gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLC10.22416/1382-4376-2018-28-4-15-22gastro-j-248Research ArticleОБЗОРЫREVIEWSИнфекция Helicobacter pylori и гепатобилиарная патологияHelicobacter pylori Infection and Hepatobiliary PathologyГерманС. В.GermanS. V.

доктор медицинских наук, ведущий научный сотрудник, 

119992, г. Москва, Погодинская ул., д. 10, стр. 1

Dr. Sci. (Med.), Leading Researcher

svgerman@yandex.ruБобровницкийИ. П.BobrovnitskyI. P.

доктор медицинских наук, академик РАН, профессор, 

119992, г. Москва, Погодинская ул., д. 10, стр. 1

Dr. Sci. (Med.), RAS Academician, Professor

1ipb@mail.ruФБГУ «Центр стратегического планирования и управления медико-биологическими рисками здоровью» Министерства здравоохранения Российской ФедерацииРоссияCentre of Strategic Planning and Management of Medical and Biological Health Risks, Ministry of Healthcare of the Russian FederationRussian Federation2018280820182841522Copyright © Герман С.В., Бобровницкий И.П., 20182018Герман С.В., Бобровницкий И.П.German S.V., Bobrovnitsky I.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/248Цель обзора

Цель обзора:  проанализировать данные о значении инфекции Helicobacter pylori для гепатобилиарных заболеваний.

Основные положения

Основные положения.  Последние два десятилетия растет число исследований, посвященных возможной причастности инфекции H. pylori к внежелудочной патологии. Обнаружено присутствие бактерии во многих органах и тканях. Доказана ее связь с развитием идиопатической железодефицитной анемии, В12-дефицитной анемии, идиопатической тромбоцитопенической пурпуры. Обсуждается возможная роль ее и в развитии гепатобилиарной патологии. У лиц с гепатобилиарными заболеваниями выявлено присутствие бактерии в образцах ткани печени, желчных путей, в желчи, желчных конкрементах. Участие H. pylori в образовании желчных конкрементов считается возможным. Неалкогольная жировая болезнь печени (НАЖБП) чаще диагностирована у инфицированных H. pylori лиц по сравнению с не инфицированными. Отмечено прогрессирование воспаления в печени любой природы при наличии инфекции H. pylori. Разные виды рода Helicobacter, в том числе H. pylori, могут влиять на развитие рака печени. Однако некоторые исследователи приводят данные против участия H. pylori в патогенезе различных гепатобилиарных заболеваний.

Заключение

Заключение.  Полученные авторами к настоящему времени результаты неоднозначны, поэтому необходимо продолжение исследований. Учитывая высокую повсеместную распространенность H. pylori-инфекции и значительную частоту гепатобилиарной патологии, подтверждение связи между ними может иметь большое эпидемиологическое, профилактическое и клиническое значение. 

Aim

Aim.  The aim of this review is to analyze and systematize data on the effect of Helicobacter pylori infection on hepatobiliary diseases.

Background

Background.  Over the past two decades, a growing number of studies have been devoted to the possible involvement of H. pylori infection in the extragastric pathology. The presence of the bacterium was detected in many organs and tissues. Its relationship with the development of idiopathic iron-deficiency anemia, B12 deficiency anemia, idiopathic thrombocytopenic purpura is proved. The possible role of the bacterium in the development of hepatobiliary pathology is also discussed. The presence of the bacterium has been revealed in samples taken from the liver tissue, biliary tract, bile and gallstones of patients suffering from hepatobiliary diseases. The involvement of H. pylori in the formation of gallstones is considered possible. Non-alcoholic fatty liver disease (NAFLD) is more often diagnosed in H. pylori infected individuals compared to those not infected. The progression of inflammation in the liver of any nature is noted in the presence of H. pylori infection. Different species of the Helicobacter genus, including H. pylori, are shown to contribute to the development of liver cancer. However, some researchers report data against the involvement of H. pylori in the pathogenesis of various hepatobiliary diseases.

Conclusion

Conclusion.  The results obtained by the authors cannot be considered unambiguous, thus requiring further research. Given the high prevalence of H. pylori infection and the significant incidence of hepatobiliary pathology, the confirmation of their relationship can be of great epidemiological, preventive and clinical importance. 

