H pylori poster-web
1
Treatment of H. pylori Clinical outcomes of infection Infection Risk factors for gastric cancer Environmental ■ Smoking ■ Diet high in salt ■ Diet low in fresh fruit and vegetables ■ Iron deficiency Host genetics ■ Genes associated with increased risk of H. pylori infection: TLR1 ■ Genes associated with increased risk of gastric cancer: IL1B, TNF, IL8, PSCA Bacterial Photo Photo H. pylori are spiral-shaped Gram-negative bacteria with polar flagella that can survive in the human gastric mucosa. The bacteria have evolved intricate mechanisms to avoid the bactericidal acid in the gastric lumen and to survive near to, to attach to, and to subvert the human gastric epithelium and immune system. Diagnosis of H. pylori Noninvasive (preferred) ■ Serology: IgG against H. pylori ■ Stool antigen test ■ Breath test for diagnosis of H. pylori infection Invasive (requires endoscopy) ■ Histology: gastric biopsy samples stained for H. pylori using haematoxylin and eosin, immunohistochemistry, silver staining, Genta stain or alcian yellow–toluidine blue ■ Culture of gastric biopsy samples ■ Rapid urease test If H. pylori is present, urea is converted into ammonia and carbon dioxide by their urease enzymes. The breakdown of urea increases the pH level of the solution, triggering a colour change from yellow to pink. H. pylori positive H. pylori negative Urea and pH indicator (e.g. phenol red) Biopsy samples from the stomach antrum The patient is given a drink containing urea labelled with nonradioactive carbon-13. If H. pylori is present, their urease enzyme breaks down urea to form carbon dioxide, which is exhaled. After taking the urea-based drink, the patient blows into the sample tube or bag which is then tested for an increase in the proportion of carbon dioxide containing carbon-13. A positive result indicates presence of H. pylori and the appropriate eradication therapy can then be prescribed. Tailored Rx Available H. pylori infection History of antibiotic use? Previously treated for H. pylori? Susceptibility testing Not available Current available drugs 13 C Urea Urease CO 2 + NH 3 13 CO 2 in blood 13 CO 2 in breath In the USA, the prevalence of resistance is ~15% to clarithromycin and 25% to metronidazole, but is much higher in individuals who have taken those antibiotics for other infections. If susceptibility of the pathogen is known, a number of regimens will be effective. If not, the preferred regimens in Western countries are 14-day concomitant therapy and 10–14 day bismuth-quadruple therapy. Choice depends on patient and physician preference and specific allergies or interactions with other drugs the patient is taking. As failure does not stop progression of the disease and treatment failures are common, a noninvasive test for cure is recommended. All consensus statements agree that whenever H. pylori is diagnosed it should be cured if possible. H. pylori eradication reduces gastric cancer risk. In regions where gastric cancer is common, such as Japan, it is prudent to also assess gastric cancer risk to ascertain whether marked risk remains and, thus, whether surveillance for subsequent gastric cancer might be indicated. Antibiotic regimen* Clarithromycin Amoxicillin Metronidazole PPI Tetracycline Bismuth Levofloxacin Concomitant (14 days) – – – Hybrid (14 days) Days 1–7 – – – – – Days 8–14 – – – Bismuth (10–14 days) – – – Clarithromycin ‡ (14 days) – – – – Sequential § (14 days) Days 1–7 – – – – – Days 8–14 – – – – Levofloxacin || (14 days) – – – – *All regimens are useful as tailored therapies when treating based on known antibiotic susceptibility patterns. ‡ Limited to low clarithromycin-resistance areas (<5%). § Limited to low metronidazole-resistance areas (<20%). || Limited to low fluoroquinolone-resistance areas (<5%). Indications for eradication ■ Confirmed H. pylori infection ■ Peptic ulcer disease ■ Gastric MALT lymphoma ■ First-degree relative of patient with gastric cancer ■ After curative endoscopic resection of primary gastric cancer ■ Non-ulcer dyspepsia ■ Long-term use of PPI therapy ■ Chronic aspirin or nonsteroidal anti-inflammatory drug therapy Normal Atrophy Treatment requires antibiotics to kill the bacteria and anti-acid medications to ensure they are effective in the stomach. Which therapy? For most other infections, culture is available and specific antibiotics can be chosen. With H. pylori, this approach is generally unavailable and the doctor must use other factors to decide. Considerations Knowledge of antibiotic usage in the population and information about the presence of resistance in the region or other similar regions provides a basis for considering some antibiotics and not others. Discussion with the patient and identifying which antibiotics have been used in the past provides information about possible resistance, as H. pylori often becomes resistant when