Alimentary Pharmacology and Therapeutics Letters to the Editors Table 2 | Eradication rates of the therapy prescribed Treatment
n
Helicobacter pylori eradicated
Success rate
PARC PBRC Personalised therapy
63 25 10
57 25 9
91% 100% 90%
was 100% (n = 25, 95% CI: 88–100). Patients requiring alternative salvage therapies were given novel personalised combinations consisting of bismuth, rifabutin and either tetracycline or furazolidone; the eradication rate for this small group was 90% (n = 10, 95% CI: 57–99). Although the sample size is small, this encouraging analysis indicates that the PARC and PBRC salvage therapies can be confidently prescribed without the expense of standard antimicrobial susceptibility testing. The efficacies of alternative antibiotic combinations with small sample sizes are continuously being monitored in our clinic. It is important to note that antibi-
Letter: complications of coeliac disease despite a gluten-free diet A. Tursi Gastroenterology Service, ASL BAT, Andria, BT, Italy. E-mail:
[email protected] doi:10.1111/apt.12227
SIRS, In their recent paper, Lebwohl and colleagues report an interesting finding: persistent villous atrophy (VA) does not seem to be associated with increased mortality in coeliac disease (CD).1 This conclusive statement is quite surprising. As already stated by the authors, CD patients are at risk of earlier death,2, 3 and failure in mucosal healing has been thought to be the main factor.4, 5 This study seems to call into question this consolidate hypothesis, and it deserves some comments from a clinical practice’s point of view. We know that histological recovery takes different times, according to the age when gluten-free diet (GFD) has started. In our experience, subdividing the patients according to age, only the younger patients (5– 30 years) showed significant improvement of histology within 12 months (P < 0.034); older patients Aliment Pharmacol Ther 2013; 37: 752-766 ª 2013 Blackwell Publishing Ltd
otic resistant profiles vary from country to country. As a result, the proposed salvage therapies in our previous publication2, PARC and PBRC, are suitable only for countries with low rates of resistance to quinolone and rifabutin.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Tursi A. Letter: curing Helicobacter pylori infection in a clinical setting. Aliment Pharmacol Ther 2013; 37: 757–8. 2. Tay CY, Windsor HM, Thirriot F, et al. Helicobacter pylori eradication in Western Australia using novel quadruple therapy combinations. Aliment Pharmacol Ther 2012; 36: 1076–83. 3. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection–the Maastricht IV/Florence Consensus Report. Gut 2012; 61: 646–64.
(>30 years) showed histological improvement, but this was not statistically significant, even after 24 months on a GFD.6 Gluten-free diet is generally advised to CD patients for three main reasons: treating symptoms related to the disease; preventing immunological gluten-related disorders; and preventing neoplastic complications. GFD and adherence to diet are considered the key factors in obtaining mucosal healing and in preventing occurrence of complications.7, 8 In our experience, the time to the occurrence of complications with GFD seems to be related to type of disease rather than to the severity of the histological lesion at the time of the diagnosis. In fact, considering the time of appearance of complications after GFD had started, complications occurred after a mean/median time with GFD of 6.5/5 years [standard deviation (s.d.) 5.08] in classical CD, and after a mean/median time of 3.5/4 years (s.d. 1) in subclinical CD. However, looking at the compliance to GFD in patients developing complications, we found that 6/14 (42.9%) patients with classical CD were not fully compliant with GFD, whilst 2/4 (50%) of subclinical CD were not fully compliant (P = n.s.).9 In light of our and Lebwohl’s experience, should a GFD still be advised to prevent complications? Despite the retrospective design, Lebwohl’s study calls into ques759
Letters to the Editors tion whether and why an increased complication rate (increased mortality rate included) occurs in CD. Furthermore, confirmative and prospective studies are, therefore, welcomed.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and mortality in coeliac disease. Aliment Pharmacol Ther 2013; 37: 332–9. 2. Tio M, Cox MR, Eslick GD. Meta-analysis: Coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy. Aliment Pharmacol Ther 2012; 35: 540–51. 3. Ludvigsson JF, Montgomery SM, Ekbom A, Brandt L, Granath F. Small-intestinal histopathology and mortality risk in celiac disease. JAMA 2009; 302: 1171–8.
