Helicobacter pylori Infection Modulates Reflux Esophagitis Severity in Obesity: Paradoxical Associations from a Retrospective Cohort Study

Helicobacter pylori Infection Modulates Reflux Esophagitis Severity in Obesity: Paradoxical Associations from a Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Helicobacter pylori Infection Modulates Reflux Esophagitis Severity in Obesity: Paradoxical Associations from a Retrospective Cohort Study Lyujia Cheng, Yuzhou Yang, Haoran Ou, Zhenpeng Wu, Yi Wang, Zhuowen Sun, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6456131/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Reflux esophagitis (RE) is common in obese individuals and impairs quality of life. We aimed to investigate the association between RE and Helicobacter pylori (Hp) infection in obese patients and provide evidence for Hp management strategies in this population. Methods A retrospective cohort study was conducted on obese patients (BMI ≥ 28 kg/m²) scheduled for bariatric surgery between July 2019 and June 2023. Patients were categorized into RE and non-RE groups based on endoscopic findings. Demographic, metabolic and Hp infection data were analyzed using t-tests, chi-square tests and logistic regression. Results Among 548 patients, the RE prevalence was 34.1%. The Hp-positive rate was significantly lower in the RE group (21.6% vs. 37.0%, P = 0.004), and Hp infection severity (ΔDOB 3.28 vs. 6.12, P = 0.002) was reduced in RE patients. Mild RE (LA-A) was more common in Hp-negative patients (19.1% vs. 9.6%, P = 0.023). Subgroup analyses revealed stronger Hp-associated protection in females and in obese patients with BMI over 32.5kg/m 2 . After adjusting confounders, Hp infection remained inversely associated with RE risk (OR = 0.416, 95% CI: 0.245–0.709). Conclusions Hp infection is inversely correlated with RE in obese populations, particularly among females. These findings challenge the universal eradication of Hp in obese patients and highlight the need for tailored management strategies to avoid exacerbating reflux symptoms. Reflux esophagitis Helicobacter pylori Obesity Figures Figure 1 Figure 2 Key Points 1. Obese patients with Helicobacter pylori (Hp) infection exhibited a significantly lower prevalence and severity of reflux esophagitis (RE), with Hp-positive individuals showing reduced RE risk (adjusted OR = 0.416, 95% CI: 0.245–0.709). 2.The protective effect of Hp against RE was more pronounced in females and individuals with severe obesity (BMI > 32.5 kg/m²). 3.Our findings challenge universal Hp eradication in obese populations, advocating for tailored strategies to avoid exacerbating reflux symptoms while balancing risks of Hp-related comorbidities. Introduction Gastroesophageal reflux disease (GERD) is characterized by the reflux of gastric contents to the esophagus, leading to various symptoms and/or complications, including esophageal reflux symptoms (heartburn and/or regurgitation), esophageal mucosal injury, and extraesophageal manifestations[ 1 ]. Its prevalence in the general population ranges from 8–33% [ 1 – 3 ]. Reflux esophagitis (RE), a phenotypic manifestation of GERD, is defined as visible mucosal damage in the distal esophagus [ 4 ]. RE accounts for 30% of GERD cases, with its prevalence rising steadily, and it’s complex and diverse symptoms significantly impair quality of life[ 5 ]. Furthermore, RE has been confirmed to contribute to Barrett’s esophagus (BE) or esophageal adenocarcinoma (EAC), posing substantial risks to human health[ 6 ]. Therefore, identifying risk factors for RE is critical for preventing and managing this disease and its complications. With the increasing burden of metabolic diseases, the relationship between obesity and RE has garnered significant attention. A Japanese study reported a 24.2% prevalence of RE in obese individuals, with a positive correlation between RE incidence and body mass index (BMI) [ 7 ]. Compared to generalized obesity, central obesity may exert a stronger promoting effect on RE. A recent meta-analysis revealed that central obesity increased the risk of RE by 51%, particularly in individuals with a waist circumference exceeding 87 cm[ 2 ]. Traditional theories propose that visceral fat accumulation promotes reflux through mechanisms such as elevated intra-abdominal pressure, imbalanced adiponectin/leptin ratios, and increased transient lower esophageal sphincter (LES) relaxation [ 3 , 8 , 9 ]. However, recent studies suggest that Helicobacter pylori (Hp) infection may play a pivotal role in the pathogenesis of obesity-related RE. As one of the most prevalent chronic pathogens globally, Hp infects approximately 43.1% of the population worldwide, with a lower prevalence in obese individuals (32.3%) [ 10 , 11 ]. A recent meta-analysis of 36 studies demonstrated that Hp-positive individuals had a 30% lower risk of developing RE compared to Hp-negative individuals (OR = 0.70, 95% CI: 0.58–0.84) [ 12 ], which was supported by subsequent research [ 13 , 14 ]. Moreover, Hp eradication therapy was associated with a 42% increased risk of new-onset RE, without significant improvement in GERD symptoms, which further supporting Hp’s protective role in RE [ 15 ]. Despite these insights, current medical guidelines do not address the dual role of Hp in obese populations, where obesity itself is a risk factor for RE. For instance, a study investigating GERD in obese patients undergoing sleeve gastrectomy