Helicobacter pylori Recurrence after Eradication Therapy in Jiangjin District, Chongqing, China.

Purpose To investigate the recurrence rate of Helicobacter pylori infection after eradication in Jiangjin District, Chongqing, China, and to analyze the related causes. Methods Outpatients who were eradicated of H. pylori infection with standard therapy between August 2014 and August 2017 were included in this study. The recurrence rate was investigated 1 year later. Data regarding gender, smoking, alcohol intake, frequency of eating out, and treatment strategy were recorded, and their relationships with the recurrence rate were analyzed. Multivariate logistic regression analysis was performed to determine the independent risk factors for H. pylori infection recurrence. Results In total, 400 patients (225 males and 175 females) were included in this study. Of them, the recurrence rate of H. pylori infection was 4.75% (19/400), with 5.33% (12/225) in males and 4.57% (7/175) in females, showing no gender difference. The recurrence rate was 7.03% (9/128) in smokers and 3.68% (10/272) in nonsmokers, while it was 6.45% (12/186) in those who drink alcohol and 3.27% (7/214) in those who do not drink alcohol, showing no significant differences. The higher the frequency of eating out, the higher the recurrence rate of H. pylori infection (P = 0.001). There was a statistically significant difference in the recurrence rate between patients receiving treatment alone and patients whose family members also received treatment (6.08% vs. 0.96%, P = 0.035). Drinking and dining out were independent risk factors for H. pylori infection recurrence (P = 0.014 for drinkers and P = 0.015 and P = 0.003 for those who sometimes and often dine out, respectively). Conclusions The overall recurrence rate after H. pylori eradication by standard therapy in Jiangjin District is 4.75%. Reducing the frequency of eating out and family members receiving treatment may reduce the recurrence of H. pylori infection.


Introduction
Chronic gastritis is one of the most common life-long inflammatory diseases. More than half of the world's population are estimated to have chronic gastritis to some extent [1]. Helicobacter pylori infection is one major cause of chronic gastritis. About 20% of H. pylori-infected patients develop peptic ulcers, and 1% of infected patients develop gastric malignancies, including gastric cancer and mucosa-associated lymphoid tissue lymphoma [2][3][4]. In addition, H. pylori is thought to be associated with some extragastric disorders, such as cardiovascular, skin, and blood system diseases [3,4].
The prevalence of H. pylori infection varies greatly geographically. In developing countries, it is estimated that more than 80% of the population is H. pylori positive, even in children and adolescents, while in developed countries, less than 40% of the population is H. pylori positive, and children have a lower rate of infection than adults and the elderly [5]. Since H. pylori infection is very common and leads to many diseases, both domestic and international guidelines recommend eradication therapy for H. pylori-infected patients [6][7][8]. However, studies have shown that despite regular treatment, there is still a risk of H. pylori recurrence [9][10][11], with a higher rate in developing countries than in developed countries. H. pylori recurrence is defined as negative detection of H. pylori at 4 weeks after eradication therapy but positive detection at some later time [12]. H. pylori recurrence can occur either by recrudescence or reinfection. Recrudescence refers to the recolonization of the same strain, while reinfection refers to colonization with a new strain [9,10]. Most cases of H. pylori recurrence are due to recrudescence.
Many risk factors for H. pylori infection have been reported, including socioeconomic factors, education, family density, lifestyle, and other factors [13][14][15][16]. These factors are also possible risk factors for H. pylori recurrence, since reinfection is one form of recurrence. A meta-analysis has shown that H. pylori recurrence rates are significantly and inversely correlated with socioeconomic development metrics [17].
H. pylori recurrence after eradication will reduce the clinical significance of eradication of H. pylori, inevitably increase the difficulty of drug selection, and aggravate H. pylori resistance [9,18]. The H. pylori infection rate is 54.59% in western Chongqing [19], which is a highprevalence area with many patients, but the recurrence rate of H. pylori infection remains unclear. This study was aimed at investigating the recurrence rate of H. pylori infection after eradication in patients living in Jiangjin District, Chongqing, China, and at examining the related factors.

