoleni LE, Sander GB, Francesconi CF, Mazzoleni F, etra DM, De Bona LR, Milbradt TC, Von Reisswitz PS, Berwanger O, Bressel M, Edelweiss MI, Marini SS, Molina CG, Folador L, Lunkes RP, Heck R, Birkhan OA, Spindler BM, Katz N, Colombo Bda S, Guerrieri PP, Renck LB, Grando E, Hocevar de Moura B, Dahmer FD, Rauber J, Prolla JC. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med. 2011;171:1929-36. ), in a randomized clinical trial, analyzed 408 patients with functional dyspepsia, with improvement demonstrated in gastrointestinal symptoms (50%) with H pylori eradication in infected patients, compared with the group receiving a proton pump inhibitor in a single daily dose (37%). Cost/benefit analyses of this therapeutic option available today estimate the number needed to treat (NNT) as being between 8 and 14, i.e. 8-14 patients must be treated for a single one to benefit from improved symptoms, particularly epigastric pain( 134134. Mazzoleni LE, Sander GB, Francesconi CF, Mazzoleni F, etra DM, De Bona LR, Milbradt TC, Von Reisswitz PS, Berwanger O, Bressel M, Edelweiss MI, Marini SS, Molina CG, Folador L, Lunkes RP, Heck R, Birkhan OA, Spindler BM, Katz N, Colombo Bda S, Guerrieri PP, Renck LB, Grando E, Hocevar de Moura B, Dahmer FD, Rauber J, Prolla JC. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med. 2011;171:1929-36. , 143143. Moayyedi P, Soo S, Deeks J. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006;9;CD002096. ).

The long-term effects of eradicating H pylori in functional dyspepsia patients have also been evaluated. In a randomized controlled trial, 1,517 patients with functional dyspepsia were followed for up to 7 years after H pylori eradication. A cumulative gain over time was shown, with a 25% reduction in medical visits due to dyspeptic complaints in patients who had eradicated the bacteria( 8989. Harvey RF, Lane JA, Nair P, Egger M, Harvey I, Donovan J, Murray L. Clinical trial: prolonged beneficial effect of Helicobacter pylori eradication on dyspepsia consultations - the Bristol Helicobacter Project. Aliment Pharmacol Ther. 2010;32:394-400. ). H pylori eradication in patients with functional dyspepsia is now a consensus recommendation established by leading experts in different regions of the world( 132132. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report. Gut. 2012; 61:646-64. , 141141. Miwa H, Ghoshal UC, Gonlachanvit S, Gwee KA, Ang TL, Chang FY, Fock KM, Hongo M, Hou X, Kachintorn U, Ke M, Lai KH, Lee KJ, Lu CL, Mahadeva S, Miura S, Park H, Rhee PL, Sugano K, Vilaichone RK, Wong BC, Bak YT. Asian consensus report on functional dyspepsia. J Neurogastroenterol Motil. 2012;18:150-68. , 192192. Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada JR, Stanghellini V. Functional gastroduodenal disorders. Gastroenterology. 2006;130:1466-79. , 207207. World Gastroenterology Organization - Global Guideline: Helicobacter pylori in developing countries. J Clin Gastroenterol. 2011;45:383-8. ).

  Statement 8:

Eradication of H pylori is the first therapeutic alternative in functional dyspepsia Agreement level: 86.2%; Recommendation grade: A; Evidence level: 1A

Functional dyspepsia treatment is still unsatisfactory for many patients, with the different approaches providing little significant therapeutic gain. While H pylori eradication promotes an 8%-14% therapeutic gain, rates achieved using proton pump inhibitors vary between 7% and 10%. Less consistent data having similar results are also obtained using prokinetic agents, H2 blocker antagonists, tricyclic antidepressants and serotonin reuptake inhibitors( 112112. Lacy BE, Talley NJ, Locke GR 3rd, Bouras EP, DiBaise JK, El-Serag HB, Abraham BP, Howden CW, Moayyedi P, Prather C. Review article - Current treatment options and management of functional dyspepsia. Aliment Pharmacol Ther. 2012;36:3-15. ). Recent evidence has demonstrated the long-term effects of H pylori eradication in reducing consultations for dyspeptic complaints( 8989. Harvey RF, Lane JA, Nair P, Egger M, Harvey I, Donovan J, Murray L. Clinical trial: prolonged beneficial effect of Helicobacter pylori eradication on dyspepsia consultations - the Bristol Helicobacter Project. Aliment Pharmacol Ther. 2010;32:394-400. , 129129. Maconi G, Sainaghi M, Molteni M, Bosani M, Gallus S, Ricci G, Alvisi V, Porro GB. Predictors of long-term outcome of functional dyspepsia and duodenal ulcer after successful Helicobacter pylori eradication in a 7-year follow-up study. Eur J Gastroenterol Hepatol. 2009;21:387-93. ). Cost-effectiveness analyses show variations in different regions of the world, depending on differing factors, with the best results obtained in regions where the infection is highly prevalent. Thus, studies in Asia and Brazil have shown benefit in the treatment of infection with NNT of 3.6 to 13 and 8 respectively( 8787. Gwee KA, Teng L, Wong RK, Ho KY, Sutedja DS, Yeoh KG. The response of Asian patients with functional dyspepsia to eradication of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 2009;21:417-24. , 105105. Jin X, Li YM. Systematic review and meta-analysis from Chinese literature: the association between Helicobacter pylori eradication and improvement of functional dyspepsia. Helicobacter. 2007;12:541-6. , 134134. Mazzoleni LE, Sander GB, Francesconi CF, Mazzoleni F, etra DM, De Bona LR, Milbradt TC, Von Reisswitz PS, Berwanger O, Bressel M, Edelweiss MI, Marini SS, Molina CG, Folador L, Lunkes RP, Heck R, Birkhan OA, Spindler BM, Katz N, Colombo Bda S, Guerrieri PP, Renck LB, Grando E, Hocevar de Moura B, Dahmer FD, Rauber J, Prolla JC. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med. 2011;171:1929-36. , 145145. Moayyedi P. The health economics of Helicobacter pylori infection. Best Pract Res Clin Gastroenterol. 2007;21:347-61. ). Additional advantages of this procedure include reduced transmission of the infection and its main clinical sequelae, peptic ulcer and gastric cancer.

  Statement 9:

The test-and-treat strategy, using noninvasive testing and treating the infected individuals, should be considered in adults under 35 years of age, with no alarm signs and no family history of gastric cancer Agreement level: 100%; Recommendation grade: A; Evidence level: 1B

Several strategies have been suggested for young patients up to 35 years of age with no alarm symptoms, nor a family history of gastric cancer. Patients' history and physical examination are neither sensitive nor specific enough to predict which patients' dyspeptic organic nosology will be detected y endoscopy( 144144. Moayyedi P, Talley NJ, Fennerty MB, Vakil N. Can the clinical history distinguish between organic and functional dyspepsia? JAMA. 2006;295:1566-76. , 200200. Value of the unaided clinical diagnosis in dyspeptic patients in primary care. Am J Gastroenterol. 2001;96:1417-21. ). The low prevalence of cancer in this population and the high rate of irrelevant findings on endoscopy have encouraged the use of empirical treatment (H pylori eradication or a cycle with proton pump inhibitors) before performing an invasive and relatively costly procedure (upper endoscopy with biopsies). A Cochrane Collaboration review showed that, in the absence of alarm symptoms, the test-and-treat strategy is more effective than an initial endoscopy and empiric use of proton pump inhibitors( 3939. Delaney B, Ford AC, Forman D, Moayyedi P, Qume M. Initial management strategies for dyspepsia. Cochrane Database Syst Rev. 2005;(4):CD001961. ). The review also showed that the test-and-treat strategy was cheaper than the initial endoscopy. The non-invasive approach for initial diagnosis of H pylori infection can be performed using the labeled urea breath test, fecal antigen test or serology. Although serology is unable to define the presence of active infection, in areas where infection is highly prevalent its positivity has a high positive predictive value, and is considered an acceptable diagnostic alternative. The most commonly used serological tests are those performed by ELISA, as previously validated in Brazil( 146146. Monici LT, Nishimura NF, Hara NH, Zeitune JMR. Validação de um método imunoenzimático para detecção da infecção pelo Helicobacter pylori. J etr Patol. 1999;35:65-70. , 169169. Rocha GA, Oliveira AM, Queiroz DM, Mendes EM, Moura SB, Oliveira CA, Ferrari TC. Serodiagnosis of Helicobacter pylori intection by Cobas Core ELISA in adults from Minas Gerais, Brazil. Braz J et Biol Res. 1998;31:1263-8. ). To control bacteria eradication in the test-and-treat strategy, only the labeled urea breath test and a fecal antigen survey are recommended, both of which have also been validated in Brazil already( 2626. Coelho LG, Reber M, Passos MC, Aguiar RO, Casaes PE, Bueno ML, Yazaki FR, Castro FJ, Vieira WL, Franco JM, Castro LP. Application of isotopeselective non-dispersive infrared spectrometry for the evaluation of the 13C-urea breath test: comparison with three concordant methods. Braz J Med Biol Res. 1999;32:1493-7. , 189189. Silva JMK, Villares CA, Monteiro MS, Colaúto C, Santos AF, Mattar R. Validation of a rapid stool antigen test for diagnosis of Helicobacter pylori infection. Rev Inst Med Trop Sao Paulo. 2010;52:125-8. ).

  Statement 10:

Eradication control should be done at least 4 weeks after treatment ends Agreement level: 100%; Degree of recommendation: B; Evidence level: 2B

Infection cure control should be performed in no less than 4 weeks to avoid the occurrence of false-negatives( 130130. Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56:772-81. ). The 13C-urea breath test is the ideal noninvasive method for achieving eradication control. It is highly sensitive and specific, moderate cost, and is gradually becoming available in Brazil. Testing for fecal antigens has also been used with excellent results. If neither the breath test or fecal antigen test is available, or an endoscopic evaluation is needed (gastric ulcer, MALT lymphoma, etc.), eradication control can be done by endoscopy, studying the bacteria in histological sections and with the urease test, using fragments of the antrum and gastric corpus in this situation. The quantitative serology is not an established method for confirming bacterial eradication.

  Statement 11:

Eradication control should be done in patients with gastroduodenal ulcer, MALT lymphoma after an early gastric cancer resection and in patients with persistent symptoms after undergoing the test-and-treat strategy Agreement level: 100; Recommendation grade: D; Evidence level: 5

Although from the pharmacological monitoring standpoint eradication control should be performed on all patients undergoing anti-H pylori, the Consensus held that eradication confirmation always be sought, at least in patients with gastroduodenal ulcer, MALT lymphoma after early gastric cancer resection and in those with persistent symptoms after undergoing the test-and-treat strategy.

