Acta Clinica Belgica International Journal of Clinical and Laboratory Medicine

ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20

Helicobacter Pylori and Gastroduodenal Disorders M. Deltenre To cite this article: M. Deltenre (1992) Helicobacter Pylori and Gastroduodenal Disorders, Acta Clinica Belgica, 47:5, 299-302, DOI: 10.1080/17843286.1992.11718247 To link to this article: http://dx.doi.org/10.1080/17843286.1992.11718247

Published online: 16 May 2016.

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Date: 24 August 2017, At: 19:11

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In 1983, Warren and Marshall (I) desc ribed unidentified piral haped bac illi on the gastric .e,,epi thelium of patients with chronic acti ve gastriti s. >. Thi s mi croo rgani sm, ca ll ed "Campylobacter ~~ Pyloridis" then "Campylobacter Pylori" and ir . finally "Helicobacter pylori" (HP) was at first . ti.st as a commensa l >rC!I const'deredb y many scien ifi co loni zi ng infl amed mu cosa . Later on, a >rit'tremendous amount of research (more than 900 la papers published in 199 1) revealed HP is a worlde iii/ wide pread pathogen and plays a key role in the ~oil'developmentand maintenance of gastri ti s, peptic 19 ulcer di sease and perhaps gastric cancer. is

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Epidemiology

Thi s mi croaero bi c, gram-nega ti ve, non inva ive microorganism li ves on the surface of gastric epithelium, both in fundu and antrum. It in i panly protected by the gastric mucous layer ! va and may coloni ze areas of gastric metap lasia in ~! the duodenal bulb. HP i an urea e positi ve germ !e and despite the fac t it is very sensiti ve to acid, it ~I survi ves in the ga tric milieu by metaboli zing n urea in ammonia and maintaining an alkaline ~e microenvironment. The prevalence of HP infecn lion is correlated to age (2) and in We tern ~ Europe, around 50 % of the population between .~ 5 0 and 60 year-old has been contaminated. The 11 1 nl prevalence is much higher among com munities

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of mentally retarded children and may reach 90 to I 00% of 30 year-old popul ation in developing countri es such a Peru , Algeria or Vietnam. The lowest the socioeconomic leve l, the hi ghest the prevalence among young peopl es. The mechani sm of contaminati on has not been co mpletely exp lai ned so far, but the feco-oral route seems the mo t probab le way even if HP has never been cultured from stools pecimens. The first description of "coccoid forms" by Mai et al. in 1988 (3) could be an exp lanation. When confronted to unfavorable conditi ons, HP is able to turn into a vegetati ve fo rm th at can tran sform back into full infective organi sm under favorable environment.

/-IP and Gastritis. Is Heli cobacter pylori a true pathogen? This questi on remained controversial for a long time, mainly becau se mo st HP carriers are asymptomati c (4). Nevenhele s, HP is respon ible for loca l (lgA) and general (IgG) immune reaction (5) with ac ute gastriti s (at the time of inva ion) then chronic gastriti s (with round cells infiltrate) or even chronic active gastriti s (with polymorphonuclear infi lt rate) (6,7) . Gastriti s improves when the organism is cleared and hea l when HP is eradicated (8) . The abse nce of close correlation between clinical compl aints of patients with "Non Ul cer Dyspepsia" (upper abdominal and dyspeptic sy mptoms in pati ents with normal upper GI endoscopy and upper abdominal ec hography) remains a problem (6) even if, as showed by our group (6), the preva lence of the organism is stati stica ll y correlated to the activity of the gastriti s. Acta Clinica Belgica 47.5 ( 1992)

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HP and Peptic Ulcer.

