1. Helicobacter pylori:
tutto chiaro?
Luigi GATTA
Gastroenterology & Endoscopy Unit, Versilia Hospital, Lido di Camaiore

2. Summary
 Influence of PPI on diagnosis of Helicobacter pylori
 Helicobacter pylori and Gastric Cancer
 Helicobacter pylori and Gastric MALT Lymphoma
 Regimens for treatment of Helicobacter pylori

3. Effect of PPI
on diagnosis of H. Pylori

4. Effect of PPI on diagnosis of H. Pylori
Nakshabendi IM et al. Helicobacter 1996;1:155-8.
Before PPI
After 8 weeks of PPI
30
20
10
0
Urease Activity
units/ml
Before PPI
After 8 weeks of PPI
2000
1500
1000
500
0
H. pylori Density
CFU x mg of tissue

5. Effect of PPI on diagnosis of H. Pylori
Graham D et al. Am J Gastroenterol 2003;98:1005-1009.

6. Effect of PPI on diagnosis of H. Pylori
Lahner E et al. Helicobacter 2014 in press.
49% on PPI!!!

7. Effect of PPI on diagnosis of H. Pylori
Wash-out suggested:
at least 2 Weeks, please!!!

8. H. pylori & Gastric Cancer

9. Infection & Cancer
Epstein-Barr virus
Hodgkin’s Lymphoma
Burkitt’s Lymphoma
Primary CNS Lymphomas
Human Herper Virus 8
Primary Effusion Lymphomas
Castleman’s Disease
HCV Lymphomas related to essential
mixed cryoglobulinemia
HTLV Human T-cell leukemia virus type 1
and adult T-cell lymphoma
Borrelia Burgdoferi Cutaneos MALT lymphoma

10. H. Pylori & Gastric Cancer
Parsonnet J et al. NEJM 1991;325:1127-1131.

11. World Health Organisation
International Agency Research Cancer
Helicobacter pylori
Class 1 Carcinogen
IARC Monogr Eval Carcinog Risks Hum. 1994; 61: 1-241.

12. Gastrite cronica
Gastrite atrofica
Metaplasia intestinale
Displasia
H. pylori
?
Carcinoma

13. H pylori Eradication in Healthy Individuals
Ford AC et al. BMJ 2014;348:g3174.
to Prevent Gastric Cancer
NNT 124 (95% CI: 78 to 843)

14. H pylori Eradication in Healthy Individuals
to Prevent Gastric Cancer
NNT in Meta-Analysis vary according to
the assumed risk of the control group

15. H pylori Eradication in Healthy Individuals
to Prevent Gastric Cancer

16. H pylori Eradication in Healthy Individuals
Ford AC et al. BMJ 2014;348:g3174.
to Prevent Gastric Cancer

17. H pylori Eradication in Healthy Individuals:
effect on mortality from Gastric Cancer
 Limited, moderate quality evidence
that searching for and eradicating H
pylori reduces the incidence of
gastric cancer in healthy
asymptomatic infected Asian
individuals.
 These data cannot necessarily be
extrapolated to other populations.
Ford AC et al. BMJ 2014;348:g3174.

18. H. Pylori &
Gastric MALT lymphoma

19. WHO 2008
MALT Lymphoma

20. Gastric NHL & H. pylori
Wotherspoon AC et al. Lancet 1991;338:1175-6.

21. Gastric NHL & H. pylori
Parsonnet J et al. N Engl J Med 1994;330:1267-71.

22. Gastric MALT lymphoma & H. pylori
Wotherspoon AC et al. Lancet 1993;342:575-7.

23. ESMO & EGILS Guidelines
If the presence of active H. pylori infection is not
demonstrated by histology or immunohistochemistry, it must
be ruled out by serology, urea breath test and/or stool
antigen test.
Zucca E et al. Ann Oncol 2013;24 Suppl 6:vi144-8.
Ruskone-Fourmestraux A et al. Gut 2011;60:747-58.

24. on Early Stage (IE-IIE2) Gastric MALT Lymphoma
p value
H. pylori eradication
Zullo A et al. Clin Gastroenterol Hepatol 2010;8:105-10.
Overall CR 77.5% (95% CI: 75.3 to 79.7)
CR stage I 78.4% (95% CI: 76.2 to 80.6)
0.0003
CR stage II 55.6% (95% CI: 42.3 to 68.8)
Remission
time
5 months (median)
24 months in all but 3 patients
(up to 72 months reported in literature)

25. H. pylori eradication
on Early Stage (IE-IIE2) Gastric MALT Lymphoma
Zullo A et al. Clin Gastroenterol Hepatol 2010;8:105-10.

