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  • Review Article
  • Published:

Clinical effects of Helicobacter pylori outside the stomach

Nature Reviews Gastroenterology & Hepatology volume 11, pages 234–242 (2014)Cite this article

Subjects

Key Points

  • Since 1994, H. pylori infection has been associated with the development of some diseases localized outside the stomach

  • H. pylori can trigger a low-grade inflammatory state and induce molecular mimicry mechanisms by expressing virulence peptides that mimic host proteins

  • H. pylori might interfere with the absorbance of different nutrients and drugs, potentially influencing the development or clinical evolution of many diseases outside the gastrointestinal tract

  • Idiopathic thrombocytopenic purpura, unexplained iron deficiency anaemia and vitamin B12 deficiency are believed to be caused by H. pylori infection

  • The association of H. pylori with some cardiovascular, hepatobiliary, pancreatic and neurodegenerative diseases as well as colorectal cancer is currently under investigation, with interesting results

Abstract

The discovery of Helicobacter pylori infection in the stomach could be considered as one of the most important events of modern gastroenterology. Understanding of the natural history of many disorders of the upper gastrointestinal tract, including chronic gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma, was altered by this discovery. Interestingly, epidemiological studies have also revealed a correlation between H. pylori infection and some diseases localized outside the stomach, especially those characterized by persistent and low-grade systemic inflammation. Of note, H. pylori has an important role in iron deficiency anaemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency. Moreover, the association of this bacterial pathogen with many other diseases, including hepatobiliary, pancreatic, cardiovascular and neurodegenerative disorders is currently under investigation. In this Review, we summarize the results of the most important studies performed to date surrounding the association of H. pylori infection with extragastric diseases, as well as the strength of the evidence. We also provide information concerning bacterial–host interactions and the mechanisms implicated in the pathogenesis of each of these extragastric diseases.

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Figure 1: Pathogenic hypothesis on the possible role of CagA-positive strains in ischaemic heart disease.
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References

  1. Franceschi, F., Genta, R. M. & Sepulveda, A. R. Gastric mucosa: long-term outcome after cure of Helicobacter pylori infection. J. Gastroenterol. 37 (Suppl. 13), 17–23 (2002).

    PubMed  Google Scholar 

  2. Dooley, C. P. et al. Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N. Engl. J. Med. 321, 1562–1566 (1989).

    CAS  PubMed  Google Scholar 

  3. Calvet, X., Ramirex Lazaro, M. J., Lehours, P. & Megraud, F. Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter 18 (Suppl. 1), 5–11 (2013).

    PubMed  Google Scholar 

  4. Moyaert, H. et al. Extragastric manifestations of Helicobacter pylori infection: other Helicobacters. Helicobacter 13 (Suppl. 1), 47–57 (2008).

    PubMed  Google Scholar 

  5. Figura, N. et al. Extragastric manifestations of Helicobacter pylori infection. Helicobacter 15 (Suppl. 1), 60–68 (2010).

    PubMed  Google Scholar 

  6. Mendall, M. A. et al. Relation of Helicobacter pylori infection and coronary heart disease. Br. Heart J. 71, 437–439 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Whincup, P. et al. Prospective study of potentially virulent strains of Helicobacter pylori and coronary heart disease in middle-aged men. Circulation 101, 1647–1652 (2000).

    CAS  PubMed  Google Scholar 

  8. Rathbone, B., Martin, D., Stephens, J., Thompson, J. R. & Samani, N. J. Helicobacter pylori seropositivity in subjects with acute myocardial infarction. Heart 76, 308–311 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Pasceri, V. et al. Association of virulent Helicobacter pylori strains with ischemic heart disease. Circulation 97, 1675–1679 (1998).

    CAS  PubMed  Google Scholar 

  10. Pasceri, V. et al. Virulent strains of Helicobacter pylori and vascular diseases: a meta-analysis. Am. Heart J. 151, 1215–1222 (2006).

