LETTERS TO THE EDITOR

nature publishing group

Could Population Changes in Smoking Habits Help Explain the Change in Incidence and Prevalence of Celiac Disease? S. Veldhuyzen van Zanten, MD, PhD1 doi:10.1038/ajg.2014.345

To the Editor: Your recent publication “Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK over two decades: population-based study” by West et al. was read with great interest (1). The data convincingly show that the incidence of celiac disease has risen significantly over the 20-year study period. I agree with the conclusion that only a part of this increase is explained by better available serological diagnostic tests. Indeed there appears to be variability in the incidence in different segments of the population. I wonder whether changing patterns in smoking behavior may be one of the environmental factors that could further help explain the findings. There are data that show a new diagnosis of celiac disease is made significantly less frequently in smokers than in non-smokers (2,3). Furthermore, there also is evidence that smoking may mask the clinical manifestations of celiac disease rather than prevent its occurrence (4). This is a testable hypothesis. Data from the 2011 General Lifestyle Survey, collected by the Office for National Statistics in the UK, show that the prevalence of smoking since 1974 has decreased from 45% to 20% in 2011 (5). Furthermore, the number of adults who are heavy smokers (more than 20 cigarettes a day) also dropped significantly from 26% to 6% in men and from 13% to 4% in women. I wonder if the investigators have access to smoking data in their patient population; if not, it should be assessed in future studies. © 2014 by the American College of Gastroenterology

CONFLICT OF INTEREST The author declares no conflict of interest. REFERENCES 1. West J, Fleming KM, Tata LJ et al. Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK over two decades: population-based study. Am J Gastroenterol 2014;109:757–68. 2. Snook JA, Dwyer L, Lee-Elliott C et al. Adult coeliac disease and cigarette smoking. Gut 1996;39:60–2. 3. Lear JT, English JSC. Adult coeliac disease, dermetitis herpetiformis and cigarette smoking. Gut 1997;40:289. 4. van Zanten SJOV. Case Report: Recurrent diarrhea and weight loss associated with cessation of smoking in a patient with undiagnosed celiac disease. Gut 2001;49:588. 5. Office for National Statistics UK. Smoking prevalence among adults has declined by half since 1974. Part of General Lifestyle Survey, 2011. Released: 28 March 2013. http://www.ons. gov.uk/ons/rel/ghs/general-lifestyle-survey/2011/ sty-smoking-report.html 1

Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada. Correspondence: S. Veldhuyzen van Zanten, MD, PhD, Division of Gastroenterology, 130 University Campus, University of Alberta, Edmonton, Alberta, CanadaT6G 2X8. E-mail: [email protected]

Response to van Zanten Joe West, PhD1, Kate M. Fleming, PhD1, Laila J. Tata, PhD1, Timothy R. Card, PhD1 and Colin J. Crooks, PhD1 doi:10.1038/ajg.2014.348

To the Editor: We thank you for your interest (1) in our paper (2) and your hypothesis regarding smoking. We agree that changes in population smoking rates could be part of the explanation for our observation of an increase in the incidence of celiac disease. We have now repeated our analysis including a variable derived for the whole population at risk for having ever smoked in our model. When we carried out this analysis it became confirmed that incident celiac disease, in our population, had a negative association with smoking history (hazard ratio=0.94, 95%

confidence interval 0.90–0.98, adjusted for age, gender, region, and year). However, the adjusted increase in celiac disease from 1990 to 2011 remained unchanged from the figure we published in our study when we added this smoking variable to our model (hazard ratio for 2011 compared to 1990=3.60, 95% confidence interval 2.71–4.78), indicating that, as far as we can infer, smoking behaviour had a minimal influence on the observed trends. CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1. van Zanten SV. Could population changes in smoking habits help explain the change in incidence and prevalence of celiac disease? Am J Gastroenterol 2014;109:1953 (this issue). 2. West J, Fleming KM, Tata LJ et al. Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK over two decades: population-based study. Am J Gastroenterol 2014;109:757–68. 1

University Hospital—Epidemiology and Public Health, Division of Epidemiology and Public Health, Nottingham University Medical School, QMC, Nottingham, UK. Correspondence: Joe West, PhD, University Hospital—Epidemiology and Public Health, Division of Epidemiology and Public Health, Nottingham University Medical School, QMC, Nottingham NG& 2UH, UK. E-mail: [email protected]

Treatment Strategy for Hepatitis C: A Dilemma for the Payers and the Providers Mahumudul Haque, MD, PhD1 and Asheen Zariat, BS1 doi:10.1038/ajg.2014.320

To the Editor: We are facing the dilemma of identifying a pragmatic treatment approach to hepatitis C virus (HCV) along with many challenges with detection of The American Journal of GASTROENTEROLOGY