Bacterial gastritis of the antrum (and the fundus) is associated to ga tri c ulcer in 60-70% of cases and i present in 100 % of duodenal ulcers (8) when pati ents who took NSAID or developed ischemic ul ceration( ) .are excluded. Duodenal ulcer would be related to the coloni zati on of gastri c metapla ia area by HP that induce a chroni c bulbitis and fin ally ulceration. Moreover, mucosa! in fec tion by HP in the stomach induces a significa nt hyperga trinemia with, consequent! y, a chronic increa e of acid secretion. All tJ1e mechani m of HP pathogenicity are not co mpl e te ly ex pl a in ed (tox in ( )? rol e of ammoni a?) but there i a key point: since the initial tudy by oghl an et al. (9), fifteen tri al showed that pontaneou one-year relapse rate of du denal ulcer drop from 80-85 % of case to 025 % when HP is eradi cated. So far, all patients who relap e after HP eradication were found to have been recontaminated by the organi m. HP and Gastric ancer

L ng term pathology tudi e done by Finni h group I 0) ugge t that chronic non immune atrophic gastriti , a well known prene pl a ti c conditi on, could be the end stage of HP related gastriti . pidemi ologic studies, both in United state ( I I) and Europe ( 12), revealed a correlation between the occurrence of intestinal-type ga tric carcin oma and former infec tion by HP. Nevertheless, when ga tric cancer i present, HP ha usually di sappeared from the ga tric mucosa (it ca nnot be fo und in area ofin te Lin al metaplasia) and addition al factors mu t be present fo r developing carcinoma. ome preliminary re ults of in vitro studi e , done by our group, uggc t th at inn ammati on induced by HP in fec ti on increase the mitotic index of ga tric muco a. Treatment: who and how?

Since there is no correlati on between tJ1e presence of HP-as ociated gastriti s and symptoms Acta Clinica Belgica 47.5 ( 1992)

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among patients with "Non Ulcer Dyspepsia", r tJiere is, so far, no clear indication for eradication ) of HP in tJii s group. The relevance of preventi on s of peptic ulcer or even gastric cancer by systematic) eradication is not proven yet. Moreover, in deve· loping countries with a hi gh prevalence of HP d (and ga tric carcinoma), both recontaminati on 1 and res istance to antim icrobi al therapies are fre· 5 quent and the long term aim of researches would 3 be the development of an effi cient vacc ination. ~

On the other hand , all pati ents with HP pos i· u ti ve peptic ul cer di sease must benefit from an c attempt of eradi cation, in order to prevent com· s' plication , surgery and ex pensive long term maintenance treatment by H2 blockers or other inhibitors of ac id secretion. ti I . Diagnos is methods must be sensitive

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A correct monitoring of the result of the c treatment depend on the sensitivity of our ti di ag nos is too ls. Se rol ogy is use ful fo r 11 epidemiology but o far, is not useful to diagnos u acti ve di ease. Rapid urease tests ( uch as "CLO e Test" from Delta West- 13) are useful for qui ck p ini tial di ag nos is: a biopsy spec im en i "s1 immedi ately pushed into a capsule containing ct a bu ffe red 2 % urea gel and Phenol red for f1 indicator. If HP is pre ent, tJie hydrolysis of urea b produces ammoni a, a ri se in pH occurs and the tt gel turns pink. But, for follow-up studies, when is tJie detecti on of a very low amount of germ s is g neces ary, rapid urease tests are not sensitive' d enough (J 4). A correct di agnosis will be based on hi tology (modified Giemsa staining techni· 31 que, 87 % sensiti vity) and culture on Columbia' tc Horse blood or Chocolate agar. Culture is known bi to be technically difficult. HP is very"susceptible re to des iccati on or hi gh concentration of oxygen. b The biopsy sample must be sent in sterile isotonic ' saline or semi - solid agar transport medium and C< · h a maximum · re processed as soon as poss1'bl e wit Cl delay of two hours (unl ess stored at -30 degrees). The specificity of culture is I 00 % and it allow ~:

RS l-IELICOBACTER PYLORI AND GASTRODUODENAL DISORDERS ')

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to study the susceptibility of the strain to different antimicrobials. Using a mod ified culture 1", medium (the Brusse ls Campylobacter Charcoal on Agar or BCC-14), our group reported a 94 % on sensitivity rate of t11e culture ( 14). tic A nother elegant, non in . vas .ive tee hnique . of

~e~ diagnosis, very useful for follow-up studi es is the

I 3C Urea breath test: a test mea l containing a

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~n small amount of I 3C urea is given to the patient ~~ afterovemi ghtfasting. lfHPi s present,i tquick ly 1

