Abstract
The chapter is a review of current knowledge on the impact of H. pylori infection on the clinical course of patients with various forms of liver damage. H. pylori infection is found in 50–90% of the world population. The bacteria not only mainly contribute to occurrence of gastric mucosa inflammation but also to gastric ulcer and cancer. H. pylori contains an active antioxidative system, which not only neutralizes free radicals but also synthesizes specific VacA toxin, which leads to destruction and apoptosis of the cells. A specific system of bacterial CagA genes has a special role in carcinogenesis. There is an increasing number of reports describing lesions in the circulatory system, pancreas, or the skin, connected with H. pylori infection. Liver colonization by H. pylori happens after transmission of the bacteria from the stomach, with blood, through the portal vein or directly through the bile ducts. The bacteria promote liver function deterioration in the course of toxic injury, autoimmune inflammation, chronic HBV, and HCV infection. Infections among people with liver cirrhosis are especially dangerous. In this group of patients, H. pylori infection may significantly worsen liver function, leading to hyperammonemia, increased portal pressure, and development of esophageal varices. Thus, testing for and treating this infection among patients with liver cirrhosis is especially important.
Keywords
- H. pylori
- hepatitis
- hepatic liver cirrhosis
- liver and biliary tract cancer
1. Introduction
In developed countries, infection by these bacteria is detected in about 50% of the population, while in developing countries, the percentage may even reach 90% [2]. Still, however, there are no definitive pointers as to risk factors of
Bacterial DNA contains genes encoding cytotoxin synthesis system. VacA toxin (vacuolating toxin) is encoded by a changing system of genes in 40–60% of bacterial strains. This underlies different toxic properties. In epithelial cells, VacA promotes fusion of several lysosomes and formation of large vacuoles, which changes the construction of cytoskeleton. VacA toxin induces apoptosis of epithelial cells and shows highly immunogenic properties.
Specific system of CagA genes encodes synthesis of CagA toxin, demonstrating properties reorganizing cytoskeleton and cell shape. Moreover, the toxin controls transcription and proliferation of the cell, as well as inflammatory reaction. CagA toxin plays a very important role in carcinogenesis in the stomach and other organs, when CagA-synthesizing
2. Organ pathologies connected with H. pylori infection
3. Liver injury
Liver colonization by
Experimental studies performed on mice and rats infected with
4. Chronic HBV and HCV infections
The frequency of
Among people chronically infected with HBV with primary liver cancer,
Among patients infected with
Evaluation of
5. Autoimmune diseases and liver steatosis
Studies performed among patients with chronic viral autoimmune and toxic hepatitis and coexisting
Infection by these bacteria worsens the course of underlying disease; however, pathogenesis is not completely clear [28, 29]. In the group of patients with PBC and AIH,
Reports on the effect of
6. Liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCC)
Inflammation of gastric mucosa is a frequent complication of liver cirrhosis. Usually, occurrence of chronic inflammation is observed, described as portal gastropathy.
Although in some studies more frequent
In experimental studies performed on dogs, an association between
In the pathogenesis of biliary duct carcinoma,
7. Conclusions
Current research on the impact of
Acknowledgments
Studies have been done, and the manuscript was written without the support of other persons and sponsors.
References
- 1.
Bachir M, Allem R, Tifrit A, Medjekane M, Drici AE, Diaf M, Douidi KT. Primary antibiotic resistance and its relationship with cagA and vacA genes in Helicobacter pylori isolates from Algerian patients. Brazilian Journal of Microbiology. 2018;49 (3): 544-551. doi: 10.1016/j.bjm.2017.11.003 - 2.
Mitchell H, Katelaris P. Epidemiology, clinical impacts and current clinical management of Helicobacter pylori infection. The Medical Journal of Australia. 2016;204 (10):376-380 - 3.
Hatakeyama M. Structure and function of Helicobacter pylori CagA, the first-identified bacterial protein involved in human cancer. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences. 2017;93 (4):196-219. DOI: 10.2183/pjab.93.013 - 4.
Wroblewski LE, Peek RM Jr. Helicobacter pylori , cancer, and the gastric microbiota. Advances in Experimental Medicine and Biology. 2016;908 :393-408. DOI: 10.1007/978-3-319-41388-4_19 - 5.
Sun X, Xu Y, Wang L, Zhang F, Zhang J, Fu X, Jing T, Han J. Association between TNFA gene polymorphisms and Helicobacter pylori infection: A meta-analysis. PLoS One. 2016;11 (1):e0147410. DOI: 10.1371/journal.pone.0147410 - 6.
Waluga M, Kukla M, Żorniak M, Bacik A, Kotulski R. From the stomach to other organs: Helicobacter pylori and the liver. World Journal of Hepatology. 2015;7 (18):2136-2146. DOI: 10.4254/wjh.v7.i18.2136 - 7.
