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We read with interest the commentary of Dr Howden regarding our paper describing the effect of proton pump inhibitors (PPIs) on serious infections in cirrhotic veterans.[1, 2] There are several important points raised in this letter that highlight the controversial nature of this topic.

The hazard ratios were arrived at after controlling for several factors that can affect infection risk, i.e. age, co-morbidities, concurrent medications, alcoholic aetiology and prior hospitalisations in our advanced cirrhotic population.[3] We still found a significant increase in the rate, 1.66, i.e. 66% increase for all infections and 1.75, 75% increase for acid-suppression infections. We argue that this is clinically significant for this population, which has an extremely high mortality from infections compared with non-infected cirrhotics and noncirrhotic infected patients.[4] This increased rate gains higher importance, given that we only restricted ourselves to those who initiated PPI after decompensation, to infections associated with hospitalisation and to those patients whose exact PPI doses could be tracked.

Although we agree that pneumonia, as well as other infections, has risk factors other than acid-suppression, we found an overall increase in risk of all infections in those who initiated PPI, just that it was higher for those with acid suppression-related infections. We do agree that re-evaluation of the indication for PPI use is important as prior studies demonstrate that a significant percentage of cirrhotic patients receive PPI therapy for unknown indications.[5, 6] However, this dataset did not allow us to analyse indications.

Given the poor survival in decompensated cirrhotics with infections, any modifiable factor that can reduce this risk including, but not limited to, reassessing non-indicated PPI use, is worth investigating and acting upon. Therefore, we believe that these findings do not overstate the risk of infections with PPI initiation, given the controlled nature of the analysis.

Acknowledgement

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  2. Acknowledgement
  3. References

The authors' declarations of personal and financial interests are unchanged from those in the original article.2

References

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  2. Acknowledgement
  3. References