Alimentary Pharmacology and Therapeutics Invited Commentaries P = 0.037
P = 0.18
P = 0.003
P = 0.52
100 80
%
60 40 20
Steatosis
Lobular inflammation
Ballooning
GG
CC or CG
GG
CC or CG
GG
CC or CG
GG
CC or CG
0
Fibrosis
Steatosis: 1; Lobular inflammation & Ballooning: 0; Fibrosis: 0 Steatosis: 2; Lobular inflammation & Ballooning: 1; Fibrosis: 1–2 Steatosis: 3; Lobular inflammation & Ballooning: 2; Fibrosis: 3–4
Figure 1 | PNPLA3 polymorphism and histological severity in 147 NAFLD patients (genotypes: CC, n = 34; CG, n = 69; GG, n = 44).
4. Wong VW, Hui AY, Tsang SW, et al. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006; 4: 1154–61. 5. Wong VW, Chu WC, Wong GL, et al. Prevalence of nonalcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut 2012; 61: 409–15.
6. Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011; 53: 1883–94. 7. Shen J, Chan HL, Wong GL, et al. Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers. J Hepatol 2012; 56: 1363–70.
Commentary: the proton pump inhibitor test – does it have a role in eosinophilic oesophagitis?
ophilia. Interestingly, despite symptomatic and histological response to PPI, the two patient groups were similar in almost all demographic, histological and clinical parameters that were assessed in this study. The study was retrospective and included a relatively small number of patients in each group, despite the inclusion of patients from the Swiss EOE database and Walter Reed National Military Medical Center. As with all retrospective studies, the main shortcoming is limited documentation of patients’ clinical course. Furthermore, studies have shown that up to 50% of the patients with EOE will demonstrate a histological and clinical response to PPI treatment.2–4 However, clear definition of response to PPI treatment in EOE remains elusive. Furthermore, it remains unclear if there is a dose– response effect (the higher the dose the greater the number of responders) and if longer duration of PPI administration results in more responders.
R. Fass & C. Maradey-Romero The Oesophageal and Swallowing Center, Division of Gastroenterology and Hepatology. MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA. E-mail: [email protected] doi:10.1111/apt.12672
Moawad et al. used a retrospective design to compare demographics, histological and clinical characteristics between patients with eosinophilic oesophagitis (EOE) who were not with those who were responsive to double-dose proton pump inhibitor (PPI) treatment.1 The latter group is termed PPI-responsive oesophageal eosin896
Aliment Pharmacol Ther 2014; 39: 894-898 ª 2014 John Wiley & Sons Ltd
Invited Commentaries Patients treated with at least 6 weeks of twice-daily PPI were included.1 It is possible that some of the EOE patients may require a longer duration of treatment (up to 3 months), before full response to PPI could be achieved. In addition, comparison with nontreated EOE patients could have helped to determine the contribution of the natural course of the disease to fluctuations in oesophageal eosinophilic count. The main finding of the study is that, with the exception of a response to PPI treatment, there are no other unique characteristics that can identify the PPI-responsive oesophageal eosinophilia group. Consequently, the PPI test, which was found to have a diagnostic value in gastroesophageal reflux disease and noncardiac chest pain, may also have a pivotal role in EOE.5, 6 Future studies should look into the role of the PPI test in this challenging patient population.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None.
Commentary: the proton pump inhibitor test – does it have a role in eosinophilic oesophagitis? Authors’ reply F. J. Moawad* & A. M. Schoepfer† *Gastroenterology Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, MD, USA. † Department of Gastroenterology, University of Lausanne, Lausanne, Switzerland. E-mail: [email protected] doi:10.1111/apt.12676
We thank Drs Fass and Maradey-Romero for their interest in our paper.1 To address their first comment,2 the sample size of our study was relatively small because we focused on cases of oesophageal eosinophilia diagnosed since the publication of the 2011 consensus statement, in which proton pump inhibitor responsive oesophageal eosinophilia (PPI-REE) was formally recognised.3 Our study was retrospective in design; however, the data from both study sites were obtained from clinical databases, which are carefully maintained by the authors who prospectively enrol and collect data on patients with eosinophilic oesophagitis (EoE) and PPI-REE. Additionally, all enrolled patients complete one or more clinical questionnaires at index endoscopy and during follow-up visits. Aliment Pharmacol Ther 2014; 39: 894-898 ª 2014 John Wiley & Sons Ltd
REFERENCES 1. Moawad FJ, Schoepfer AM, Safroneeva E, et al. Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings. Aliment Pharmacol Ther 2014; 39: 603–8. 2. Desai TK, Stecevic V, Chang CH, Goldstein NS, Badizadegan K, Furuta GT. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc 2005; 61: 795–801. 3. Moawad FJ, Veerappan GR, Dias JA, Baker TP, Maydonovitch CL, Wong RD. Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia. Am J Gastroenterol 2013; 108: 366–72. 4. Molina-Infante J, Ferrando-Lamana L, Ripoll C, et al. Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults. Clin Gastroenterol Hepatol 2011; 9: 110–7. 5. Fass R, Fennerty MB, Ofman JJ, et al. The clinical and economic value of a short course of omeprazole in patients with noncardiac chest pain. Gastroenterology 1998; 115: 42–9. 6. Fass R, Ofman JJ, Gralnek IM, et al. Clinical and economic assessment of the omeprazole test in patients with symptoms suggestive of gastroesophageal reflux disease. Arch Intern Med 1999; 159: 216–8.