    CAS  PubMed  Google Scholar 

  11. Pellicano, R., Mladenova, I., Broutet, N., Salmi, L. R. & Mégraud, F. Is there an association between Helicobacter pylori infection and coronary heart disease? Eur. J. Epidemiol. 15, 611–619 (1999).

    CAS  PubMed  Google Scholar 

  12. Franceschi, F. et al. CagA antigen of Helicobacter pylori and coronary instability: insight from a clinico-pathological study and a meta-analysis of 4241 cases. Atherosclerosis 202, 535–542 (2009).

    CAS  PubMed  Google Scholar 

  13. Carter, A. M. et al. The influence of Helicobacter pylori status on circulating levels of the coagulation factors fibrinogen, von Willebrand factor, factor VII, and factor VIII. Helicobacter 1, 65–69 (1996).

    CAS  PubMed  Google Scholar 

  14. Satoh, H., Saijo, Y., Yoshioka, E. & Tsutsui, H. Helicobacter pylori infection is a significant risk for modified lipid profile in Japanese male subjects. J. Atheroscler. Thromb. 17, 1041–1048 (2010).

    CAS  PubMed  Google Scholar 

  15. Jia, E. Z. et al. Helicobacter pylori infection is associated with decreased serum levels of high density lipoprotein, but not with the severity of coronary atherosclerosis. Lipids Health Dis. 8, 59 (2009).

    PubMed  PubMed Central  Google Scholar 

  16. Kountouras, J., Polyzos, S. A., Deretzi, G., Katsinelos, P. & Kyriakou, P. Helicobacter pylori infection and the risk for cardiovascular disease. Eur. J. Intern. Med. 22, e146–e147 (2011).

    PubMed  Google Scholar 

  17. Harvey, R. et al. Effect of Helicobacter pylori infection on blood pressure: a community based cross sectional study. BMJ 323, 264–265 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu, L. et al. Pathogen burden in essential hypertension. Circ. J. 71, 1761–1764 (2007).

    PubMed  Google Scholar 

  19. Vahdat, K. et al. Association of pathogen burden and hypertension: The Persian Gulf Healthy Heart Study. Am. J. Hypertens. 26, 1140–1147 (2013).

    PubMed  Google Scholar 

  20. Migneco, A. et al. Eradication of Helicobacter pylori infection improves blood pressure values in patients affected by hypertension. Helicobacter 8, 585–589 (2003).

    PubMed  Google Scholar 

  21. Takenaka, R. et al. Helicobacter pylori heat-shock protein 60 induces inflammatory responses through the Toll-like receptor-triggered pathway in cultured human gastric epithelial cells. Microbiology 150, 3913–3922 (2004).

    CAS  PubMed  Google Scholar 

  22. Lenzi, C. et al. H. pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease. World J. Gastroenterol. 12, 7815–7820 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Birnie, D. H. et al. Association between antibodies to heat shock protein 65 and coronary atherosclerosis. Possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk. Eur. Heart J. 19, 387–394 (1998).

    CAS  PubMed  Google Scholar 

  24. Bourantas, C. V., Garcia-Garcia, H. M., Diletti, R., Muramatsu, T. & Serruys, P. W. Early detection and invasive passivation of future culprit lesions: a future potential or an unrealistic pursuit of chimeras? Am. Heart J. 165, 869–881.e4 (2013).

    PubMed  Google Scholar 

  25. Franceschi, F. et al. Cross-reactivity of anti-CagA antibodies with vascular wall antigens: possible pathogenic link between Helicobacter pylori infection and atherosclerosis. Circulation 106, 430–434 (2002).

    CAS  PubMed  Google Scholar 

  26. Rozankociv, P. B. et al. Influence of CagA-positive Helicobacter pylori strains on atherosclerotic carotid disease. J. Neurol. 258, 753–761 (2011).