single antibiotics are used for other infections. Their prior use might exclude them from specific H. pylori therapy. ■ H. pylori colonization of the stomach can result in severe gastric pathology ■ H. pylori infection is the strongest known risk factor for gastroduodenal ulcer development; infection is present in 95% of duodenal ulcers and 60–80% of gastric ulcers ■ H. pylori is also causally related to gastric adenocarcinoma ■ The pattern of gastritis predicts the risk of different outcomes, but gastritis tends to progress leading to gastric atrophy ■ The risk of serious clinical outcomes is related to interactions between the host, bacteria and environment Concomitant therapy for 14 days or best locally approved Rx Rx failure Treatment naive: no prior macrolide, fluoroquinolone, metronidazole use At risk for clarithromycin- metronidazole resistance or prior treatment failure Bismuth-PPI-tetracycline- metronidazole quadruple therapy for 10–14 days or best alternate locally approved Rx Future medical therapies The cause of gastric cancer is known —H. pylori infection. The Japanese government approved population-wide H. pylori eradication in 2013 as part of their gastric cancer prevention programme. Hopefully, this action will prompt other governments to ask why H. pylori is not eradicated from their populations. In developing countries, the burden of H. pylori is high and reinfection following curative therapy is common. A vaccine to prevent H. pylori would potentially solve this problem. Despite a number of attempts to develop an H. pylori vaccine for humans, progress has been slow and funding has been scarce. We eagerly await a breakthrough to make this possible. H. pylori is transmitted between humans and is facilitated by poor household hygiene and sanitary conditions. As such, the bacterium is disappearing in societies with good sanitation, clean water and high standards of living, but remains most common where these conditions are still lacking. Gastric ulcer stomach 1–12% of infected people Progressive atrophy Progressive decrease in acid secretion Gastric cancer stomach 1–12% of infected people Atrophic pangastritis leading to gastric atrophy Acid secretion Duodenal ulcer stomach 10–15% of infected people Antral predominant gastritis Acid secretion Asymptomatic stomach Most common phenotype Nonatrophic pangastritis Normal acid secretion Pore formation VacA cagA cag PAI cag-encoded TFSS babA and other adhesin genes BabA etc. OipA vacA oipA 20–30 31–40 41–50 70–80 81–90 Incidence of H. pylori (%) Risk stratification: is surveillance needed? ■ Pepsinogens are proteolytic stomach enzymes and are useful noninvasive biomarkers of gastric atrophy ■ Pepsinogen I is present in the gastric corpus; pepsinogen II is present in the gastric corpus and antrum ■ Low serum levels of pepsinogen I or a low pepsinogen I:II ratio is associated with gastric atrophy, which is then confirmed using endoscopy High gastric cancer incidence Test for H. pylori Pepsinogen testing in serum and eradication treatment No follow-up required Low levels Moderate–severe atrophy Surveillance Endoscopy for atrophic changes Confirm eradication success No atrophy Normal levels Low gastric cancer incidence Test for H. pylori Eradication treatment Epidemiology The incidence rate of H. pylori infection is far greater in resource-constrained areas, including South America and Africa, than in industrialized countries including North America and the UK. Of note, the prevalence of H. pylori in industrialized countries is often higher among immigrant populations. Supplement to Nature Publishing Group journals Helicobacter pylori David Y. Graham and Emad M. El-Omar Helicobacter pylori is a common and important human pathogen and the primary cause of peptic ulcer disease and gastric cancer. H. pylori is transmitted between humans and is facilitated by poor household hygiene and sanitary conditions. The pathogen causes progressive gastric mucosal inflammation that might eventuate in atrophic gastritis and gastric atrophy. For a population, elimination of H. pylori will essentially eliminate gastric cancer risk. For the individual, H. pylori eradication will reduce gastric cancer risk depending on the extent of damage (that is, level of risk) when eradication is accomplished. Where gastric cancer is common, H. pylori eradication should be coupled with assessment of cancer risk to identify whether surveillance for gastric cancer is indicated. Aptalis Pharma Inc. is a privately held, leading specialty pharmaceutical company providing innovative, effective therapies for unmet medical needs including cystic fibrosis and gastrointestinal disorders. Aptalis has manufacturing and commercial operations in the United States, the European Union and Canada. Aptalis also formulates and clinically develops enhanced pharmaceutical and biopharmaceutical products for itself and others using its proprietary technology platforms including bioavailability enhancement of poorly soluble drugs, custom release profiles, and taste-masking/orally disintegrating tablet (ODT) formulations. For more information, visit www.aptalispharma.com. Abbreviations PPI proton pump inhibitor PSCA prostate stem cell antigen TFSS type IV secretion system TLR1 Toll-like receptor 1 TNF tumour necrosis factor References 1. Malfertheiner, P. et al. Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report. European Helicobacter Study Group. Gut 61, 646–664 (2012). Latest Maastricht Guidelines consensus paper, relevant to diagnosis, treatment and indications for treatment. 2. Cancer Research UK. Stomach cancer incidence [online] http://www.cancerresearchuk.org/cancer-info/cancerstats/world/ stomach-cancer-world/ (2011). 3. The Helicobacter Foundation. Epidemiology [online] http://www.helico.com/?q=Epidemiology (2013). 4. Amieva, M. & El-Omar, E. M. Host–bacterial interactions of Helicobacter pylori infection. Gastroenterology 134, 306–323 (2008). 5. Polk, D. B. & Peek, R. M. Jr. Helicobacter pylori: gastric cancer and beyond. Nat. Rev. Cancer 10, 403–414 (2010). 6. Mayerle, J. et al. Identification of genetic loci associated with Helicobacter pylori serologic status. JAMA 309, 1912–1920 (2013). 7. Graham, D. Y., Lee, Y.-C. & Wu, M.-S. Rational Helicobacter pylori therapy: Evidence-based medicine rather than medicine-based evidence. Clin. Gastroenterol. Hepatol. http://dx.doi.org/10.1016/ j.cgh.2013.05.028. Affiliations and acknowledgements Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX 77030, USA (D. Y. Graham). Division of Applied Medicine, Institute of Medical Sciences, School of Medicine & Dentistry, Aberdeen University, Foresterhill, Aberdeen AB25 2ZD, UK (E. M. El-Omar). Edited by Katherine Smith. Designed by Laura Marshall. The poster content is peer reviewed, editorially independent and the sole responsibility of Nature Publishing Group. © 2013 Nature Publishing Group. http://www.nature.com/nrgastro/posters/helicobacterpylori
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Transcript of H pylori poster-web
Treatment of H. pyloriClinical outcomes of infection
Infection
Risk factors for gastric cancerEnvironmental■ Smoking■ Diet high in salt■ Diet low in fresh fruit and vegetables■ Iron de�ciency
Host genetics■ Genes associated with increased risk of H. pylori infection: TLR1■ Genes associated with increased risk of gastric cancer: IL1B, TNF, IL8, PSCA
Bacterial
Photo
Photo
H. pylori are spiral-shaped Gram-negative bacteria with polar�agella that can survive in the human gastric mucosa. Thebacteria have evolved intricate mechanisms to avoid thebactericidal acid in the gastric lumen and to survive near to,to attach to, and to subvert the human gastric epitheliumand immune system.
Diagnosis of H. pylori
Noninvasive (preferred)■ Serology: IgG against H. pylori■ Stool antigen test■ Breath test for diagnosis of H. pylori infection
Invasive (requires endoscopy)■ Histology: gastric biopsy samples stained for H. pylori using haematoxylin and eosin, immunohistochemistry, silver staining, Genta stain or alcian yellow–toluidine blue■ Culture of gastric biopsy samples■ Rapid urease test
If H. pylori is present, urea isconverted into ammonia andcarbon dioxide by their ureaseenzymes. The breakdown of ureaincreases the pH level of thesolution, triggering a colourchange from yellow to pink.
H. pylori positive
H. pylorinegative
Urea and pHindicator (e.g. phenol red)
Biopsy samples fromthe stomach antrum
The patient is given a drinkcontaining urea labelled withnonradioactive carbon-13.If H. pylori is present, their ureaseenzyme breaks down urea to formcarbon dioxide, which is exhaled.After taking the urea-based drink,the patient blows into the sampletube or bag which is then testedfor an increase in the proportionof carbon dioxide containingcarbon-13. A positive resultindicates presence of H. pyloriand the appropriate eradicationtherapy can then be prescribed.
Tailored Rx
Available
H. pylori infection
History of antibiotic use? Previously treated for H. pylori?
Susceptibility testing
Not available
Current available drugs
13C Urea
UreaseCO2+
NH3
13CO2in blood
13CO2 in breath
In the USA, the prevalence of resistance is ~15% to clarithromycin and 25% to metronidazole, but is much higherin individuals who have taken those antibiotics for other infections. If susceptibility of the pathogen is known, anumber of regimens will be effective. If not, the preferred regimens in Western countries are 14-day concomitanttherapy and 10–14 day bismuth-quadruple therapy. Choice depends on patient and physician preference andspeci�c allergies or interactions with other drugs the patient is taking. As failure does not stop progression of the disease and treatment failures are common, a noninvasive test for cure is recommended.
