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Reflux esophagitis and Helicobacter pylori: is there an association in children?

INTRODUCTION

Over the past decade there has been a significant change in epidemiology of gastrointestinal disorders noted with substantial global increase in gastroesophageal reflux disease (GERD) prevalence [1-4]. Disease often starts in childhood [5-7].

According to the definition established at the Montreal Global Consensus (2005) reflux-esophagitis (RE) is a typical GERD complication [8]. In children frequency of this diagnosis based on endoscopic examination reaches 30% [9].

GERD has a multifactorial genesis, so in the development of this disease many factors play a role (infectious agents, nutrition, physical development, exogenous xenobiotics, stress, physical overexertion, genetic predisposition, and anatomic anomalies) [10]. However, available published results don't allow giving a final assessment to the role of certain etiological agents in the formation and progression of the disease [10-12]. Insufficient data regarding predisposing factors in the pathogenesis of GERD prevents the development of optimal prophylactic measures and treatment of disturbances associated with GERD.

The role of the Helicobacter pylori (Hp) infection as a possible protective or etiological/ triggering factor in GERD pathogenesis is one of the most disputable subjects [13-18]. A significant decrease in the prevalence of Hp infection in developed countries, which has negative correlation with GERD incidence, becomes an additional reason for that [4,19]. Republic of Belarus belongs to regions with high Hp incidence, but the frequency of typical esophageal complaints increases [20].

However, despite major interest by gastroenterologists and an increasing number of studies there is no unity of opinions about many factors regarding the association of GERD and Hp. Additionally, there are only a few pediatric studies investigating this association and those are limited by small sample size.

The objective of this study was to determine the clinical and epidemiological association between RE and Hp infection in older children.

MATERIALS AND METHODS

Study group. Children aged between 12 and 18 years, who during esophagogastroduodenoscopy (EGD) revealed inflammatory changes in the mucosa of the esophagus or/and the stomach, were involved in this retrospective case-control study. Indications for EGD were abdominal pain and dyspeptic complaints. All patients were divided in two groups: 308 children with RE (1st group) and 418 patients with microscopically verified CG without RE (2nd group). Children with erosive and non-erosive variants of RE were included in the 1st group. The survey was performed at 3 rd and 4th Children's Hospitals in Minsk, Belarus in 2008-2012.

Both groups were evaluated for age and sex (Table 1).

Biopsy specimens were taken from the gastric antrum in all children. The specimens were immediately fixed in 10% buffered formalin solution, embedded in paraffin, cut at 4- to 6-pm thick, and stained with hematoxylin-eosin (H&A) for histologic evaluation. Diagnosis of CG was made on the basis of a stromal lymphoplasmatic infiltrate of the glandular epithelium. Histological evaluation of gastritis and the Hp contamination degree of the gastric mucosa was conducted semiquantitatively in accordance with the Sydney classification of gastritis [20] graded from 0 to 3 (0 grade -the absence of the microorganism, 1 mild degree, 2--moderate, and 3--severe degree of infection). Diagnosis of RE was established in accordance with Los Angeles endoscopic grade system, and in the most of cases confirmed microscopically. The exclusion criteria: treatment with any medications more than seven days over the past 2 months; pervious Hp eradication; severe neurologic disorders (cerebral palsy, etc.): infections.

Personal data collection for the complaints and anamnesis analysis was carried out by interviewing. As the clinical symptoms associated with RE patients were evaluated for the presence of typical complaints of GERD--heartburn and regurgitation, epigastric abdominal pain and other dyspeptic complaints (nausea, vomiting, eructation) over six months period. Esophageal symptoms of GERD, as recommended by the Montreal consensus, were considered as positive if the above mentioned complaints were present at least once a week. A similar assessment was used for other symptoms, received by questionnaire. Anamnesis data included disease duration.

HP infection diagnosis

Hp infection was identified based on histology (with Giemsa and H&A stain) and/or rapid urease test (test kit manufactured by UE <<SEMPER>>, Belarus).

Ethical issues

In accordance with Helsinki 2nd Declaration each patient and his parents were informed verbally and in writing about the purpose of study and methods used. All patients and their parents gave the written consent.

