La malattia peptica: dall'Helicobacter pylori al corretto utilizzo dei PPI - Fenoglio Luigi M SC Med Interna AO S Croce e Carle Cuneo - Planning ...
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La malattia peptica:
dall’Helicobacter pylori al
corretto utilizzo dei PPI
Fenoglio Luigi M
SC Med Interna
AO S Croce e Carle
Cuneo
Il sottoscritto Luigi Fenoglio
ai sensi dell’art. 3.3 sul Conflitto di Interessi, pag. 18,19
dell’Accordo Stato-Regione del 19 aprile 2012, per conto di
Planning Congressi srl,
dichiara
che negli ultimi due anni NON ha avuto rapporti diretti di
finanziamento con soggetti portatori di interessi commerciali in
campo sanitario.
Peptic diseases
The result from distinctive but overlapping
pathogenic mechanisms leading to
either excessive acid secretion
or diminished mucosal defense.
Expert Rev Clin Pharmacol. 2009
Peptic diseases
Etiologies and disease associations
Definite mechanisms
Idiopathic
Non-Helicobacter pylori, non-NSAID peptic ulcer
Comorbid disease associated with
decompensated chronic disease
or acute multysistemic failure
UpToDate 2019
Helicobacter pylori McColl K. N Engl J Med 2010;362:1597-1604
HP IARC Group 1 carcinogen
The story of H. pylori
In 1892 G. Bizzozero
In 1982 Marshall BJ, Warren JR.
In 1987, Thomas Borody invented the first triple therapy for the treatment
of duodenal ulcer.
In 1994, the National Institutes of Health (USA) published an opinion
stating most recurrent duodenal and gastric ulcers were caused by H.
pylori, and recommended antibiotics be included in the treatment
regimen
In 1997 was sequenced the complete genome of H. pylori strain 26695
isolated in UK in early 1980s
In 1997 European Helicobacter Pylori Study Group. Current European
concepts in the management of Helicobacter pylori infection.
The Maastricht Consensus Report. Gut 1997.
In 2015 Guidelines Management of Helicobacter pylori infection—the
Maastricht V/ Florence Consensus Report Gut 2017
Sulle ghiandole tubulari del tubo gastroenterico e sui rapporti del loro epitelio coll’epitelio di rivestimento della mucosa. Bizzozero G. Atti della Reale Accademia delle Scienze di Torino 28:233-251. Ueber die schlauchformigen drusen des magendarmkanals und die bezienhungen ihres epithels zu dem oberflachenepithel der schleimhaut. Bizzozero G. Arch. Mikr Anat. 1893;42:82.
The story of H. pylori
In 1892 G. Bizzozero
In 1982 Marshall BJ, Warren JR.
In 1987, Thomas Borody invented the first triple therapy for the treatment
of duodenal ulcer.
In 1994, the National Institutes of Health (USA) published an opinion
stating most recurrent duodenal and gastric ulcers were caused by H.
pylori, and recommended antibiotics be included in the treatment
regimen
In 1997 was sequenced the complete genome of H. pylori strain 26695
isolated in UK in early 1980s
In 1997 European Helicobacter Pylori Study Group. Current European
concepts in the management of Helicobacter pylori infection.
The Maastricht Consensus Report. Gut 1997.
In 2015 Guidelines Management of Helicobacter pylori infection—the
Maastricht V/ Florence Consensus Report Gut 2017A silver stain of H. pylori on gastric mucus-secreting epithelial cells From Dr. Marshall's stomach biopsy taken 8 days after he drank a culture of H. pylori .
The story continues………
In 1987, Thomas Borody invented the first triple therapy for the treatment
In 2019 Professor
of duodenal Fulvio Pomero organizes the Alba update of HP.
ulcer.
In 1994,
-the NIH (USA) published an opinion stating most recurrent duodenal
and gastric ulcers were caused by H. pylori, and recommended
antibiotics be included in the treatment regimen.
-HP is classified as a type I (definite) carcinogen.