found no significant difference in symptomatic GERD prevalence between Hp-positive and Hp-negative groups (22.4% vs. 23.9%, P = 0.74) [ 16 ]. However, this study relied solely on subjective symptoms for GERD diagnosis without endoscopic confirmation of esophagitis[ 16 ]. Conversely, another study reported that Hp infection increased the preoperative risk of GERD by 51% in metabolic surgery candidates, and symptom improvement after Hp eradication was significantly greater in Hp-positive patients compared to Hp-negative individuals (44.4% vs. 19%, P = 0.036), suggesting Hp as a harmful factor in GERD [ 17 ]. Nevertheless, limitations such as small sample size (n = 176), reliance on immunohistochemical staining of gastric specimens for Hp detection, and subjective GERD diagnostic criteria weaken these conclusions [ 17 ]. To overcome these limitations, our study utilized a bariatric surgery database from Chinese tertiary-center, to evaluate the correlation between Hp infection and preoperative RE in obese patients. It may provide individualized management strategies of RE in obese population. Materials and Methods Study Design and Data Sources This single-center retrospective cohort study enrolled patients scheduled for bariatric-metabolic surgery at the First Affiliated Hospital of Jinan University between July 2019 and June 2023. Inclusion criteria were as follows: age between 18 to 70 years old, preoperative BMI ≥ 28 kg/m² (Chinese diagnostic criteria for obesity), and completion of standardized gastroscopy and 13 C-urea breath test ( 13 C-UBT) preoperatively. Exclusion criteria were history of Hp eradication therapy, gastroesophageal malignancy or hiatal hernia identified on gastroscopy, use of proton pump inhibitors (PPIs) within two weeks prior to endoscopy, and postoperative loss to follow-up or missing critical data. The study was approved by the Ethics Committee of the First Affiliated Hospital of Jinan University, and all patients provided written informed consent for the anonymized use of their data in research. Diagnosis of Reflux Esophagitis RE was diagnosed using the Los Angeles Classification under gastroscopy[ 18 ]. Two independent endoscopists blinded to patient data assessed mucosal damage. Discrepant cases were resolved by a senior endoscopist. Severity was categorized as follows: Grade A Mucosal break(s) ≤ 5 mm in length. Grade B Mucosal break(s) > 5 mm without fusion. Grade C Mucosal breaks involving < 75% of the esophageal circumference. Grade D Mucosal breaks involving ≥ 75% of the esophageal circumference. Hp Infection Status: Hp infection was determined by the 13 C-UBT. Infection severity was quantified using the Delta Over Baseline (DOB) value, reflecting the incremental change in 13 CO2/ 12 CO2 ratio. Patients ingested 75 mg of 13 C-labeled urea mixed with 100 mL of orange juice. Breath samples were collected at baseline (T0) and 30 minutes post-ingestion (T30). A DOB value ≥ 4.0‰ was considered positive for Hp infection [ 19 , 20 ]. Data Collection Two independent authors reviewed medical records to collect, such as age, sex, smoking history, comorbidities, preoperative BMI, waist circumference (WC), fasting blood glucose, triglycerides, high-density lipoprotein (HDL), Hp infection status and RE severity (LA classification). Statistical Analysis Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range, IQR) and compared using t-tests or Mann-Whitney U tests. Categorical variables were described as frequencies (percentages) and compared using χ² tests or Fisher’s exact tests. Univariate logistic regression calculated crude odds ratios (ORs) with 95% confidence intervals (CIs) for Hp infection and RE risk. Multivariate analysis employed hierarchical logistic regression models adjusted for confounders. All analyses were performed with Statistical Package for the Social Sciences (SPSS version 25.0, IBM, Chicago, USA). P -value < 0.05 was considered statistically significant. Results Patient Characteristics A total of 798 obese patients scheduled for bariatric-metabolic surgery at the First Affiliated Hospital of Jinan University between July 2019 and October 2023 were initially enrolled. After excluding 250 patients based on exclusion criteria, 548 patients were included in the final analysis. The mean age of participants was 33.4 years, with males comprising 8.2% (45/548). The mean BMI was 36.8 kg/m². Preoperative RE prevalence was 18.6% (102/548), with A, B, and C-D grades accounting for 15.9%, 2.4% and 0.4%, respectively. Significant baseline differences were observed between two groups. Compared with non-RE group, RE group displayed higher proportions of males (20.6% vs. 5.4%, p < 0.001), smoking history (30.4% vs. 17.9%, p = 0.007), hypertension (30.4% vs. 20.6%, p = 0.045), metabolic syndrome (54.9% vs. 38.6%, p = 0.004), and larger waist circumference (114 vs. 111 cm, p = 0.034). However, patients with RE showed lower infection rates (21.6% vs. 37.0%, p = 0.004) and Hp DOB values (4.83 vs. 8.89, p = 0.002) than those without. No significant differences were found regarding age, BMI, alcohol consumption history, and serum level of HDL-C and triglycerides (all P >0.05) ( Table 1 ). Table 1 Comparison of baseline characteristics of obese patients with or without reflux esophagitis Variable Overall (n= 548) non- RE (n = 446) RE (n = 102) P value Los Angeles classification grading none 446 (81.4) 446 (100.0) 0 (0.0) - grading A 87 (15.9) 0 (0.0) 87 (85.3) - B 13 (2.4) 0 (0.0) 13 (12.7) - C 2 (0.4) 0 (0.0) 2 (2.0) - Gender male 45 (8.2) 24 (5.4) 21 (20.6) <0.001 female 503 (91.8) 422 (94.6) 81 (79.4) - Age (year) 33.41 (7.97) 33.25 (7.83) 34.11(8.56) 0.328 Smoking no 437 (79.7) 366 (82.1) 71 (69.6) 0.007 yes 111 (20.3) 80 (17.9) 31 (30.4) - Drinking (%) no 432 (78.8) 358 (80.3) 74 (72.5) 0.112 yes 116 (21.2) 88 (19.7) 28 (27.5) BMI (kg/m 2 ) 36.76 (6.29) 36.54 (6.25) 37.68 (6.42) 0.099 BMI category >=37.5kg/m 2 208 (38.0) 161 (36.1) 47 (46.1) 0.153 32.5-37.5kg/m 2 187 (34.1) 155 (34.8) 32 (31.4) 28-32.5 kg/m 2 153 (27.9) 130 (29.1) 23 (22.5) WC (cm) 111.58(14.50) 110.95(14.37) 114.33(14.83) 0.034 MS no 320 (58.4) 274 (61.4) 46 (45.1) 0.004 yes 228 (41.6) 172 (38.6) 56 (54.9) Hp infection no 361 (65.9) 281 (63.0) 80 (78.4) 0.004 yes 187 (34.1) 165 (37.0) 22 (21.6) DOB value 5.59 (8.36) 6.12 (8.89) 3.28 (4.83) 0.002 FBG < 6.1 mmol/L 378 (69.0) 308 (69.1) 70 (68.6) 1.000 ≥6.1 mmol/L 170 (31.0) 138 (30.9) 32 (31.4) Hypertension no 425 (77.6) 354 ( 79.4) 71 ( 69.6) 0.045 yes 123 (22.4) 92 ( 20.6) 31 ( 30.4) HDL-C(mmol/L) 1.15 (0.26) 1.15 (0.26) 1.11 (0.25) 0.121 TG (mmol/L) 2.09 (2.39) 2.00 (2.39) 2.45 (2.37) 0.086 RE, reflux esophagitis; BMI , body mass index; WC , waist circumference; MS, metabolic syndrome; Hp , helicobacter pylori; DOB , delta over baseline; FBG, fasting blood glucose; HDL-C, high density lipoprotein cholesterol; TG , triglycerides Association Between Hp Infection and Reflux Esophagitis Among obese patients, 34.1% (187/548) were Hp-positive. The proportion of RE was significantly lower in Hp-positive vs. Hp-negative groups (21.6% vs. 78.4%, P = 0.004) ( Table 1 ). Stratifying RE into none, mild (Grading A) and moderate/severe (Grading B to D), it revealed that Hp infection prevalence (37.0% vs 27.2%, P =0.001) and severity (6.3 vs 3.4, P < 0.001) were only significant between none and mild group, and in the non-RE group compared to mild and moderate/severe RE groups, the trend between non-RE and mild group, ( Fig. 1 ). Subgroup analyses stratified by sex, FBG, obesity severity and metabolic syndrome, demonstrated that Hp infection conferred stronger protection against RE in female ( P < 0.001) and obese patients with BMI ≥ 32.5 kg/m² ( P < 0.05) ( Fig. 2A and C ). Risk Factors for RE in Obese Population For univariate Analysis, Hp infection reduced RE risk by 53.2% (OR 0.468, 95% CI 0.281–0.780, P = 0.004). Female sex was also a protective factor (OR 0.219, 95% CI 0.117–0.413, P <0.001), while risk factors included hypertension (OR 1.680, 95% CI 1.039–2.716, P = 0.034) and smoking (OR 1.998, 95% CI 1.228–3.249, P = 0.005). After adjusting for sex, hypertension and smoking, Hp infection remained independently protective for RE (OR 0.416, 95% CI 0.245 – 0.709, P = 0.001). Females exhibited an 81.3% lower risk of suffering from RE compared to males ( P <0.001) ( Table 2 ). Table 2. Univariate and multivariate logistic regression analysis of the risk of reflux esophagitis Variable Univariate Multivariate OR (95%CI) P value OR (95%CI) P value Gender 0.219 (0.117-0.413) < 0.00 1 0.187 (0.074-0.472) < 0.00 1 Age (years) 1.013 (0.987-1.041) 0.327 - - Hypertension 1.680 (1.039-2.716) 0.034 1.297 (0.774-2.174) 0.323 Smoking 1.998 (1.228-3.249) 0.005 0.871 (0.421-1.799) 0.708 Drinking 1.539 (0.940-2.521) 0.087 - - BMI category 0.606 (0.350-1.050) 0.074 - - BMI 1.027 (0.995-1.061) 0.100 - - TG 1.065 (0.988-1.148) 0.101 - - HDL-C 0.493 (0.201-1.207) 0.122 - - FBG 1.020 (0.642-1.623) 0.932 - - Hp infection 0.468 (0.281-0.780) 0.004 0.416 (0.245-0.709) 0.001 RE, reflux esophagitis; BMI , body mass index; TG , triglycerides; HDL-C, high density lipoprotein cholesterol; FBG, fasting blood glucose; Hp , helicobacter pylori Discussion This study, investigating obese patients scheduled for bariatric surgery from one Chinese tertiary-center, is the first to systematically elucidate the independent protective effect of Helicobacter pylori (Hp) infection against reflux esophagitis (RE) in obese populations, while exploring the modifying role of metabolic disturbances. Hp infection demonstrated a significant inverse correlation with RE risk, particularly for mild RE (LA-A grade). We observed 58.4% reduction in RE risk among Hp-infected obese patients, aligning with previous meta-analyses in general populations (OR = 0.70, 95% CI: 0.58–0.84) [ 12 ]. However, the stronger protective effect in obese individuals may reflect their inherently higher baseline RE susceptibility. In contrast, studies from Turkey and Greece failed to replicate this trend[ 16 , 17 ], likely due to regional variations in Hp strains. East-Asian CagA strains (carrying the EPIYA-D motif) exhibit greater virulence, reducing parietal cell mass and suppressing gastric acid secretion[ 21 ]. Additionally, Hp, especially CagA-positive strains, enhances esophageal mucosal defense by stimulating gastric mucin release[ 22 ]and modulates gastric microbiota to mitigate oxidative stress and inflammation in the esophageal mucosa[ 23 ]. These findings challenge the simplistic notion of Hp as universally harmful, urging re-evaluation of its pathophysiological role in obese populations. The gender disparity in Hp’s protective effects, with females deriving greater benefit, may stem from hormonal differences, as estrogen may upregulate esophageal tight junction proteins such as occluding and increase the barrier resistance of the esophageal mucosa[ 24 , 25 ]. Metabolic