    Google Scholar 

  27. Wang, Z. W. et al. Helicobacter pylori infection contributes to high risk of ischemic stroke: evidence from a meta-analysis. J. Neurol. 259, 2527–2537 (2012).

    PubMed  Google Scholar 

  28. De Bastiani, R. et al. High prevalence of Cag-A positive H. pylori strains in ischemic stroke: a primary care multicenter study. Helicobacter 13, 274–277 (2008).

    CAS  PubMed  Google Scholar 

  29. Chen, B. F. et al. Relationship between Helicobacter pylori infection and serum interleukin-18 in patients with carotid atherosclerosis. Helicobacter 18, 124–128 (2013).

    PubMed  Google Scholar 

  30. Corcoran, P. A. et al. The effect of different strains of Helicobacter pylori on platelet aggregation. Can. J. Gastroenterol. 21, 367–370 (2007).

    PubMed  PubMed Central  Google Scholar 

  31. Chen, Y., Segers, S. & Blaser, M. J. Association between Helicobacter pylori and mortality in the NHANES III study. Gut 62, 1262–1269 (2013).

    PubMed  Google Scholar 

  32. Cremonini, F., Gabrielli, M., Gasbarrini, G., Pola, P. & Gasbarrini, A. The relationship between chronic H. pylori infection, CagA seropositivity and stroke: meta-analysis. Atherosclerosis 173, 253–259 (2004).

    CAS  PubMed  Google Scholar 

  33. Shenoy, V., Kanasaki, K. & Kalluri, R. Pre-eclampsia: connecting angiogenic and metabolic pathways. Trends Endocrinol. Metab. 21, 529–536 (2010).

    CAS  PubMed  Google Scholar 

  34. Steegers E. A. et al. Pre-eclampsia. Lancet 376, 631–644 (2010).

    PubMed  Google Scholar 

  35. Cardaropoli, S., Rolfo, A., Piazzese, A., Ponzetto, A. & Todros, T. Helicobacter pylori's virulence and infection persistence define pre-eclampsia complicated by fetal growth retardation. World J. Gastroenterol. 17, 5156–5165 (2011).

    PubMed  PubMed Central  Google Scholar 

  36. Franceschi, F. et al. Antibodies anti-CagA cross-react with trophoblast cells: a risk factor for pre-eclampsia? Helicobacter 17, 426–434 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Gasbarrini, A., Serricchio, M., Tondi, P., Gasbarrini, G. & Pola, P. Association of Helicobacter pylori infection with primary Raynaud phenomenon. Lancet 348, 966–967 (1996).

    CAS  PubMed  Google Scholar 

  38. Gasbarrini, A. et al. Helicobacter pylori eradication ameliorates primary Raynaud's phenomenon. Dig. Dis. Sci. 43, 1641–1645 (1998).

    CAS  PubMed  Google Scholar 

  39. Gasbarrini, A. et al. Association between Helicobacter pylori cytotoxic type I CagA-positive strains and migraine with aura. Cephalalgia 20, 561–565 (2000).

    CAS  PubMed  Google Scholar 

  40. Faraji, F., Zarinfar, N., Zanjani, A. T. & Morteza, A. The effect of Helicobacter pylori eradication on migraine: a randomized, double blind, controlled trial. Pain Physician 15, 495–498 (2012).

    PubMed  Google Scholar 

  41. Tunca, A., Ardiçog˘lu, Y., Kargili, A. & Adam, B. Migraine, Helicobacter pylori, and oxidative stress. Helicobacter 12, 59–62 (2007).

    CAS  PubMed  Google Scholar 

  42. Marignani, M. et al. Reversal of long-standing iron deficiency anaemia after eradication of Helicobacter pylori infection. Scand. J. Gastroenterol. 32, 617–622 (1997).

    CAS  PubMed  Google Scholar 

  43. Yuan, W. et al. Iron deficiency anemia in Helicobacter pylori infection: meta-analysis of randomized controlled trials. Scand. J. Gastroenterol. 45, 665–676 (2010).