инфекция H. pyloriжелчнокаменная болезньнеалкогольная жировая болезнь печеницирроз печенипеченочноклеточный ракхолангиогенный ракCagAH. pylori infectioncholelithiasisnon-alcoholic fatty liver diseaseliver cirrhosishepatocellular carcinomacholangiocarcinomaCagAReferencesШептулин А.А., Лапина Т.Л., Кайбышева В.О. Новое в изучении инфекции Helicobacter pylori. Положения Согласительного совещания Маастрихт V (2016). Рос журн гастроэнт гепатол колопроктол. 2017;27(1):35– 43. DOI: 10.22416/1382-4376-2017-27-1-35-43 [Sheptulin A.A., Lapina T.L., Kaybysheva V.O. Update on Helicobacter pylori infection study and key points of «Maastricht-V» consensus conference (2016). Rus J. Gastroenterol. Hepatol. Coloproctol. 2017;27(1):35–43. DOI: 10.22416/1382-4376-2017-27-1-35-43 (In Rus.)].Шептулин А.А., Лапина Т.Л., Кайбышева В.О. Новое в изучении инфекции Helicobacter pylori. Положения Согласительного совещания Маастрихт V (2016). Рос журн гастроэнт гепатол колопроктол. 2017;27(1):35– 43. DOI: 10.22416/1382-4376-2017-27-1-35-43 [Sheptulin A.A., Lapina T.L., Kaybysheva V.O. Update on Helicobacter pylori infection study and key points of «Maastricht-V» consensus conference (2016). Rus J. Gastroenterol. Hepatol. Coloproctol. 2017;27(1):35–43. DOI: 10.22416/1382-4376-2017-27-1-35-43 (In Rus.)].Polyzos S.A., Kountouras J., Papatheodorou A., Patsiaoura K., Katsiki E., Zafeiriadou E., et al. Helicobacter pylori infection in patients with nonalcoholic fatty liver disease. Metabolism. 2013;62:121–6. DOI: 10.1016/ jmetabol.2012.06.007Polyzos S.A., Kountouras J., Papatheodorou A., Patsiaoura K., Katsiki E., Zafeiriadou E., et al. Helicobacter pylori infection in patients with nonalcoholic fatty liver disease. Metabolism. 2013;62:121–6. DOI: 10.1016/ jmetabol.2012.06.007Pirouz T., Zounubi L., Keivani H., Rakhshani N., Hormazdi M. Detection of Helicobacter pylori in paraffinembedded speicimens from pacients with chronic liver diseases, using the amplification method. Dig Dis Sci. 2009;54:1456–9.Pirouz T., Zounubi L., Keivani H., Rakhshani N., Hormazdi M. Detection of Helicobacter pylori in paraffinembedded speicimens from pacients with chronic liver diseases, using the amplification method. Dig Dis Sci. 2009;54:1456–9.Dogan Z., Filik L., Ergul B., Sarikaya M., Akbal E. Association between Helicobacter pylori and liver-to-spleen ratio: a randomized-controlled single-blind study. Eur J Gastroenterol Hepatol. 2013;25:107–10.Dogan Z., Filik L., Ergul B., Sarikaya M., Akbal E. Association between Helicobacter pylori and liver-to-spleen ratio: a randomized-controlled single-blind study. Eur J Gastroenterol Hepatol. 2013;25:107–10.Pellicano R., Menard A., Rizzetto M., Megraud F. Helicobacter species and liver diseases: association or causation?. Lancet Infect Dis. 2008;8:254–60. DOI: 10.1016/ S1473-3099(08)70066-5Pellicano R., Menard A., Rizzetto M., Megraud F. Helicobacter species and liver diseases: association or causation?. Lancet Infect Dis. 2008;8:254–60. DOI: 10.1016/ S1473-3099(08)70066-5Исаева Г.Ш., Абузарова Э.Р., Валеева Ю.В., Поздеев О.К., Муравьева Е.В. Helicobacter pylori у больных с заболеваниями гепатобилиарной системы. Журнал микробиологии, эпидемиологии, иммунобиологии. 2009;2:96–101. [Isaeva G.Sh., Abuzarova E.R., Valeeva Yu.V., Pozdeev O.K., Muravyova E.V. Helicobacter pylori among the patients with hepatobiliary system diseases. Journal of Microbiology, Epidemiology and Immunobiology. 2009;2:96–101 (In Rus.)].Исаева Г.Ш., Абузарова Э.Р., Валеева Ю.В., Поздеев О.К., Муравьева Е.В. Helicobacter pylori у больных с заболеваниями гепатобилиарной системы. Журнал микробиологии, эпидемиологии, иммунобиологии. 2009;2:96–101. [Isaeva G.Sh., Abuzarova E.R., Valeeva Yu.V., Pozdeev O.K., Muravyova E.V. Helicobacter pylori among the patients with hepatobiliary system diseases. Journal of Microbiology, Epidemiology and Immunobiology. 2009;2:96–101 (In Rus.)].Abayli B., Colakoglu S., Serin M., Erdogan S., Isiksal Y.F., Tuncer I., et al. Helicobacter pylori in the etiology of cholesterol gallsnones. J Clin Gastroenterol. 2005;39: 134–7.Abayli B., Colakoglu S., Serin M., Erdogan S., Isiksal Y.F., Tuncer I., et al. Helicobacter pylori in the etiology of cholesterol gallsnones. J Clin Gastroenterol. 