**Conflict of interest**

None declared.

#### **Author details**

Felicia Galoș1,2\*† , Cătălin Boboc2,†, Gabriela Năstase<sup>2</sup> , Anca Orzan1,2, Cristina Coldea1,2, Mălina Anghel2 and Mihaela Bălgrădean1,2

[8] Cosgun Y, Yildirim A, Yucel M, Karakoc AE, Koca G, Gonultas A, et al. Evaluation of invasive and noninvasive methods for the diagnosis of *Helicobacter pylori* infection. Asian Pacific Journal of Cancer Prevention. 2016;**12**:5265-5272. DOI: 10.22034/

Endoscopical Aspects of *Helicobacter pylori* Gastritis in Children

http://dx.doi.org/10.5772/intechopen.81437

[9] Łazowska-Przeorek I, Kotowska M, Banasiuk M, Karolewska-Bochenek K, Banaszkiewicz A, Gawronska A, et al. Value of antral nodularity for the diagnosis of *Helicobacter pylori* infection in children. Medical Science Monitor. 2015;**21**:1827-1830. DOI: 10.12659/

[10] Yang HR. Update on the diagnosis of *Helicobacter pylori* infection in children: What are the differences between adults and children? Pediatric Gastroenterology, Hepatology &

[11] Oderna G, Mura S, Valori A, Brustia R. Idiopathic peptic ulcers in children. JPGN.

[12] Kalach N, Bontems P, Koletzko S, Mourad-Baars P, Shcherbakov P, Celinska-Cedro D, et al. Frequency and risk factors of gastric and duodenal ulcers or erosions in children: A prospective 1-month European multicenter study. European Journal of Gastroenterology

[13] Kato S, Kikuchi S, Nakajima S. When does gastric atrophy develop in Japanese children?

[14] Kato S, Nakajima S, Nishino Y, Ozawa K, Minoura T, Konno M, et al. Association between gastric atrophy and *Helicobacter pylori* infection in Japanese children: A retrospective multicenter study. Digestive Diseases and Sciences. 2006;**51**(1):99-104. DOI:

[15] Arents N, Thijs JC, van Zwet AA, Kleibeuker JH. Does the declining prevalence of *Helicobacter pylori* unmask patients with idiopathic peptic ulcer disease? Trends over an 8 years period. European Journal of Gastroenterology & Hepatology. 2004;**16**:779-783.

[16] Tam YH, Lee KH, To KF, Chan KW, Cheung ST. *Helicobacter pylori* positive versus *Helicobacter pylori* negative idiopathic peptic ulcers in children with their long-term out-

[17] Mărginean CO, Cotoi OS, Pitea AM, Mocanu S, Mărginean C. Assessment of the relationship between *Helicobacter pylori* infection, endoscopic appearance and histological chnges of the gastric mucosa in children with gastritis (a single center experience).

[18] Magistà AM, Ierardi E, Castellaneta S, Miniello VL, Lionetti E, Francavilla A, et al. Helicobacter status and symptoms assessment two years after eradication in pediatric

Romanian Journal of Morphology and Embryology. 2013;**54**(3):709-715

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& Hepatology. 2010;**22**(10):1174-1181. DOI: 10.1097/MEG.0b13e32833d36de

Helicobacter. 2008;**13**(4):278-281. DOI: 10.1111/j.1523-5378.2008.00611.x.

Nutrition. 2016;**19**(2):96-103. DOI: 10.5223/pghn.2016.19.2.96

APJCP.2016.17.12.5265

MSM.893467

2009;**48**(3):268-270

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comes. JPGN. 2009;**48**(3):299-305

\*Address all correspondence to: felicia\_galos@yahoo.com


† These two authors contributed equally to this work.

#### **References**


[8] Cosgun Y, Yildirim A, Yucel M, Karakoc AE, Koca G, Gonultas A, et al. Evaluation of invasive and noninvasive methods for the diagnosis of *Helicobacter pylori* infection. Asian Pacific Journal of Cancer Prevention. 2016;**12**:5265-5272. DOI: 10.22034/ APJCP.2016.17.12.5265

**Conflict of interest**

None declared.

**Author details**

Felicia Galoș1,2\*†

Mălina Anghel2

**References**

0000000000001594

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1-18. DOI: 05US14EBP1368

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, Cătălin Boboc2,†, Gabriela Năstase<sup>2</sup>

1 University of Medicine and Pharmacy Carol Davila, Bucharest, Romania

2 Maria Sklodowska Curie Children's Emergency Hospital, Bucharest, Romania

[1] Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, et al. Joint ESPGHAN/NASPGHAN guidelines for the management of *H. pylori* infection in children and adolescents (update 2016). JPGN. 2017;**64**:991-1003. DOI: 10.1097/MPG.