    CAS  PubMed  Google Scholar 

  44. Huang, X. et al. Iron deficiency anaemia can be improved after eradication of Helicobacter pylori. Postgrad. Med. J. 86, 272–278 (2010).

    PubMed  Google Scholar 

  45. Huang, X. et al. Iron deficiency anaemia can be improved after eradication of Helicobacter pylori. Postgrad. Med. J. 86, 272–278 (2010).

    PubMed  Google Scholar 

  46. Franceschi, F. & Gasbarrini, A. Helicobacter pylori and extragastric diseases. Best Pract. Res. Clin. Gastroenterol. 21, 325–334 (2007).

    CAS  PubMed  Google Scholar 

  47. Gasbarrini, A. et al. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet 352, 878 (1998).

    CAS  PubMed  Google Scholar 

  48. Tsumoto, C. et al. Long-term efficacy of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura: 7-year follow-up prospective study. Ann. Hematol. 88, 789–793 (2009).

    CAS  PubMed  Google Scholar 

  49. Veneri, D. et al. Analysis of B- and T-cell clonality and HLA class II alleles in patients with idiopathic thrombocytopenic purpura: correlation with Helicobacter pylori infection and response to eradication treatment. Platelets 16, 307–311 (2005).

    CAS  PubMed  Google Scholar 

  50. Veneri, D., Krampera, M. & Franchini, M. High prevalence of sustained remission of idiopathic thrombocytopenic purpura after Helicobacter pylori eradication: a long-term follow-up study. Platelets 16, 117–119 (2005).

    CAS  PubMed  Google Scholar 

  51. Veneri, D. et al. Idiopathic thrombocytopenic purpura, Helicobacter pylori infection, and HLA class II alleles. Blood 100, 1925–1926 (2002).

    CAS  PubMed  Google Scholar 

  52. Godeau, B. & Michel, M. Treatment of chronic immune thrombocytopenic purpura in adults. Ann. Hematol. 89 (Suppl.), 55–60 (2010).

    Google Scholar 

  53. Franceschi, F., Christodoulides, N., Kroll, M. H. & Genta, R. M. Helicobacter pylori and idiopathic thrombocytopenic purpura. Ann. Intern. Med. 140, 766–767 (2004).

    PubMed  Google Scholar 

  54. Diamantidis, M. D. et al. High prevalence of Helicobacter pylori infection in Greek patients with myelodysplastic syndromes. Acta Haematol. 124, 141–149 (2010).

    PubMed  Google Scholar 

  55. Malik, A. A., Ganti, A. K., Potti, A., Levitt, R. & Hanley, J. F. Role of Helicobacter pylori infection in the incidence and clinical course of monoclonal gammopathy of undetermined significance. Am. J. Gastroenterol. 97, 1371–1374 (2002).

    PubMed  Google Scholar 

  56. Soler, J. A. et al. H. pylori eradication does not reduce paraprotein levels in monoclonal gammopathy of unknown significance (MGUS): a prospective cohort study. Ann. Hematol. 88, 769–773 (2009).

    CAS  PubMed  Google Scholar 

  57. Asadi-Pooya, A. A., Dehghani, S. M., Petramfar, P., Emami, M. & Mahmoodi, M. Helicobacter pylori infection in patients with epilepsy. Seizure 21, 21–23 (2012).

    PubMed  Google Scholar 

  58. Long, Y. et al. Helicobacter pylori infection in neuromyelitis optica and multiple sclerosis. Neuroimmunomodulation 20, 107–112 (2012).

    PubMed  Google Scholar 

  59. Yoshimura, S. et al. Distinct genetic and infectious profiles in Japanese neuromyelitis optica patients according to anti-aquaporin 4 antibody status. J. Neurol. Neurosurg. Psychiatry 84, 29–34 (2013).