2005;39: 134–7.Neri V., Margiotta M., Francesco V., Ambrosi A., Valle N.D., Fersini A., et al. DNA sequences and proteic antigens of Helicobacter pylori in cholecystic bile and tissue of patients with gallstones. Aliment Pharmacol Ther. 2005;22:715–20.Neri V., Margiotta M., Francesco V., Ambrosi A., Valle N.D., Fersini A., et al. DNA sequences and proteic antigens of Helicobacter pylori in cholecystic bile and tissue of patients with gallstones. Aliment Pharmacol Ther. 2005;22:715–20.Lee J.-W., Lee D.H., Jung Il., Jeong S., Kwon K.S., Kim H.G., et al. Identification of Helicobacter pylori in gallstone, Bile and other hepatobiliary tissues of patients with cholecystitis. Gut Liver. 2010;4(1):60–7. DOI: 10.5009/gnl.2010.4.1.60.Lee J.-W., Lee D.H., Jung Il., Jeong S., Kwon K.S., Kim H.G., et al. Identification of Helicobacter pylori in gallstone, Bile and other hepatobiliary tissues of patients with cholecystitis. Gut Liver. 2010;4(1):60–7. DOI: 10.5009/gnl.2010.4.1.60.Waluga M., Kukla M., Zorniak M., Bacik A., Kotulski R. From the stomach to other organs: Helicobacter pylori and the liver. World J Gastroenterol. 2015;7(18):2136–46. DOI: 10.4254vjh.v7.i18.2136Waluga M., Kukla M., Zorniak M., Bacik A., Kotulski R. From the stomach to other organs: Helicobacter pylori and the liver. World J Gastroenterol. 2015;7(18):2136–46. DOI: 10.4254vjh.v7.i18.2136Baeg M.K., Yoon S.K., Ko S.-H., Noh Y.-S., Lee I.-S., Choj M.-G. Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease. World J Gastroenterol. 2016;22(8):2592–600. DOI:10.3748/wjg.v22.i8.2592Baeg M.K., Yoon S.K., Ko S.-H., Noh Y.-S., Lee I.-S., Choj M.-G. Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease. World J Gastroenterol. 2016;22(8):2592–600. DOI:10.3748/wjg.v22.i8.2592Okushin K., Takahashi Y., Yamamichi N., Shimamoto T., Enooku K., Fujinaga H., et al. Helicobacter pylori infection is not associated with fatty liver disease including non-alcoholic fatty liver disease: a large-scale cross-sectional study in Japan. BMC Gastronterol. 2015;15.25.Okushin K., Takahashi Y., Yamamichi N., Shimamoto T., Enooku K., Fujinaga H., et al. Helicobacter pylori infection is not associated with fatty liver disease including non-alcoholic fatty liver disease: a large-scale cross-sectional study in Japan. BMC Gastronterol. 2015;15.25.Kawaguchi M., Saito T., Ohno H., Midorikawa S., Sanji T., Handa Y., et al. Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa. J Gastroenterol. 1996;31:294–8.Kawaguchi M., Saito T., Ohno H., Midorikawa S., Sanji T., Handa Y., et al. Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa. J Gastroenterol. 1996;31:294–8.Farshad S., Alborzi A., Malek Hosseini S.A., et al. Identification of Helicobacter pylori DNA in Iranian patients with gallstones. Epidemiol Infect. 2004;132:1185–9.Farshad S., Alborzi A., Malek Hosseini S.A., et al. Identification of Helicobacter pylori DNA in Iranian patients with gallstones. Epidemiol Infect. 2004;132:1185–9.Zhou D., Wen-bin Guan, Jian-dong Wang, Zang Y., Gong W., Zhi-wei Quan. A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa. PLOS. 2013;8(7):e70265.Zhou D., Wen-bin Guan, Jian-dong Wang, Zang Y., Gong W., Zhi-wei Quan. A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa. PLOS. 2013;8(7):e70265.Bulajic M., Maisonneuve P., Schneider-Brachert W., Muller P., Reischl U., et al. Helicobacter pylori and the risk of benign and malignant biliary tract disease. Cancer. 2002;95:1946–53.Bulajic M., Maisonneuve P., Schneider-Brachert W., Muller P., Reischl U., et al. Helicobacter pylori and the risk of benign and malignant biliary tract disease. Cancer. 2002;95:1946–53.Dar M.Y., Ali S., Raina A.H., Raina M.A., Shah O.J., Mudassar S. Association of Helicobacter pylori with hepatobiliary stone disease, a prospective case control study. Indian J Gastroenterol. 2016;35(5):343–6. DOI: 10.1007/ s12664-016-0675-7Dar M.Y., Ali S., Raina A.H., Raina M.A., Shah O.J., Mudassar S. Association of Helicobacter pylori with hepatobiliary stone disease, a prospective case control study. Indian J Gastroenterol. 2016;35(5):343–6. DOI: 10.1007/ s12664-016-0675-7Sherafat S.J., Tajeddin E., Majidi M.R.S., Vaziri F., Alebouyen M., Alizade A.H.M., et al. Lack of association between Helicobacter pylori infection and biliary tract diseases. Polish J Microbiol. 