GROUP 2. H pylori, GASTRIC ADENOCARCINOMA AND MALT LYMPHOMA

  Statement 12:

H pylori is the single most relevant risk factor for gastric adenocarcinoma and MALT lymphoma Agreement level: 100%; Recommendation grade: A; Evidence level: 1A

Infection by H pylori is today the greatest risk factor for developing stomach adenocarcinoma and has, since 1994, been considered a type 1 carcinogen (defined) for developing gastric cancer in humans( 100100. IARC Working Group. IARC working group on the evaluation of carcinogenic risks to humans: some industrial chemicals Lyon, 15-22 February 1994. IARC Monogr Eval Carcinog Risks Hum. 1994;60:1-560. ). Current epidemiological evidence confers an 18.3 to 21 times higher risk in infected compared to uninfected individuals, especially in distal gastric cancer( 77. Bornschein J, Selgrad M, Warnecke M, Kuester D, Wex T, Malfertheiner P. H. pylori infection is a key risk factor for proximal gastric cancer. Dig Dis Sci. 2010;55:3124-31. , 1010. Brenner H, Arndt V, Stegmaier C, Ziegler H, Rothenbacher D. Is Helicobacter pylori infection a necessary condition for noncardia gastric cancer? Am J Epidemiol. 2004;159:252-8. , 4646. Ekström AM, Held M, Hansson LE, Engstrand L, Nyrén O. Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection. Gastroenterology. 2001;121:784-91. ). Experimental evidence and animal models have demonstrated a causal relationship between infection with H pylori and development of lesions leading to gastric cancer( 8888. Hagiwara T, Mukaisho K, Nakayama T, Sugihara H, Hattori T. Long-term proton pump inhibitor administration worsens atrophic corpus gastritis and promotes adenocarcinoma development in Mongolian gerbils infected with Helicobacter pylori. Gut. 2011;60:624-30. , 204204. Wei J, Nagy TA, Vilgelm A, Zaika E, Ogden SR, Romero-Gallo J, Piazuelo MB, Correa P, Washington MK, El-Rifai W, Peek RM, Zaika A. Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. Gastroenterology. 2010;139:1333-43. ). It is accepted that the microorganism takes part in the development of gastric cancer through direct action by its virulent factors, with the most recognized among them being the CagA oncoprotein, or, indirectly, through the initiation and maintenance of chronic inflammation in the gastric mucosa. Despite the advancement of knowledge, there is no specific recommendation to search for the presence of bacterial virulence factors in daily practice. Recently, experimental studies in mice colonized with H felis have added other alternatives to the epithelial theory for gastric carcinogenesis. In this study, after becoming atrophic the infected gastric mucosa would be colonized by bone marrow stem cells that would differentiate into intestinal cells thus giving sequence to the intestinal metaplasia cascade, dysplasia and intraepithelial cancer( 9595. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306:1568-71. ).

Host factors also influence the risk of developing gastric adenocarcinoma, especially those related to the presence of cytokine polymorphisms. After initial studies involving increased risk of gastric atrophy and gastric cancer in patients with IL-1b polymorphisms, other genes have been implicated, especially IL-10, interferon-gamma, IL-8 and tumor necrosis factor( 22. Amieva MR, El-Omar EM. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology. 2008;134:306-23. , 4848. El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, Stanford JL, Mayne ST, Goedert J, Blot WJ, Fraumeni JF Jr, Chow WH. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology. 2003;124:1193-201. , 9494. Hou L, El-Omar EM, Chen J, Grillo P, Rabkin CS, Baccarelli A, Yeager M, Chanock SJ, Zatonski W, Sobin LH, Lissowska J, Fraumeni JF Jr, Chow WH. Polymorphisms in Th1-type cell-mediated response genes and risk of gastric cancer. Carcinogenesis. 2007;28:118-23. ). However, from a clinical standpoint, so far no specific markers exist to be investigated in the search for increased risk of developing gastric cancer.

Nutritional and environmental factors also play a part in gastric cancer development, including smoking, alcohol consumption, salt, salty foods and N-nitroso compounds, among others. Increasing fruit and vegetable consumption continues to be considered a factor capable of lowering the risk of developing gastric cancer, although recent prospective studies have not been able to confirm this effect( 8181. González CA, Pera G, Agudo A, Bueno-de-Mesquita HB, Ceroti M, Boeing H, Schulz M, Del Giudice G, Plebani M, Carneiro F, Berrino F, Sacerdote C, Tumino R, Panico S, Berglund G, Simán H, Hallmans G, Stenling R, Martinez C, Dorronsoro M, Barricarte A, Navarro C, Quiros JR, Allen N, Key TJ, Bingham S, Day NE, Linseisen J, Nagel G, Overvad K, Jensen MK, Olsen A, Tjønneland A, Büchner FL, Peeters PH, Numans ME, Clavel-Chapelon F, Boutron-Ruault MC, Roukos D, Trichopoulou A, Psaltopoulou T, Lund E, Casagrande C, Slimani N, Jenab M, Riboli E. Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Cancer. 2006;118:2559-66. , 167167. Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr. 2003;78:559s-69s. ). Neither was vitamin supplementation in the diet also able to reduce the gastric cancer risk( 66. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004;364:1219-28. ). An important conclusion from recent extensive European study states that any nutritional effects on gastric cancer are strictly dependent on the presence of H pylori infection, and are minimal in its absence( 1111. Buckland G, Agudo A, Luján L, Jakszyn P, Bueno-de-Mesquita HB, Palli D, Boeing H, Carneiro F, Krogh V, Sacerdote C, Tumino R, Panico S, Nesi G, Manjer J, Regnér S, Johansson I, Stenling R, Sanchez MJ, Dorronsoro M, Barricarte A, Navarro C, Quirós JR, Allen NE, Key TJ, Bingham S, Kaaks R, Overvad K, Jensen M, Olsen A, Tjønneland A, Peeters PH, Numans ME, Ocké MC, Clavel-Chapelon F, Morois S, Boutron-Ruault MC, Trichopoulou A, Lagiou P, Trichopoulos D, Lund E, Couto E, Boffeta P, Jenab M, Riboli E, Romaguera D, Mouw T, González CA. Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am J Clin Nutr. 2010;91:381-90. , 8080. González CA, Jakszyn P, Pera G, Agudo A, Bingham S, Palli D, Ferrari P, Boeing H, del Giudice G, Plebani M, Carneiro F, Nesi G, Berrino F, Sacerdote C, Tumino R, Panico S, Berglund G, Simán H, Nyrén O, Hallmans G, Martinez C, Dorronsoro M, Barricarte A, Navarro C, Quirós JR, Allen N, Key TJ, Day NE, Linseisen J, Nagel G, Bergmann MM, Overvad K, Jensen MK, Tjonneland A, Olsen A, Bueno-de-Mesquita HB, Ocke M, Peeters PH, Numans ME, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Psaltopoulou T, Roukos D, Lund E, Hemon B, Kaaks R, Norat T, Riboli E. Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst. 2006;98:345-54. ).

The gastric MALT (mucosa-associated lymphoid tissue) lymphoma represents approximately 7% of all non-Hodgkin lymphoma and can stem from any extranodal region. At least one third of them present themselves as a gastric MALT lymphoma. Epidemiologic studies have shown its association with previous H pylori infection( 157157. Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, Orentreich N, Vogelman JH, Friedman GD. Helicobacter pylori infection and gastric lymphoma. N Engl J Med. 1994;330:1267-71. ). In vitro studies have shown that proliferation of low-grade MALT lymphomas, of stomach B cells, can be stimulated via T-lymphocytes and cytokines by specific strains of H pylori ( 208208. Wotherspoon AC, Ortiz Hidalgo C, Falzon MR, Isaacson PG. Helicobacter pylori associated gastritis and primary B-cell gastric lymphoma. Lancet. 1991;338:1175-6. ). Because it is a rare disease, there are no prospective randomized trials to assess the effect of H pylori eradication in gastric MALT lymphoma remission. A recent systematic review evaluating 32 studies involving 1,408 patients with low-grade MALT lymphoma showed the presence of H pylori infection in 88.2% of cases and complete remission of the tumor just by eradicating the bacteria in over 75% of cases( 214214. Zullo A, Hassan C, Cristofari F, Andriani A, De Francesco V, Ierardi E, Tomao S, Stolte M, Morini S, Vaira D. Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma. Clin Gastroenterol Hepatol. 2010;8:105-10. ). A recent consensus meeting acknowledges H pylori eradication to be a first line treatment for gastric MALT lymphoma( 177177. Ruskoné-Fourmestraux A, Fischbach W, Aleman BM, Boot H, Du MQ, Megraud F, Montalban C, Raderer M, Savio A, Wotherspoon A. EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT. Gut. 2011 ;60 :747-58. ).

  Statement 13:

H pylori eradication reduces the risk of gastric cancer precursor lesions developing. Chronic active gastritis is reversed by H pylori eradication, whereas stopping Pelayo Correa's carcinogenic cascade. Agreement level: 100%; Recommendation grade: A; Evidence level: 1A

H pylori is the most important factor in the pathogenesis of chronic gastritis, which is considered an essential factor in up to 90% of cases of gastric cancer( 4141. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International Workshop on the Histopathology of Gastritis, Houston, 1994. Am J Surg Pathol. 1996;20:1161-81. ). Different studies and meta-analysis, as well as trials on animals, have shown that, in the absence of more advanced changes (atrophic gastritis and intestinal metaplasia), H pylori eradication promotes remission of inflammatory lesions in the gastric mucosa in a variable period of time( 6565. Fuccio L, Zagari RM, Eusebi LH, Laterza L, Cennamo V, Ceroni L, Grilli D, Bazzoli F. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151:121-8. , 151151. Nozaki K, Shimizu N, Ikehara Y, Inoue M, Tsukamoto T, Inada K, Tanaka H, Kumagai T, Kaminishi M, Tatematsu M. Effect of early eradication on Helicobacter pylori-related gastric carcinogenesis in Mongolian gerbils. Cancer Sci. 2003;94:235-9. , 206206. Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY, Fong DY, Ho J, Ching CK, Chen JS; China Gastric Cancer Study Group. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291:187-94. , 210210. You WC, Brown LM, Zhang L, Li JY, Jin ML, Chang YS, Ma JL, Pan KF, Liu WD, Hu Y, Crystal-Mansour S, Pee D, Blot WJ, Fraumeni JF Jr, Xu GW, Gail MH. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 2006;98:974-83. ).

  Statement 14:

Does H pylori eradication reduce/regress gastric cancer precursor lesions?YES, for atrophic gastritis of the corpus Agreement level: 100%; Recommendation grade: B; Evidence level: 2A

The carcinogenetic H pylori infection sequence (r) chronic gastritis (r) glandular atrophy (r) intestinal metaplasia (r) dysplasia (r) intestinal-type adenocarcinoma, proposed by Pelayo Correa( 3333. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process-First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992;52:6735-40. ), provides the basis for initial studies on gastric adenocarcinoma prevention based on H pylori eradication. Atrophic gastritis and intestinal metaplasia observed in H pylori infected individuals are considered preneoplastic conditions indicating increased gastric cancer risk( 9090. Hattori T. Development of adenocarcinomas in the stomach. Cancer. 1986;57:1528-34. , 198198. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784-9. ). A key issue in establishing gastric cancer prevention strategies is to define the exact point within the evolutionary cascade of chronic gastritis from which regression of histological changes after eradication of the microorganism is no longer observed. Although controversial, due to possible sampling errors, a recent meta-analysis suggests that atrophic gastritis of the corpus can reverse after H pylori eradication( 203203. Wang J, Xu L,Shi R, Huang X, Li SW, Huang Z, Zhang G. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion. 2011;83:253-60. ).