Statistical analysis was performed by using the software package Statistica 8.0. Given the abnormal age distribution is presented as median (Me) and lower and upper quartiles (LQ/UQ). To describe the relative frequency of binary features 95% confidence interval (CI) was used. Nonparametric methods of statistical analysis were used: [chi square] test--to evaluate the association between the presence of Hp infection and the following features: the frequency of RE, its erosive form, as well as clinical symptoms (heartburn, abdominal pain, dyspeptic complaints); the association of Hp infection and duration of illness; Mann-Whitney U-test--to estimate mean age in groups and the relationship of destructive esophageal lesions frequency with the degree of Hp infection. All tests were considered as significant at p value <0.05.

RESULTS

According to the results of our study, Hp infection was diagnosed in 137 (44.5% (95% CI 38.950.2%)) of the patients with RE. Hp infection rate in the 2nd group was 179 (42.8% (95% CI 38.1-47.6%)) ([chi square] = 0,20; p = 0.66) (Figure 1).

Further analysis showed that male patients with RE had Hp infection more often than females, but difference was no statistically significant (Table 2).

Erosive lesions of the esophagus (A-D grade esophagitis) were detected in 50.5% (95% CI 44.9-56.1%) of surveyed children. Among Hp-positive children with RE frequency of destructive esophageal lesions was slightly higher compared to the Hp-negative patients (51.8% and 50.9% respectively, p = 0.89). Furthermore, it does not depend on the extent of bacterial infection (p = 0.81).

The results of main symptoms comparison in Hp-positive and Hp-negative patients with RE demonstrated a slight increase in the frequency of heartburn and epigastric pain in the Hp-positive children, but the differences in the frequency of various clinical symptoms were not significant.

Further analysis showed that the incidence of Hp infection decreased with increasing of disease duration, the difference was statistically significant (p = 0.04).

DISCUSSION

There have been theoretical attempts to establish Hp infection involvement in the pathophysiology of GERD [3, 10].

As evidence of the protective role of Hp in GERD, the following arguments are described: the development of Hp-associated gastritis in the fundus is accompanied by a decrease in the hydrochloric acid secretion (by inhibiting the production of histamine along with increased synthesis of interleukin (IL)-1[beta] and tumor necrotizing factor (TNF-a)); proximal gastritis improves the gastroesophageal junction barrier function; hypergastrinemia associated with Hp infection leads to increased pressure of the lower esophageal sphincter (LES), high urease activity of Hp partially neutralizes the aggressive action of hydrochloric acid; Hp can increase antisecretory effect of main antisecretory drugs--proton pump inhibitors [14, 15, 18].

On the other hand, there are explanations of Hp infection as a factor contributing to the activation of pathophysiological mechanisms of GERD: inflammation, extending to the stomach cardia, leading to decreased LES pressure; antrum predominant Hp gastritis increases gastric secretion, and also delayed gastric emptying; Hp cytotoxins cause damage to the esophageal epithelium, activation of apoptosis and increase the risk of carcinogenesis [3, 10, 17, 18].

As follows from our results, the development of esophagitis was not accompanied by changes in the frequency of Hp infection compared with patients without RE.

Published data presented from previous studies conducted in children and adults is controversial. Thus, the few studies in pediatric patients with RE showed that Hp infection was more common [21, 22] or its frequency did not differ from children without RE [23]. For example, Moon et al. [22] reported a high (81.3%) risk of RE development among the Hp-positive children compared with 38.1% in the Hp-negative patients. Data published about adults is ambiguous and indicates a lack of association with RE and Hp infection [24, 25], reflect reverse [26, 27] or direct [28] relationship between the infection frequency and the esophageal inflammation development.

The results of our study do not support the participation of Hp infection in the pathogenesis of more severe esophageal damage. The published research data does not provide an unambiguous assessment of this relationship [9, 23-28].

High frequency of epigastric pain in patients with RE may reflect that they have a combined pathology of the esophagus and stomach, which is typical [9].

Other researchers also found no differences in clinical presentation, depending on the availability of Hp infection, but such an assessment was carried out mainly after Hp eradication [29-31].