All consensus statements agree that whenever H. pylori is diagnosed it should be cured if possible. H. pylorieradication reduces gastric cancer risk. In regions where gastric cancer is common, such as Japan, it is prudentto also assess gastric cancer risk to ascertain whether marked risk remains and, thus, whether surveillance forsubsequent gastric cancer might be indicated.
Antibiotic regimen* Clarithromycin Amoxicillin Metronidazole PPI Tetracycline Bismuth Levo�oxacin
Concomitant (14 days) � � � � – – –
Hybrid (14 days)
Days 1–7 – � – � – – –
Days 8–14 � � � � – – –
Bismuth (10–14 days) – – � � � � –
Clarithromycin‡ (14 days) � � – � – – –
Sequential§ (14 days)
Days 1–7 – � – � – – –
Days 8–14 � – � � – – –
Levofloxacin|| (14 days) – � – � – – �
*All regimens are useful as tailored therapies when treating based on known antibiotic susceptibility patterns. ‡Limited to low clarithromycin-resistanceareas (<5%). §Limited to low metronidazole-resistance areas (<20%). ||Limited to low �uoroquinolone-resistance areas (<5%).
Indications for eradication■ Con�rmed H. pylori infection■ Peptic ulcer disease■ Gastric MALT lymphoma■ First-degree relative of patient with gastric cancer■ After curative endoscopic resection of primary gastric cancer■ Non-ulcer dyspepsia■ Long-term use of PPI therapy■ Chronic aspirin or nonsteroidal anti-in�ammatory drug therapy
Normal Atrophy
Treatment requires antibiotics to kill the bacteria and anti-acid medications to ensure they are effective in the stomach.Which therapy?For most other infections, culture is availableand speci�c antibiotics can be chosen. WithH. pylori, this approach is generally unavailableand the doctor must use other factors to decide.Considerations Knowledge of antibiotic usage in the populationand information about the presence ofresistance in the region or other similar regionsprovides a basis for considering some antibioticsand not others. Discussion with the patient andidentifying which antibiotics have been used inthe past provides information about possibleresistance, as H. pylori often becomes resistantwhen single antibiotics are used for otherinfections. Their prior use might exclude themfrom speci�c H. pylori therapy.
■ H. pylori colonization of the stomach can result in severe gastric pathology■ H. pylori infection is the strongest known risk factor for gastroduodenal ulcer development; infection is present in 95% of duodenal ulcers and 60–80% of gastric ulcers■ H. pylori is also causally related to gastric adenocarcinoma■ The pattern of gastritis predicts the risk of different outcomes, but gastritis tends to progress leading to gastric atrophy ■ The risk of serious clinical outcomes is related to interactions between the host, bacteria and environment
Concomitant therapyfor 14 days or
best locally approved Rx
Rx failure
Treatment naive: no priormacrolide, �uoroquinolone,
metronidazole use
At risk for clarithromycin-metronidazole resistanceor prior treatment failure
Bismuth-PPI-tetracycline-metronidazole quadrupletherapy for 10–14 days or
best alternate locallyapproved Rx
Future medical therapiesThe cause of gastric cancer is known—H. pylori infection. The Japanese governmentapproved population-wide H. pylori eradicationin 2013 as part of their gastric cancerprevention programme. Hopefully, this action will promptother governments to ask why H. pylori is not eradicatedfrom their populations. In developing countries, the burdenof H. pylori is high and reinfection following curative therapy iscommon. A vaccine to prevent H. pylori would potentially solvethis problem. Despite a number of attempts to develop an H. pylorivaccine for humans, progress has been slow and funding has beenscarce. We eagerly await a breakthrough to make this possible.
H. pylori is transmitted between humansand is facilitated by
poor household hygiene and sanitary conditions.
As such, the bacterium is disappearing in societies with
good sanitation, clean water and high standards of living,
but remains most common where these conditions
are still lacking.
Gastric ulcer stomach1–12% of infected peopleProgressive atrophy Progressive decreasein acid secretion
Gastric cancer stomach1–12% of infected peopleAtrophic pangastritis leadingto gastric atrophy Acid secretion
Duodenal ulcer stomach10–15% of infected peopleAntral predominant gastritis Acid secretionAsymptomatic stomach
Most common phenotypeNonatrophic pangastritisNormal acid secretion
Pore formation
VacA cagA cag PAI
cag-encoded TFSS
babA and otheradhesin genes
BabA etc. OipA
vacA oipA
20–3031–4041–5070–8081–90
Incidence of H. pylori (%)
Risk stratification: is surveillance needed?