dysregulation, such as insulin resistance, appears to amplify Hp’s protective role by impairing immune responses, disrupting the gastric mucosal barrier, and facilitating Hp colonization[ 26 ]. Reduced gastric acid secretion creates a more favorable environment for Hp, while insulin resistance-associated hormonal imbalances (e.g., gastrin and leptin dysregulation) and hyperglycemia-induced oxidative damage further compromise mucosal repair [ 26 ]. Notably, the protective effect of Hp was more pronounced in patients with severe obesity (BMI ≥ 32.5 kg/m²), likely due to the counteraction of Hp’s acid-suppressive effects against mechanical dysfunction of lower esophageal sphincter caused by extreme visceral adiposity[ 9 ]. Our findings have critical implications for Hp management in obese patients. For those with mild RE scheduled for bariatric surgery, indiscriminate Hp eradication may exacerbate reflux symptoms due to post-eradication acid rebound, whereas retaining Hp could aid symptom control [ 27 ]. It should especially be warranted in females and severely obese patients (BMI ≥ 32.5 kg/m²), where Hp’s protective value may be heightened. Current guidelines lack robust evidence to support routine Hp eradication in patients with isolated GERD/RE and no additional Hp-related conditions (e.g., peptic ulcers, gastric cancer family history, or MALT lymphoma) [ 28 – 30 ]. For Hp-negative patients at high reflux risk, Roux-en-Y gastric bypass (RYGB) should be prioritized over sleeve gastrectomy (SG) to minimize postoperative RE. However, existing Hp guidelines, predominantly based on general population data, lack obesity-specific recommendations [ 29 – 33 ]. Our study underscores the unintended consequences of blind Hp eradication in obese populations and highlights the urgent need for RCTs to establish tailored management of these patients. While this study provides novel insights through large-scale, multidimensional analyses, several limitations should be acknowledged. First, residual confounding bias may persist due to unmeasured factors such as dietary patterns (e.g., frequency of high-fat intake) and socioeconomic status. Second, the depth of Hp strain characterization was limited, and Hp detection relied solely on the 13C-urea breath test without whole-genome sequencing, potentially missing the effects of virulence factors like CagA, BabA and VacA [ 34 ]. Additionally, the cross-sectional design precludes establishing dynamic causal relationships between Hp infection and the development of reflux esophagitis (RE) following metabolic-bariatric surgery. Future studies should prioritize multicenter randomized controlled trials to compare long-term outcomes between Hp eradication and retention groups in obese RE patients, with a focus on monitoring Barrett’s esophagus and esophageal adenocarcinoma risks. Furthermore, integrating metagenomics and metabolomics to precisely subtype Hp strains could identify subtypes with the strongest RE-protective effects, thereby advancing the development of targeted Hp vaccines. Conclusions This study confirms that Hp infection is inversely associated with RE risk in obese populations, with amplified protection in females. These findings challenge conventional Hp management paradigms, advocating for stratified screening and treatment strategies in obesity-related RE. Mechanistic and interventional studies are essential to clarify Hp’s dual roles and optimize personalized therapeutic approaches. Declarations Author Contributions LJC, YZY, HRO, SFH and JGY were responsible for the study concept and design. ZPW, YW, ZWS, YH and LNW contributed to the acquisition of data. LJC, YZY and HRO analyzed the data and wrote the initial draft. SFH and JGY critically reviewed the manuscript. All authors read and approved the final version of the manuscript. Availability of data and material The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval Ethical committees of the First Affiliated Hospital of Jinan University. Consent to participate Written consent was obtained from all individual participants included in the study. Conflict of interest The authors declare that they have no conflict of interest. References Dunbar KB. Gastroesophageal Reflux Disease. Ann Intern Med. 2024; 177: Itc113-itc28. Zhan J, Yuan M, Zhao Y, et al. Abdominal obesity increases the risk of reflux esophagitis: a systematic review and meta-analysis. Scand J Gastroenterol. 2022; 57: 131–42. Xie M, Deng L, Fass R, et al. Obesity is associated with higher prevalence of gastroesophageal reflux disease and reflux related complications: A global healthcare database study. Neurogastroenterol Motil. 2024; 36: e14750. Fass R, Boeckxstaens GE, El-Serag H, et al. Gastro-oesophageal reflux disease. Nat Rev Dis Primers. 2021; 7: 55. Maret-Ouda J, Markar SR, Lagergren J. Gastroesophageal Reflux Disease: A Review. Jama. 2020; 324: 2536–47. 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Helicobacter pylori World Gastroenterology Organization Global Guideline. J Clin Gastroenterol. 2023; 57: 111–26. Jung BW, Kim YJ, Park CH. Nationwide Trends in Helicobacter pylori Eradication Therapies in Korea: Impact of Guideline Updates on Treatment Practices. Helicobacter. 2024; 29: e13152. Aguilar C, Pauzuolis M, Pompaiah M, et al. Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis. Nat Commun. 2022; 13: 5878. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6456131","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453296567,"identity":"1d2af958-e246-4535-9150-3f44ae79a312","order_by":0,"name":"Lyujia Cheng","email":"","orcid":"","institution":"Department of Gastrointestinal Surgery, the First Affiliated Hospital of Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Lyujia","middleName":"","lastName":"Cheng","suffix":""},{"id":453296568,"identity":"de2a4148-cfa9-4320-9748-d060c1e0f503","order_by":1,"name":"Yuzhou Yang","email":"","orcid":"","institution":"Department of Gastrointestinal Surgery, the First Affiliated Hospital of Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Yuzhou","middleName":"","lastName":"Yang","suffix":""},{"id":453296569,"identity":"f54a6da0-e896-47e9-ab10-8daeaee23624","order_by":2,"name":"Haoran Ou","email":"","orcid":"","institution":"Department of Gastrointestinal Surgery, the First Affiliated Hospital of Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Haoran","middleName":"","lastName":"Ou","suffix":""},{"id":453296570,"identity":"175c5ecf-696c-4df5-80e1-1fcdcb90b1aa","order_by":3,"name":"Zhenpeng Wu","email":"","orcid":"","institution":"Department of Gastrointestinal Surgery, the First Affiliated Hospital of Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Zhenpeng","middleName":"","lastName":"Wu","suffix":""},{"id":453296571,"identity":"f63ad6f2-b2d2-4688-af98-092ba94aae04","order_by":4,"name":"Yi Wang","email":"","orcid":"","institution":"International School, Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Wang","suffix":""},{"id":453296572,"identity":"3f31a0c4-6a11-4377-b847-d179e84cf202","order_by":5,"name":"Zhuowen Sun","email":"","orcid":"","institution":"International School, Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Zhuowen","middleName":"","lastName":"Sun","suffix":""},{"id":453296573,"identity":"28d76e16-7f36-4eb5-9dfd-7c3c70b66cf0","order_by":6,"name":"Yi Hu","email":"","orcid":"","institution":"Department of Gastrointestinal Surgery, the First Affiliated Hospital of Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Hu","suffix":""},{"id":453296574,"identity":"58cdbf09-9b80-4a14-a839-3ff63a002815","order_by":7,"name":"Lina Wu","email":"","orcid":"","institution":"Department of Gastrointestinal Surgery, the First Affiliated Hospital of Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Lina","middleName":"","lastName":"Wu","suffix":""},{"id":453296575,"identity":"833edd15-a742-4cfc-9647-ce41b86ad1d6","order_by":8,"name":"Shifang Huang","email":"","orcid":"","institution":"Department of Intensive Care Medicine, First Affiliated Hospital of Jinan University","correspondingAuthor":false,"prefix":"","firstName":"Shifang","middleName":"","lastName":"Huang","suffix":""},{"id":453296576,"identity":"ba758aca-19ad-4fba-a2a2-4182dc49f901","order_by":9,"name":"Jingge Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYDCCA2xAgodBjo29+QBpWoz5eI4lkKKFgSFxnkSOAnE6+G6kJT7mkalNb2PIYWD4UbGNsBbJG2mHjXl4jue2MZw9wNhz5jZhLQY30tukeXiO5bYx9iUwM7YRp6X9N1BLOhszjwGxWtKOMfPw1CSwsRGrRfLMs2TJOTwHDNt42BIOEuUXvuNphh/e9tTJy89/fPDBjwoitIAAE2/PYTDjAHHqgYDxx486ohWPglEwCkbBCAQAKu08yLO/11YAAAAASUVORK5CYII=","orcid":"","institution":"Department of Gastrointestinal Surgery, the First Affiliated Hospital of Jinan University","correspondingAuthor":true,"prefix":"","firstName":"Jingge","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-04-15 15:08:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6456131/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6456131/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82620612,"identity":"8d3f98a6-ddd4-4609-bf45-4e78ad0dad81","added_by":"auto","created_at":"2025-05-13 12:15:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":58915,"visible":true,"origin":"","legend":"\u003cp\u003eDifferences in Helicobacter pylori infection rate (\u003cstrong\u003eA\u003c/strong\u003e) and infection severity (\u003cstrong\u003eB\u003c/strong\u003e) in different grades of reflux esophagitis group\u003c/p\u003e","description":"","filename":"floatimage133.png","url":"https://assets-eu.researchsquare.com/files/rs-6456131/v1/a9ef6d078674a406574b70ca.png"},{"id":82620611,"identity":"ec932b2c-b62a-4ff0-87de-70f5bfed5908","added_by":"auto","created_at":"2025-05-13 12:15:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":130990,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis to explore the relationship between Helicobacter pylori infection and the prevalence of reflux esophagitis. \u003cstrong\u003eA \u003c/strong\u003ewas stratified by gender, \u003cstrong\u003eB \u003c/strong\u003eby fasting blood glucose, \u003cstrong\u003eC\u003c/strong\u003e by obesity severity, and\u003cstrong\u003e D \u003c/strong\u003eby metabolic syndrome\u003c/p\u003e","description":"","filename":"floatimage219.png","url":"https://assets-eu.researchsquare.com/files/rs-6456131/v1/016735375afcdc6c66f28d6d.png"},{"id":91159527,"identity":"ec80f838-5304-4d86-be7f-37cad99f9126","added_by":"auto","created_at":"2025-09-12 08:46:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":999885,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6456131/v1/60413b45-dfca-41e0-a9c1-07d19234c366.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Helicobacter pylori Infection Modulates Reflux Esophagitis Severity in Obesity: Paradoxical Associations from a Retrospective Cohort Study","fulltext":[{"header":"Key Points","content":"\u003cp\u003e1. Obese patients with Helicobacter pylori (Hp) infection exhibited a significantly lower prevalence and severity of reflux esophagitis (RE), with Hp-positive individuals showing reduced RE risk (adjusted OR\u0026thinsp;=\u0026thinsp;0.416, 95% CI: 0.245\u0026ndash;0.709).