Suzuki H, Franceschi F, Nishizawa T, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection. Helicobacter. 2011;16 (Suppl 1):65-69. DOI: 10.1111/j.1523-5378.2011.00883.x - 8.
Figura N, Palazzuoli A, Vaira D, Campagna M, Moretti E, Iacoponi F, Giordano N, Clemente S, Nuti R, Ponzetto A. Cross-sectional study: CagA-positive Helicobacter pylori infection, acute coronary artery disease and systemic levels of B-type natriuretic peptide. Journal of Clinical Pathology. 2014;67 (3):251-257. DOI: 10.1136/jclinpath-2013-201743 - 9.
Wang JW, Tseng KL, Hsu CN, Liang CM, Tai WC, Ku MK, Hung TH, Yuan LT, Nguang SH, Yang SC, Wu CK, Chiu CH, Tsai KL, Chang MW, Huang CF, Hsu PI, Wu DC, Chuah SK. Association between Helicobacter pylori eradication and the risk of coronary heart diseases. PLoS One. 2018;13 (1):e0190219. DOI: 10.1371/journal.pone.0190219 - 10.
Yang YJ, Wu CT, Ou HY, Lin CH, Cheng HC, Chang WL, Chen WY, Yang HB, Lu CC, Sheu BS. Male non-insulin users with type 2 diabetes mellitus are predisposed to gastric corpus-predominant inflammation after H. pylori infection. Journal of Biomedical Science. 2017;24 (1):82. DOI: 10.1186/s12929-017-0389-x - 11.
Rabelo-Gonçalves EM, Roesler BM, Zeitune JM. Extragastric manifestations of Helicobacter pylori infection: Possible role of bacterium in liver and pancreas diseases. World Journal of Hepatology. 2015;7 (30):2968-2979. DOI: 10.4254/wjh.v7.i30.2968 - 12.
Guarneri C, Lotti J, Fioranelli M, Roccia MG, Lotti T, Guarneri F. Possible role of Helicobacter pylori in diseases of dermatological interest. Journal of Biological Regulators and Homeostatic Agents. 2017;31 (Suppl. 2):57-77 - 13.
Pellicano R, Menard A, Rizzetto M, Megraud F. Helicobacter species and liver diseases: Association or causation? The Lancet Infectious Diseases. 2008;8 :254-260. DOI: 10.1016/S1473-3099(08)70066-5 - 14.
Goo MJ, Ki MR, Lee HR, Yang HJ, Yuan DW, Hong IH, Park JK, Hong KS, Han JY, Hwang OK, Kim DH, Do SH, Cohn RD, Jeong KS. Helicobacter pylori promotes hepatic fibrosis in the animal model. Laboratory Investigation. 2009;89 :1291-1303. DOI: 10.1038/labinvest.2009.90 - 15.
Stalke P, Al-Soud WA, Bielawski KP, Bakowska A, Trocha H, Stepinski J, Wadstrom T. Detection of Helicobacter species in liver and stomach tissues of patients with chronic liver diseases using polymerase chain reaction-denaturing gradient gel electrophoresis and immunohistochemistry. Scandinavian Journal of Gastroenterology. 2005;40 :1032-1041. DOI: 10.1080/00365520510023251 - 16.
Silva LD, Rocha AM, Rocha GA, de Moura SB, Rocha MM, Dani R, de Melo FF, Guerra JB, de Castro LP, Mendes GS, Ferrari TC, Lima AS, Queiroz DM. The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient. Memórias do Instituto Oswaldo Cruz. 2011;106 :748-754 - 17.
Wang J, Chen RC, Zheng YX, Zhao SS, Li N, Zhou RR, Huang Y, Huang ZB, Fan XG. Helicobacter pylori infection may increase the risk of progression of chronic hepatitis B disease among the Chinese population: A meta-analysis. International Journal of Infectious Diseases. 2016;50 :30-37. DOI: 10.1016/j.ijid.2016.07.014 - 18.
Huang J, Cui J. Evaluation of Helicobacter pylori infection in patients with chronic hepatic disease. Chinese Medical Journal. 2017;130 (2):149-154. DOI: 10.4103/0366-6999.197980 - 19.
Zhang XH, He Y, Feng R, Xu LP, Jiang Q, Jiang H, Lu J, Fu HX, Liu H, Wang JW, Wang QM, Feng FE, Zhu XL, Xu LL, Xie YD, Ma H, Wang H, Liu KY, Huang XJ. Helicobacter pylori infection influences the severity of thrombocytopenia and its treatment response in chronic hepatitis B patients with compensatory cirrhosis: A multicenter, observational study. Platelets. 2016;27 (3):223-229. DOI: 10.3109/09537104.2015.1077946 - 20.