Patients.
From August 2014 to August 2017, outpatients with H. pylori infection confirmed by the 14 C-urea breath test from Jiangjin District, Chongqing, China, were enrolled in this study. The outpatients received a quadruple treatment regimen to eradicate H. pylori: rabeprazole capsules (10 mg bid), amoxicillin (1 g bid), clarithromycin (0.5 g bid), and pectin bismuth (300 mg bid), for 14 days. If a family member was confirmed to be infected as well, the same treatment was given to the family member. One month after the end of treatment, the subjects who were H. pylori negative, as confirmed by the 14 C-urea breath test, were included in this study. The eradication was confirmed according to the Fifth National Consensus Opinion on the Diagnosis and Treatment of H. pylori [6].
The inclusion criteria were as follows: age between 18 and 65 years; not a recurrent patient; no use of proton pump inhibitors, H2-receptor antagonists, expectorants, or antibi-otics within 4 weeks; no related drug allergy history; no gastrointestinal bleeding, pyloric obstruction, perforation, or other complications; no history of digestive tract surgery; and no serious heart, lung, liver, or kidney dysfunction. Exclusion criteria were patients with severe gastric epithelial dysplasia, a pathological diagnosis of malignancy, or lactating or pregnant women.
The protocol of this prospective study was approved by the Ethics Committee of Jiangjin Central Hospital of Chongqing. All patients with H. pylori infection, as confirmed by the 14 C-urea breath test, were enrolled after informed consent.

Data Collection.
Gender, smoking history, drinking history, and frequency of eating out (seldom, <1 per month; sometimes, <1 per week and >1 per month; and often, >1 per week) were recorded. One year later, the recurrence of H. pylori infection was measured by the 14 C-urea breath test.

Statistical Methods.
Statistical analysis was performed using the SPSS 17.0 software. Continuous data are expressed as the mean ± standard deviation (SD). The count data are expressed as a percentage. Comparisons between two groups were performed using the t test or χ 2 test. Variants with a P value < 0.2 in the univariate analysis were included in the multivariate analysis. Multivariate logistic regression analysis was performed to determine the independent risk factors for H. pylori infection recurrence. The difference was considered statistically significant at P < 0:05.

Clinical
Characteristics of the Participants. The flow chart of the present study is presented in Figure 1, and the baseline characteristics of the participants are shown in Table 1 Table 4). The recurrence rate was significantly higher in the often ate out group than in the other two groups.     3 Gastroenterology Research and Practice regression analysis was performed to determine the independent risk factors for H. pylori infection recurrence. The results showed that drinking and dining out were independent risk factors for H. pylori infection recurrence (P = 0:014 for drinkers and P = 0:015 and P = 0:003 for those who sometimes and often dine out, respectively; Table 6).