\u003c/p\u003e\u003cp\u003e2.The protective effect of Hp against RE was more pronounced in females and individuals with severe obesity (BMI\u0026thinsp;\u0026gt;\u0026thinsp;32.5 kg/m\u0026sup2;).\u003c/p\u003e\u003cp\u003e3.Our findings challenge universal Hp eradication in obese populations, advocating for tailored strategies to avoid exacerbating reflux symptoms while balancing risks of Hp-related comorbidities.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eGastroesophageal reflux disease (GERD) is characterized by the reflux of gastric contents to the esophagus, leading to various symptoms and/or complications, including esophageal reflux symptoms (heartburn and/or regurgitation), esophageal mucosal injury, and extraesophageal manifestations[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Its prevalence in the general population ranges from 8\u0026ndash;33% [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Reflux esophagitis (RE), a phenotypic manifestation of GERD, is defined as visible mucosal damage in the distal esophagus [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. RE accounts for 30% of GERD cases, with its prevalence rising steadily, and it\u0026rsquo;s complex and diverse symptoms significantly impair quality of life[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Furthermore, RE has been confirmed to contribute to Barrett\u0026rsquo;s esophagus (BE) or esophageal adenocarcinoma (EAC), posing substantial risks to human health[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, identifying risk factors for RE is critical for preventing and managing this disease and its complications.\u003c/p\u003e \u003cp\u003eWith the increasing burden of metabolic diseases, the relationship between obesity and RE has garnered significant attention. A Japanese study reported a 24.2% prevalence of RE in obese individuals, with a positive correlation between RE incidence and body mass index (BMI) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Compared to generalized obesity, central obesity may exert a stronger promoting effect on RE. A recent meta-analysis revealed that central obesity increased the risk of RE by 51%, particularly in individuals with a waist circumference exceeding 87 cm[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Traditional theories propose that visceral fat accumulation promotes reflux through mechanisms such as elevated intra-abdominal pressure, imbalanced adiponectin/leptin ratios, and increased transient lower esophageal sphincter (LES) relaxation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, recent studies suggest that Helicobacter pylori (Hp) infection may play a pivotal role in the pathogenesis of obesity-related RE.\u003c/p\u003e \u003cp\u003eAs one of the most prevalent chronic pathogens globally, Hp infects approximately 43.1% of the population worldwide, with a lower prevalence in obese individuals (32.3%) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A recent meta-analysis of 36 studies demonstrated that Hp-positive individuals had a 30% lower risk of developing RE compared to Hp-negative individuals (OR\u0026thinsp;=\u0026thinsp;0.70, 95% CI: 0.58\u0026ndash;0.84) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], which was supported by subsequent research [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Moreover, Hp eradication therapy was associated with a 42% increased risk of new-onset RE, without significant improvement in GERD symptoms, which further supporting Hp\u0026rsquo;s protective role in RE [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Despite these insights, current medical guidelines do not address the dual role of Hp in obese populations, where obesity itself is a risk factor for RE. For instance, a study investigating GERD in obese patients undergoing sleeve gastrectomy found no significant difference in symptomatic GERD prevalence between Hp-positive and Hp-negative groups (22.4% vs. 23.9%, P\u0026thinsp;=\u0026thinsp;0.74) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, this study relied solely on subjective symptoms for GERD diagnosis without endoscopic confirmation of esophagitis[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Conversely, another study reported that Hp infection increased the preoperative risk of GERD by 51% in metabolic surgery candidates, and symptom improvement after Hp eradication was significantly greater in Hp-positive patients compared to Hp-negative individuals (44.4% vs. 19%, P\u0026thinsp;=\u0026thinsp;0.036), suggesting Hp as a harmful factor in GERD [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Nevertheless, limitations such as small sample size (n\u0026thinsp;=\u0026thinsp;176), reliance on immunohistochemical staining of gastric specimens for Hp detection, and subjective GERD diagnostic criteria weaken these conclusions [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo overcome these limitations, our study utilized a bariatric surgery database from Chinese tertiary-center, to evaluate the correlation between Hp infection and preoperative RE in obese patients. It may provide individualized management strategies of RE in obese population.