    PubMed  Google Scholar 

  60. Kountouras, J. et al. Potential implications of Helicobacter pylori-related neutrophil-activating protein. World J. Gastroenterol. 18, 489–490 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Kountouras, J. et al. Aquaporin 4, Helicobacter pylori and potential implications for neuromyelitis optica. J. Neuroimmunol. 263, 162–163 (2013).

    CAS  PubMed  Google Scholar 

  62. Nielsen, H. H., Qiu, J., Friis, S., Wermuth, L. & Ritz, B. Treatment for Helicobacter pylori infection and risk of Parkinson's disease in Denmark. Eur. J. Neurol. 19, 864–869 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Dobbs, S. M. et al. Differential effect of Helicobacter pylori eradication on time-trends in brady/hypokinesia and rigidity in idiopathic parkinsonism. Helicobacter 15, 279–294 (2010).

    PubMed  PubMed Central  Google Scholar 

  64. Kountouras, J. et al. Five-year survival after Helicobacter pylori eradication in Alzheimer disease patients. Cogn. Behav. Neurol. 23, 199–204 (2010).

    PubMed  Google Scholar 

  65. Roubaud-Baudron, C., Krolak-Salmon, P., Quadrio, I., Megraud, F. & Salles N. Impact of chronic Helicobacter pylori infection on Alzheimer's disease: preliminary results. Neurobiol. Aging 33, 1009.e11–19 (2012).

    CAS  Google Scholar 

  66. Roubaud Baudron, C. et al. Does Helicobacter pylori infection increase incidence of dementia? The Personnes Agees QUID Study. J. Am. Geriatr. Soc. 61, 74–78 (2013).

    PubMed  Google Scholar 

  67. Beydoun, M. A., Beydoun, H. A., Shroff, M. R., Kitner-Triolo, M. H. & Zonderman, A. B. Helicobacter pylori seropositivity and cognitive performance among US adults: evidence from a large national survey. Psychosom. Med. 75, 486–496 (2013).

    PubMed  PubMed Central  Google Scholar 

  68. Katan, M. et al. Infectious burden and cognitive function: the Northern Manhattan Study. Neurology 80, 1209–1215 (2013).

    PubMed  PubMed Central  Google Scholar 

  69. Zhou, X., Wu, J. & Zhang, G. Association between Helicobacter pylori and asthma: a meta-analysis. Eur. J. Gastroenterol. Hepatol. 25, 460–468 (2013).

    CAS  PubMed  Google Scholar 

  70. Oertli, M. & Müller, A. Helicobacter pylori targets dendritic cells to induce immune tolerance, promote persistence and confer protection against allergic asthma. Gut Microbes 3, 566–571 (2012).

    PubMed  PubMed Central  Google Scholar 

  71. Deshpande, N. et al. Helicobacter pylori IgG antibodies in aqueous humor and serum of subjects with primary open angle and pseudo-exfoliation glaucoma in a South Indian population. J. Glaucoma 17, 605–610 (2008).

    PubMed  Google Scholar 

  72. Zavos, C. et al. Histological presence of Helicobacter pylori bacteria in the trabeculum and iris of patients with primary open-angle glaucoma. Ophthalmic Res. 47, 150–156 (2012).

    PubMed  Google Scholar 

  73. Zullo, A. et al. Glaucoma and Helicobacter pylori: eyes wide shut? Dig. Liver Dis. 44, 627–628 (2012).

    PubMed  Google Scholar 

  74. Pajic´-Penavic´, I., Danic´, D., Maslovara, S. & Gall-Trošelj, K. Absence of Helicobacter pylori in healthy laryngeal mucosa. J. Laryngol. Otol. 126, 196–199 (2012).

    PubMed  Google Scholar 

  75. Gong, H. et al. Helicobacter pylori infection of the larynx may be an emerging risk factor for laryngeal squamous cell carcinoma. Clin. Transl. Oncol. 14, 905–910 (2012).

