Editing Helicobacter pylori (section)

==Infection==
[[File:H pylori ulcer diagram en.png|thumb|upright=1.5| Diagram of stages of ulcer development]]
An infection with ''Helicobacter pylori'' can either have no symptoms even when lasting a lifetime, or can harm the stomach and duodenal [[Mucous membrane|linings]] by [[Inflammation|inflammatory responses]] induced by several mechanisms associated with a number of [[virulence factor]]s. [[Colonisation (biology)|Colonization]] can initially cause ''H. pylori induced gastritis'', an [[Gastritis|inflammation of the stomach lining]] that became a listed disease in [[ICD11]].<ref name="Maastricht 2022"/><ref name="ICD11"/><ref name="medscape2024" /> This will progress to [[chronic gastritis]] if left untreated. Chronic gastritis may lead to [[atrophic gastritis|atrophy]] of the stomach lining, and the development of [[peptic ulcer]]s (gastric or duodenal). These changes may be seen as stages in the development of [[gastric cancer]], known as ''Correa's cascade''.<ref name="Repetto">{{cite journal |vauthors=Repetto O, Vettori R, Steffan A, Cannizzaro R, De Re V |title=Circulating Proteins as Diagnostic Markers in Gastric Cancer |journal=Int J Mol Sci |volume=24 |issue=23 |date=November 2023 |page=16931 |pmid=38069253 |pmc=10706891 |doi=10.3390/ijms242316931 |doi-access=free |url=}}</ref><ref name="Livzan">{{cite journal |vauthors=Livzan MA, Mozgovoi SI, Gaus OV, Shimanskaya AG, Kononov AV |title=Histopathological Evaluation of Gastric Mucosal Atrophy for Predicting Gastric Cancer Risk: Problems and Solutions |journal=Diagnostics |volume=13 |issue=15 |date=July 2023 |page=2478 |pmid=37568841 |pmc=10417051 |doi=10.3390/diagnostics13152478 |doi-access=free |url=}}</ref> Extragastric complications that have been linked to ''H. pylori'' include [[anemia]] due either to iron-deficiency or vitamin B12 deficiency, diabetes mellitus, cardiovascular, and certain neurological disorders.<ref name="WJG2020" />

Peptic ulcers are a consequence of inflammation that allows stomach acid and the digestive enzyme [[pepsin]] to overwhelm the protective mechanisms of the [[mucous membranes]]. The location of colonization of ''H.&nbsp;pylori'', which affects the location of the ulcer, depends on the acidity of the stomach.<ref name="Dixon">{{cite journal | vauthors = Dixon MF | title = Patterns of inflammation linked to ulcer disease | journal = Baillière's Best Practice & Research. Clinical Gastroenterology | volume = 14 | issue = 1 | pages = 27–40 | date = February 2000 | pmid = 10749087 | doi = 10.1053/bega.1999.0057 }}</ref> In people producing large amounts of acid, ''H.&nbsp;pylori'' colonizes near the [[pyloric antrum]] (exit to the duodenum) to avoid the acid-secreting [[parietal cells]] at the [[fundus (stomach)|fundus]] (near the entrance to the stomach).<ref name="Kusters2006"/> [[G cell]]s express relatively high levels of [[PD-L1]] that protects these cells from ''H. pylori''-induced immune destruction.<ref>{{cite journal | vauthors = Mommersteeg MC, Yu BT, van den Bosch TP, von der Thüsen JH, Kuipers EJ, Doukas M, Spaander MC, Peppelenbosch MP, Fuhler GM | title = Constitutive programmed death ligand 1 expression protects gastric G-cells from Helicobacter pylori-induced inflammation | journal = Helicobacter | volume = 27 | issue = 5 | pages = e12917 | date = October 2022 | pmid = 35899973 | doi = 10.1111/hel.12917| pmc = 9542424 | s2cid = 251132578 }}</ref> In people producing normal or reduced amounts of acid, ''H.&nbsp;pylori'' can also colonize the rest of the stomach.

[[File:2414 Stomach.jpg|thumb|upright=0.8|Diagram showing parts of the stomach]]
The inflammatory response caused by bacteria colonizing near the pyloric antrum induces G cells in the antrum to secrete the hormone [[gastrin]], which travels through the bloodstream to parietal cells in the fundus.<ref name="pmid14755326">{{cite journal | vauthors = Blaser MJ, Atherton JC | title = Helicobacter pylori persistence: biology and disease | journal = The Journal of Clinical Investigation | volume = 113 | issue = 3 | pages = 321–33 | date = February 2004 | pmid = 14755326 | pmc = 324548 | doi = 10.1172/JCI20925 }}</ref> Gastrin stimulates the parietal cells to secrete more acid into the stomach lumen, and over time increases the number of parietal cells, as well.<ref name="Schubert 2008">{{cite journal | vauthors = Schubert ML, Peura DA | title = Control of gastric acid secretion in health and disease | journal = Gastroenterology | volume = 134 | issue = 7 | pages = 1842–60 | date = June 2008 | pmid = 18474247 | doi = 10.1053/j.gastro.2008.05.021 | s2cid = 206210451 }}</ref> The increased acid load damages the duodenum, which may eventually lead to the formation of ulcers.