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Data Sources\u003c/h2\u003e \u003cp\u003eThis single-center retrospective cohort study enrolled patients scheduled for bariatric-metabolic surgery at the First Affiliated Hospital of Jinan University between July 2019 and June 2023. Inclusion criteria were as follows: age between 18 to 70 years old, preoperative BMI\u0026thinsp;\u0026ge;\u0026thinsp;28 kg/m\u0026sup2; (Chinese diagnostic criteria for obesity), and completion of standardized gastroscopy and \u003csup\u003e13\u003c/sup\u003eC-urea breath test (\u003csup\u003e13\u003c/sup\u003eC-UBT) preoperatively. Exclusion criteria were history of Hp eradication therapy, gastroesophageal malignancy or hiatal hernia identified on gastroscopy, use of proton pump inhibitors (PPIs) within two weeks prior to endoscopy, and postoperative loss to follow-up or missing critical data. The study was approved by the Ethics Committee of the First Affiliated Hospital of Jinan University, and all patients provided written informed consent for the anonymized use of their data in research.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDiagnosis of Reflux Esophagitis\u003c/h3\u003e\n\u003cp\u003eRE was diagnosed using the Los Angeles Classification under gastroscopy[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Two independent endoscopists blinded to patient data assessed mucosal damage. Discrepant cases were resolved by a senior endoscopist. Severity was categorized as follows:\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eGrade A\u003c/strong\u003e \u003cp\u003eMucosal break(s)\u0026thinsp;\u0026le;\u0026thinsp;5 mm in length.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eGrade B\u003c/strong\u003e \u003cp\u003eMucosal break(s)\u0026thinsp;\u0026gt;\u0026thinsp;5 mm without fusion.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eGrade C\u003c/strong\u003e \u003cp\u003eMucosal breaks involving\u0026thinsp;\u0026lt;\u0026thinsp;75% of the esophageal circumference.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eGrade D\u003c/strong\u003e \u003cp\u003eMucosal breaks involving\u0026thinsp;\u0026ge;\u0026thinsp;75% of the esophageal circumference.\u003c/p\u003e \u003c/p\u003e\n\u003ch3\u003eHp Infection Status:\u003c/h3\u003e\n\u003cp\u003eHp infection was determined by the \u003csup\u003e13\u003c/sup\u003eC-UBT. Infection severity was quantified using the Delta Over Baseline (DOB) value, reflecting the incremental change in \u003csup\u003e13\u003c/sup\u003eCO2/\u003csup\u003e12\u003c/sup\u003eCO2 ratio. Patients ingested 75 mg of \u003csup\u003e13\u003c/sup\u003eC-labeled urea mixed with 100 mL of orange juice. Breath samples were collected at baseline (T0) and 30 minutes post-ingestion (T30). A DOB value\u0026thinsp;\u0026ge;\u0026thinsp;4.0\u0026permil; was considered positive for Hp infection [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eTwo independent authors reviewed medical records to collect, such as age, sex, smoking history, comorbidities, preoperative BMI, waist circumference (WC), fasting blood glucose, triglycerides, high-density lipoprotein (HDL), Hp infection status and RE severity (LA classification).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median (interquartile range, IQR) and compared using t-tests or Mann-Whitney U tests. Categorical variables were described as frequencies (percentages) and compared using χ\u0026sup2; tests or Fisher\u0026rsquo;s exact tests. Univariate logistic regression calculated crude odds ratios (ORs) with 95% confidence intervals (CIs) for Hp infection and RE risk. Multivariate analysis employed hierarchical logistic regression models adjusted for confounders. All analyses were performed with Statistical Package for the Social Sciences (SPSS version 25.0, IBM, Chicago, USA). \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 798 obese patients scheduled for bariatric-metabolic surgery at the First Affiliated Hospital of Jinan University between July 2019 and October 2023 were initially enrolled. After excluding 250 patients based on exclusion criteria, 548 patients were included in the final analysis.\u003c/p\u003e\n\u003cp\u003eThe mean age of participants was 33.4 years, with males comprising 8.2% (45/548). The mean BMI was 36.8 kg/m\u0026sup2;. Preoperative RE prevalence was 18.6% (102/548), with A, B, and C-D grades accounting for 15.9%, 2.4% and 0.4%, respectively. Significant baseline differences were observed between two groups. Compared with non-RE group, RE group displayed higher proportions of males (20.6% vs. 5.4%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), smoking history (30.4% vs. 17.9%, \u003cem\u003ep\u003c/em\u003e = 0.007), hypertension (30.4% vs. 20.6%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.045), metabolic syndrome (54.9% vs. 38.6%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.004), and larger waist circumference (114 vs. 111 cm, \u003cem\u003ep\u003c/em\u003e = 0.034). However, patients with RE showed lower infection rates (21.6% vs. 37.0%, \u003cem\u003ep\u003c/em\u003e = 0.004) and Hp DOB values (4.83 vs. 8.89, \u003cem\u003ep\u003c/em\u003e = 0.002) than those without. No significant differences were found regarding age, BMI, alcohol consumption history, and serum level of HDL-C and triglycerides (all \u003cem\u003eP\u003c/em\u003e \u0026gt;0.05) (\u003cstrong\u003eTable 1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Comparison of baseline characteristics of obese patients with or without reflux esophagitis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"637\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall (n= 548)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e\u003cstrong\u003enon-\u003c/strong\u003e\u003cstrong\u003eRE\u003c/strong\u003e\u003cstrong\u003e(n = 446)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRE\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(n = 102)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eLos Angeles classification grading\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003enone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e446 (81.