Letter: mucosal healing and mortality in coeliac disease ~ares*, M. Esteve* & J. P. Gisbert† F. Fernandez-Ban *Department of Gastroenterology, Hospital Universitari Mutua Terrassa, CIBERehd, Terrassa, Barcelona, Spain. † Department of Gastroenterology, Hospital Universitario de la Princesa, IP, CIBERehd, Madrid, Spain. E-mail:
[email protected] doi:10.1111/apt.12229
SIRS, We read the interesting paper by Lebwohl et al.1 The authors concluded that there was no association between persistence of villous atrophy and mortality in coeliac disease (CD). However, the study design and the interpretation of results raise some concerns. In spite of the impressive number of patients evaluated, it is of note that only 26% of the CD-diagnosed patients during the study period had a follow-up biopsy, with the reason why these biopsies were taken unknown and therefore, as the authors mention in their discussion, ascertainment bias cannot be excluded. It has recently been emphasised that small bowel biopsy remains the gold standard for monitoring mucosal healing in CD.2, 3 Persistent villous atrophy was associated with a more than threefold increased risk of osteoporosis, refractory CD and malignancies irrespective of symptom resolution on a gluten-free diet (GFD).4 Thus, the question that emerges is whether the CD patients in this study cohort were adequately followed up. 760
4. Rubio-Tapia A, Rahim MW, See JA, Lahr BD, Wu TT, Murray JA. Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet. Am J Gastroenterol 2010; 105: 1412–20. 5. Kaukinen K, Peraaho M, Lindfors K, et al. Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther 2007; 25: 1237–45. 6. Cosnes J, Cellier C, Viola S; Groupe D’Etude et de Recherche Sur la Maladie Coeliaque, et al. Incidence of autoimmune diseases in celiac disease: protective effect of the gluten-free diet. Clin Gastroenterol Hepatol 2008; 6: 753–8. 7. Tursi A, Brandimarte G, Giorgetti GM, et al. Endoscopic and histological findings in the duodenum of adults with celiac disease before and after changing to a glutenfree diet: a 2-year prospective study. Endoscopy 2006; 38: 702–7. 8. Fasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med 2012; 367: 2419–26. 9. Tursi A, Elisei W, Giorgetti GM, Brandimarte G, Aiello F. Complications in celiac disease under gluten-free diet. Dig Dis Sci 2009; 54: 2175–82.
A recent paper showed that medical follow-up evaluation in patients with CD is highly variable and often inadequate. In fact, follow-up consistent with current American Gastroenterology Association recommendations was observed in only 35% of patients.5 Currently, clear guidelines on when to repeat small-bowel biopsy are lacking. However, a systematic review of studies reporting the long-term management of CD suggested that follow-up biopsy at 1–2 years after commencement of the GFD is recommended, and that if histological improvement is incomplete, biopsies probably should be performed again in 1–2 years.6 Thus, the evaluated cohort of patients would not be useful to assess how persistent villous atrophy influenced mortality in CD, as the rate of follow-up small-bowel biopsy was quite low, the reason why these biopsies were taken was unknown, and there were no additional follow-up biopsies performed when histological improvement was incomplete. Likewise, follow-up biopsy in the study by Lebwohl et al.1 demonstrated that there was persistent villous atrophy in 43% of the cohort. It is reasonable to think that in these patients, dietary measures to improve GFD adherence were taken, as lack of dietary adherence is considered the main reason for persistence of villous atrophy. Improvement in dietary adherence would have influenced survival, and decreased mortality to the level of patients who have mucosal healing. In this sense, the problem in the long-term management of CD is the nondiagnosed persistent villous atrophy. Only once it is Aliment Pharmacol Ther 2013; 37: 752-766 ª 2013 Blackwell Publishing Ltd