26. Gastric MALT lymphoma & H. pylori
 Searching for H. pylori
 CR for stage I : 75%

27. Eradication Treatments
for H. Pylori

28. 1981: Cimetidine vs. Bismuth
Relapse rates of duodenal ulcer after healing
30%
Martin DF et al. Lancet 1981; 1: 7-10.

29. Marshall BJ et al. Lancet 1988; 2: 1437-1442.
80
70
60
50
40
30
20
10
0
CIM/p CIM/T CBS/p CBS/T
Eradication Rate (%)
1988: The First RCT

30. The MACH 1 Study
Lind T et al. Helicobacter 1996;1:138-44.

31. The MACH 2 Study
Lind T et al. Gastroenterology 1999;116:248-53.

32. Efficacy of Triple Therapy
Janssen MJ et al. Aliment Pharmacol Ther 2001;15:613-24.
85
84
83
82
81
80
79
78
77
76
PPI + A +C PPI + A + N
Eradication Rate %
ITT
PP

33. Triple or Bismuth Quadruple?
Luther J et al. Am J Gastroenterol 2010; 105:65–73.
100
80
60
40
20
0
Triple Therapy Quadruple Therapy
Eradication (%)

34. Sequential Therapy
Zullo A et al. Aliment Pharmacol Ther 2000;14:715-8.

35. Sequential Therapy
Zullo A et al. Aliment Pharmacol Ther 2000;14:715-8.
100
95
90
85
80
75
70
Sequential Therapy
Eradication Rate %
ITT = PP

36. Sequential Therapy: Meta-analysis
Gatta L et al. BMJ 2013;347:f4587.
Comparisons
RR
(95% CI)
Prediction
Intervals
I2
ST versus 7-TT
1.21
(1.17 to 1.25)
1.12 to 1.31 20.2%
ST versus 10-TT
1.11
(1.04 to 1.19)
0.89 to 1.39 67%
ST versus 14-TT
1.00
(0.94 to 1.06)
0.83 to 1.19 54.3%
ST versus BCT
1.01
(0.95 to 1.06)
0.89 to 1.14 21.1%
ST versus NBCT
1.00
(0.95 to 1.05)
0.88 to 1.13 40%

37. Sequential Therapy in Italy:
a meta-analysis
Gatta L et al. BMJ 2013;347:f4587.

38. Sequential Therapy in Italy:
a meta-analysis
I² = 0%
Number of Patients: 847
Gatta & Zullo & De Vincenzo. Data on File.

39. Concomitant Therapy

40. Hybrid Therapy

41. Sequential Therapy in Italy:
a meta-analysis
0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Sequential Tx 10 days (Arms = 13 - Patients = 1814)
Concomitant Tx 14 Days (Arms = 2 - Patients = 153)
Concomitant Tx 5 Days ( (Arms = 2 - Patients = 200)
Hybrid Tx Lasting 14 Days (Arms = 2 - Patients = 151)
Hybrid Tx Lasting 7 Days (Arms = 1 - Patients = 90)
PPI + CLA1000 + AMO2000 14 Days (Arms = 4 - Patients = 562)
PPI + CLA500 + AMO2000 14 Days (Arms = 1 - Patients = 89)
PPI + AMO2000 + ME/TI100014 Days (Arms = 3 - Patients = 112)
PPI + CLA1000 + METRO1000 14 Days (Arms = 2 - Patients = 196)
PPI + CLA500 + METRO1000 14 Days (Arms = 1 - Patients = 33)
PPI + CLA3000 + METRO750 14 Days (Arms = 1 - Patients = 54)
Eradication Rate
Gatta & Zullo & De Vincenzo. Data on File.

42. The Cost-Effectiveness Plane

43. The Cost-Effectiveness Plane
Regimens
Duration
(days)
No of Tablets Cost (Euros)
Sequential 10 50 26
Concomitant 14 112 61
Hydrid 14 84 41.4
Triple Therapy (A) 14 84 40.6
Triple Therapy (T) 14 84 49.5
Gatta, Zullo, De Vincenzo. Data on File.

44. H. Pylori Treatment
 Sequential Therapy seems to be the
treatment with the best cost-effectiveness
ratio in Italy

45. Thank you