''Helicobacter pylori'' is a class I [[carcinogen]], and potential cancers include gastric [[mucosa-associated lymphoid tissue]] (MALT) [[lymphoma]]s and [[gastric cancer]].<ref name="Matsuo"/><ref name="Marghalani"/><ref name="Abbas">{{cite journal | vauthors = Abbas H, Niazi M, Makker J | title = Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Colon: A Case Report and a Literature Review | journal = The American Journal of Case Reports | volume = 18 | pages = 491–497 | date = May 2017 | pmid = 28469125 | pmc = 5424574 | doi = 10.12659/AJCR.902843 }}</ref> Less commonly, [[diffuse large B-cell lymphoma]] of the stomach is a risk.<ref name="pmid25852262">{{cite journal | vauthors = Paydas S | title = Helicobacter pylori eradication in gastric diffuse large B cell lymphoma | journal = World Journal of Gastroenterology | volume = 21 | issue = 13 | pages = 3773–6 | date = April 2015 | pmid = 25852262 | pmc = 4385524 | doi = 10.3748/wjg.v21.i13.3773 | doi-access = free }}</ref> Infection with ''H. pylori'' is responsible for around 89 per cent of all gastric cancers, and is linked to the development of 5.5 per cent of all cases of cancer worldwide.<ref name="Shin"/><ref name="Violeta"/> Although the data varies between different countries, overall about 1% to 3% of people infected with ''Helicobacter pylori'' develop gastric cancer in their lifetime compared to 0.13% of individuals who have had no ''H.&nbsp;pylori'' infection.<ref>{{cite journal | vauthors = Kuipers EJ | title = Review article: exploring the link between Helicobacter pylori and gastric cancer | journal = Alimentary Pharmacology & Therapeutics | volume = 13 | pages = 3–11 | date = March 1999 | issue = Suppl 1 | pmid = 10209681 | doi = 10.1046/j.1365-2036.1999.00002.x | s2cid = 19231673 }}</ref><ref name="Kusters2006"/> ''H.&nbsp;pylori''-induced gastric cancer is the third highest cause of worldwide cancer mortality as of 2018.<ref name="Feral">{{cite journal | vauthors = Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F | title = Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods | journal = International Journal of Cancer | volume = 144 | issue = 8 | pages = 1941–1953 | date = April 2019 | pmid = 30350310 | doi = 10.1002/ijc.31937 | doi-access = free }}</ref> Because of the usual lack of symptoms, when gastric cancer is finally diagnosed it is often fairly advanced. More than half of gastric cancer patients have lymph node metastasis when they are initially diagnosed.<ref name="pmid24744586">{{cite journal | vauthors = Deng JY, Liang H | title = Clinical significance of lymph node metastasis in gastric cancer | journal = World Journal of Gastroenterology | volume = 20 | issue = 14 | pages = 3967–75 | date = April 2014 | pmid = 24744586 | pmc = 3983452 | doi = 10.3748/wjg.v20.i14.3967 | doi-access = free }}</ref>
[[File: Helicobacter pylori2.jpg|thumb|Micrograph of ''H. pylori'' colonizing the [[gastric mucosa|stomach lining]]]]
Chronic inflammation that is a feature of cancer development is characterized by infiltration of [[neutrophil]]s and [[macrophage]]s to the gastric epithelium, which favors the accumulation of [[inflammatory cytokine|pro-inflammatory cytokines]], [[reactive oxygen species]] (ROS) and [[reactive nitrogen species]] (RNS) that cause [[DNA damage]].<ref name=Valenzuela>{{cite journal | vauthors = Valenzuela MA, Canales J, Corvalán AH, Quest AF | title = Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis | journal = World Journal of Gastroenterology | volume = 21 | issue = 45 | pages = 12742–56 | date = December 2015 | pmid = 26668499 | pmc = 4671030 | doi = 10.3748/wjg.v21.i45.12742 | doi-access = free }}</ref> The [[DNA oxidation|oxidative DNA damage]] and levels of [[oxidative stress]] can be indicated by a biomarker, [[DNA oxidation#Increased 8-oxo-dG in carcinogenesis and disease|8-oxo-dG]].<ref name=Valenzuela/><ref name="Raza">{{cite journal | vauthors = Raza Y, Khan A, Farooqui A, Mubarak M, Facista A, Akhtar SS, Khan S, Kazi JI, Bernstein C, Kazmi SU | title = Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis | journal = Pathology & Oncology Research | volume = 20 | issue = 4 | pages = 839–46 | date = October 2014 | pmid = 24664859 | doi = 10.1007/s12253-014-9762-1 | s2cid = 18727504 }}</ref> Other damage to DNA includes [[double-strand break]]s.<ref name=Koeppel>{{cite journal | vauthors = Koeppel M, Garcia-Alcalde F, Glowinski F, Schlaermann P, Meyer TF | title = Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells | journal = Cell Reports | volume = 11 | issue = 11 | pages = 1703–13 | date = June 2015 | pmid = 26074077 | doi = 10.1016/j.celrep.2015.05.030 | doi-access = free }}</ref>