  Statement 15:

Does H pylori eradication reduce/regress gastric cancer precursor lesions?NOT for atrophic gastritis of the antrum Agreement level: 100%; Recommendation grade: B; Evidence level: 2B

Pathologists often disagree over the diagnosis of atrophic antrum gastritis. This can be explained by the smaller number of gastric glands in the normal antral mucosa( 1818. Capelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries RA, Bruno MJ, van Dekken H, Meijer J, van Grieken NC, Kuipers EJ The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-8. , 152152. Offerhaus GJ, Price AB, Haot J, ten Kate FJ, Sipponen P, Fiocca R, Stolte M, Dixon MF. Observer agreement on the grading of gastric atrophy. Histopathology. 1999;34:320-5. ). The results of H pylori eradication on atrophic gastritis are often controversial( 3838. De Vries AC, Kuipers EJ, Rauws EA. Helicobacter pylori eradication and gastric cancer: when is the horse out of the barn? Am J Gastroenterol. 2009;104:1342-5. , 102102. Islami F, Sheikhattari P, Ren JS, Kamangar F. Gastric atrophy and risk of oesophageal cancer and gastric cardia adenocarcinoma - a systematic review and meta-analysis. Ann Oncol. 2011;22:754-60. , 111111. Kodama M, Murakami K, Okimoto T, Abe T, Nakagawa Y, Mizukami K, Uchida M, Inoue K, Fujioka T. Helicobacter pylori improves gastric atrophy and intestinal metaplasia in long-term observation. Digestion. 2012;85:126-30. , 203203. Wang J, Xu L,Shi R, Huang X, Li SW, Huang Z, Zhang G. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion. 2011;83:253-60. ). A recent meta-analysis study involving 12 trials analyzing 2,648 patients with atrophic gastritis of the antrum found no significant reversibility of atrophic changes in the antrum following H pylori eradication( 203203. Wang J, Xu L,Shi R, Huang X, Li SW, Huang Z, Zhang G. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion. 2011;83:253-60. ).

  Statement 16:

Does H pylori eradication reduce/regress gastric cancer precursor lesions?NOT for intestinal metaplasia Agreement level: 100%; Recommendation grade: B; Evidence level: 2A

Intestinal metaplasia of the stomach refers to the gradual replacement of the gastric epithelium by an intestinal-type epithelium, that is, by a newly formed epithelium presenting morphological and biochemical features (under both optical and electron microscopy) of the intestinal epithelium, of either the small intestine or the colon. As such, the metaplastic epithelium may consist of different lineages of proper intestinal mucosal cells such as goblet cells, absorptive cells, Paneth cells and endocrine cells. These cells are easily identified in the gastric mucosa since they are not present in the normal gastric mucosa and their identification presents high inter-observer agreement( 1818. Capelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries RA, Bruno MJ, van Dekken H, Meijer J, van Grieken NC, Kuipers EJ The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-8. ). Although it also presents discordant studies, different studies and meta-analysis have been unable to demonstrate intestinal metaplasia regression after H pylori eradication( 113113. Lahner E, Bordi C, Cattaruzza MS, Iannoni C, Milione M, Delle Fave G, Annibale B. Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection. Aliment Pharmacol Ther. 2005;22:471-81. , 121121. Ley C, Mohar A, Guarner J, Herrera-Goepfert R, Figueroa LS, Halperin D, Johnstone I, Parsonnet J. Helicobacter pylori eradication and gastric preneoplastic conditions: a randomized, double-blind, placebo-controlled trial. Cancer Epidemiol Biomark Prev. 2004;13:4-10. , 153153. Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y, Yokoyama T, Watanabe M. Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med. 2001;134:380-6. , 172172. Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. The long-term impact of Helicobacter pylori eradication on gastric histology: a systematic review and meta-analysis. Helicobacter. 2007;12(Suppl 2):32-8. , 203203. Wang J, Xu L,Shi R, Huang X, Li SW, Huang Z, Zhang G. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion. 2011;83:253-60. , 213213. Zhou L, Sung JJ, Lin S, Jin Z, Ding S, Huang X, Xia Z, Guo H, Liu J, Chao W. A five-year follow-up study on the pathological changes of gastric mucosa after H pylori eradication. Chin Med J (Engl). 2003;116:11-4. ).

  Statement 17:

The optimal timing of H pylori eradication to prevent gastric cancer is before the appearance of preneoplastic conditions (atrophic gastritis and intestinal metaplasia) Agreement level: 100%; Recommendation grade: A; Evidence level: 1A

Intervention studies conducted in Latin America and Asia and meta-analysis have shown that H pylori eradication is an effective step in preventing gastric cancer, particularly if treatment is performed on patients prior to development of precancerous conditions (atrophic gastritis and intestinal metaplasia)( 6565. Fuccio L, Zagari RM, Eusebi LH, Laterza L, Cennamo V, Ceroni L, Grilli D, Bazzoli F. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151:121-8. , 139139. Mera R, Fontham ET, Bravo LE, Bravo JC, Piazuelo MB, Camargo MC, Correa P. Long term follow up of patients treated for Helicobacter pylori infection. Gut. 2005;54:1536-40. , 193193. Take S, Mizuno M, Ishiki K, Nagahara Y, Yoshida T, Yokota K, Oguma K, Okada H, Shiratori Y. The effect of eradicating Helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease. Am J Gastroenterol. 2005;100:1037-42. , 206206. Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY, Fong DY, Ho J, Ching CK, Chen JS; China Gastric Cancer Study Group. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291:187-94. , 210210. You WC, Brown LM, Zhang L, Li JY, Jin ML, Chang YS, Ma JL, Pan KF, Liu WD, Hu Y, Crystal-Mansour S, Pee D, Blot WJ, Fraumeni JF Jr, Xu GW, Gail MH. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 2006;98:974-83. ). Studies using animal models have also confirmed that gastric cancer development can be prevented by early eradication of the microorganism( 1414. Cai X, Carlson J, Stoicov C, Li H, Wang TC, Houghton J. Helicobacter felis eradication restores normal architecture and inhibits gastric cancer progression in C57BL/6 mice. Gastroenterology. 2005;128:1937-52. , 151151. Nozaki K, Shimizu N, Ikehara Y, Inoue M, Tsukamoto T, Inada K, Tanaka H, Kumagai T, Kaminishi M, Tatematsu M. Effect of early eradication on Helicobacter pylori-related gastric carcinogenesis in Mongolian gerbils. Cancer Sci. 2003;94:235-9. ).

  Statement 18:

Even with preneoplastic conditions already established, eradicating H pylori reduces the risk of gastric cancer Agreement level: 100%; Recommendation grade: A; Evidence level: 1C

Randomized controlled trials conducted in Colombia and China have demonstrated a beneficial effect of eradicating the bacteria even in patients with precancerous conditions( 3434. Correa P, Fontham ET, Bravo JC, Bravo LE, Ruiz B, Zarama G, Realpe JL, Malcom GT, Li D, Johnson WD, Mera R. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy. J Natl Cancer Inst. 2000;92:1881-8. , 120120. Leung WK, Lin SR, Ching JY, To KF, Ng EK, Chan FK, Lau JY, Sung JJ. Factors predicting progression of gastric intestinal metaplasia: results of a etracycli trial on Helicobacter pylori eradication. Gut. 2004;53:1244-9. , 139139. Mera R, Fontham ET, Bravo LE, Bravo JC, Piazuelo MB, Camargo MC, Correa P. Long term follow up of patients treated for Helicobacter pylori infection. Gut. 2005;54:1536-40. ). Even though the further advanced the existing preneoplastic condition is, the less likely it is that H pylori eradication will stop gastric cancer development( 3737. De Vries AC, Kuipers EJ. Review article: Helicobacter pylori eradication for the prevention of gastric cancer. Aliment Pharmacol Ther. 2007;26(Suppl 2):25-35. , 5959. Fock KM, Talley N, Moayyedi P, Hunt R, Azuma T, Sugano K, Xiao SD, Lam SK, Goh KL, Chiba T, Uemura N, Kim JG, Kim N, Ang TL, Mahachai V, Mitchell H, Rani AA, Liou JM, Vilaichone RK, Sollano J. Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol. 2008;23:351-65. ), a randomized study of patients undergoing H pylori eradication following early gastric cancer resection was able to demonstrate a reduction in the appearance of metachronous gastric cancer( 6666. Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, etracycli controlled trial. Lancet. 2008;372:392-7. ).

  Statement 19:

In Brazil, surveying and treating the population as a measure to prevent gastric cancer is not indicated Agreement level: 100%; Recommendation grade: D; Evidence level: 4

In 2008, the Asia-Pacific Consensus for Gastric Cancer Prevention recommended surveying and treating the entire populations for H pylori infection in high risk regions, defined as those where the incidence of gastric cancer in the population is higher than 20/100,000 inhabitants( 5959. Fock KM, Talley N, Moayyedi P, Hunt R, Azuma T, Sugano K, Xiao SD, Lam SK, Goh KL, Chiba T, Uemura N, Kim JG, Kim N, Ang TL, Mahachai V, Mitchell H, Rani AA, Liou JM, Vilaichone RK, Sollano J. Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol. 2008;23:351-65. ). The recently published Maastricht IV Consensus believes that this approach should be considered in other high-risk areas in the world( 132132. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report. Gut. 2012; 61:646-64. ). According to the Consensus, indication of treatment for the entire infected population is not currently recommended among us. Data on incidence and mortality of gastric cancer showed intermediate values (incidence of 13 cases to 100,000 in the male population and 7 cases per 100,000 inhabitants in the female population)( 101101. Instituto Nacional do Câncer. Estimativa 2012. Incidência de câncer no Brasil [Internet] [cited 2012 September 19]. Available from http://www.inca.gov.br/estimativa/2012/.
http://www.inca.gov.br/estimativa/2012/...
). Furthermore, epidemiological data on gastric cancer is incomplete in many regions, and non-invasive methods for diagnosing the infection are not widely available.

  Statement 20:

Indications for eradication of H pylori as a measure to prevent gastric cancer:First-degree relatives of gastric cancer carriers Agreement level: 100%; Recommendation grade: A; Evidence level: 1B After gastric resection, endoscopic or surgical adenocarcinoma Agreement level: 100%; Recommendation grade: A; Evidence level: 1B Patients with severe pangastritis, atrophic gastritis and/or intestinal metaplasia Agreement level: 100%; Recommendation grade: B: Evidence level: 1B