Wang L, Zollinger T, Zhang J. Association between Helicobacter pylori infection and liver cancer mortality in 67 rural Chinese counties. Cancer Causes & Control. 2013;24 (7):1331-1337. DOI: 10.1007/s10552-013-0211-3 - 21.
Mohamed AA, Elshimy AA, El Sadik AO, Ezzat E, Nasar M, Elshaer SSM, Sayed MM. Association between severity of liver disease, frequency of Helicobacter pylori infection, and degree of gastric lesion in Egyptian patients with hepatitis B virus infection. The American Journal of Tropical Medicine and Hygiene. 2018;98 (1):221-226. DOI: 10.4269/ajtmh.17-0291 - 22.
Gutwerk A, Wex T, Stein K, Langner C, Canbay A, Malfertheiner P, Link A. Helicobacter Pylori serology in relation to hepatitis C virus infection and IL28B single nucleotide polymorphism. Journal of Clinical Medicine. 2018;7 (3):44-55. doi:10.3390/jcm7030044 - 23.
Hanafy AS, El Hawary AT, Hamed EF, Hassaneen AM. Impact of Helicobacter pylori eradication on refractory thrombocytopenia in patients with chronic HCV awaiting antiviral therapy. European Journal of Clinical Microbiology & Infectious Diseases. 2016;35 (7):1171-1176. DOI: 10.1007/s10096-016-2650-8 - 24.
Wang J, Li WT, Zheng YX, Zhao SS, Li N, Huang Y, Zhou RR, Huang ZB, Fan XG. The association between Helicobacter pylori infection and chronic hepatitis C: A meta-analysis and trial sequential analysis. Gastroenterology Research and Practice. 2016;2016 :8780695. DOI: 10.1155/2016/8780695 - 25.
Sakr SA, Badrah GA, Sheir RA. Histological and histochemical alterations in liver of chronic hepatitis C patients with Helicobacter pylori infection. Biomedicine & Pharmacotherapy. 2013;67 (5):367-374. DOI: 10.1016/j.biopha.2013.03.004 - 26.
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. Advanced Biomedical Research. 2014;3 :131. DOI: 10.4103/2277-9175.133256 - 27.
Shapira Y, Agmon-Levin N, Renaudineau Y, Porat-Katz BS, Barzilai O, Ram M, Youinou P, Shoenfeld Y. Serum markers of infections in patients with primary biliary cirrhosis: Evidence of infection burden. Experimental and Molecular Pathology. 2012; 93 (3):386-390. DOI: 10.1016/j.yexmp.2012.09.012 - 28.
Casswall TH, Németh A, Nilsson I, Wadström T, Nilsson HO. Helicobacter species DNA in liver and gastric tissues in children and adolescents with chronic liver disease. Scandinavian Journal of Gastroenterology. 2010; 45 (2):160-167. DOI: 10.3109/00365520903426915 - 29.
Dzierzanowska-Fangrat K, Nilsson I, Wozniak M, Jozwiak P, Rozynek E, Woynarowski M, Socha J, Ljungh A, Wadström T. Lack of an association between Helicobacter infection and autoimmune hepatitis in children. Polish Journal of Microbiology. 2006;55 (2):157-159 - 30.
Toyoda M, Yokomori H, Kaneko F, Yoshida H, Hoshi K, Takeuchi H, Tahara K, Takahashi A, Kudo T, Motoori T, Ohbu M, Kondo H, Hibi T. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome concomitant with systemic sclerosis, immune thrombocytopenic purpura. Internal Medicine. 2009; 48 (23):2019-2023 - 31.
Buzás GM. Metabolic consequences of Helicobacter pylori infection and eradication. World Journal of Gastroenterology. 2014;20 (18):5226-5234. DOI: 10.3748/wjg.v20.i18.5226 - 32.
Castaño-Rodríguez N, Mitchell HM, Kaakoush NO. NAFLD, Helicobacter species and the intestinal microbiome. Best Practice & Research. Clinical Gastroenterology. 2017;31 (6):657-668. DOI: 10.1016/j.bpg.2017.09.008 - 33.
Sumida Y, Kanemasa K, Imai S, Mori K, Tanaka S, Shimokobe H, Kitamura Y, Fukumoto K, Kakutani A, Ohno T, Taketani H, Seko Y, Ishiba H, Hara T, Okajima A, Yamaguchi K, Moriguchi M, Mitsuyoshi H, Yasui K, Minami M, Itoh Y. Helicobacter pylori infection might have a potential role in hepatocyte ballooning in nonalcoholic fatty liver disease. Journal of Gastroenterology. 2015;50 (9):996-1004. DOI: 10.1007/s00535-015-1039-2 - 34.