In 1995, the risk of gastric Malt Lymphoma is significantly increased
In 1996 European Helicobacter Pylori Study Group. Current European
concepts in the management of Helicobacter pylori infection.
The Maastricht Consensus Report. Gut 1997.
In 1997 ,was sequenced the complete genome of H. pylori strain 26695
isolated in UK in early 1980s
In 2015 Guidelines Management of Helicobacter pylori infection
The Maastricht V Consensus Report. Gut 2017Gastroenterology 2017 4,4 miliardi H pylori +ve
H. pylori Infection transmission • Transmissible – Oral-oral and oral-fecal • Infects the human stomach • Produces inflammatory response • This brings up the point of the importance of “hand washing”
Per cortesia di Alberto Comino SC Anatomia Patologica
Dynamics of H.pylori infection
Dr.T.V.Rao MD 18La storia Clinica
H.P. gastritis is an infectious disease with the recommendation
of treatment of all H. pylori infected subjects.
Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015
UpToDate 2019Le manifestazioni Cliniche
- Deficit di B12
GUT 2016Le manifestazioni Cliniche
La diagnostica
sensitivity 88 to 95 %
specificity 95 to 100 %
sensitivity and specificity
comparable to the UBT
sensitivity 90 %
specificity 95 %
sensitivity 95 %
specificity 98 %
low sensitivity as HP is difficult to culture
N Engl J Med 2010
UpToDate 2019Tasso di eradicazione totale della triplice terapia
7-day TT 71.4% (69.3 to 73.3)
10-day TT 75.4% (72.4 to 78.2)
14-day TT 80.8% (78.3 to 83.2)
69 74 79 84
proportion (95% confidence interval)
BMJ 2013Terapia di prima linea
2015Terapia di prima linea
APT 2018, D VairaSecond line therapy
Number of
Therapy regimen Duration (days)
tablets
Sequential 10 50
Concomitant 14 112
Pylera 10 140257/746 triple-resistant HP pts
12 days
esomeprazole 40 mg bid
amoxicillin 1 g bid
rifabutin 150 mg od
J Clin Gastroenterol. 2018 FebJ Clin Microbiol. 2017 Aug;55(8):2400-2405. doi: 10.1128/JCM.00506-17. Epub 2017 May 17. A Novel Stool PCR Test for Helicobacter pylori May Predict Clarithromycin Resistance and Eradication of Infection at a High Rate. Beckman E, Saracino I, Fiorini G, Clark C, Slepnev V, Patel D, Gomez C, Ponaka R, Elagin V, Vaira D.
The end of the story
PPIs
Proton pump inhibitors are drugs blocking the gastric
H,K-ATPase, inhibiting gastric acid secretion.
Proton pump inhibitors
are among the top
They are used for treatment of
10ulcersmost
disease widely used drugs
• gastroesophageal reflux disease
• peptic
• hypersecretory disorders ( Zollinger-Ellisson Syndrome )
in thepylori
• the eradication of Helicobacter world
as part of combination
INNAPROPRIATE
regimens. SITUATIONS
• prophylaxis of upper gastrointestinal injury caused by drugs
• nonvariceal upper GI bleeding
GUT 2015
AMJ 2014; 7 ( 11)(H+, K+ adenosintrifosfatasi)
Rapporto dose-risposta simili quando utilizzati a dosaggio comparabile
Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition.We Are Using Too Many PPIs, and
We Need To Stop:
A European Perspective
Am J Gastroenterol 2016PPIs have become a victim
of their own success.
Osservatorio Nazionale sull’impiego dei Medicinali.
Spesa procapite IPP : 13.35 E L’uso dei farmaci in Italia. Rapporto Nazionale 2017. AIFA, 2018.Regione Piemonte - 2016
Inappropriate prescription of proton pump inhibitors, very high at admission (62 %), remained equally high at discharge (63 %).