■ Pepsinogens are proteolytic stomach enzymes and are useful noninvasive biomarkers of gastric atrophy■ Pepsinogen I is present in the gastric corpus; pepsinogen II is present in the gastric corpus and antrum■ Low serum levels of pepsinogen I or a low pepsinogen I:II ratio is associated with gastric atrophy, which is then con�rmed using endoscopy
High gastric cancer incidence
Test for H. pylori
Pepsinogen testing in serum and eradication treatment
No follow-uprequired
Low levels
Moderate–severeatrophy
Surveillance
Endoscopy foratrophic changes
Con�rmeradication
success
Noatrophy
Normallevels
Low gastriccancer
incidence
Test forH. pylori
Eradicationtreatment
EpidemiologyThe incidence rate of H. pylori infection is far greater in resource-constrainedareas, including South America and Africa, than in industrialized countriesincluding North America and the UK. Of note, the prevalence of H. pylori inindustrialized countries is often higher among immigrant populations.
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Helicobacter pyloriDavid Y. Graham and Emad M. El-Omar
Helicobacter pylori is a common and important human pathogen and the primary cause of peptic ulcer disease and gastric cancer. H. pylori is transmitted between humans and is facilitated by poor household hygiene and sanitary conditions. The pathogen causes progressive gastric mucosal inflammation that might eventuate in atrophic gastritis and gastric atrophy. For a population, elimination of H. pylori will
essentially eliminate gastric cancer risk. For the individual, H. pylori eradication will reduce gastric cancer risk depending on the extent of damage (that is, level of risk) when eradication is accomplished. Where gastric cancer is common, H. pylori eradication should be coupled with assessment of cancer risk to identify whether surveillancefor gastric cancer is indicated.
Aptalis Pharma Inc. is a privately held, leading specialty pharmaceutical company providing innovative, effective therapies for unmet medical needs including cystic fibrosis and gastrointestinal disorders. Aptalis has manufacturing and commercial operations in the United States, the European Union and Canada. Aptalis also formulates and clinically develops enhanced pharmaceutical and biopharmaceutical products for itself and others using its proprietary technology platforms including bioavailability enhancement of poorly soluble drugs, custom release profiles, and taste-masking/orally disintegrating tablet (ODT) formulations.
For more information, visit www.aptalispharma.com.
Abbreviations PPI proton pump inhibitorPSCA prostate stem cell antigenTFSS type IV secretion systemTLR1 Toll-like receptor 1TNF tumour necrosis factor
References1. Malfertheiner, P. et al. Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report.
European Helicobacter Study Group. Gut 61, 646–664 (2012). Latest Maastricht Guidelines consensus paper, relevant to diagnosis, treatment and indications for treatment. 2. Cancer Research UK. Stomach cancer incidence [online] http://www.cancerresearchuk.org/cancer-info/cancerstats/world/ stomach-cancer-world/ (2011).3. The Helicobacter Foundation. Epidemiology [online] http://www.helico.com/?q=Epidemiology (2013).4. Amieva, M. & El-Omar, E. M. Host–bacterial interactions of Helicobacter pylori infection. Gastroenterology 134, 306–323 (2008).
5. Polk, D. B. & Peek, R. M. Jr. Helicobacter pylori: gastric cancer and beyond. Nat. Rev. Cancer 10, 403–414 (2010). 6. Mayerle, J. et al. Identification of genetic loci associated with Helicobacter pylori serologic status. JAMA 309, 1912–1920 (2013). 7. Graham, D. Y., Lee, Y.-C. & Wu, M.-S. Rational Helicobacter pylori therapy: Evidence-based medicine rather than medicine-based evidence. Clin. Gastroenterol. Hepatol. http://dx.doi.org/10.1016/ j.cgh.2013.05.028.
Affiliations and acknowledgementsMichael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX 77030, USA (D. Y. Graham). Division of Applied Medicine, Institute of Medical Sciences, School of Medicine & Dentistry, Aberdeen University, Foresterhill, Aberdeen AB25 2ZD, UK (E. M. El-Omar). Edited by Katherine Smith. Designed by Laura Marshall.The poster content is peer reviewed, editorially independent and the sole responsibility of Nature Publishing Group.
© 2013 Nature Publishing Group.
http://www.nature.com/nrgastro/posters/helicobacterpylori