Meta-analysis( 173173. Rokkas T, Sechopoulos P, Robotis I, Margantinis G, Pistiolas D. Cumulative H pylori eradication rates in clinical practice by adopting first and second-line regimens proposed by the Maastricht III consensus and a third-line empirical regimen. Am J Gastroenterol. 2009;104:21-5. ) and case-control studies conducted in Asia( 188188. Shin CM, Kim N, Yang HJ, Cho SI, Lee HS, Kim JS, Jung HC, Song IS. Stomach cancer risk in gastric cancer relatives: interaction between Helicobacter pylori infection and family history of gastric cancer for the risk of stomach cancer. J Clin Gastroenterol. 2010;44:e34-e9. ), Europe( 4747. El-Omar EM, Oien K, Murray LS, El-Nujumi A, Wirz A, Gillen D, Williams C, Fullarton G, McColl KE. Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H pylori. Gastroenterology. 2000;118:22-30. , 6161. Foschi R, Lucenteforte E, Bosetti C, Bertuccio P, Tavani A, La Vecchia C, Negri E. Family history of cancer and stomach cancer risk. Int J Cancer. 2008;123:1429-32. ) and Latin America( 149149. Muñoz N, Plummer M, Vivas J, Moreno V, De Sanjosé S, Lopez G, Oliver W. A case-control study of gastric cancer in Venezuela. Int J Cancer. 2001;93:417-23. ), including Brazil( 147147. Motta CR, Cunha MP, Queiroz DM, Cruz FW, Guerra EJ, Mota RM, Braga LL. Gastric precancerous lesions and Helicobacter pylori infection in relatives of gastric cancer patients from Northeastern Brazil. Digestion. 2008;78:3-8. ), show that first-degree relatives of gastric cancer carriers have a 2 to 3 times higher risk of developing neoplasia, so search and eventual eradication of bacteria in this population is fully justified. Metachronous tumors in the gastric remnant have been described in up to 10% of patients undergoing gastric, endoscopic or surgical resection for early gastric cancer( 182182. Sano T, Sasako, M, Kinoshita, T, Maruyama, K. Recurrence of early gastric cancer. Follow-up of 1475 patients and review of the Japanese literature. Cancer. 1993;72:3174-8. , 187187. Seto Y, Nagawa H, Muto T. Impact of lymph node metastasis on survival with early gastric cancer. World J Surg. 1997;21:186-9. , 194194. Takeda J, Toyonaga A, Koufuji K, Kodama I, Aoyagi K, Yano S, Ohta J, Shirozu K. Early gastric cancer in the remnant stomach. Hepatogastroenterology. 1998;45:1907-11. ). A recent randomized controlled trial from Japan showed that eradication of H pylori in patients undergoing endoscopic resection for early gastric cancer, followed for 3 years, was able to reduce the risk of developing metachronous gastric cancer from 4 per 100 persons per year to 1.4 per 100 persons per year in the eradicated group( 6666. Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, etracycli controlled trial. Lancet. 2008;372:392-7. ). Also considered high-risk patients for development of gastric cancer are those undergoing gastric resections for benign diseases (peptic ulcer, for example) and patients carrying other gastric neoplasias such as adenoma and MALT lymphoma. Besides bacteria eradication, endoscopic monitoring at regular intervals in this population is recommended( 1717. Capelle LG, de Vries AC, Looman CW, Casparie MK, Boot H, Meijer GA, Kuipers EJ. Gastric MALT lymphoma: epidemiology and high adenocarcinoma risk in a nation-wide study. Eur J Cancer. 2008;44:2470-6. , 180180. Safatle-Ribeiro AV, Ribeiro Júnior U, Sakai P, Iriya K, Ishioka S, Gama-Rodrigues J. Gastric stump mucosa: is there a risk for carcinoma? Arq Gastroenterol. 2001;38:227-31. , 190190. Sinning C, Schaefer N, Standop J, Hirner A, Wolff M. Gastric stump carcinoma - epidemiology and current concepts in pathogenesis and treatment. Eur J Surg Oncol. 2007;33:133-9. , 195195. Tersmette AC, Offerhaus GJ, Tersmette KW, Giardiello FM, Moore GW, Tytgat GN, Vandenbroucke JP. Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions. Cancer Res. 1990 ;50 :6486-9. ).

One epidemiological study suggests that prolonged use (more than 1 year) of proton pump inhibitors might be associated with increased gastric cancer risk( 159159. Poulsen AH, Christensen S, McLaughlin JK, Thomsen RW, Sørensen HT, Olsen JH, Friis S. Proton pump inhibitors and risk of gastric cancer: a population-based cohort study. Br J etrac. 2009;100:1503-7. ). Prolonged use and high doses of antisecretories in an animal model has been capable of promoting adenocarcinoma development in H pylori infected animals, strengthening the recommendation for it to be eradicated as a measure of preventing gastric cancer in this group of individuals (see below)( 8888. Hagiwara T, Mukaisho K, Nakayama T, Sugihara H, Hattori T. Long-term proton pump inhibitor administration worsens atrophic corpus gastritis and promotes adenocarcinoma development in Mongolian gerbils infected with Helicobacter pylori. Gut. 2011;60:624-30. , 132132. Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ; European Helicobacter Study Group. Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report. Gut. 2012; 61:646-64. ).

  Statement 21:

After eradication of H pylori , the follow-up of patients carrying precancerous conditions should be done with:Endoscopic examinations with collection of two fragments from the gastric corpus and antrum Agreement level: 100%; Recommendation grade: C; Evidence level: 2B 3-year interval between endoscopic examinations for patients with atrophy and/or extensive intestinal metaplasia in the gastric antrum and corpus Agreement level: 100%; Recommendation grade: D; Evidence level: 4

The number and location of the biopsies to be taken during the endoscopic follow-up examination of patients with preneoplastic conditions is cause for major divergence, because of the lack of methodologically well-designed studies to support them. Even assuming that the technological progress of endoscopes and more comprehensive studies can substantially change this decision, the Consensus opted to follow the European recommendation to perform, at least, the removal of two fragments in the antrum and at least two fragments in the gastric corpus, in both small and large curvature( 4040. Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O'Connor A, Pereira C, Pimentel-Nunes P, Correia R, Ensari A, Dumonceau JM, Machado JC, Macedo G, Malfertheiner P, Matysiak-Budnik T, Megraud F, Miki K, O'Morain C, Peek RM, Ponchon T, Ristimaki A, Rembacken B, Carneiro F, Kuipers EJ; European Society of Gastrointestinal Endoscopy; European Helicobacter Study Group; European Society of Pathology; Sociedade Portuguesa de Endoscopia Digestiva. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy. 2012;44:74-94. ). It is also recommended that histological analysis of the fragments be made under the criteria established by the updated Sydney System( 4141. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International Workshop on the Histopathology of Gastritis, Houston, 1994. Am J Surg Pathol. 1996;20:1161-81. ) and, where possible, through it, to promote the atrophy and intestinal metaplasia graduation as recently described by systems, OLGA - Operative Link Assessment on Gastritis - and OLGIM - Operative Link on Gastritis by Intestinal Metaplasia( 1818. Capelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries RA, Bruno MJ, van Dekken H, Meijer J, van Grieken NC, Kuipers EJ The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-8. , 176176. Rugge M, Meggio A, Pennelli G, Piscioli F, Giacomelli L, De Pretis G, Graham DY. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007;56:631-6. ).

When atrophy and/or intestinal metaplasia is classified as mild or moderate and restricted to the antrum, the European group does not recommend follow-up, although the indication for H pylori eradication is formal, with a view to avoiding progression to dysplasia and cancer. Moreover, endoscopic surveillance is recommended for patients with extensive atrophy or extensive intestinal metaplasia (that is, extensive atrophy and/or extensive intestinal metaplasia in the gastric antrum and corpus); this follow-up should be done every 3 years( 4040. Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O'Connor A, Pereira C, Pimentel-Nunes P, Correia R, Ensari A, Dumonceau JM, Machado JC, Macedo G, Malfertheiner P, Matysiak-Budnik T, Megraud F, Miki K, O'Morain C, Peek RM, Ponchon T, Ristimaki A, Rembacken B, Carneiro F, Kuipers EJ; European Society of Gastrointestinal Endoscopy; European Helicobacter Study Group; European Society of Pathology; Sociedade Portuguesa de Endoscopia Digestiva. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy. 2012;44:74-94. ).

GROUP 3. H pylori AND OTHER ASSOCIATED DISORDERS

  Statement 22:

Epidemiologic and animal studies suggest an inverse relationship between H pylori infection and bronchial asthma or atopies Agreement level: 100%; Recommendation grade: B; Evidence level: 2B

Epidemiological data indicate an increasing growth in bronchial asthma and atopies. The causes of this growth, although some correlations have been described, are not fully clarified( 133133. Matricardi PM, Rosmini F, Riondino S, Fortini M, Ferrigno L, Rapicetta M, Bonini S. Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study. BMJ. 2000;320:412-7. , 191191. Strachan DP, Carey IM. Home environment and severe asthma in adolescence: a population based case-control study. BMJ. 1995;311:1053-6. ). Recent publications point to an inverse association between H pylori infection in the childhood and the development of asthma and allergic diseases in the U.S., but not in Europe( 2222. Chen Y, Blaser MJ. Inverse associations of Helicobacter pylori with asthma and allergy. Arch Intern Med. 2007;167:821-7. , 6767. Fullerton D, Britton JR, Lewis SA, Pavord ID, McKeever TM, Fogarty AW. Helicobacter pylori and lung function, asthma, atopy and allergic disease population-based cross-sectional study in adults. Int J Epidemiol. 2009;38:419-26. , 165165. Reibman J, Marmor M, Filner J, Fernandez-Beros ME, Rogers L, Perez-Perez GI, etrac MJ. Asthma is inversely associated with Helicobacter pylori status in an urban population. PloS One. 2008;3:e4060. ). However, randomized controlled trials are needed to better establish and determine the causal relationship between asthma-atopy and H pylori infection.

  Statement 23

In upper gastrointestinal bleeding secondary to peptic ulcer, H pylori eradication is more effective than antisecretory treatment alone (with or without maintenance treatment) in preventing recurrent bleeding Agreement level: 100%; Recommendation grade: A; Evidence level: 1A

Randomized studies and meta-analysis have demonstrated that, in patients carrying a peptic ulcer complicated with upper digestive bleeding, H pylori infection treatment was more effective than antisecretory treatment without eradication (with or without long-term antisecretory treatment) in preventing recurrent bleeding. Therefore all patients with peptic ulcer bleeding must be tested for H pylori and eradication treatment should be prescribed for infected patients( 7070. Gisbert JP, Khorrami S, Carballo F, Calvet X, Gene E, Dominguez-Muñoz E. .Meta-analysis: Helicobacter pylori eradication therapy vs antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. Aliment Pharmacol Ther. 2004;19:617-29. , 125125. Liu CC, Lee CL, Chan CC, Tu TC, Liao CC, Wu CH, Chen TK. Maintenance treatment is not necessary after Helicobacter pylori eradication and healing of bleeding peptic ulcer: a 5-year prospective, randomized, controlled study. Arch Intern Med. 2003;163:2020-4. ).

  Statement 24:

Regarding the role of H pylori and the occurrence of upper gastrointestinal bleeding in users of NSAIDs and aspirin:H pylori eradication reduces the risk of peptic ulceration and bleeding in patients on chronic use of NSAIDs and aspirin Agreement level: 100%; Recommendation grade: A; Evidence level: 2A In patients on long-term use of NSAIDs, with a history of peptic ulcer disease, the mere eradication of H pylori is not sufficient to prevent recurrence of the ulcer and/or bleeding Agreement level: 100%; Recommendation grade: A; Evidence level: 1B Testing for and eradicating H pylori is indicated, prior to treatment with long-term aspirin in patients at high risk for peptic ulcer disease or complications Agreement level: 100%; Recommendation grade: A; Evidence level: 2B H pylori eradication reduces the risk of recurrent bleeding in patients taking aspirin long term and with a history of gastrointestinal peptic ulcer bleeding Agreement level: 100%; Recommendation grade: B; Evidence level: 1B

The relationship between H pylori infection and NSAID users and gastroduodenal pathology is complex, since both are risk factors for digestive bleeding. On its own, H pylori infection increases this risk 1.78 times and NSAID 4.89 times. The risk of a bleeding ulcer increases 6.13 times when both are present( 9797. Huang JQ, Shidhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease:a meta-analysis. Lancet. 2002;359:14-22. ).

It is well established that the risk of association between NSAIDs and peptic disease and its complications, also depends on other risk factors inherent to the patient, including advanced age, presence of co-morbidities, concomitant drugs, smoking and a history of peptic ulcer disease and bleeding( 126126. Loke YK, Trivedi AN, Singh S. Meta-analysis gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther. 2008;27:31-40. , 205205. Weil J, Langman MJ, Wainwright P, Lawson DH, Rawlins M, Logan RF, Brown TP, Vessey MP, Murphy M, Colin-Jones DG. Peptic ulcer bleeding:accessory risk factors and interactions with non-steroidal anti-inflammatory drugs. Gut. 2000;46:27-31. ). The risk of NSAIDs causing ulceration and bleeding also varies with the toxicity, dosage and duration of the medication used( 185185. Seager JM, Hawkey CJ. ABC of the upper gastrointestinal tract: indigestion and non-steroidal anti-inflammatory drugs. BMJ. 2001;323:12369. ).