2012;61(4):309–22.Sherafat S.J., Tajeddin E., Majidi M.R.S., Vaziri F., Alebouyen M., Alizade A.H.M., et al. Lack of association between Helicobacter pylori infection and biliary tract diseases. Polish J Microbiol. 2012;61(4):309–22.de Alwis N.M., Day C.P. Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol. 2008;48(1):1004–112.de Alwis N.M., Day C.P. Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol. 2008;48(1):1004–112.Bellentani S., Scaglioni F., Marino M., Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig Dis. 2010;28:155–61.Bellentani S., Scaglioni F., Marino M., Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig Dis. 2010;28:155–61.Bhala N., Jouness R.I., Bugianesi E. Epidemiology and natural history of patients with NAFLD. Curr Pharm Des. 2013;19:5169–76.Bhala N., Jouness R.I., Bugianesi E. Epidemiology and natural history of patients with NAFLD. Curr Pharm Des. 2013;19:5169–76.Ивашкин В.Т., Маевская М.В., Павлов Ч.С., Тихонов И.Н., Широкова Е.Н, Буеверов и др. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Рос журн гастроэнт гепатол колопроктол. 2016;26(2):24– 42 [Ivashkin V.T., Mayevskaya M.V., Pavlov Ch.S., Tikhonov I.N., Shirokova Ye.N., Buyeverov A.O., et al. Diagnostics and treatment of non-alcoholic fatty liver disease: clinical guidelines of the Russian Scientific Liver Society and the Russian gastroenterological association. Rus J Gastroenterol Hepatol Coloproctol. 2016;26(2):24–42 (in Rus.)].Ивашкин В.Т., Маевская М.В., Павлов Ч.С., Тихонов И.Н., Широкова Е.Н, Буеверов и др. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Рос журн гастроэнт гепатол колопроктол. 2016;26(2):24– 42 [Ivashkin V.T., Mayevskaya M.V., Pavlov Ch.S., Tikhonov I.N., Shirokova Ye.N., Buyeverov A.O., et al. Diagnostics and treatment of non-alcoholic fatty liver disease: clinical guidelines of the Russian Scientific Liver Society and the Russian gastroenterological association. Rus J Gastroenterol Hepatol Coloproctol. 2016;26(2):24–42 (in Rus.)].Драпкина О.М., Корнеева О.Н. Континуум неалкогольной жировой болезни печени: от стеатоза печени до сердечно-сосудистого риска. Рациональная фармакотерапия в кардиологии. 2016;12(4):424–9 [Drapkina O.M., Korneeva O.N. Continuum of non-alcoholic fatty liver disease: from liver steatosis to cardiovascular risk. Rational pharmacotherapy in cardiology. 2016;12 (4):424–9 (in Rus.)].Драпкина О.М., Корнеева О.Н. Континуум неалкогольной жировой болезни печени: от стеатоза печени до сердечно-сосудистого риска. Рациональная фармакотерапия в кардиологии. 2016;12(4):424–9 [Drapkina O.M., Korneeva O.N. Continuum of non-alcoholic fatty liver disease: from liver steatosis to cardiovascular risk. Rational pharmacotherapy in cardiology. 2016;12 (4):424–9 (in Rus.)].Rinella M.E. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313:2263–73.Rinella M.E. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313:2263–73.Anstee Q.M., Targher G., Day C.P. Progression of NAFLD to diabetes mellitus, cardiovascular diseases or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10:330–44.Anstee Q.M., Targher G., Day C.P. Progression of NAFLD to diabetes mellitus, cardiovascular diseases or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10:330–44.Henao-Mejia J., Elinav E., Jin C., Hao L., Mehal W.Z., Strowig T., et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482:179–85.Henao-Mejia J., Elinav E., Jin C., Hao L., Mehal W.Z., Strowig T., et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482:179–85.Le Roy T., Llopis M., Lepage P., Bruneau A., Rabot S., Bevilacqua C., et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut. 2013;62:1787–94.Le Roy T., Llopis M., Lepage P., Bruneau A., Rabot S., Bevilacqua C., et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut. 2013;62:1787–94.Cindoruk M., Cirak M.Y., Unal S., Karakan T., Erkan G., Engin D., et al. Identification of Helicobacter species by 16s rDNA PCR and sequence analysis in human liver samples from patients with various etiologies of benign liver diseases. Eur J Gastroenterol Hepatol. 2008;20:33–6.Cindoruk M., Cirak M.Y., Unal S., Karakan T., Erkan G., Engin D., et al. Identification of Helicobacter species by 16s rDNA PCR and sequence analysis in human liver samples from patients with various etiologies of benign liver diseases. Eur J Gastroenterol Hepatol. 