Small [[Gastric polyp|gastric]] and [[colorectal polyp]]s are [[adenoma]]s that are more commonly found in association with the mucosal damage induced by ''H. pylori'' gastritis.<ref name="Markowski"/><ref name="Dong">{{cite journal |vauthors=Dong YF, Guo T, Yang H, Qian JM, Li JN |title=[Correlations between gastric Helicobacter pylori infection and colorectal polyps or cancer] |language=Chinese |journal=Zhonghua Nei Ke Za Zhi |volume=58 |issue=2 |pages=139–142 |date=February 2019 |pmid=30704201 |doi=10.3760/cma.j.issn.0578-1426.2019.02.011 |url=}}</ref> Larger polyps can in time become cancerous.<ref name="Zuo"/><ref name="Markowski"/> A modest association of ''H. pylori'' has been made with the development of [[colorectal cancer]]s, but as of 2020 causality had yet to be proved.<ref name="Papastergiou">{{cite journal |vauthors=Papastergiou V, Karatapanis S, Georgopoulos SD |title=Helicobacter pylori and colorectal neoplasia: Is there a causal link? |journal=World J Gastroenterol |volume=22 |issue=2 |pages=649–58 |date=January 2016 |pmid=26811614 |pmc=4716066 |doi=10.3748/wjg.v22.i2.649 |doi-access=free |url=}}</ref><ref name="Zuo">{{cite journal |vauthors=Zuo Y, Jing Z, Bie M, Xu C, Hao X, Wang B |title=Association between Helicobacter pylori infection and the risk of colorectal cancer: A systematic review and meta-analysis |journal=Medicine (Baltimore) |volume=99 |issue=37 |pages=e21832 |date=September 2020 |pmid=32925719 |pmc=7489651 |doi=10.1097/MD.0000000000021832 |url=}}</ref>

=== Signs and symptoms ===
Most people infected with ''H.&nbsp;pylori'' never experience any symptoms or complications, but will have a 10% to 20% risk of developing [[peptic ulcer]]s or a 0.5% to 2% risk of stomach cancer.<ref name="de Brito"/><ref name="Debowski"/> ''H. pylori induced gastritis'' may present as acute gastritis with [[stomach ache]], [[nausea]], and ongoing [[dyspepsia]] (indigestion) that is sometimes accompanied by depression and anxiety.<ref name="de Brito"/><ref name="Cureus">{{cite journal |vauthors=Al Quraan AM, Beriwal N, Sangay P, Namgyal T |title=The Psychotic Impact of Helicobacter pylori Gastritis and Functional Dyspepsia on Depression: A Systematic Review |journal=Cureus |volume=11 |issue=10 |pages=e5956 |date=October 2019 |pmid=31799095 |pmc=6863582 |doi=10.7759/cureus.5956 |doi-access=free |url=}}</ref> Where the gastritis develops into chronic gastritis, or an ulcer, the symptoms are the same and can include [[indigestion]], stomach or abdominal pains, nausea, [[bloating]], [[belching]], feeling hunger in the morning, feeling full too soon, and sometimes [[vomiting]], heartburn, bad breath, and weight loss.<ref name="medlineplus2024">{{cite web |title=Helicobacter Pylori (H. Pylori) Tests: MedlinePlus Medical Test |url=https://medlineplus.gov/lab-tests/helicobacter-pylori-h-pylori-tests/ |website=medlineplus.gov |access-date=16 February 2024 |language=en |archive-date=16 February 2024 |archive-url=https://web.archive.org/web/20240216210728/https://medlineplus.gov/lab-tests/helicobacter-pylori-h-pylori-tests/ |url-status=live }}</ref><ref name="NIDDK">{{cite web |title=Symptoms & Causes of Peptic Ulcers (Stomach or Duodenal Ulcers) - NIDDK |url=https://www.niddk.nih.gov/health-information/digestive-diseases/peptic-ulcers-stomach-ulcers/symptoms-causes |website=National Institute of Diabetes and Digestive and Kidney Diseases |access-date=17 February 2024 |archive-date=17 February 2024 |archive-url=https://web.archive.org/web/20240217131321/https://www.niddk.nih.gov/health-information/digestive-diseases/peptic-ulcers-stomach-ulcers/symptoms-causes |url-status=live }}</ref>