    PubMed  Google Scholar 

  76. Ki, M. R. et al. Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-β1-induced inflammatory signaling. Lab. Invest. 90, 1507–1516 (2010).

    CAS  PubMed  Google Scholar 

  77. Le Roux-Goglin, E. et al. Helicobacter infection induces podosome assembly in primary hepatocytes in vitro. Eur. J. Cell Biol. 91, 161–170 (2012).

    CAS  PubMed  Google Scholar 

  78. Polyzos, S. A. et al. Helicobacter pylori infection in patients with nonalcoholic fatty liver disease. Metabolism 62, 121–126 (2013).

    CAS  PubMed  Google Scholar 

  79. Esmat, G., El-Bendary, M., Zakarya, S., Ela, M. A. & Zalata, K. Role of Helicobacter pylori in patients with HCV-related chronic hepatitis and cirrhosis with or without hepatocellular carcinoma: possible association with disease progression. J. Viral Hepat. 19, 473–479 (2012).

    CAS  PubMed  Google Scholar 

  80. Sakr, S. A., Badrah, G. A. & Sheir, R. A. Histological and histochemical alterations in liver of chronic hepatitis C patients with Helicobacter pylori infection. Biomed. Pharmacother. 67, 367–374 (2013).

    PubMed  Google Scholar 

  81. Hu, B. L., Wang, H. Y. & Yang, G. Y. Association of Helicobacter pylori infection with hepatic encephalopathy risk: a systematic review. Clin. Res. Hepatol. Gastroenterol. http://dx.doi.org/10.1016/j.clinre.2013.05.004.

  82. Kountouras, J., Zavos, C. & Deretzi, G. Helicobacter pylori might contribute to persistent cognitive impairment after resolution of overt hepatic encephalopathy. Clin. Gastroenterol. Hepatol. 9, 624 (2011).

    PubMed  Google Scholar 

  83. Kountouras, J. et al. Helicobacter pylori induced cognitive dysfunction might be associated with falls and fractures in cirrhosis. Hepatology 57, 1284 (2013).

    PubMed  Google Scholar 

  84. Kountouras, J., Zavos, C. & Chatzopoulos, D. A concept on the role of Helicobacter pylori infection in autoimmune pancreatitis. J. Cell. Mol. Med. 9, 196–207 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Shinji, A. et al. Autoimmune pancreatitis is closely associated with gastric ulcer presenting with abundant IgG4-bearing plasma cell infiltration. Gastrointest. Endosc. 59, 506–511 (2004).

    PubMed  Google Scholar 

  86. Guarneri, F., Guarneri, C. & Benvenga, S. Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry? J. Cell. Mol. Med. 9, 741–744 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Okazaki, K., Uchida, K. & Fukui, T. Recent advances in autoimmune pancreatitis: concept, diagnosis, and pathogenesis. J. Gastroenterol. 43, 409–418 (2008).

    CAS  PubMed  Google Scholar 

  88. Frulloni, L. et al. Identification of a novel antibody associated with autoimmune pancreatitis. N. Engl. J. Med. 361, 2135–2142 (2009).

    CAS  PubMed  Google Scholar 

  89. Takayama, S., Takahashi, H., Matsuo, Y., Okada, Y. & Manabe, T. Effects of Helicobacter pylori infection on human pancreatic cancer cell line. Hepatogastroenterology 54, 2387–2391 (2007).

    CAS  PubMed  Google Scholar 

  90. de Martel, C. et al. Helicobacter pylori infection and development of pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 17, 1188–1194 (2008).

    CAS  PubMed  Google Scholar 

  91. Risch, H. A., Yu, H., Lu, L. & Kidd, M. S. ABO blood group, Helicobacter pylori seropositivity, and risk of pancreatic cancer: a case–control study. J. Natl Cancer Inst. 102, 502–505 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Risch, H. A. Pancreatic cancer: Helicobacter pylori colonization, N-nitrosamine exposures, and ABO blood group. Mol. Carcinog. 51, 109–118 (2012).