2008;20:33–6.Sumida Y., Kanemasa K., Imai S., Mori K., Tanaka S., Shimokobe H., et al. Helicobacter pylori infection might have a potential role in hepatocyte ballooning in nonalcoholic fatty liver disease. J Gastroenterol. 2015;50:996–1004.Sumida Y., Kanemasa K., Imai S., Mori K., Tanaka S., Shimokobe H., et al. Helicobacter pylori infection might have a potential role in hepatocyte ballooning in nonalcoholic fatty liver disease. J Gastroenterol. 2015;50:996–1004.Li M., Shen Z., Li Y.M. Potential role of Helicobacter pylori infection in nonalchoholic fatty liver disease. World J Gastroenterol. 2013;19:7024–31.Li M., Shen Z., Li Y.M. Potential role of Helicobacter pylori infection in nonalchoholic fatty liver disease. World J Gastroenterol. 2013;19:7024–31.Eshraghian A., Eshraghian H., Ranjbar Omrani G. Insulin resistance and metabolic syndrome: is Helicobacter pylori criminal?. Minerva Gastroenterol Dietol. 2011;57:379–85.Eshraghian A., Eshraghian H., Ranjbar Omrani G. Insulin resistance and metabolic syndrome: is Helicobacter pylori criminal?. Minerva Gastroenterol Dietol. 2011;57:379–85.Jeon C.Y., Haan M.N., Cheng C., Clayton E.R., Mayeda E.R., Miller J.W., Aiello A.E. Helicobacter pylori infection is associated with an increase rate of diabetes. Diabetes Care. 2012;35:520–5.Jeon C.Y., Haan M.N., Cheng C., Clayton E.R., Mayeda E.R., Miller J.W., Aiello A.E. Helicobacter pylori infection is associated with an increase rate of diabetes. Diabetes Care. 2012;35:520–5.Vafaeimanesh J., Parham M., Seyyedmajidi M., Bagherzadeh M. Helicobacter pylori infection and insulin resistance in diabetic and nondiabetic population. Sci Word J. 2014;2014:1–5. DOI: 10.1155/2014/391250Vafaeimanesh J., Parham M., Seyyedmajidi M., Bagherzadeh M. Helicobacter pylori infection and insulin resistance in diabetic and nondiabetic population. Sci Word J. 2014;2014:1–5. DOI: 10.1155/2014/391250Zhou X., Liu W., Gu M., Zhou H., Zhang G. Helicobacter pylori infection causes hepatic insulin resistance through the с-Jun/miR-203/SOCS3 signaling pathway. Gastroenterology. 2015;148(4):83. DOI: 10.1016/s0016- 5085(15)30287-0Zhou X., Liu W., Gu M., Zhou H., Zhang G. Helicobacter pylori infection causes hepatic insulin resistance through the с-Jun/miR-203/SOCS3 signaling pathway. Gastroenterology. 2015;148(4):83. DOI: 10.1016/s0016- 5085(15)30287-0Gen R., Demir M., Ataseven H. Effect of Helicobacter pylori eradication on insulin resistance, serum lipids and lowgrade inflammation. South Med J. 2010;103(3):190–6. DOI: 10.1097/smj.0b013e3181cf373fGen R., Demir M., Ataseven H. Effect of Helicobacter pylori eradication on insulin resistance, serum lipids and lowgrade inflammation. South Med J. 2010;103(3):190–6. DOI: 10.1097/smj.0b013e3181cf373fGunji T., Matsuhashi N., Sato H., Fujibayashi K., Okumura M., Sasabe N., Urabe A. Helicobacter pylori infection significantly increases insulin resistance in the asymptomatic Japanese population. Helicobacter. 2009;14(5):496–502. DOI: 10.1111/J.1523- 5378.2009.00705.XGunji T., Matsuhashi N., Sato H., Fujibayashi K., Okumura M., Sasabe N., Urabe A. Helicobacter pylori infection significantly increases insulin resistance in the asymptomatic Japanese population. Helicobacter. 2009;14(5):496–502. DOI: 10.1111/J.1523- 5378.2009.00705.XPark S.H., Jeon W.K., Kim S.H., Kim H.J., Park D.I., Cho Y.K., et al. Helicobacter pylori eradication has no effect on metabolic and inflammatory parameters. J Natl Med Assoc. 2005;97(4):508–13.Park S.H., Jeon W.K., Kim S.H., Kim H.J., Park D.I., Cho Y.K., et al. Helicobacter pylori eradication has no effect on metabolic and inflammatory parameters. J Natl Med Assoc. 2005;97(4):508–13.Stalke P., Zoltowska A., Orlowski M., Ellert-Zygadlowska J., Witczak-Malinowska K., Michalska Z., et al. Correlation between liver damage and degree of gastric mucose colonization by Helicobacter pylori in subjects with parenchymatous liver damage. Med Sci Monit. 2001;7(Suppl 1):271–6.Stalke P., Zoltowska A., Orlowski M., Ellert-Zygadlowska J., Witczak-Malinowska K., Michalska Z., et al. Correlation between liver damage and degree of gastric mucose colonization by Helicobacter pylori in subjects with parenchymatous liver damage. Med Sci Monit. 