[2] Mégraud F, Lehours P. *Helicobacter pylori* detection and antimicrobial susceptibility testing. Clinical Microbiology Reviews. 2007;**20**:280-322. DOI: 10.1128/CMR. 00033-06

[3] Ricci C, Holton J, Vaira D. Diagnosis of *Helicobacter pylori*: Invasive and non-invasive tests. Best Practice & Research. Clinical Gastroenterology. 2007;**21**:299-313. DOI: 10.1016/

[4] Gold BD, Gilger MA, Czinn S. New diagnostic strategies for detection of *Helicobacter pylori* infection in paediatric patients. Gastroenterology & Hepatology. 2014;**10**(12 Suppl 7):

[5] Sierra MS, Hastings EV, Goodman KJ. What do we know about benefits of *H. pylori* treat-

[6] Pacifico L, Anania C, Osborn JF, Feraro F, Chiesa C. Consequences of *Helicobacter pylori* infection in children. World Journal of Gastroenterology. 2010;**16**(41):5181-5194. DOI:

[7] Kato S, Nishino Y, Ozawa K, Konno M, Maisawa S, Toyoda S, et al. The prevalence of *Helicobacter pylori* in Japanese children with gastritis or peptic ulcer disease. Journal of

ment in childhood? Gut Microbes. 2013;**4**:549-567. DOI: 10.4161/gmic.27000

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 and Mihaela Bălgrădean1,2 \*Address all correspondence to: felicia\_galos@yahoo.com

44 Helicobacter Pylori - New Approaches of an Old Human Microorganism

† These two authors contributed equally to this work.

, Anca Orzan1,2, Cristina Coldea1,2,


[19] Nardone G, Staibano S, Rocco A, Mezza E, Balzano T, Salvatore G, et al. Effect of *Helicobacter pylori* on gastric cell proliferation and genomic stability in a paediatric population of southern Italy. Digestive and Liver Disease. 2001;**33**:743-749. DOI: 10.1016/ S1590-8658(01)80690-3

**Chapter 4**

**Provisional chapter**

**The Importance of** *H. pylori* **Infection in Liver Diseases**

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

**Keywords:** *H. pylori*, hepatitis, hepatic liver cirrhosis, liver and biliary tract cancer

*Helicobacter pylori* (*H. pylori*) is a microaerophile described for the first time by Marshal and Warren in 1982. This Gram-negative bacillus is resistant to the activity of gastric acid. Active, vegetative form of the bacteria is spiral, while the sporulation form is granular [1]. The bacte-

rium contains stable DNA and a system of very effective DNA repair.

**The Importance of** *H. pylori* **Infection in Liver Diseases**

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.79969

Tadeusz Wojciech Łapiński

Tadeusz Wojciech Łapiński

**Abstract**

important.

**1. Introduction**

http://dx.doi.org/10.5772/intechopen.79969

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

[20] Michalkiewicz J, Helmin-Basa A, Grzywa R, Czerwionka-Szaflarska M, Szaflarska-Poplawaska A, Mierzwa G, et al. Innate immunity components and cytokines in gastric mucosa in children with *Helicobacter pylori* infection. In: Mediators of Inflammation. Hindawi Publishing Corporation; 2015. DOI: 10.1155/2015/176726

#### **The Importance of** *H. pylori* **Infection in Liver Diseases The Importance of** *H. pylori* **Infection in Liver Diseases**

DOI: 10.5772/intechopen.79969

Tadeusz Wojciech Łapiński Tadeusz Wojciech Łapiński

[19] Nardone G, Staibano S, Rocco A, Mezza E, Balzano T, Salvatore G, et al. Effect of *Helicobacter pylori* on gastric cell proliferation and genomic stability in a paediatric population of southern Italy. Digestive and Liver Disease. 2001;**33**:743-749. DOI: 10.1016/

[20] Michalkiewicz J, Helmin-Basa A, Grzywa R, Czerwionka-Szaflarska M, Szaflarska-Poplawaska A, Mierzwa G, et al. Innate immunity components and cytokines in gastric mucosa in children with *Helicobacter pylori* infection. In: Mediators of Inflammation.

Hindawi Publishing Corporation; 2015. DOI: 10.1155/2015/176726

S1590-8658(01)80690-3

46 Helicobacter Pylori - New Approaches of an Old Human Microorganism

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.79969

#### **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**

*Helicobacter pylori* (*H. pylori*) is a microaerophile described for the first time by Marshal and Warren in 1982. This Gram-negative bacillus is resistant to the activity of gastric acid. Active, vegetative form of the bacteria is spiral, while the sporulation form is granular [1]. The bacterium contains stable DNA and a system of very effective DNA repair.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 *H. pylori* infection.

