Letters to the Editor
Letter: complications of coeliac disease despite a gluten-free diet – authors' reply
Article first published online: 5 MAR 2013
© 2013 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 37, Issue 7, pages 762–763, April 2013
How to Cite
Lebwohl, B., Granath, F., Ekbom, A., Montgomery, S. M., Murray, J. A., Rubio-Tapia, A., Green, P. H. R. and Ludvigsson, J. F. (2013), Letter: complications of coeliac disease despite a gluten-free diet – authors' reply. Alimentary Pharmacology & Therapeutics, 37: 762–763. doi: 10.1111/apt.12243
- Issue published online: 5 MAR 2013
- Article first published online: 5 MAR 2013
- Manuscript Received: 22 JAN 2013
- Manuscript Accepted: 22 JAN 2013
We appreciate the points raised by Dr Tursi. We agree that the purpose of the gluten-free diet (GFD) is the alleviation of symptoms and the prevention of complications, including mortality. Our null findings with regard to mucosal healing concern mortality risk, but not the risk of significant morbidity, including autoimmune disease, fracture, malignancy and impaired quality of life. Data on mucosal healing and these other important outcomes (apart from mortality) are absent, and mucosal healing may ultimately prove a useful risk-stratification marker, even though it does not predict mortality.
Complications can occur years after the diagnosis of coeliac disease (CD), but the mortality increase is most apparent in the first year after diagnosis. This may account, in part, for our null findings; patients who underwent follow-up biopsy had all already survived the period of greatest hazard. While our study showed that mucosal healing does not predict mortality, there is convincing evidence among all patients with CD that the GFD reduces mortality. The elevated mortality risk observed in CD changes over time, with multiple studies showing that this risk elevation declines towards the null in the years following CD diagnosis.[4, 5] The most likely explanation for this change in risk is the beneficial effect of the GFD. Thus, we believe that our findings may call into question the practice of routine follow-up biopsy as a risk-stratification tool, but that the GFD remains an essential, potentially life-saving intervention.
Dr Fernández-Bañares and colleagues raise an important caveat regarding the potential for ascertainment bias, given that most patients with CD in our study did not undergo follow-up biopsy. Indeed, the overall mortality rate of patients who underwent follow-up biopsy was slightly lower than those who did not. However, as we point out in the Discussion, when excluding those patients who died within 6 months of initial diagnosis, their mortality rate was similar (HR: 0.97, 95% CI: 0.89–1.06).
The assertion that persistent villous atrophy is associated with an increased risk of osteoporosis and malignancy was based on a single-centre study with a sample size of 13 patients with persistent villous atrophy. While this might ultimately prove to be true, we believe that the small sample size in that paper mandates further study.
We agree that among those with persistent villous atrophy on first follow-up biopsy, a proportion may have gone on to full histological recovery. This may account for our null finding with regard to mortality. Thus, we can conclude that initial follow-up biopsy is not predictive of mortality; whether the results of subsequent biopsies are useful for predicting morbidity or mortality remains unknown.
We read with interest the findings reported by Kadauke and colleagues regarding elevated levels of stool Adnab-9 antigen in CD patients on a gluten-containing diet. It would be important to establish whether this biomarker is predictive of malignancy risk in this population.
The authors' declarations of personal and financial interests are unchanged from those in the original article.2