For primary prevention of peptic ulcer and complications, H pylori eradication before starting NSAIDs significantly diminishes its occurrence as well as bleeding, despite concomitant use of proton pump inhibitors( 2020. Chan FK, To KF, Wu JC, Yung MY, Leung WK, Kwok T, Hui Y, Chan HL, Chan CS, Hui E, Woo J, Sung JJ. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomized trial. Lancet. 2002;359:9-13. , 201201. Vergara M, Catalán M, Gisbert JP, Calvet X. Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users. Aliment Pharmacol Ther. 2005;21:1411-8. ).

In patients taking NSAIDs for a long time, merely eradicating H pylori is not sufficient to eliminate the risk of peptic ulceration and bleeding. In this scenario, using a proton pump inhibitor is better than simply eradicating the bacteria( 1919. Chan FK, Chung SC, Suen BY, Lee YT, Leung WK, Leung VK, Wu JC, Lau JY, Hui Y, Lai MS, Chan HL, Sung JJ. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med. 2001;344:967-73. ). The best protection for the patient in these cases is to apply both, namely, the proton pump inhibitor and eradicating H pylori ( 2020. Chan FK, To KF, Wu JC, Yung MY, Leung WK, Kwok T, Hui Y, Chan HL, Chan CS, Hui E, Woo J, Sung JJ. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomized trial. Lancet. 2002;359:9-13. ).

The risk of bleeding in patients taking aspirin is dose-related and irrespective of formulation( 109109. Kelly JP, Kaufman DW, Jurgelon JM, Sheehan J, Koff RS, Shapiro S. Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product. Lancet. 1996;348:1413-6. ). Gastrointestinal bleeding risk in aspirin users is increased in H pylori infected patients (OR = 4.7) and those with a history of ulcers (OR = 15.2)( 117117. Lanas A, Fuentes J, Benito R, Serrano P, Bajador E, Sáinz R. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther. 2002;16:779-86. , 158158. Pilotto A, Franceschi M, Longoa MG, Scarcelli C, Orsitto G, Perri FC, D'Ambrosio LP, Leandro G. Helicobacter pylori infection and the prevention of peptic ulcer with proton pump inhibitors in elderly subjects taking low-dose aspirin. Dig Liver Dis. 2004;36:666-70. ). Eradicating H pylori as the primary prevention role prior to using aspirin is not well established in all patients, but it is reasonable and justifiable in patients with other risk factors for ulcers and digestive bleeding( 118118. Lanas A, Scheiman J. Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment. Curr Med Res Opin. 2007;23:163-73. ).

H pylori eradication in patients on long-term treatment with acetylsalicylic acid and with a history of ulcers and intestinal bleeding effectively reduces the risk of rebleeding. The best approach in these cases, besides eradicating H pylori, is to indicate the maintenance use of proton pump inhibitors( 1919. Chan FK, Chung SC, Suen BY, Lee YT, Leung WK, Leung VK, Wu JC, Lau JY, Hui Y, Lai MS, Chan HL, Sung JJ. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med. 2001;344:967-73. , 114114. Lai KC, Lam SK, Chu KM, Wong BC, Hui WM, Hu WH, Lau GK, Wong WM, Yuen MF, Chan AO, Lai CL, Wong J. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med. 2002;346:2033-8. ).

  Statement 25:

H pylori should be eradicated in patients with idiopathic thrombocytopenic purpura Agreement level: 100%; Recommendation grade: B; Evidence level: 3A

Meta-analysis and systematic reviews have shown a 50% increase in platelet count in patients with idiopathic thrombocytopenic purpura who underwent H pylori eradication. The exact mechanism by which this response is achieved remains unknown( 33. Arnold DM, Bernotas A, Nazi I, Stasi R, Kuwana M, Liu Y, Kelton JG, Crowther MA. Platelet count response to H pylori treatment in patients with immune thrombocytopenic purpura with and without H pylori infection: a systematic review. Haematologica. 2009;94:850-6. , 6262. Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D. Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta-analysis. J Antimicrobial Chem. 2007;60:237-46. , 6868. Gao X-Z, Qiao X-L, Song W-C, Wang X-F, Liu F. Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication. World J Gastroenterol. 2010;16:4357-62. ).

  Statement 26:

H pylori infection may be a risk factor for deficit hemoglobin, decreased levels of ferritin and iron deficiency anemia Agreement level: 100%; Recommendation grade: B; Evidence level: 2A

Studies suggest an association between H pylori and iron deficiency anemia, especially in risk groups with a relatively high demand for iron, such as children and adult women. H pylori eradication is recommended in these cases where the iron deficiency anemia etiology cannot be determined( 9898. Huang X, Qu X, Yan W, Huang Y, Cai M, Hu B, Wu L, Lin H, Chen Z, Zhu C, Lu L, Sun X, Rong L, Jiang Y, Sun D, Zhong L, Xiong P. Iron deficiency anaemia can be improved after eradication of Helicobacter pylori. Postgrad Med J. 2010;86:272-8. , 148148. Muhsen K, Cohen D. Helicobacter pylori infection and iron stores: a systematic review and meta-analysis. Helicobacter. 2008;13:323-40. , 161161. Qu XH, Huang XL, Xiong P, Zhu CY, Huang YL, Lu LG, Sun X, Rong L, Zhong L, Sun DY, Lin H, Cai MC, Chen ZW, Hu B, Wu LM, Jiang YB, Yan WL. Does Helicobacter pylori infection play a role in iron deficiency anemia? A meta-analysis. World J Gastroenterol. 2010;16:886-96. , 211211. Yuan W, Li Yumin, Yang Kehu, Ma Bin, Guan Quanlin, Wang D, Yang L. Iron deficiency anemia in Helicobacter pylori infection: meta-analysis of randomized controlled trials. Scand J Gastroenterol. 2010;45:665-76. ).

  Statement 27:

Eradication of H pylori does not favor the appearance of GERD Agreement level: 100%; Recommendation grade: B; Evidence level: 1B

The H pylori treatment does not seem to worsen GERD symptoms, or induce erosive esophagitis. H pylori should be eradicated and searched in GERD patients who require chronic use of proton pump inhibitors( 142142. Moayyedi P, Bardhan C, Young L, Dixon MF, Brown L, Axon AT. Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease. Gastroenterology. 2001;121:1120-6. , 178178. Saad AM, Choudhary A, Bechtold ML. Effect of Helicobacter pylori treatment on gastroesophageal reflux disease (GERD): meta-analysis of randomized controlled trials. Scand J Gastroenterol. 2012;47:129-35. , 209209. Yaghoobi M, Farrokhyar F, Yuan Y, Hunt RH. Is there an increased risk of GERD after Helicobacter pylori eradication? A meta-analysis. Am J Gastroenterol. 2010;105:1007-13. ).

GROUP 4. H pylori, TREATMENT AND RETREATMENT

  Statement 28:

The conventional triple therapy (a proton pump inhibitor at standard dose, amoxicillin 1.0 g, and clarithromycin 0.5 g, administered twice daily for 7 days) is the first treatment option Agreement level: 100%; Recommendation grade: A; Evidence level: 1A