*H. pylori* infection is associated with many skin conditions. Higher incidence of chronic urticaria, acne rosacea, idiopathic thrombocytopatic purpura, psoriasis, atopic dermatitis, and some other dermatological conditions among patients infected with *H. pylori* has been dem-

The Importance of *H. pylori* Infection in Liver Diseases http://dx.doi.org/10.5772/intechopen.79969

Liver colonization by *H. pylori* happens after transmission of the bacteria from the stomach,

Experimental studies performed on mice and rats infected with *H. pylori* have shown the effect of this infection onto up triggered fibrosis and development of liver cirrhosis [14]. One of the first studies performed in patients with chronic liver injury pointed to the presence of *Helicobacter* genus bacteria in the liver tissue in 26% of patients [15]. Current studies in patients infected with HBV, HCV, and patients with chronic noninfectious liver conditions point to much higher incidence of *H. pylori* or bacterial DNA in the liver tissue. Infections are thought to occur in effect of disturbances in patients' immune functions [16]. Both experimental and clinical studies demonstrate unfavorable effect of *H. pylori* infection onto the course of liver injury, especially exacerbated fibrosis. One of the reasons for this is the influence of infection onto metabolic changes connected with carbohydrate turnover, synthesis of highenergy compounds (mainly ATP), and increased concentration of proinflammatory cytokines.

The frequency of *H. pylori* infection among patients with chronic hepatitis B is around 30–80% [17]. *H. pylori* infection is confirmed in 79% of patients with postinflammatory liver cirrhosis connected with HBV infection [18]. Favorable effect of *H. pylori* eradication on the course of the disease, including increased platelet count, has been demonstrated in the studies on patients chronically infected with HBV, with compensated liver cirrhosis and thrombocyto-

Among people chronically infected with HBV with primary liver cancer, *H. pylori* infection is found in 69% of patients. In the group of patients with primary liver cancer, but without HBV infection, *H. pylori* infection is much less frequent, as it is found in 33% of patients. These observations consistently point to unfavorable effect of *H. pylori* infection among HBV-infected patients with liver cirrhosis onto the risk of occurrence of primary liver cancer. Frequency of *H. pylori* infection among patients with chronic hepatitis B correlates with the incidence of hepatocellular cancer, both in men and women [20]. Among this type of patients, fast progression of inflammatory changes in the liver is observed, as well as intensified fibro-

Among patients infected with *H. pylori* and HBV, liver function is impaired (prothrombin time is extended, and AST activity and bilirubin concentration increased), and esophageal varices, ascites and hyperammonemia with hepatic encephalopathy occur much more frequently [18].

sis, which promotes occurrence of primary neoplastic lesions [17, 21].

with blood, through the portal vein or directly through the bile ducts [13].

**4. Chronic HBV and HCV infections**

onstrated [12].

**3. Liver injury**

penia [19].

*H. pylori* produces high amounts of ureases, enzymes catalyzing urea decomposition to ammonia. This is especially important for the neutralization of hydrochloric acid in the stomach, which contributes to the growth of the bacteria. Bacteria demonstrate also the ability to pump out H<sup>+</sup> ions from cells. This leads to changes in the pH in the stomach, which in turn causes destruction of gastric mucosa.

*H. pylori* has an active antioxidizing system, which neutralizes free radicals. The system contains catalase, superoxide dismutase, and specific proteins MdaB and NapA.

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 *H. pylori* is detected [3, 4].

*H. pylori* is mainly present on the surface of epithelial cells of the mucosa, in the prepyloric part of the stomach. It has cilia allowing transport into intercellular spaces, and thanks to produced adhesins, it adheres to cell surface [1].

*H. pylori* infection influences local (in the gastric mucosa) and systemic increase in proinflammatory cytokines IL-1, -2, -4, -6, -8, -10, -17, interferon-β, and TNF-α [5]. This leads not only to development of local inflammatory reaction, but also potentiates generalized inflammatory reactions in the organism. *H. pylori* causes chronic atrophic gastritis, metaplasia, and dysplasia, leading to the development of gastric cancer. According to World Health Organization (WHO), the bacteria are a class I carcinogen. *H. pylori* may also potentiate extragastric organ disturbances, exacerbating the diseases of cardiovascular system or metabolic diseases, deteriorating normal function of the liver, especially in patients with cirrhosis [6].