    CAS  PubMed  Google Scholar 

  93. Risch, H. A. et al. ABO blood group and risk of pancreatic cancer: a study in Shanghai and meta-analysis. Am. J. Epidemiol. 177, 1326–1337 (2013).

    PubMed  PubMed Central  Google Scholar 

  94. Malfertheiner, P., Selgrad, M. & Bornschein, J. Helicobacter pylori: clinical management. Curr. Opin. Gastroenterol. 28, 608–614 (2012).

    CAS  PubMed  Google Scholar 

  95. Kountouras, J., Kapetanakis, N., Zavos, C. & Romiopoulos, I. Impact of Helicobacter pylori infection on normal colorectal mucosa, adenomatous polyps and the adenocarcinoma sequence. Colorectal Dis. http://dx.doi.org/10.1111/codi.12356.

  96. Machida-Montani, A. et al. Atrophic gastritis, Helicobacter pylori, and colorectal cancer risk: a case–control study. Helicobacter. 12, 328–332 (2007).

    PubMed  Google Scholar 

  97. Zhang, Y., Hoffmeister, M., Weck, M. N., Chang-Claude, J. & Brenner, H. Helicobacter pylori infection and colorectal cancer risk: evidence from a large population-based case–control study in Germany. Am. J. Epidemiol. 175, 441–450 (2012).

    PubMed  Google Scholar 

  98. Wu, Q., Yang, Z. P., Xu, P., Gao, L. C. & Fan, D. M. Association between Helicobacter pylori infection and the risk of colorectal neoplasia: a systematic review and meta-analysis. Colorectal Dis. 15, e352–e364 (2013).

    CAS  PubMed  Google Scholar 

  99. Sonnenberg, A. & Genta, R. M. Helicobacter pylori is a risk factor for colonic neoplasms. Am. J. Gastroenterol. 108, 208–215 (2013).

    PubMed  Google Scholar 

  100. Zhou, X., Zhang, C., Wu, J. & Zhang, G. Association between Helicobacter pylori infection and diabetes mellitus: a meta-analysis of observational studies. Diabetes Res. Clin. Pract. 99, 200–208 (2013).

    PubMed  Google Scholar 

  101. Jeon, C. Y. et al. Helicobacter pylori infection is associated with an increased rate of diabetes. Diabetes Care 35, 520–525 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Shin, D. W. et al. Association between metabolic syndrome and Helicobacter pylori infection diagnosed by histologic status and serological status. J. Clin. Gastroenterol. 46, 840–845 (2012).

    PubMed  Google Scholar 

  103. Chen, Y. & Blaser, M. J. Association between gastric Helicobacter pylori colonization and glycated hemoglobin levels. J. Infect. Dis. 205, 1195–1202 (2012).

    PubMed  PubMed Central  Google Scholar 

  104. Akanuma, M. et al. Influence of Helicobacter pylori eradication on the management of type 2 diabetes. Hepatogastroenterology 59, 641–645 (2012).

    PubMed  Google Scholar 

  105. Tseng, C. H. Diabetes, insulin use and Helicobacter pylori eradication: a retrospective cohort study. BMC Gastroenterol. 9, 12–46 (2012).

    Google Scholar 

  106. Chung, G. E. et al. Helicobacter pylori seropositivity in diabetic patients is associated with microalbuminuria. World J. Gastroenterol. 19, 97–102 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Zhou, X., Zhang, C., Wu, J. & Zhang, G. Association between Helicobacter pylori infection and diabetes mellitus: a meta-analysis of observational studies. Diabetes Res. Clin. Pract. 99, 200–208 (2013).