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tran sforms 13C Urea into ammoni a and l3C02. The isotopic measurement of ex pired I 3C02 by the patient during the nex t 30 minute i a clear cut method for detecting th e presence (or absence) of HP in the gastri c mucosa. 2. Eradication is difficult to obtain

While review ing the results of therapeutic tria ls, one mu st be aware of the prominent difference between clearance and eradication. he Clearance mean s that HP is no more detectable in ur the gastric mucosa immedi ate ly at the end of a or treatment course but, in fact, alI t11erapeutic studies •s using a monotherapy with one antimicrobial (or • even, Omeprazole alone) revea l that thi s supck pression is tran sient: when the patient is reasi "sessed four weeks later, HP is again present in ng detectable amount. True eradicati on means th at 'or fundus and antrum biopsies, culture and I 3C ·ea., breath test are negati ve at least four weeks after he the end of the therapeutic course: thi s condition en is necessary to observe progressive healing of i , gastriti s and prolonged remiss ion of peptic ulcer ve di sease. ed In vitro, HP is susceptible to many antibiotics

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rli· and to bi smuth salts. But all monotherapies failed >ia' to eradicate HP in vivo ( 15). This di screpancy ,_,n between in vitro and in vivo results could be >le related to many factors:.effect of low pH on anti !~. biotics' activity, failure to reach effi cient local 11 ~ concentration of the antimicrobial agent, di ffen rences in daily dosage, innuence of gastric im emptyin . g, occurrence o f res .istan ce d unn . g s). treatment. On th e other hand , tri th erapi es w (combining Amoxycillin or Tetracycline with

bismuth salts and Metronidazole) are responsibl e for moderate to severe side effects in around 30% of patients even if they provide an up to 80 % eradication rate ( 16). The best t11erapeutic regimen is the combination of Amoxyci llin solute 4 x 500 mg /day plus Tinidazole 2x 500 mg/day for one week: in our ex perience, thi s treatment provides eradi cation in 75 % of t11e cases if the strain is susceptible to imidazole derivates. The association olloidal Bismuth Subcitrate (C BS) 120 mg qid with Tinidazole was less active (54 % eradication) but Burettect al. ( 17) recentl y reported an interesting study: the assoc iation Amoxicillin 500 mg qid for 16 days, plus Metronidazole 500 mg tid and CBS 120 mg qid for the first I 0 days leads to erad ica tion of 70 % of th e patients with Metronidazole res istant strain. Another way to overcome imidazo le resistance co uld be the associ ati on of macro lide with Omeprazole. The potent inhibitory action of Omeprazole on acid secretion reali zes optimal pH conditions for macro lides' activity. We succeeded to eradicate imidazole re i tant HP in 50% of patients with the assoc iation Erythromyc ine ethylsuccinate 500 mg qid plu Omeprazo le40 mg uidandCBS I 20mg qid for one week. More recentl y, a one-week course of Omeprazo le 40 mg uid plus Clarithromycin 250 mg qid plus CBS 120 mg qid ac hi eved bac terial eradication in 66 % of patients. The combination of high dose of Omeprazole (40 and 80 mg/day) with amoxicillin has been cl aimed to reac h 50 % (18) or even 85 % eradication rate. We were unabl e to observe such high eradication rates wit11 the assoc iation Omeprazole 40 mg plus Amoxicillin 500 mg qid for one or two weeks.

CONCLUSION Helicobacter pylori is now proven to have a key role in chronic gastriti s, "peptic" ulcer di sease and perhaps, the development of intestinal -type gastri c carcinoma. Much work remains to be Acta Clinica Belgica 47.5 ( 1992)

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done for full understandin g of the mode of contamination and palhogeni city. Eradication of HP remains a significant problem and so far, bior trilhe rapi es are necessary. Pre- and posttrealmenl resistance Lo imidazole clcrivates and frequent side effects of efficient drugs' combinati ons nece sitate further re earches and trials in order to develop a safe eradication regimen with succe s rate above 95 %. ln the future, preventi ve vaccination could be the on ly oluti on, mainly in devc l pin g co untri es where e nd e mi a an d recontamination rate are hi gh.