1953

1954

Letters to the Editor

patients and accessibility of direct-acting anti-HCV agents (DAA). Dr Muir has presented a timely and balanced review of the prevalence and treatment strategies for chronic HCV, but we have a long way to go in terms of treating a sizeable proportion of those afflicted (1). While HCV is highly prevalent, affecting more than four million patients (2), only 25% of these cases are known (3). Active efforts to detect cases using the new Centers for Disease Control and Prevention screening guidelines are needed. As we cannot wait to treat a certain group of patients with risk factors for rapid progress of fibrosis or with advanced fibrosis, DAA definitely have great value and excellent cost-saving potential in these cases in the short and long run. However, for asymptomatic 0–2 fibrosis cases the value of this treatment may be relatively lower, as two-thirds may have slow progression and one-third may not develop cirrhosis (4) (http://www.cdc.gov/hepatitis/HCV/ HCVfaq.htm#section1). For asymptomatic patients with the early disease without risk factors, can we wait for short periods for the more cost-effective regimens to appear? In addition, as rightly stated by Dr Muir, there are concerns about the accessibility of DAA. Dr Muir’s article implies ~60% of HCV patients are likely uninsured or under Medicaid and/or Medicare. A sizeable number may not have any insurance due to some states’ rejection of federal money for Medicaid expansion (1). Only one-third of the HCV patients have private insurance (1). This could have chilling effects on both public (Medicaid/Medicare/health exchanges) and private healthcare funding agencies. Many payers do not have the money to fund these expensive treatments. For example, Oregon’s Medicaid needed $360 million to cover DAA alone, whereas its total annual prescription drug budget is only $370 million (http://www.washingtonpost.com/blogs/ wonkblog/wp/2014/07/24/the-drugthats-forcing-americas-most-importantand-uncomfortable-health-care-debate/). Owing to high costs, many state Medicaid agencies have already restricted the use of DAA to solely stage 3–4 fibrosis cases.

The American Journal of GASTROENTEROLOGY

nature publishing group

The inaccessibility of DAA cases also raises the following issue: what treatment options are available for Medicaid patients with stage 0–2 chronic HCV, or for patients supported by lower-budget county health plans that support older regimens through non-profit foundations, since American Association for the Study of Liver Diseases/Infectious Diseases Society of America (AASLD/ IDSA) guidelines do not recommend older regimens like ribavirin/pegylated interferon/ 1st gen protease inhibitor treatment (even though they are 65–80% effective) (http://www.hcvguidelines.org/full-report/ initial-treatment-hcv-infection-patientsstarting-treatment)? Hopefully, we will formulate a more pragmatic regimen within the next 18–24 months. By this time multiple new products will hopefully be approved, and free market competition will bring prices down to an affordable level. However, there is concern that a “shadow pricing” strategy may limit the decline in price (http://www.washingtonpost.com/blogs/wonkblog/wp/2014/07/24/ the-drug-thats-forcing-americas-mostimportant-and-uncomfortable-health-caredebate/). As providers, we should continue to seek better coverage for our vulnerable patients and work to improve detection of this disease. CONFLICT OF INTEREST The author declares no conflict of interest. REFERENCES 1. Muir AI. The rapid evolution of treatment strategies for hepatitis C. Am J Gastroenterol 2014;109:628–35. 2. Denniston MM, Jiles RB, Klkevens RM et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med 2014;160:293–300. 3. IOM (Institute of Medicine). Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C The National Academies Press: Washington, DC, 2010. 4. Seeff LB. The history of the “natural history” of hepatitis C (1968–2009). Liver Int 2009;29: (Suppl 1)89–99.

1

Digestive Diseases Care for ALL LLC, Lakeland, Florida, USA. Correspondence: Mahumudul Haque, MD, PhD, Digestive Diseases Care for ALL LLC, 3126 Highlands Lakeview Circle, Lakeland, Florida 33812, USA. E-mail: [email protected]

Somatic Mosaicism in Esophageal Atresia Damian Bednarczyk, MSc1, Izabela Makowska, MSc1, Maria Malgorzata Sasiadek, MD1 and Robert Smigiel, MD2 doi:10.1038/ajg.2014.346

To the Editor: Congenital esophageal atresia (EA; OMIM 189960) is a developmental defect characterized by loss of continuity of the esophagus often with an abnormal connection between the trachea and the esophagus—tracheoesophageal fistula (TEF). The incidence of EA/TEF is approx. 1 per 4,100 births (1). Forty-five percent of patients with EA present an isolated form without any additional associated anomalies. In the remaining patients, EA coexists with other defects (syndromic form) (1). In the group of syndromic patients VACTERL (vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects) association, CHARGE (congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina) syndrome, another non-chromosomal syndrome, Down’s syndrome, Edward’s syndrome, or another chromosomal syndrome can be diagnosed (1). The pathogenesis of EA is poorly understood and therefore etiology seems to be enigmatic, but it is thought that this defect arises due to errors in early embryonic development. In recent years, a number of genetic alterations have been identified in patients with syndromic EA (2,3), but there is no literature that reports diseasecausing mutations in patients with isolated EA. Therefore, the specific risk factors for congenital EA still remain unknown (4). The female patient was born at 38 weeks of gestation by cesarean delivery because of fetal multiple congenital defects diagnosed by ultrasonography. At birth her weight was 2600 g (3–10 centile), and length was 50 cm (10 centile). Physical and diagnostic examinations after birth revealed EA/TEF

VOLUME 109 | DECEMBER 2014 www.amjgastro.com