It can be assumed that the reduction of Hp infection with increasing disease duration in patients with RE is associated with the active treatment of Hp in connection to concomitant gastroduodenal pathology. However, the available data on the increased risk of RE after the elimination of Hp infection is controversial, which indicates the need for further study of this relationship in pediatrics [29-31].

CONCLUSIONS

Thus, there was no clear association between reflux esophagitis and H. pylori infection. Moreover, the severity of inflammation and the clinical symptoms frequency were also not associated with Hp infection incidence rate. Meanwhile, in patients with a long medical history Hp infection is rare. Further research is required to establish the role of Hp in the occurrence and progression of GERD, the debut of which often falls on the pediatric population.

ACKNOWLEDGMENTS

The authors have no potential conflicts to declare. No funding an outside source was obtained for this study.

REFERENCES

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Zagorski SE. (1) *, Nazarenko ON. (2)

(1) Associated Professor, Department of General Medicine, Polessky State University, Pinsk, Belarus

(2) Department of Pediatrics, Belarusian State Medical University, Minsk, Belarus

* Corresponding author:

Department of General Medicine Polessky State University 225710, Pushkina Str. 4-3610 Pinsk, Belarus

Tel.: +(375)296414748

e-mail: sergzagorsky@rambler.ru

Received: 09.12.2013

Accepted: 29.03.2014
Table 1. Characteristics of the studied groups

Characteristics      Children with   Children without      P value
                        reflux-          reflux-
                      esophagitis      esophagitis
                        (n=308)          (n=418)

Age, years (Median       16.0             15.75            p=0.79
  (LQ/UQ): lower     (14.75/17.0)      (14.5/17.0)
  quartile/upper
  quartile) *
Sex: Female Male      146 (47.4%)      211 (50.5%)      [chi square]
                      162 (52.6%)      207 (49.5%)      = 0.32 p=0.57

*--the distribution of the surveyed children by age was not
suitable to the normal distribution (according to the W-criterion
of the Shapiro-Wilk test, W=0.95 and W=0.93 respectively; p<0.001).

Table 2. Comparison of Hp-positive vs Hp-negative patients with RE.

Characteristics     Hp-positive (n = 137)    Hp-negative (n = 171)
                       No./% (95% CI))          No./% (95% CI))

Sex Male Female     79/57.7% (48.9-66.1%)    83/48.5% (40.8-56.3%)
                    58/42.3% (34.0-51.1%)    88/51.5% (43.7-59.2%)
RE form Erosive     71/51.8% (43.1-60.4%)    84/50.9% (43.7-58.6%)
  Non-erosive       66/48.2% (39.6-56.9%)    81/49.1% (41.2-57.0%)
Symptoms            93/67.9% (59.4-75.6%)    109/63.7% (56.1-70.9%)
  Heartburn         109/79.6% (71,8-86,0%)   131/76.6% (69.5-82.7%)
  (regurgitation)   84/61.3% (52.6-69.5%)    95/55.6% (47.8-63.1%)
  Epigastric
  pain Other
  dyspeptic
  complaints
Duration of         30/57.7% (43.2-71.3%)    22/42.3% (28.7-56.8%)
  illness < one     107/41.8% (35.7-48.1%)   149/58.2% (51.9-64.3%)
  year > one year

Characteristics              P value ([chi square])

Sex Male Female     [chi square] = 2.54; P = 0.11

RE form Erosive     [chi square] = 0.03; P = 0.89
  Non-erosive
Symptoms            [chi square] = 0.58; P = 0.45
  Heartburn         [chi square] = 0.39; P = 0.53
  (regurgitation)   [chi square] = 1.04; p = 0.31
  Epigastric
  pain Other
  dyspeptic
  complaints
Duration of         [chi square] = 4.42; p = 0.04
  illness < one
  year > one year

Figure 1. Hp-infection incidence
rate in comparing groups.

children with esophagitis   44,5%
  (n = 308)
children with gastritis     42,8%
  without esophagitis
  (n = 418)

Note: Table made from bar graph.
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Author:Zagorski, S.E.; Nazarenko, O.N.
Publication:Progress in Health Sciences
Article Type:Report
Date:Jun 1, 2014
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