2001;7(Suppl 1):271–6.Goo M.J., Ki M.R., Lee H.R., Yang H.J., Yuan D.W., Hong I.H., et al. Helicobacter pylori promotes hepatic fibrosis in the animal model. Lab Invest. 2009;89:1291–303. DOI: 10.138/labinvest.2009.90Goo M.J., Ki M.R., Lee H.R., Yang H.J., Yuan D.W., Hong I.H., et al. Helicobacter pylori promotes hepatic fibrosis in the animal model. Lab Invest. 2009;89:1291–303. DOI: 10.138/labinvest.2009.90Figura N. Hypothesis: Helicobacter toxins and liver. Helicobacter. 1996;1:187–9.Figura N. Hypothesis: Helicobacter toxins and liver. Helicobacter. 1996;1:187–9.Salehi H., Minakari M., Yaghoutkar A., Tabesh E., Salehi M., Mirbagher L. The effect of Helicobacter pylori eradication on liver enzymes in patients referring with unexplained hypertransaminasemia. Adv Biomed Res. 2014;3:131.Salehi H., Minakari M., Yaghoutkar A., Tabesh E., Salehi M., Mirbagher L. The effect of Helicobacter pylori eradication on liver enzymes in patients referring with unexplained hypertransaminasemia. Adv Biomed Res. 2014;3:131.Feng H., Zhou X., Zhang G. Association between cirrhosis and Helicobacter pylori infection: a meta-analysis. Eur J Gastroenterol Hepatol. 2014;26:1309–19.Feng H., Zhou X., Zhang G. Association between cirrhosis and Helicobacter pylori infection: a meta-analysis. Eur J Gastroenterol Hepatol. 2014;26:1309–19.Takuma Y. Helicobacter pylori infection and liver disease. Gan To Kagaku Ryoho. 2011;38:362–4.Takuma Y. Helicobacter pylori infection and liver disease. Gan To Kagaku Ryoho. 2011;38:362–4.Jiang H.X., Qin S.Y., Min Z.G., Xie M.Z., Lin T., Hu B.L., Guo X.Y. Association of Helicobacter pylori with elevated blood ammonia levels in cirrhotic patients: a meta-analysis. Yonsei Med J. 2013;54:832–8.Jiang H.X., Qin S.Y., Min Z.G., Xie M.Z., Lin T., Hu B.L., Guo X.Y. Association of Helicobacter pylori with elevated blood ammonia levels in cirrhotic patients: a meta-analysis. Yonsei Med J. 2013;54:832–8.Mitrica D., Plesa A., Constantinescu R., Drug V., Stanciu C. Efficacy of Helicobacter pylori eradication therapy in cirrhotic patients with peptic ulcer disease. Rev Med Chir Soc Med Nat Iasi. 2011;115:367–74.Mitrica D., Plesa A., Constantinescu R., Drug V., Stanciu C. Efficacy of Helicobacter pylori eradication therapy in cirrhotic patients with peptic ulcer disease. Rev Med Chir Soc Med Nat Iasi. 2011;115:367–74.Chang S.S., Hu H.Y. H. pylori eradication lower ulcers in cirrhosis. J Dig Dis. 2014;15:451–8.Chang S.S., Hu H.Y. H. pylori eradication lower ulcers in cirrhosis. J Dig Dis. 2014;15:451–8.Demirtȕrk L., Yazgan Y., Ozel M., Togrol E., Gȕltepe M., Gȕrbȕz A.K., Yildirim S. The effect of Helicobacter pylori eradication on gastric juice and blood ammonia concentrations and on visual evoked potentials in cirrhotics. Helicobacter. 2001;6:325–30.Demirtȕrk L., Yazgan Y., Ozel M., Togrol E., Gȕltepe M., Gȕrbȕz A.K., Yildirim S. The effect of Helicobacter pylori eradication on gastric juice and blood ammonia concentrations and on visual evoked potentials in cirrhotics. Helicobacter. 2001;6:325–30.Nandakumar R., Naik A.S., Pandit B., Kamat R., Bhatia S.J. Effect of Helicobacter pylori eradication on serum ammonia levels in patients with chronic liver disease. Indian J Gastroenterol. 2003;22:221–3.Nandakumar R., Naik A.S., Pandit B., Kamat R., Bhatia S.J. Effect of Helicobacter pylori eradication on serum ammonia levels in patients with chronic liver disease. Indian J Gastroenterol. 2003;22:221–3.Schulz C., Schutte K., Malfertheiner P. Does H. pylori eradication therapy benefit patients with hepatic encephalopathy? Systematic review. J Clin Gastroenterol. 2014;48;491–9. DOI: 10.1097/MCG00108Schulz C., Schutte K., Malfertheiner P. Does H. pylori eradication therapy benefit patients with hepatic encephalopathy? Systematic review. J Clin Gastroenterol. 2014;48;491–9. DOI: 10.1097/MCG00108Huber M., Rossle M., Siegerstetter V., Ochs A., Haag K., Kist M., Blum H.E. Helicobacter pylori infection does not correlate with plasma ammonia concentration and hepatic encephalopathy in patients with cirrhosis. Hepatogastroenterology. 2001;48:541–4.Huber M., Rossle M., Siegerstetter V., Ochs A., Haag K., Kist M., Blum H.E. Helicobacter pylori infection does not correlate with plasma ammonia concentration and hepatic encephalopathy in patients with cirrhosis. Hepatogastroenterology. 