The triple therapy is still the most used and recommended worldwide and also in Brazil( 44. Assem M, El Azab G, Rasheed MA, Abdelfatah M, Shastery M. Efficacy and safety of levofloxacin, clarithromycin and csomeprazol as first line triple therapy for Helicobacter pylori eradication in Middle East. Prospective, randomized, blind, comparative, multicenter study. Eur J Int Med. 2010;21:310-4. , 1313. Buzás GM. First-line eradication of Helicobacter pylori: are the standard triple therapies obsolete? A different perspective. World J Gastroenterol. 2010;16:3865-70. , 2929. Coelho LG, Mattos AA, Francisconi CF, Castro LP, André SB. Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg, twice daily for 7 days, in the eradication of Helicobacter pylori in patients with peptic ulcer. Arq Gastroenterol. 2004;41:71-6. , 3131. Coelho LG, Zaterka S; Representantes indicados pela Federação Brasileira de Gastroenterologia e Núcleo Brasileiro para o Estudo do Helicobacter II Consenso Brasileiro sobre Helicobacter pylori. Arq Gastroenterol. 2005;42:128-32. , 5454. Felga G, Silva FM, Barbuti RC, Navarro-Rodriguez T, Zaterka S, Eisig JN. Clarithromycin-based triple therapy for Helicobacter pylori treatment in peptic ulcer patients. J Infect Dev Ctries. 2010;4:712-6. , 6868. Gao X-Z, Qiao X-L, Song W-C, Wang X-F, Liu F. Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication. World J Gastroenterol. 2010;16:4357-62. , 124124. Liou JM, Lin JT, Chang CY, Chen MJ, Cheng TY, Lee YC, Chen CC, Sheng WH, Wang HP, Wu MS. Levofloxacin-based and clarithromycin-based triple therapies as first-line and second-line treatments for Helicobacter pylori infection: a etracycli comparative trial with crossover design. Gut. 2010;58:572-8. , 134134. Mazzoleni LE, Sander GB, Francesconi CF, Mazzoleni F, etra DM, De Bona LR, Milbradt TC, Von Reisswitz PS, Berwanger O, Bressel M, Edelweiss MI, Marini SS, Molina CG, Folador L, Lunkes RP, Heck R, Birkhan OA, Spindler BM, Katz N, Colombo Bda S, Guerrieri PP, Renck LB, Grando E, Hocevar de Moura B, Dahmer FD, Rauber J, Prolla JC. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med. 2011;171:1929-36. , 166166. Ribeiro LT, Lima LMSTB, Costa-Neto JW, Mota RMG, Luz NMLM, Marinho JR, Veras DM, Wanderley VE. Comparação entre quatro esquemas tríplices para o tratamento do Helicobacter pylori: estudo prospectivo, randomizado, multicêntrico. GED Gastroenterol Endosc Dig. 2004;23:101-6. , 207207. World Gastroenterology Organization - Global Guideline: Helicobacter pylori in developing countries. J Clin Gastroenterol. 2011;45:383-8. ). Its effectiveness basically depends on rates of resistance to clarithromycin and is not recommended in areas where these rates among the population are higher than 20%. The few Brazilian studies on clarithromycin resistance show rates below this value( 4545. Eisig JN, Silva FM, Barbuti RC, Navarro-Rodrigues T, Moraes-Filho JP, Pedrazzoli Jr J. Helicobacter pylori antibiotic resistance in Brazil: clarithromycin is still a good option. Arq Gastroenterol. 2011;48:261-4. , 7878. Godoy AP, Ribeiro ML, Benvengo YH, Vitiello L, Miranda Mde C, Mendonça S, Pedrazzoli J Jr. Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates. BMC Gastroenterol. 2003;3(8):20. , 123123. Lins AK, Lima RA, Magalhães M. Clarithromycin-resistant Helicobacter pylori in Recife, Brazil, directly identified from gastric biopsies by polymerase chain reaction. Arq Gastroenterol. 2010;47:379-82. , 160160. Prazeres-Magalhaes P, Queiroz DMM, Campos DVB, Rocha GA, Mendes EM, Santos A, Correa PRV, Rocha AMC, Teixeira LM, Oliveira CA. Helicobacter pylori primary resistance to metronidazole and clarithromycin in Brazil. Antimicrob Agents Chemother. 2002;46:2021-3. ). While not outstanding, in the last 10 years this regimen has shown eradication rates close to 80% among us( 2929. Coelho LG, Mattos AA, Francisconi CF, Castro LP, André SB. Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg, twice daily for 7 days, in the eradication of Helicobacter pylori in patients with peptic ulcer. Arq Gastroenterol. 2004;41:71-6. , 5454. Felga G, Silva FM, Barbuti RC, Navarro-Rodriguez T, Zaterka S, Eisig JN. Clarithromycin-based triple therapy for Helicobacter pylori treatment in peptic ulcer patients. J Infect Dev Ctries. 2010;4:712-6. , 134134. Mazzoleni LE, Sander GB, Francesconi CF, Mazzoleni F, etra DM, De Bona LR, Milbradt TC, Von Reisswitz PS, Berwanger O, Bressel M, Edelweiss MI, Marini SS, Molina CG, Folador L, Lunkes RP, Heck R, Birkhan OA, Spindler BM, Katz N, Colombo Bda S, Guerrieri PP, Renck LB, Grando E, Hocevar de Moura B, Dahmer FD, Rauber J, Prolla JC. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med. 2011;171:1929-36. , 166166. Ribeiro LT, Lima LMSTB, Costa-Neto JW, Mota RMG, Luz NMLM, Marinho JR, Veras DM, Wanderley VE. Comparação entre quatro esquemas tríplices para o tratamento do Helicobacter pylori: estudo prospectivo, randomizado, multicêntrico. GED Gastroenterol Endosc Dig. 2004;23:101-6. ). Such results have also recently been described by a Spanish group while treating H pylori infection over 12 years( 7777. Gisbert JP, McNicholl AG. Maintenance of Helicobacter pylori eradication rates with triple therapy over 12 years in a Spanish hospital. Helicobacter. 2012;17:160-1. ). A recent randomized trial, involving seven Latin American countries, including Chile and Colombia, achieved 82.2% H pylori eradication with the triple classic therapy scheme for 14 days( 8585. Greenberg ER, Anderson GL, Morgan DR, Torres J, Chey WD, Bravo LE, Dominguez RL, Ferreccio C, Herrero R, Lazcano-Ponce EC, Meza-Montenegro MM, etr R, etr EM, Salazar-Martínez E, Correa P, etracyc ME, Valdivieso M, Goodman GE, Crowley JJ, Baker LH. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial. Lancet. 2011;378:507-14. ). Most of the recommendations by the consensus groups recommend a period of 7 days, especially because of the cost factor. In reality, meta-analysis studies have shown a 4% gain by extending to 10 days and 5% with 14 days( 1515. Calvet X, García N, López T, Gisbert JP, Gené E, Roque M. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxicillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther. 2000;14:603-9. , 6060. Ford A, Moayyedi P. How can the current strategies for Helicobacter pylori eradication therapy be improved? Can J Gastroenterol. 2003;17(Suppl B):36B-40B. , 6464. Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F. Meta-analysis: duration of first-line proton pump inhibitor based triple therapy for Helicobacter pylori eradication. Ann Intern Med. 2007;147:553-62. , 9191. Haydee B, Salvana A, Ang ELR, Estanialao NI, Velasquez ME, Ong J, Nolasco ER, Daez ML, Banez V. Duration of proton-pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis. Gastroenterology. 2010;138(5)(Suppl.1):S340. ). For patients with a possible or proven history of penicillin allergy to the scheme described above is recommended replacing amoxicillin with the furazolidone 200 mg twice a day( 3131. Coelho LG, Zaterka S; Representantes indicados pela Federação Brasileira de Gastroenterologia e Núcleo Brasileiro para o Estudo do Helicobacter II Consenso Brasileiro sobre Helicobacter pylori. Arq Gastroenterol. 2005;42:128-32. , 3535. Dani R, Queiroz DM, Dias MG, Franco JM, Magalhães LC, Mendes GS, Moreira LS, De Castro LP, Toppa NH, Rocha GA, Cabral MM, Salles PG. Omeprazole, clarithromycin and furazolidone for the eradication of Helicobacter pylori in patients with duodenal ulcer. Aliment Pharmacol Ther. 1999;13:1647-52. ). Other options include using metronidazole or levofloxacin instead of amoxicillin or adopting schemes employing tetracycline and metronidazole and bismuth salts( 7272. Gisbert JP, Gisbert JL, Marcos S, Olivares D, Pajares JM. Helicobacter pylori first-line treatment and rescue options in patients allergic to penicillin. Aliment Pharmacol Ther. 2005;22:1041-6. , 7373. Gisbert JP, Abraira V. Accuracy of Helicobacter pylori diagnostic tests in patients with bleeding peptic ulcer: a systematic review and meta-analysis. Am J Gastroenterol. 2006;101:848-63. , 171171. Rodríguez-Torres M, Salgado-Mercado R, Ríos-Bedoya CF, Aponte-Rivera E, Marxuach-Cuétara AM, Rodríguez-Orengo JF, Fernández-Carbia A. High eradication rates of Helicobacter pylori infection with first- and second-line combination of esomeprazole, etracycline and metronidazole in patients allergic to penicillin. Dig Dis Sci. 2005;50:634-9. ). Further studies evaluating the antimicrobial resistance profile of H pylori in the Brazilian population are urgently needed to better define future therapeutic strategies among us.

  Statement 29:

Due to the absence of national validation studies, the alternative first-line regimens in eradicating H pylori such as the sequential therapy, concomitant scheme without bismuth, or those containing bismuth salts or levofloxacin are not routinely recommended in Brazil. In special situations, regimens containing furazolidone may be used Agreement level: 86.2 to 89%; Recommendation grade: D; Evidence level: 5

Alternative regimens to classical triple therapy, recommended for situations where rates of resistance to clarithromycin are high, above 20%, have been increasingly employed in different countries. The sequential scheme, developed by Italian researchers, consists of administering a standard dose of proton pump inhibitor with 1.0 g of amoxicillin, twice daily for the 1st 5 days, followed by administering of the standard dose of proton pump inhibitor, 500 mg of clarithromycin and 500 mg of tinidazole administered twice daily for a further 5-day period. Although most studies are still restricted to a single country, the initial results show eradication rates around 90%( 5858. Focareta R, Forte G, Forte F. Could the 10-days sequential therapy be considered a first choice treatment for the eradication of Helicobacter pylori infection? Dig Liver Dis. 2003;35(Suppl 4):S33. , 104104. Jafri NS, Hornung CA, Howden CW. Meta-analysis: sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naïve to treatment. Ann Intern Med. 2008;148:923-31. , 199199. Vaira D, Zullo A, Vakil N, Gatta L, Ricci C, Perna F, Hassan C, Bernabucci V, Tampieri A, Morini S. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med. 2007;146:556-63. , 216216. Zullo A, Vaira D, Vakil N, Hassan C, Gatta L, Ricci C, De Francesco V, Menegatti M, Tampieri A, Perna F, Rinaldi V, Perri F, Papadìa C, Fornari F, Pilati S, Mete LS, Merla A, Potì R, Marinone G, Savioli A, Campo SM, Faleo D, Ierardi E, Miglioli M, Morini S. High eradication rates of Helicobacter pylori with a new sequential treatment. Aliment Pharmacol Ther. 2003;17:719-26. Received 11/2/2013. ), with some Asian studies showing less significant results( 2323. Choi WH, Park DI, Oh SJ, Baek YH, Hong CH, Hong EJ, Song MJ, Park SK, Park JH, Kim HJ, Cho YK, Sohn CI, Jeon WK, Kim BI. Effectiveness of 10 day-sequential therapy for Helicobacter pylori eradication in Korea. Korean J Gastroenterol. 2008;5:280-4. ). There is a lack of confirmatory studies as to the effectiveness of this scheme among us. In a recent randomized Latin American trial where 486 patients received the sequential regimen, H pylori eradication rates came to 76.5%( 8585. Greenberg ER, Anderson GL, Morgan DR, Torres J, Chey WD, Bravo LE, Dominguez RL, Ferreccio C, Herrero R, Lazcano-Ponce EC, Meza-Montenegro MM, etr R, etr EM, Salazar-Martínez E, Correa P, etracyc ME, Valdivieso M, Goodman GE, Crowley JJ, Baker LH. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial. Lancet. 2011;378:507-14. ). The concomitant scheme (without bismuth) consisting of administering the standard dose of a proton pump inhibitor, amoxicillin, clarithromycin and metronidazole for 7 to 14 days has proven to be an effective, safe and well tolerated option for regions where no bismuth salts are available or efficacy of triple therapy is unacceptably low. Being less complex than sequential therapy, it encourages adherence to treatment. Recent meta-analysis demonstrated the superiority of concomitant therapy over triple therapy, with eradication rates per intention to treat analysis of 89.7% (95% CI: 86.8% to 92.1%)( 127127. Luther J, Higgins PD, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD. Empiric quadruple vs triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol. 2010;105:65-73. ). Although resistance to clarithromycin may reduce the efficacy of concomitant therapy, this seems to mean less impact on the eradication rates when compared with triple therapy. Studies with concomitant therapy without bismuth in patients with strains resistant to metronidazole are still limited. A recent randomized clinical trial, in Colombia, encountered similar eradication rates employing during 10 (85.3% eradication) or 14 (86.8%) days a combination of clarithromycin 500 mg twice daily, metronidazole 500 mg 3 times daily and amoxicillin 500 mg 3 times daily with or without a proton pump inhibitor( 5757. Fischbach LA, Bravo LE, Zarama GR, Bravo JC, Ojha RP, Priest EL, Collazos T,Casabon AL,Guerrero LZ,Singh KP,Correa P. A randomized clinical trial to determine the efficacy of regimens containing clarithromycin, metronidazole, and amoxicillin among histologic subgroups for Helicobacter pylori eradication in a developing country. Helicobacter. 2009;14:100-8. ).

The quadruple therapy containing proton pump inhibitor in standard dose + colloidal bismuth subcitrate 120 mg, 4 times daily + tetracycline hydrochloride 500 mg 4 times daily + metronidazole 250 mg 4 times a day for 7-10 days is a well established scheme in regions with high rates of resistance to clarithromycin. It has recently, been available in kits in the U.S. and Europe. A randomized clinical trial involving 39 centers in Europe, compared the classic triple therapy for 7 days with a quadruple therapy containing tetracycline, metronidazole and bismuth salt in a single formulation, and proton pump inhibitor, administered for 10 days on 440 patients undergoing anti-H pylori treatment for the first time. Eradication rates were 55% for the triple scheme and 80% for the quadruple scheme (P<0.0001). It is noteworthy that 70% of the strains were resistant to metronidazole and 20% to clarithromycin( 131131. Malfertheiner P, Bazzoli F, Delchier JC, Celiñski K, Giguère M, Rivière M, Mégraud F; Pylera Study Group. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet. 2011;377:905-13. ). Recent meta-analysis showed that quadruple therapy provides eradication rates similar to those observed with classical triple therapy( 127127. Luther J, Higgins PD, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD. Empiric quadruple vs triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol. 2010;105:65-73. ). Its drawback is the need to ingest a large number of tablets per day, impairing adherence to the treatment. Although recommended by some studies as an option for first-line therapy, the use of levofloxacin is usually reserved for retreatment( 2121. Chen L-W, Chien R-N, Chang J-J, Fang K-M, Chang C. Comparison of the once-daily levofloxacin-containing triple therapy with the twice-daily standard triple therapy for first-line Helicobacter pylori eradication: a prospective randomised study. Int J Clin Pract. 2010;64:1530-4. , 142142. Moayyedi P, Bardhan C, Young L, Dixon MF, Brown L, Axon AT. Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease. Gastroenterology. 2001;121:1120-6. ).