Discussion
The present study investigated the recurrence rate of H. pylori infection after eradication in Jiangjin District, Chongqing, China. Our data showed that the recurrence rate was 4.75%. There was no statistical difference in terms of gender, smoking history, or drinking history, while there were statistical differences between those who frequently ate out compared to those who did not as well as between those whose family members were treated and those who did not have treated family members. Multivariate logistic regression showed that drinking and dining out were independent risk factors for H. pylori infection recurrence.
There are two ways that H. pylori infection reoccurs after eradication in the stomach [20]. One is recrudescence, which is caused by possible residual strains that multiply, including H. pylori that is not completely removed by the treatment. This occurs when the sensitivity of H. pylori detection methods is too low, there is a high false-negative rate, or changes occur in the H. pylori morphology. Sometimes, the spiral bacteria may transform into spherical bacteria when the environment is poor, and then they return to the spiral form when the environment is suitable, thus causing disease [21]. The other way that H. pylori infection reoccurs is reinfection of new strains, including H. pylori in oral repositories. These new strains may cause H. pylori recurrence when the bacteria move from the mouth into the stomach. Reinfection may also occur due to close contact between people or to exposure to a common source of infection [20].
The recurrence rate of H. pylori varies from place to place and is related to the local socioeconomic level [9]. The lower the economic rate, the higher the recurrence rate. For example, the 1-year recurrence rate in Latin America is as high as 11.5%, while the 1-year recurrence rate in Morocco is only 0.45% [18,22]. The present study found that the recurrence rate of H. pylori infection after eradication in Jiangjin District was 4.75%, which is a little higher than the international average (4.3%) [9,23]. The annual recurrence rate of H. pylori infection after eradication is reported to be 1.08-1.75% in China [24,25]. In addition, a meta-analysis has revealed that the pooled H. pylori recurrence rate in China is 2.2% (95% CI: 0.8-4%) [9]. The recurrence rate in the present study was a little higher than that reported previously, which may be caused by many factors, such as location, economic level, scheme selection, drug compliance, and detection method. The latest multicenter prospective study has suggested that ethnic groups, education level, family history, and residence location are independent risk factors for H. pylori recurrence   Gastroenterology Research and Practice [26]. The authors found that the recurrence rate of the residence located in Western China was significantly higher than that of other places, which may partially explain the high recurrence rate of H. pylori infection in the present study, since Chongqing is a western city in China. Of note, the recurrence rate for males was slightly higher than that for females, although the difference is not significant. There are many risk factors for H. pylori infection, including socioeconomic factors, education, family density, lifestyle, and other factors [13][14][15][16]. Some studies have suggested that smoking and drinking alcohol can reduce the H. pylori infection rate [27][28][29], while other studies show that smoking has no relationship with H. pylori infection [30][31][32]. This study showed that smoking and drinking do not lead to an increase in the recurrence of H. pylori infection. However, multivariate logistic regression revealed that drinking was an independent risk factor for H. pylori infection recurrence. A study by Amini et al. [33] has demonstrated that the long-term use of common tableware can lead to a high incidence of H. pylori infection, indicating that changing dietary habits may limit the spread of H. pylori infection. Our study showed that patients who ate out often had a significantly higher recurrence rate of H. pylori infection than those who ate out sometimes or rarely. Moreover, multivariate logistic regression indicated that dining out was an independent risk factor for H. pylori infection recurrence. This may be because frequent diners have a higher exposure to the source of infection.
H. pylori infection has the characteristics of intrafamily transmission. When the infection is successfully eradicated from a patient, he will become reinfected by the same H. pylori strain [34] carried by the spouse. Simultaneous treatment of H. pylori-infected patients in the same family will significantly improve the eradication rate [35,36]. This study also confirmed that the recurrence rate in patients whose H. pylori-infected relatives living with them also received treatment was significantly lower than that of patients receiving treatment alone. Our results indicate that H. pylori infection showed family aggregation, which may be related to close contact, having the same living and eating habits, and exposure to common sources of infection. The cotherapy of family members can improve the therapeutic effect.

Conclusions
In conclusion, our data showed that the recurrence rate of H. pylori infection in Jiangjin District, China, is generally low and not related to gender, smoking, or drinking; however, the recurrence rate is related to the frequency of eating out and the family treatment strategy. Furthermore, drinking and dining out were independent risk factors for H. pylori infection recurrence. Our study suggests that the rate of recurrence of H. pylori infection may be reduced by limiting the frequency of eating out and receiving cotreatment with family members. Due to the small number of cases included in this study and the short follow-up period, a multicenter, large-scale, randomized controlled trial is needed to confirm our conclusion.

Data Availability
The datasets generated and analyzed during the present study are available from the corresponding author on reasonable request.

Conflicts of Interest
The author declares that he has no conflicts of interest.