Andamento consumo farmaci antiacidi per
unità posologiche ASO S Croce e Carle-Cn
Choosing
wisely
Infante Lucia, Fruttero Claudia SC Farmacia Ospedaliera AO S Croce e Carle-Cn
Fenoglio Luigi SC Medicina InternaMRGE
terapia
• The most common chronic digestive disorder in which the
reflux of gastric contents into the esophagus through the
incompetent LES causes troublesome symptoms and/or
complications
• Affecting one third of the world’s population, GERD inflicts
significant direct and indirect costs and loss of productivity.
• Currently, PPI-based pharmacological therapy in combination
with lifestyle modifications remains the mainstay of GERD
management
Gut Liver 2017 Apr 24Patients with uncomplicated GERD who respond to short-term PPIs
should subsequently attempt to stop or reduce them.
Patients who cannot reduce PPIs should consider ambulatory esophageal pH/impedance
monitoring before committing to lifelong PPIs
Patients with complicated GERD should take a PPI for maintenance of
healing and long-term symptom control
There are no major differences in efficacy between the different PPIs. (Strong
recommendation, high level of evidence )
Patients with Barrett’s esophagus should consider a long-term PPI
Gastroenterology 2017; 152:706-715Gastro-oesophageal reflux events:
just another trigger in chronic cough?
• Multiples studies and meta-analyses have failed to
document a therapeutic benefit of acid suppression in
chronic cough.
• Estimated costs of PPI in extraoesophageal
manifestation of GERD is four to five times those
associated with their use in typical GERD.
GUT 2017Ppi for functional dyspepsia
Cochrane Database of Systematic Reviews-2017Ulcera peptica
terapia
• HP-associated ulcers
– 7 day treatment with PPI plus 2 antibiotics heals > 70% of PU and is as
effective as the same regimen followed by 2 to 4 additional weeks of
PPI therapy ( SOR A, meta-analysis of RCTs)
• NSAIDs-associated ulcers
– 8 wks of PPI treatment is better than 4 wks in the case of gastric
ulcers, but no more effective than 4 wks for duodenal ulcers
( SOR A, meta-analysis of RCTs ).
JFP December 2015Ulcera peptica
terapia
• HP-associated ulcers
– 7 day treatment with PPI plus 2 antibiotics heals > 70% of PU and is as
effective as the same regimen followed by 2 to 4 additional weeks of
PPI therapy ( SOR A, meta-analysis of RCTs)
• NSAIDs-associated ulcers
– 8 wks of PPI treatment is better than 4 wks in the case of gastric
ulcers, but no more effective than 4 wks for duodenal ulcers
( SOR A, meta-analysis of RCTs ).
JFP December 2015Ulcera peptica indotta da farmaci
prevenzione
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs cause considerable morbidity and mortality related
to gastric and duodenal ulcer disease.
25 % of chronic NSAID users will develop ulcer disease
and 2 – 4 % will bleed or perforate
In reumathoid arthritis at least 2,600 deaths in the USA annually.
100,000 hospital admissions annually in the United States and
between 7,000 and 10,000 deaths
Gastroenterology 2014 The risk of GI complications was
Indomethacin RR 2.25
Naproxen RR 1.83
Diclofenac RR 1.73
Piroxicam RR 1.66
Tenoxicam 1.43
Ibuprofen RR 1.43
The average duration of treatment before observing a significant
risk of GI effects was 84 days.
An increased risk was apparent as early as 7 days with
indomethacin
Ann Rheum Dis 2004UpToDate 2019
RISK FACTORS
1. History of ulcer disease or ulcer complication
2. Age >65 years
3. High dose NSAID therapy
4. Use of aspirin ( including low dose ), or glucocorticoids, or anticoagulants
GASTROINTESTINAL RISK
High risk a history of a complicated ulcer or ≥3 risk factors
Moderate the presence of one or two risk factors
Low risk none of the four risk factors
1A 1B 1BArticles reporting on PPIs potential risks.
Gastroenterology 2017;152:706–715November, 29, 2019: Page Last Updated: 04/12/2016
POTENZIAL ADVERSE EFFECTS OF PPI
Jama Internal Medicine February 2016Grazie per l’attenzione!
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