Zhang FM, Yu CH, Chen HT, Shen Z, Hu FL, Yuan XP, Xu GQ. Helicobacter pylori infection is associated with gallstones: Epidemiological survey in China. World Journal of Gastroenterology. 2015;21 (29):8912-8919. DOI: 10.3748/wjg.v21.i29.8912 - 35.
Sathar SA, Kunnathuparambil SG, Sreesh S, Narayanan P, Vinayakumar KR. Helicobacter pylori infection in patients with liver cirrhosis: Prevalence and association with portal hypertensive gastropathy. Annals of Gastroenterology. 2014;27 (1):48-52 - 36.
Licinio R, Losurdo G, Carparelli S, Iannone A, Giorgio F, Barone M, Principi M, Ierardi E, Di Leo A. Helicobacter pylori , liver cirrhosis, and portal hypertension: An updated appraisal. Immunopharmacol Immunotoxicol. 2016;38 (6):408-413. doi:10.1080/08923973.2016.1247855 - 37.
Pogorzelska J, Łapińska M, Kalinowska A, Łapiński TW, Flisiak R. Helicobacter pylori infection among patients with liver cirrhosis. European Journal of Gastroenterology & Hepatology. 2017;29 (10):1161-1165. DOI: 10.1097/MEG.0000000000000928 - 38.
Feng H, Zhou X, Zhang G. Association between cirrhosis and Helicobacter pylori infection: A meta-analysis. European Journal of Gastroenterology & Hepatology. 2014;26 :1309-1319. DOI: 10.1097/MEG.0000000000000220 - 39.
El-Masry S, El-Shahat M, Badra G, Aboel-Nour MF, Lotfy M. Helicobacter pylori and hepatitis C Virus coinfection in Egyptian patients. Journal of Global Infectious Diseases. 2010;2 (1):4-9. DOI: 10.4103/0974-777X.59244 - 40.
Takashima T, Enomoto H, Iwata Y, Nishikawa H, Yoh K, Hasegawa K, Nakano C, Yuri Y, Ishii N, Miyamoto Y, Takata R, Nishimura T, Ishii A, Sakai Y, Aizawa N, Ikeda N, Iijima H, Nishiguchi S. Effects of Helicobacter pylori eradication on the platelet count in hepatitis C virus-infected patients. Journal of Clinical Medical Research. 2016;8 (12):854-858. DOI: 10.14740/jocmr2725w - 41.
Rekha C, Phanidhar S, Sagar AV, Revathi A, Asra WA. Role of Helicobacter pylori and hyperammonemia in subclinical hepatic encephalopathy in cirrhosis of liver. Indian Journal of Clinical Biochemistry. 2007;22 (2):136-139. DOI: 10.1007/BF02913332 - 42.
Kountouras J, Deretzi G, Zavos C, Katsinelos P. Helicobacter pylori infection and liver cirrhosis: Possible association with hepatic encephalopathy and/or post-hepatic encephalopathy cognitive impairment in patients with portal hypertension. Annals of Gastroenterology. 2014;27 (3):285 - 43.
Beisele M, Shen Z, Parry N, Mobley M, Taylor NS, Buckley E, Abedin MZ, Dewhirst FE, Fox JG. Helicobacter marmotae and novelHelicobacter andCampylobacter species isolated from the livers and intestines of prairie dogs. Journal of Medical Microbiology. 2011;60 :1366-1374. DOI: 10.1099/jmm.0.032144-0 - 44.
Abu Al-Soud W, Stenram U, Ljungh A, Tranberg KG, Nilsson HO, Wadström T. DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma. Digestive and Liver Disease. 2008;40 (2):126-131. DOI: 10.1016/j.dld.2007.09.011 - 45.
Ki MR, Goo MJ, Park JK, Hong IH, Ji AR, Han SY, You SY, Lee EM, Kim AY, Park SJ, Lee HJ, Kim SY, Jeong KS. Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-β1-induced inflammatory signaling. Laboratory Investigation. 2010;90 (10):1507-1516. DOI: 10.1038/labinvest.2010.109 - 46.
Kawanishi S, Ohnishi S, Ma N, Hiraku Y, Oikawa S, Murata M. Nitrative and oxidative DNA damage in infection-related carcinogenesis in relation to cancer stem cells. Genes and Environment. 2017; 38 :26. DOI: 10.1186/s41021-016-0055-7 - 47.
Boonyanugomol W, Chomvarin C, Sripa B, Bhudhisawasdi V, Khuntikeo N, Hahnvajanawong C, Chamsuwan A. Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation. HPB: The Official Journal of the International Hepato Pancreato Biliary Association. 2012;14 (3):177-184