Is Helicobacter pylori a cause of duodenal ulcer? A methodologic critique of current evidence.
BACKGROUND
Helicobacter pylori (HP) in the gastric antrum has been strongly associated with both duodenal ulcer (DU) and chronic active gastritis (CAG). The relationship between HP and DU has been interpreted as causal by many observers. An alternate hypothesis is that HP coincidently colonizes CAG, which is independently associated with DU by some yet-unknown mechanism.


OBJECTIVE
To assess the extent to which a causal relationship between HP and DU has been demonstrated, we performed a methodologic critique of published clinical studies. We carried out a literature search to identify clinical studies that included at least 25 subjects. Of the eight studies we identified, six used a cross-sectional design and two used a prospective cohort design. We applied methodologic criteria to assess causation: strength of association, biologic gradient, temporality, and experiment.


METHODS
A strong association between HP and DU was demonstrated in all eight studies. Biologic gradient and temporality were not assessed in any study. In the two experimental studies of therapy, loss of antral HP was associated with a decreased rate of DU relapse; however, we did not interpret this as sufficient to support causality because the effect may have been due to a direct mucosal action rather than eradication of HP.


CONCLUSIONS
We conclude that published evidence does not establish HP as a cause of DU. One approach to address causality would be an observational cohort study of ulcer relapse to assess the temporal relationships between HP, CAG, and DU.
Rabeneck
L
L
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Ransohoff
D F
DF
D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004381:Duodenal Ulcer / Q000209:etiology / Q000382:microbiology*; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D013270:Stomach / Q000382:microbiology