Treatment goals in EoE include both clinical improvement and reducing oesophageal inflammation. Drs Fass and Maradey-Romero raise a valid point on whether duration and dosage of PPI may alter histological response. Indeed, we have observed that some patients with suspected EoE who respond clinically to a PPI, yet continue to demonstrate eosinophilia on endoscopy at 8 weeks, may achieve histological resolution on repeat endoscopy at 1 year with maintenance PPI. A similar concept is observed in patients with inflammatory bowel disease and coeliac disease, where improvement in clinical symptoms often precedes endoscopic and histological change. However, in cases where clinical symptoms persist after 6 to 8 weeks, we do not believe that a longer duration of PPI (e.g. 3 months) will change their clinical course. In the setting of persistent symptoms and eosinophilia, these patients are diagnosed with EoE and require an alternate form of therapy, such as topical steroids or specialised diets. We agree with the comment that the ‘PPI test’ has a role in EoE. However, in the classic sense, this test is based on symptom response alone. On the other hand, EoE cannot be diagnosed clinically; it requires histological confirmation.3 The use of PPI is not only a necessary step in differentiating EoE from PPI-REE, but also up to
897
P = 0.18
P = 0.003
P = 0.52
100 80
%
60 40 20
Steatosis
Lobular inflammation
Ballooning
GG
CC or CG
GG
CC or CG
GG
CC or CG
GG
CC or CG
0
Fibrosis
Steatosis: 1; Lobular inflammation & Ballooning: 0; Fibrosis: 0 Steatosis: 2; Lobular inflammation & Ballooning: 1; Fibrosis: 1–2 Steatosis: 3; Lobular inflammation & Ballooning: 2; Fibrosis: 3–4
Figure 1 | PNPLA3 polymorphism and histological severity in 147 NAFLD patients (genotypes: CC, n = 34; CG, n = 69; GG, n = 44).
4. Wong VW, Hui AY, Tsang SW, et al. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006; 4: 1154–61. 5. Wong VW, Chu WC, Wong GL, et al. Prevalence of nonalcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut 2012; 61: 409–15.
6. Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011; 53: 1883–94. 7. Shen J, Chan HL, Wong GL, et al. Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers. J Hepatol 2012; 56: 1363–70.
Commentary: the proton pump inhibitor test – does it have a role in eosinophilic oesophagitis?
ophilia. Interestingly, despite symptomatic and histological response to PPI, the two patient groups were similar in almost all demographic, histological and clinical parameters that were assessed in this study. The study was retrospective and included a relatively small number of patients in each group, despite the inclusion of patients from the Swiss EOE database and Walter Reed National Military Medical Center. As with all retrospective studies, the main shortcoming is limited documentation of patients’ clinical course. Furthermore, studies have shown that up to 50% of the patients with EOE will demonstrate a histological and clinical response to PPI treatment.2–4 However, clear definition of response to PPI treatment in EOE remains elusive. Furthermore, it remains unclear if there is a dose– response effect (the higher the dose the greater the number of responders) and if longer duration of PPI administration results in more responders.