Complications of an ulcer can cause severe signs and symptoms such as black or tarry stool indicative of [[bleeding]] into the stomach or duodenum; blood - either red or coffee-ground colored in vomit; persistent sharp or severe abdominal pain; dizziness, and a fast heartbeat.<ref name="medlineplus2024"/><ref name="NIDDK"/> Bleeding is the most common complication. In cases caused by ''H. pylori'' there was a greater need for [[hemostasis]] often requiring gastric resection.<ref name="Pope">{{cite journal |vauthors=Popa DG, Obleagă CV, Socea B, Serban D, Ciurea ME, Diaconescu M, Vîlcea ID, Meșină C, Mirea C, Florescu DN, Baleanu VD, Comandasu M, Tudosie MS, Tribus LC, Niculescu B |title=Role of Helicobacter pylori in the triggering and evolution of hemorrhagic gastro-duodenal lesions |journal=Exp Ther Med |volume=22 |issue=4 |pages=1147 |date=October 2021 |pmid=34504592 |pmc=8392874 |doi=10.3892/etm.2021.10582 |url=}}</ref> Prolonged bleeding may cause anemia leading to weakness and fatigue. Inflammation of the pyloric antrum, which connects the stomach to the duodenum, is more likely to lead to duodenal ulcers, while inflammation of the [[Body of stomach|corpus]] may lead to a gastric ulcer.

[[Stomach cancer]] can cause nausea, vomiting, diarrhoea, constipation, and unexplained weight loss.<ref>{{cite journal |last1=Al-Azri |first1=Mohammed |last2=Al-Kindi |first2=Jamila |last3=Al-Harthi |first3=Thuraiya |last4=Al-Dahri |first4=Manal |last5=Panchatcharam |first5=Sathiya Murthi |last6=Al-Maniri |first6=Abdullah |date=June 2019 |title=Awareness of Stomach and Colorectal Cancer Risk Factors, Symptoms and Time Taken to Seek Medical Help Among Public Attending Primary Care Setting in Muscat Governorate, Oman |url=http://link.springer.com/10.1007/s13187-017-1266-8 |journal=Journal of Cancer Education |language=en |volume=34 |issue=3 |pages=423–434 |doi=10.1007/s13187-017-1266-8 |pmid=28782080 |s2cid=4017466 |issn=0885-8195 |access-date=20 January 2024 |archive-date=24 February 2024 |archive-url=https://web.archive.org/web/20240224042108/https://link.springer.com/article/10.1007/s13187-017-1266-8 |url-status=live }}</ref> [[Gastric polyp]]s are [[adenoma]]s that are usually asymptomatic and benign, but may be the cause of dyspepsia, heartburn, bleeding from the stomach, and, rarely, gastric outlet obstruction.<ref name="Markowski">{{cite journal | vauthors = Markowski AR, Markowska A, Guzinska-Ustymowicz K | title = Pathophysiological and clinical aspects of gastric hyperplastic polyps | journal = World Journal of Gastroenterology | volume = 22 | issue = 40 | pages = 8883–8891 | date = October 2016 | pmid = 27833379 | pmc = 5083793 | doi = 10.3748/wjg.v22.i40.8883 | doi-access = free }}</ref><ref name="Wu2013">{{cite journal | vauthors = Wu Q, Yang ZP, Xu P, Gao LC, Fan DM | title = Association between Helicobacter pylori infection and the risk of colorectal neoplasia: a systematic review and meta-analysis | journal = Colorectal Disease | volume = 15 | issue = 7 | pages = e352-64 | date = July 2013 | pmid = 23672575 | doi = 10.1111/codi.12284 | s2cid = 5444584 }}</ref> Larger polyps may have [[Malignant transformation|become cancerous]].<ref name="Markowski"/>
[[Colorectal polyp]]s may be the cause of rectal bleeding, anemia, constipation, diarrhea, weight loss, and abdominal pain.<ref name="Soetikno">{{cite journal | vauthors = Soetikno RM, Kaltenbach T, Rouse RV, Park W, Maheshwari A, Sato T, Matsui S, Friedland S | title = Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults | journal = JAMA | volume = 299 | issue = 9 | pages = 1027–35 | date = March 2008 | pmid = 18319413 | doi = 10.1001/jama.299.9.1027 | doi-access = free }}</ref>