R I . Warren JR , Mar hall BJ. Unidentified curved

ba illi on ga tric epi thelium in acti ve chronic ga tritis. Lancer. 1983; i: 1273-75. 2. oo ley P, itzgibb n P, ohen H et al. Prcva len e and di tributi n f ampylobacter pylori in an asymptomati c population. Gasrroenterolog . 1988; 94 : A I 02. 3. Mai U, Geis G, Leying H, Ruhl G, pferkuch W. Di morphismof ampyl bacterPylori. Proceedings first meeting uropean ampy lobacter Pylori tudy roup. B rdeaux. 1988: I0. 4. Axon ATR. ampylobacter Pylori di : what role in ga tritis and peptic ulcer ? Br Med J. 1986; 293: 772- .

5. Rathbone BJ, Wyatt JI , Worsley BW etal. ystemic and loca l a ntib ody re pon se to gas tri c ampy lobacter pyloridi s in non ulcer dy pep ia. Cur. 1986; 27:642-7. 6. Deltenrc M., Nyst JF, Jona et al. Donnee cliniqu s, endo copi ques et hi tologiques chez I I 00 pati ent dont 574 co lonises par ampy lobacter Pylori. Gaslroenlerol fin Biol. 1989: 13: 898-95 8 . 7. Rauws EAJ, Langenberg W, Houthoff HJ et al. ampylobacter pyloridis-associated chronic antral

gastriti s. Gasrroenterology. 1988; 94: 33-40. 8. Rauws EAJ. Campylobacter Pylori . Ph. Thesi , 1 Univer. ity of Amsterdam, 1989. 9. Coghlan JG , Humphries H, Dooley C et al. Campylobacter Pylori and recurrence of duodenal ulcers: a 12 month fo llow-up study. Lancer. 1987; ii : 1109- 11. IO. Karnes WE, Samloff IM, Siurala M et al. Doe atrophic ga tritis represent the end-stage of C Pylori-a sociated gastriti s ? Gasrroentero/ogy. 1989; 96: A249. 11 . Parsonnet J, Friedman GD, Vander teen DP ct al. Helicobactcrpylori in fection and the risk of gastric S carci noma. N Engl J Med. 1991; 325: 11 27-3 1. 12. Ga barrini G, Pretolani S, Ghironzi GC et al. h. Epidem iology of Helicobacter Pylori infection in 5, the republic of San Mari no: the H.Pylori San bi Marino study. Ir J Gastroenterology. 199 1; 23 S2: bl 6.

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13. Marshall BJ, Warren JR, Francis GJ et al. Rapid w urea e test in the management of Campylobacter ir pyloridi s-associated ga triti s. Am J Gastroentero/. w 1987; 82:200. Si 14. Dcltenre M, Glupczynslci Y, De Prez C et al. The fr reliability of Urease test , hi tology and culture in the diagnosis of Campylobacter Pylori in fection. Scand J Gastroenterol. 1989; S 160: 19-24. 15. DeltemeM,DeKo Ler E,NystJF etal.Traitemenl H actuel de !'infection par ampylobacter Pylori: pourquoi et comment ? Med Mal lnfecl. 1989; J9:" ~~.

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16. 8orsch G, Mai U, Opferkuch W. Oral triple therapy re may effecti vely eradicate Campylobacter Pylori , . man: a pt·1ot tu dy. Gas/roentero Iogy 1988:.,a.L 1n 94:A44. l1. 17. Glupczyn ski Y, Burelte A. Erad icatin g re Heli cobacter Pylori (Letter). Lance/. 1992; 339: fr 54-5. th 18. Unge P, Gad A, Gnarpe H et al. Does OmeprazoJe v; improve anti mi cro bi al th era py tow a rd ei Cam pylobacter Pylori in patients with antral SL gastritis? Scand J Gas1roe11terol. 1989; S 167: 49. re 54.

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Acia linica Belgica 47.5 ( 1992)

Helicobacter pylori and gastroduodenal disorders.

Acta Clinica Belgica International Journal of Clinical and Laboratory Medicine ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://ww...
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