R. Fass & C. Maradey-Romero The Oesophageal and Swallowing Center, Division of Gastroenterology and Hepatology. MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA. E-mail: [email protected] doi:10.1111/apt.12672
Moawad et al. used a retrospective design to compare demographics, histological and clinical characteristics between patients with eosinophilic oesophagitis (EOE) who were not with those who were responsive to double-dose proton pump inhibitor (PPI) treatment.1 The latter group is termed PPI-responsive oesophageal eosin896
Aliment Pharmacol Ther 2014; 39: 894-898 ª 2014 John Wiley & Sons Ltd
Invited Commentaries Patients treated with at least 6 weeks of twice-daily PPI were included.1 It is possible that some of the EOE patients may require a longer duration of treatment (up to 3 months), before full response to PPI could be achieved. In addition, comparison with nontreated EOE patients could have helped to determine the contribution of the natural course of the disease to fluctuations in oesophageal eosinophilic count. The main finding of the study is that, with the exception of a response to PPI treatment, there are no other unique characteristics that can identify the PPI-responsive oesophageal eosinophilia group. Consequently, the PPI test, which was found to have a diagnostic value in gastroesophageal reflux disease and noncardiac chest pain, may also have a pivotal role in EOE.5, 6 Future studies should look into the role of the PPI test in this challenging patient population.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None.
Commentary: the proton pump inhibitor test – does it have a role in eosinophilic oesophagitis? Authors’ reply F. J. Moawad* & A. M. Schoepfer† *Gastroenterology Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, MD, USA. † Department of Gastroenterology, University of Lausanne, Lausanne, Switzerland. E-mail: [email protected] doi:10.1111/apt.12676
We thank Drs Fass and Maradey-Romero for their interest in our paper.1 To address their first comment,2 the sample size of our study was relatively small because we focused on cases of oesophageal eosinophilia diagnosed since the publication of the 2011 consensus statement, in which proton pump inhibitor responsive oesophageal eosinophilia (PPI-REE) was formally recognised.3 Our study was retrospective in design; however, the data from both study sites were obtained from clinical databases, which are carefully maintained by the authors who prospectively enrol and collect data on patients with eosinophilic oesophagitis (EoE) and PPI-REE. Additionally, all enrolled patients complete one or more clinical questionnaires at index endoscopy and during follow-up visits. Aliment Pharmacol Ther 2014; 39: 894-898 ª 2014 John Wiley & Sons Ltd
REFERENCES 1. Moawad FJ, Schoepfer AM, Safroneeva E, et al. Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings. Aliment Pharmacol Ther 2014; 39: 603–8. 2. Desai TK, Stecevic V, Chang CH, Goldstein NS, Badizadegan K, Furuta GT. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc 2005; 61: 795–801. 3. Moawad FJ, Veerappan GR, Dias JA, Baker TP, Maydonovitch CL, Wong RD. Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia. Am J Gastroenterol 2013; 108: 366–72. 4. Molina-Infante J, Ferrando-Lamana L, Ripoll C, et al. Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults. Clin Gastroenterol Hepatol 2011; 9: 110–7. 5. Fass R, Fennerty MB, Ofman JJ, et al. The clinical and economic value of a short course of omeprazole in patients with noncardiac chest pain. Gastroenterology 1998; 115: 42–9. 6. Fass R, Ofman JJ, Gralnek IM, et al. Clinical and economic assessment of the omeprazole test in patients with symptoms suggestive of gastroesophageal reflux disease. Arch Intern Med 1999; 159: 216–8.
Treatment goals in EoE include both clinical improvement and reducing oesophageal inflammation. Drs Fass and Maradey-Romero raise a valid point on whether duration and dosage of PPI may alter histological response. Indeed, we have observed that some patients with suspected EoE who respond clinically to a PPI, yet continue to demonstrate eosinophilia on endoscopy at 8 weeks, may achieve histological resolution on repeat endoscopy at 1 year with maintenance PPI. A similar concept is observed in patients with inflammatory bowel disease and coeliac disease, where improvement in clinical symptoms often precedes endoscopic and histological change. However, in cases where clinical symptoms persist after 6 to 8 weeks, we do not believe that a longer duration of PPI (e.g. 3 months) will change their clinical course. In the setting of persistent symptoms and eosinophilia, these patients are diagnosed with EoE and require an alternate form of therapy, such as topical steroids or specialised diets. We agree with the comment that the ‘PPI test’ has a role in EoE. However, in the classic sense, this test is based on symptom response alone. On the other hand, EoE cannot be diagnosed clinically; it requires histological confirmation.3 The use of PPI is not only a necessary step in differentiating EoE from PPI-REE, but also up to
897