    PubMed  Google Scholar 

  108. Candelli, M. et al. High reinfection rate of Helicobacter pylori in young type 1 diabetic patients: a three-year follow-up study. Eur. Rev. Med. Pharmacol. Sci. 16, 1468–1472 (2012).

    CAS  PubMed  Google Scholar 

  109. Shi, W., Liu, W., Zhou, X., Ye, F. & Zhang, G. Associations of Helicobacter pylori infection and cytotoxin-associated gene A status with autoimmune thyroid diseases: a meta-analysis. Thyroid 23, 1294–1300 (2013).

    CAS  PubMed  Google Scholar 

  110. Franceschi, F. et al. Helicobacter pylori infection in patients with Hashimoto's thyroiditis. Helicobacter 9, 369 (2004).

    PubMed  Google Scholar 

  111. Ram, M. et al. Helicobacter pylori serology in autoimmune diseases—fact or fiction? Clin. Chem. Lab. Med. 51, 1075–1082 (2012).

    Google Scholar 

  112. Cicconi, V. et al. Disappearance of antiphospholipid antibodies syndrome after Helicobacter pylori eradication. Am. J. Med. 111, 163–164 (2001).

    CAS  PubMed  Google Scholar 

  113. Tüzün, Y., Keskin, S. & Kote, E. The role of Helicobacter pylori infection in skin diseases: facts and controversies. Clin. Dermatol. 28, 478–482 (2010).

    PubMed  Google Scholar 

  114. Di Campli, C. et al. Beneficial effects of Helicobacter pylori eradication on idiopathic chronic urticaria. Dig. Dis. Sci. 43, 1226–1229 (1998).

    CAS  PubMed  Google Scholar 

  115. Ojetti, V. et al. Helicobacter pylori infection affects eosinophilic cationic protein in the gastric juice of patients with idiopathic chronic urticaria. Int. Arch. Allergy Immunol. 125, 66–72 (2001).

    CAS  PubMed  Google Scholar 

  116. Magen, E. & Mishal, J. Possible benefit from treatment of Helicobacter pylori in antihistamine-resistant chronic urticaria. Clin. Exp. Dermatol. 38, 7–12 (2013).

    CAS  PubMed  Google Scholar 

  117. El-Khalawany, M. et al. Role of Helicobacter pylori in common rosacea subtypes: a genotypic comparative study of Egyptian patients. J. Dermatol. 39, 989–995 (2012).

    CAS  PubMed  Google Scholar 

  118. Malfertheiner, P. et al. European Helicobacter Study Group. Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report. Gut 61, 646–664 (2012).

    CAS  PubMed  Google Scholar 

  119. Vitale, G. et al. Nutritional aspects of Helicobacter pylori infection. Minerva Gastroenterol. Dietol. 57, 369–377 (2011).

    CAS  PubMed  Google Scholar 

Download references

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  1. Internal Medicine Institute, Catholic University of Rome, Policlinico A. Gemelli Largo A. Gemelli, Rome, 8-00168, Italy

    Francesco Franceschi, Giuseppe Zuccalà & Davide Roccarina

  2. Internal Medicine and Gastroenterology, Catholic University of Rome, Policlinico A. Gemelli Largo A. Gemelli, Rome, 8-00168, Italy

    Antonio Gasbarrini

Authors
  1. Francesco Franceschi
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  2. Giuseppe Zuccalà
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  3. Davide Roccarina
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  4. Antonio Gasbarrini
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Contributions

D. Roccarina and G. Zuccalà researched the data for the article. F. Franceschi wrote the article. A. Gasbarrini reviewed and edited it. All authors discussed the content of the article before submission.

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Correspondence to Francesco Franceschi.

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The authors declare no competing financial interests.

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Franceschi, F., Zuccalà, G., Roccarina, D. et al. Clinical effects of Helicobacter pylori outside the stomach. Nat Rev Gastroenterol Hepatol 11, 234–242 (2014). https://doi.org/10.1038/nrgastro.2013.243

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