2001;48:541–4.Zullo A., Hassan C., Morini S. Hepatic encephalopathy and Helicobacter pylori: a critical reappraisal. J Clin Gastroenterol. 2003;37:164–8.Zullo A., Hassan C., Morini S. Hepatic encephalopathy and Helicobacter pylori: a critical reappraisal. J Clin Gastroenterol. 2003;37:164–8.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. 2013;37:619–25. DOI: 10.1016/jclinre.2013.05.004Hu B.L., Wang H.Y., Yang G.Y. Association of Helicobacter pylori infection with hepatic encephalopathy risk: a systematic review. Clin Res Hepatol Gastroenterol. 2013;37:619–25. DOI: 10.1016/jclinre.2013.05.004Kountouras J., Zavos C., Deretzi G. Helicobacter pylori might contribute to persistent cognitive impairment after resolution of overt hepatic encephalopathy. Clin Gastroenterol Hepatol. 2011;9:624–5. DOI: 10.1016/j.cgh.2011.02.011Kountouras J., Zavos C., Deretzi G. Helicobacter pylori might contribute to persistent cognitive impairment after resolution of overt hepatic encephalopathy. Clin Gastroenterol Hepatol. 2011;9:624–5. DOI: 10.1016/j.cgh.2011.02.011Nilsson H.O., Mulchandani R., Tranberg K.G., Stenram U., Wadström T. Helicobacter species identified in liver from patients with cholangiocarcinoma and hepatocellular carcinoma. Gastroenerology. 2001;120;323–4.Nilsson H.O., Mulchandani R., Tranberg K.G., Stenram U., Wadström T. Helicobacter species identified in liver from patients with cholangiocarcinoma and hepatocellular carcinoma. Gastroenerology. 2001;120;323–4.Boonyanugomol W., Chomvarin C., Sripa B., Bhuchisawasdi V., Khuntikeo N., Hahnvajanawong C., Chamsuwan A. Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation. HPB(Oxford). 2012;14(3):177–84. DOI: 10.1111/i.1477-2574.2011.00423.xBoonyanugomol W., Chomvarin C., Sripa B., Bhuchisawasdi V., Khuntikeo N., Hahnvajanawong C., Chamsuwan A. Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation. HPB(Oxford). 2012;14(3):177–84. DOI: 10.1111/i.1477-2574.2011.00423.xMurphy G., Michel A., Taylor Ph.R., Albanes D., Weinstein S.J., Virtamo J., et al. Association of seropositivity to Helicobacter species and biliary tract cancer in the ATBC study. Hepatology. 2014;60(6):1963–71.Murphy G., Michel A., Taylor Ph.R., Albanes D., Weinstein S.J., Virtamo J., et al. Association of seropositivity to Helicobacter species and biliary tract cancer in the ATBC study. Hepatology. 2014;60(6):1963–71.Fukuda Y., Bamba H., Okui M., Tamura K., Tanida N., Satomi M., et al. Helicobacter pylori infection increases mucosal permeability of the stomach and intestine. Digestion. 2001;63(1):93–6.Fukuda Y., Bamba H., Okui M., Tamura K., Tanida N., Satomi M., et al. Helicobacter pylori infection increases mucosal permeability of the stomach and intestine. Digestion. 2001;63(1):93–6.Dore M.P., Realdi G., Mura D., Graham D.Y., Sepulveda A.R. Helicobacter infection in patients with HCVrelated chronic hepatitis, cirrhosis and hepatocellular carcinoma. Dig Dis Sci. 2002;47:1638–43.Dore M.P., Realdi G., Mura D., Graham D.Y., Sepulveda A.R. Helicobacter infection in patients with HCVrelated chronic hepatitis, cirrhosis and hepatocellular carcinoma. Dig Dis Sci. 2002;47:1638–43.Abu Al-Soid W, Stenram U., Ljungh A., Tranberg K.G., Nilsson H.O., Wadström T. DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma. Dig Liver Dis. 2008;40:126–31.Abu Al-Soid W, Stenram U., Ljungh A., Tranberg K.G., Nilsson H.O., Wadström T. DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma. Dig Liver Dis. 2008;40:126–31.Leewalat K., Suksumek N., Leewalat S., Lek-Uthai U. Detection of VacA gene specific for Helicobacter pylori in hepatocellular carcinoma and cholangiocarcinoma specimes of Thai patients. Southeast Asian J Trop Med Public Health. 2007;38:881–5.Leewalat K., Suksumek N., Leewalat S., Lek-Uthai U. Detection of VacA gene specific for Helicobacter pylori in hepatocellular carcinoma and cholangiocarcinoma specimes of Thai patients. Southeast Asian J Trop Med Public Health. 