Regimens employing furazolidone associated with an antimicrobial (amoxicillin, clarithromycin or tetracycline) as first-line treatment for H. pylori infection has been used in adults and children in Brazil, with eradication rates of 79.1% (95% CI: 74.1% to 84.2%). The treatment is performed for 7 days, the doses of furazolidone used range from 100 mg (children) to 400 mg/day, with frequent adverse effects, particularly gastrointestinal( 2828. Coelho LG, Passos MC, Martins GM, Bueno ML, Gomes BS, Lopes LG, Castro LP. Once-daily Helicobacter pylori treatment to family members of gastric cancer patients. Am J Gastroenterol. 2000;95:832-3. , 3535. Dani R, Queiroz DM, Dias MG, Franco JM, Magalhães LC, Mendes GS, Moreira LS, De Castro LP, Toppa NH, Rocha GA, Cabral MM, Salles PG. Omeprazole, clarithromycin and furazolidone for the eradication of Helicobacter pylori in patients with duodenal ulcer. Aliment Pharmacol Ther. 1999;13:1647-52. , 6363. Frota LC, Cunha MP, Luz CR, de etrac-Filho AH, Frota LA, Braga LL. Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: Em open randomized clinical trial. Arq Gastroenterol. 2005;42:111-5. , 107107. Kawakami E, Machado RS, Ogata SK, Langner M, Fukushima E, Carelli AP, Bonucci VC, etracyc FR. Furazolidone-based triple therapy for H pylori gastritis in children. World J Gastroenterol. 2006;12:5544-9. , 128128. Machado RS, Silva MR, Viriato A. Furazolidone, tetracycline and omeprazole: a low-cost alternative for Helicobacter pylori eradication in children. J Pediatr (Rio J). 2008;84:160-5. ). A systematic review and meta-analysis of the effects of furazolidone and nitrofurantoinic derivatives in eradicating H pylori showed that schemes using such drugs had more frequent adverse effects and slightly less effective eradication rates when compared with the classic triple therapy( 1212. Buzás GM, Józan J. Nitrofuran-based regimens for the eradication of Helicobacter pylori infection. J Gastroenterol Hepatol. 2007;22:1571-81. ).

Although some probiotics and prebiotics, when used as adjunctive therapy, show encouraging results in reducing adverse effects from using antibiotics( 88. Bortoli N, Leonardi G, Ciancia E, Merlo A, Bellini M, Costa F, Mumolo MG, Ricchiuti A, Cristiani F, Santi S, Rossi M, Marchi S. Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J Gastroenterol. 2007;102:951-6. , 196196. Tong JL, Ran ZH, Shen J, Zhang CX, Xiao SD. Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther. 2007;25:155-68. ), the Consensus considered that its routine use in anti-H pylori therapy still needs further studies.

  Statement 30:

Triple regimens containing proton pump inhibitor, levofloxacin, amoxicillin for 10 days* or proton pump inhibitor, levofloxacin and furazolidone for 7-10 days** and quadruple regimens employing proton pump inhibitor, bismuth salt, tetracycline and furazolidonefor 10-14 days**, are recommended as second or third line therapy Agreement level: 89%; Recommendation grade: *A;**B; Evidence level:* 1A; **2C

Antibiotic resistance is the most important factor for lack of response to initial treatment. Indeed, H pylori eradication rates with classical triple therapy (proton pump inhibitor, amoxicillin and clarithromycin) are over 87% when the bacteria are sensitive to clarithromycin, against 17% when it is resistant( 135135. Megraud F, Lamouliatle H, Delchier JC, Bretagne JF, Courillon-Mallet A, De Korwin JD, Fauchere JL, Labigne A, Flejou JF. Helicobacter pylori resistance to antimicrobial agents after failure of an initial treatment and impact on results of second-line treatment strategies: a multicenter prospective study [abstract]. Gastroenterology. 2001;120(Suppl 1):A15. ). Rates for secondary resistance, or that observed after failure of the first treatment, reaches 60% or more, which means that repeated treatment with clarithromycin should be avoided, unless antimicrobial susceptibility testing is available( 9292. Heep M, Kist M, Strobel S, Beck D, LehnN. Secondary resistance among 554 isolates of Helicobacter pylori after failure of therapy. Eur J Clin Microbiol Infect Dis. 2000;19:538-41. , 136136. Megraud F. Helicobacter pylori and antibiotic resistance. Gut. 2007;56:1502. , 150150. Nagahara A, Miwa H, Ohkura R, Yamada T, Sato K, Hojo M, Sato N. Strategy for retreatment of therapeutic failure of eradication of Helicobacter pylori infection. J Gastroenterol Hepatol. 2001;16:613-8. ).

Regarding retreatment, this Consensus reiterated, with minor modifications, the recommendations of the previous Consensus( 3131. Coelho LG, Zaterka S; Representantes indicados pela Federação Brasileira de Gastroenterologia e Núcleo Brasileiro para o Estudo do Helicobacter II Consenso Brasileiro sobre Helicobacter pylori. Arq Gastroenterol. 2005;42:128-32. ). Three meta-analysis confirm that associating a standard dose of proton pump inhibitor, twice a day, amoxicillin 1.0 g twice a day and levofloxacin 500 mg once daily for 10 days achieves eradication rates of around 80%( 7474. Gisbert JP, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Aliment Pharmacol Ther. 2006;23:35-44. , 122122. Li Y, Huang X, Yao L, Shi R, Zhang G. Advantages of moxifloxacin and levofloxacin-based triple therapy for second-line treatments of persistent Helicobacter pylori infection: a meta analysis. Wien Klin Wochenschr. 2010;122:413-22. , 179179. Saad RJ, Schoenfeld P, Kim HM, Chey WD. Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis. Am J Gastroenterol. 2006;101:488-96. ). Although widely used in Brazil there are no validation studies among us. National studies employing a standard dose of proton pump inhibitor, and furazolidone 400 mg and levofloxacin 500 mg, taken once daily for 10 days, or a standard dose of proton pump inhibitor associated with furazolidone 200 mg and levofloxacin 250 mg, administered twice daily for 7 days, have obtained eradication rates close to 80%( 3030. Coelho LG, Moretzsohn LD, Vieira WL, Gallo MA, Passos MC, Cindr JM, Cerqueira MC, Vitiello L, Ribeiro ML, Mendonça S, Pedrazzoli-Júnior J, Castro LP. New once-daily, highly effective rescue triple therapy after multiple Helicobacter pylori treatment failures: a pilot study. Aliment Pharmacol Ther. 2005;21:783-7. , 4444. Eisig JN, Silva FM, Barbuti RC, Rodriguez TN, Malfertheiner P, Moraes-Filho JP, Zaterka S. Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication. BMC Gastroenterol. 2009;26:38. , 181181. Sanches BSF, Coelho LGV, Moretzsohn LD, Vieira Jr G. Failure of Helicobacter pylori treatment after regimes containing clarithromycin: new practical therapeutic options. Helicobacter. 2008;13:572-6. ).

The quadruple therapy employing a standard dose of proton pump inhibitor + colloidal bismuth subcitrate 120 mg 4 times daily + tetracycline hydrochloride 500 mg 4 times daily + metronidazole 250 mg 4 times a day for 10-14 days, is one of the most used regimens worldwide in retreating infection after the triple classical regimen has failed, with eradication rates of nearly 80%, according to European studies( 7575. Gisbert JP, Gisbert JL, Marcos S, Jimenez-Alonso I, Moreno-Otero R, Pajares JM. Empirical rescue therapy after Helicobacter pylori treatment failure: a 10-year single-centre study of 500 patients. Aliment Pharmacol Ther. 2008;27:346-54. , 119119. Lee JM, Breslin NP, Hyde DK, Buckley MJ, O'Morain CA. Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice. Aliment Pharmacol Ther. 1999;13:489-96. , 174174. Rokkas T, Sechopoulos P, Pistiolas D, Margantinis G, Koukoulis G. Helicobacter pylori infection and gastric histology in first-degree relatives of gastric cancer patients: a meta-analysis. Eur J Gastroenterol Hepatol. 2010;22:1128-33. ). Due to high rates of primary resistance to metronidazole in Latin America, few studies exist( 164164. Ramírez-Ramos A, Sánchez-Sánchez R. Contribución de Latinoamérica al estudio del Helicobacter pylori. Acta Gastroenterol Latinoam. 2009;39:197-218. ). Some studies, however, suggest that the primary resistance to imidazoles observed in vitro might be overcome by increasing the dose and/or duration of treatment( 116116. Laine L, Hunt R, El-Zimaity H, Nguyen B, Osato M, Spénard J. Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial. Am J Gastroenterol. 2003;98:562-7. , 127127. Luther J, Higgins PD, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD. Empiric quadruple vs triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol. 2010;105:65-73. , 186186. Selgrad M, Kandulski A, Malfertheiner P. Helicobacter pylori: diagnosis and treatment. Curr Opin Gastroenterol. 2009;25:549-56. ). One must also consider that the prevalence of metronidazole resistance tends to be overestimated when determined by the E-test( 155155. Osato MS, Reddy R, Reddy SG, Penland RL, Graham DY. Comparison of the Etest and the NCCLS-approved agar dilution method to detect metronidazole and clarithromycin resistant Helicobacter pylori. Int J Antimicrob Agents. 2001;17:39-44. ).

Quadruple regimens where metronidazole is replaced by furazolidone have been used in Brazil and other countries in South America to treat patients who are refractory to classic triple therapy( 4343. Eisig JN, Silva FM, Rodriguez TN, Hashimoto CL, Barbuti RC. A furazolidone-based quadruple therapy for Helicobacter pylori retreatment in patients with peptic ulcer disease. Clinics (Sao Paulo). 2005;60:485-8. , 8686. Gutierrez O, Otero W, Cardona H, Quintero F, Orozco C, Sanchez L. Terapia cuádruple con furazolidona como tratamiento de rescate para la infección de Helicobacter pylori. Rev Colomb Gastroenterol. 2003;18:222-4. , 181181. Sanches BSF, Coelho LGV, Moretzsohn LD, Vieira Jr G. Failure of Helicobacter pylori treatment after regimes containing clarithromycin: new practical therapeutic options. Helicobacter. 2008;13:572-6. ). In Brazil, the quadruple regimen recommended for retreatment is to administer a standard dose of proton pump inhibitor, amoxicillin + 1.0 g (or doxycycline 100 mg) + furazolidone 200 mg + 240 mg colloidal bismuth subcitrate (2 comp.), administered twice a day (after lunch and dinner) for 10-14 days. A study employing this regimen achieved 80% eradication in Brazil( 181181. Sanches BSF, Coelho LGV, Moretzsohn LD, Vieira Jr G. Failure of Helicobacter pylori treatment after regimes containing clarithromycin: new practical therapeutic options. Helicobacter. 2008;13:572-6. ). The use of only two daily doses, as previously suggested by Graham et al.( 8484. Graham DY, Belson G, Abudayyeh, Osato MS, Dore MP, El-Zimaity HM. Twice daily (mid-day and evening) quadruple therapy for Hpylori infection in the United States. Dig Liver Dis. 2004;36:384-7. ), appears to increase adherence and reduce the adverse effects of this regimen.