2007;38:881–5.Huang Y., Fan X.G., Wang Z.M., Zhou J.H., Tian X.F., Li N. Identification of Helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol. 2004;57:1273–7.Huang Y., Fan X.G., Wang Z.M., Zhou J.H., Tian X.F., Li N. Identification of Helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol. 2004;57:1273–7.Verhoef С., Pot R.G., de Man R.A., Zondervan P.E., Kuipers E.J., Ijzermans J.N., Kusters J.G. Detection of identical Helicobacter DNA in the stomach and in the non-cirrhotic liver of patients with hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 2003;15:1171–4.Verhoef С., Pot R.G., de Man R.A., Zondervan P.E., Kuipers E.J., Ijzermans J.N., Kusters J.G. Detection of identical Helicobacter DNA in the stomach and in the non-cirrhotic liver of patients with hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 2003;15:1171–4.Rocha M., Avenaud P., Menard A., Le Bail B., Balabaud C., Bioulac-Sage P., et al. Association of Helicobacter species with hepatitis C cirrhosis with or without hepatocellular carcinoma. Gut. 2005;54:396–401.Rocha M., Avenaud P., Menard A., Le Bail B., Balabaud C., Bioulac-Sage P., et al. Association of Helicobacter species with hepatitis C cirrhosis with or without hepatocellular carcinoma. Gut. 2005;54:396–401.Ponzetto A., Pellicano R., Leone N., Berrutti M., Turrini F., Rizzetto M. Helicobacter pylori seroprevalence in cirrhotic patients with hepatitis B virus infection. Neth J Med. 2000;56:206–10.Ponzetto A., Pellicano R., Leone N., Berrutti M., Turrini F., Rizzetto M. Helicobacter pylori seroprevalence in cirrhotic patients with hepatitis B virus infection. Neth J Med. 2000;56:206–10.Queiroz D.M., Rocha A.M., Rocha G.F., Cinque S.M., Oliveira A.G., Godoy A., Tanno H. Association between Helicobacter pylori infection and cirrhosis in patients with chronic hepatitis C virus. Dig Dis Sci. 2006;51:370–3.Queiroz D.M., Rocha A.M., Rocha G.F., Cinque S.M., Oliveira A.G., Godoy A., Tanno H. Association between Helicobacter pylori infection and cirrhosis in patients with chronic hepatitis C virus. Dig Dis Sci. 2006;51:370–3.Chen R., Fan X.G., Huang Y., Chen C.H. In vitro cytotoxicity of Helicobacter pylori on hepatocarcinoma HepG2 cells. Ai Zheng. 2004;23:44–9.Chen R., Fan X.G., Huang Y., Chen C.H. In vitro cytotoxicity of Helicobacter pylori on hepatocarcinoma HepG2 cells. Ai Zheng. 2004;23:44–9.Zhang Y., Fan X.Y., Chen R., Xiao Z.Q., Feng X.P., Tian X.F., Chen Z.H. Comparative proteome analysis of untreated and Helicobacter pylori-treated HepG2. World J Gastroenterol. 2005;11:3485–9.Zhang Y., Fan X.Y., Chen R., Xiao Z.Q., Feng X.P., Tian X.F., Chen Z.H. Comparative proteome analysis of untreated and Helicobacter pylori-treated HepG2. World J Gastroenterol. 2005;11:3485–9.Yong X., Tang Bo, Li Bo-S., Xie R., Hu C-J., Luo G., et al. Helicobacter pylori virulence factor CagA promotes tumorigenesis of gastric cancer via multiple signaling pathways. Cell Communication and Signaling. 2015;13:30. DOI: 10.1186/s12964-015-0111-0Yong X., Tang Bo, Li Bo-S., Xie R., Hu C-J., Luo G., et al. Helicobacter pylori virulence factor CagA promotes tumorigenesis of gastric cancer via multiple signaling pathways. Cell Communication and Signaling. 2015;13:30. DOI: 10.1186/s12964-015-0111-0Garcia A., Feng Y., Parry N.M., McCabe A., Mobley M.W., Lertpiriyapong K., et al. Helicobacter pylori infection does not promote hepatocellular cancer in a transgenic mouse model of hepatitis C virus pathogenesis. Gut Microbes. 2013;4:577–90.Garcia A., Feng Y., Parry N.M., McCabe A., Mobley M.W., Lertpiriyapong K., et al. Helicobacter pylori infection does not promote hepatocellular cancer in a transgenic mouse model of hepatitis C virus pathogenesis. Gut Microbes. 2013;4:577–90.Fox J.G., Feng Y., Theve E.J., Raczynski A.R., Fiala J.L., Doernte A.L., et al. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut. 2010;59:88–97.Fox J.G., Feng Y., Theve E.J., Raczynski A.R., Fiala J.L., Doernte A.L., et al. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut. 2010;59:88–97.Rabelo-Goncalves E.M.A., Roesler B.M., Zeitune J.M.R. Extragastric manifestation of Helicobacter pylori infection: possible role of bacterium in liver and pancreas diseases. World J Hepatol. 2015,7(30):2968–3979. DOI: 10.4254/wjh.v7.i30.2968Rabelo-Goncalves E.M.A., Roesler B.M., Zeitune J.M.R. Extragastric manifestation of Helicobacter pylori infection: possible role of bacterium in liver and pancreas diseases. World J Hepatol. 2015,7(30):2968–3979. DOI: 10.4254/wjh.v7.i30.2968

The authors declare that there are no conflicts of interest present.