Using furazolidone in anti-H. pylori therapy regimens has been the subject of recent controversy. Available on the market for decades and it is recommended as an anti-H. pylori alternative drug by the H. pylori Consensus in Latin American in 2000( 2727. Coelho LG, Léon-Barúa R, Quigley EMM; Representatives of the Latin-American National Gastroenterological Societies affiliated with the Inter-American Association of Gastroenterology (AIGE). Latin-American Consensus Conference on Helicobacter Infection. Am J Gastroenterol. 2000;95:2688-91. ), Brazil in 2005( 3131. Coelho LG, Zaterka S; Representantes indicados pela Federação Brasileira de Gastroenterologia e Núcleo Brasileiro para o Estudo do Helicobacter II Consenso Brasileiro sobre Helicobacter pylori. Arq Gastroenterol. 2005;42:128-32. ), China in 2008( 9696. Hu FL, Hu PJ, Liu WZ, De Wang J, Lv NH, Xiao SD, Zhang WD, Cheng H, Xie Y. Third Chinese National Consensus Report on the management of Helicobacter pylori infection. J Dig Dis. 2008;9:178-84. ) and also by the World Gastroenterology Organization, in 2011( 207207. World Gastroenterology Organization - Global Guideline: Helicobacter pylori in developing countries. J Clin Gastroenterol. 2011;45:383-8. ). Classified in 1997 by the International Agency for Research on Cancer (IARC) as a type 3 carcinogen (unclassifiable as a carcinogen in humans)( 9999. IARC Monographs on the evaluation of carcinogenic risks to humans. Furazolidone. 1998;31. ), it is no longer available in North American and European markets because of possible genotoxic and carcinogenetic effects in animals( 5050. The European Agency for the Evaluation of Medicinal Products. Veterinary Medicines Evaluation Unit. Annex IV. 1999 Oct:14. , 5151. European Medicine Agency. Science. Medicine. Health [Internet]. [cited 2011 June 12]. Available from: http://www.ema.europa.eu/
http://www.ema.europa.eu/...
, 5353. FDA Prohibits Nitrofuran Drug Use. Veterinarian Newsletter. 2002;17(2). ). It is still available in several Latin American countries, including Brazil, China and Iran, among others. While Zullo et al.( 215215. Zullo A, Ierardi E, Hassan C, De Francesco V. Furazolidone-based therapies for Helicobacter pylori infection: a pooled-data analysis. Saudi J Gastroenterol. 2012;18:11-7. ), in a recent review suggest that patients who receive their prescription should be informed about its potential effects on animals, Graham and Lu( 8282. Graham D, Lu H. Furazolidone in Helicobacter Pylori therapy: misunderstood and often unfairly maligned drug told in a story of French bread. Saudi J Gastroenterol. 2012;18:1-2. ), reviewing the processes that culminated in the withdrawal from U.S. trade, considered it to be an unfairly maligned and underused drug and particularly useful in areas where antibiotic resistance is widespread and multiple.

GROUP 5. EPIDEMIOLOGY OF INFECTION AND PROPOSALS FOR ACTION TO REDUCE ITS PREVALENCE AND IMPROVE FIGHTING IT IN BRAZIL

In general, H pylori infection is acquired early in childhood. In urban and rural Brazilian populations with a low socioeconomic status (SES) more than half the children are already colonized in the first 2-3 years of life, with numbers increasing until the 5th year, when the risk of acquiring the infection decreases. In populations with a higher SES, the risk of acquiring it also begins early, although more slowly, reaching significantly lower rates than those seen in populations with a low SES. Acquiring the infection during childhood may be decisive to the morbidity and mortality associated with chronic H pylori infection in the adult population( 4949. Escobar-Pardo ML, de Godoy AP, Machado RS, Rodrigues D, Fagundes Neto U, Kawakami E. Prevalence of Helicobacter pylori infection and intestinal parasitosis in children of the Xingu Indian reservation. J Pediatr (Rio J). 2011;87:393-8. , 140140. Miranda ACP, Machado RS, Silva EMK, Kawakami E. Seroprevalence of Helicobacter pylori infection among children of low socioeconomic level in São Paulo. Sao Paulo Med J. 2010;128:187-91. , 156156. Parente JML, da Silva BB, Palha Dias MPS, Zaterka S, Nishimura N, Zeitune JMR. Helicobacter pylori infection in children of low and high socioeconomic status in northeast Brazil. Am J Trop Med Hyg. 2006;75:509-12. , 162162. Queiroz DM, Carneiro JG, Braga-Neto MB, Fialho AB, Fialho AM, etracycl MH, Rocha GA, Rocha AM, Braga LL. Natural history of Helicobacter pylori infection in childhood: eight-year follow-up cohort study in an urban community in Northeast of Brazil. Helicobacter. 2012;17:23-9. ).

The prevalence of H. pylori infection in the adult population depends on the incidence in childhood, since infection often persists throughout the life of the individual and it is seldom caught in adulthood. In Brazil, the prevalence is much higher than the average of the world population, with variability depending on the geographic area and the development level of the population surveyed. In populations with precarious SES, resident in urban and rural areas, the prevalence of infection may reach 70% of children at 5 years of age, reaching over 80% of individuals after the age of 20. Moreover, the improvement in the population's living conditions, characterized by higher household income, higher level of education and adequate health services, provides an impact on the prevalence of H pylori infection, with a drop in the prevalence of H pylori infection( 11. Almeida-Cunha RP, Alves FP, Rocha AM, Rocha GA, Camargo LM, Nogueira PO, Camargo EP, Queiroz DM. Prevalence and risk factors associated with Helicobacter pylori infection in native populations from Brazilian Western Amazon. Trans R Soc Trop Med Hyg. 2003;97:382-6. , 3232. Coelho MC, Bomfim IM, Moreira MR, Santa-Cecilia EV, Oliveira SM, Trindade OR, Coelho LG. Infection by Helicobacter pylori among medical students in Brazil. Helicobacter. 2007;12:454. , 103103. Ito LS, Oba-Shinjo SM, Shinjo SK, Uno M, Marie SK, Hamajima N. Community-based familial study of Helicobacter pylori infection among healthy Japanese Brazilians. Gastric Cancer. 2006;9:208-16. , 108108. Kawakami E, Machado RS, Ogata SK, Langner M. Decrease in prevalence of Helicobacter pylori infection during a 10-year period in Brazilian children. Arq Gastroenterol. 2008;45:147-51. , 138138. Melo ET, Lopes EP, Almeida JR, Albuquerque MF, Moura IM. Seroprevalence of Helicobacter pylori antibodies in medical students and residents in Recife, Brazil. J Clin Gastroenterol. 2003;36:134-8. , 170170. Rodrigues MN, Queiroz DM, Braga AB, Rocha AM, Eulailo EC, Braga LL. History of breastfeeding and Helicobacter pylori infection in children: results of a community-based study from Northeastern Brazil. Trans R Soc Trop Med Hyg. 2006;100:470-5. , 183183. Santos IS, Boccio J, Santos AS, Valle NC, Halal CS, Bachilli MC, Lopes RD. Prevalence of Helicobacter pylori infection and associated factors among adults in Southern Brazil: a population-based cross-sectional study. BMC Public Health. 2005;5:118. , 202202. Vergueiro,CSV, Cordiolli R, Martucci D, Peres V, Kiyamu, AR, Ribeiro KCB, Chiattone CS. Soroprevalência e fatores associados à infecção pelo Helicobacter pylori em doadores de medula óssea de São Paulo. Rev Bras Epidemiol. 2008;11:196-203. , 12212. Zaterka S, Eizig JN, Chinzon D, Rotchstein W. Factors related to Helicobacter pylori prevalence in an adult population in Brazil. Helicobacter. 2007;12:82-8. ).

The primary risk factors for acquiring H pylori in Brazil are related to unfavorable living conditions experienced during childhood, including low family income, low education levels of the children's parents, lack of proper household sanitary facilities, household crowding or high density housing or in institutions; improper personal hygiene habits, presence of an infected family member, especially the mother, and deficient basic public health services such as supply of piped drinking water, household garbage collection and sewerage with treatment plants for collected waste( 99. Braga AB, Fialho AM, Rodrigues MN, Queiroz DM, Rocha AM, Braga LL. Helicobacter pylori colonization among children up to 6 years: results of a community-based study from Northeastern Brazil. J Trop Pediatr. 2007;53:393-7. , 3636. Dattoli VC, Veiga RV, da Cunha SS, Pontes-de-Carvalho LC, Barreto ML, Alcântara-Neves NM. Seroprevalence and potential risk factors for Helicobacter pylori infection in Brazilian children. Helicobacter. 2010;15:273-8. , 5555. Fialho AM, Braga AB, Queiroz DM, Rodrigues MN, Herbster ID, Braga LL. The association between Helicobacter pylori infection and height in children from an urban community in north-east Brazil. Ann Trop Paediatr. 2007;27:55-61. , 5656. Fialho AM, Braga AB, Braga-Neto MB, Carneiro JG, Rocha AM, Rodrigues MN, Queiroz DM, Braga LL. Younger siblings play a major role in Helicobacter pylori transmission among children from a low-income community in the Northeast of Brazil. Helicobacter. 2010;15:491-6. , 7979. Gomes B, Martinis E. Fate of Helicobacter pylori artificially inoculated in lettuce and carrot samples. Braz J Microbiol. 2004;35:145-50. , 110110. Kignel S, de Almeida Pina F, André EA, Alves Mayer MP, Birman EG. Occurrence of Helicobacter pylori in dental plaque and saliva of dyspeptic patients. Oral Dis. 2005;11:17-21. ).

The group has listed a set of measures needed to reduce the risk of acquiring the infection (Figure 2), as well as suggestions for actions to be implemented by government agencies to reduce infection rates in Brazil (Figure 3).

FIGURE 2
Measures to reduce the risk of H pylori infection in Brazil

FIGURE 3
Suggestions by the Brazilian Center for studying H pylori to reduce H pylori infection rates in Brazil

DISCLOSURES

LG Coelho: consultant from Ache and Medley. I. Maguilnik: consultant from Medley. JPP Moraes-Filho: consultant from Medley, Reckitt Benckiser, and Takeda. JM Parente: consultant from Abbott Brasil and Janssen Brasil. MCF Passos: consultant from Abbott Brasil, Ache, Apsen, Janssen Brasil, Medley, and Takeda. S Zaterka: advisory board from Takeda.

PARTICIPANTS

Aloísio Carvalhaes (SP); Antônio Frederico Novaes de Magalhães (SP); Celso Mirra de Paula e Silva (MG); Décio Chinzon (SP); Edson Pedro da Silva (SC); Elizabete Kawakami (SP); Maria do Carmo Friche Passos (MG); Farid Butros Iunan Nader (RS); Guilherme Sander (RS); Helenice P. Breyer (RS); Ismael Maguilnik (RS); Jaime Natan Eisig (SP); James Ramalho Marinho (AL); Joaquim Prado Pinto de Moraes Filho (SP); Jorge Luis Jorge (SC); José Miguel Luz Parente (PI); José Pedrazzoli Júnior (SP); José Roberto de Almeida (PE); José Vitor Zir (RS); Laercio Tenório Ribeiro (AL); Lúcia Libanez Bessa Campelo Braga (CE); Luiz Edmundo Mazzoleni (RS); Luize Meurer (RS); Robert Genta (EUA); Marcio Matheus Tolentino (SP); Mauro Baffutto (GO); Miriam Aparecida da Silva Trevisan (SP); Odery Ramos Junior (PR); Ricardo Correa Barbuti (SP); Schlioma Zaterka (SP); Tárik Olivar de Nunes Valente (PA).

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  • The Brazilian Helicobacter Study Nucleus had grant support from Medley and Ache. The fundings source had no role in the study design, conduct, data collection, statistical analysis, manuscript preparation, interpretation or decision to submit the manuscript for publication.

Publication Dates

  • Publication in this collection
    19 Apr 2013
  • Date of issue
    Apr-Jun 2013

History

  • Received
    11 Feb 2013
  • Accepted
    14 Feb 2013
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