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e446 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003egrading\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e87 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e87 (85.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e13 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e13 (12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e2 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e2 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e45 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e24 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e21 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e503 (91.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e422 (94.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e81 (79.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e33.41 (7.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e33.25 (7.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e34.11(8.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.328\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eSmoking\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e437 (79.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e366 (82.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e71 (69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e111 (20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e80 (17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e31 (30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eDrinking (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e432 (78.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e358 (80.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e74 (72.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.112\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e116 (21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e88 (19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e28 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e36.76 (6.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e36.54 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e37.68 (6.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eBMI category\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026gt;=37.5kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e208 (38.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e161 (36.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e47 (46.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e32.5-37.5kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e187 (34.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e155 (34.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e32 (31.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e28-32.5 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e153 (27.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e130 (29.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e23 (22.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eWC (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e111.58(14.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e110.95(14.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e114.33(14.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e320 (58.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e274 (61.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e46 (45.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e228 (41.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e172 (38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e56 (54.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eHp infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e361 (65.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e281 (63.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e80 (78.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e187 (34.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e165 (37.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e22 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eDOB value\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e5.59 (8.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e6.12 (8.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e3.28 (4.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eFBG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026lt; 6.1\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003emmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e378 (69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e308 (69.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e70 (68.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026ge;6.1\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003emmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e170 (31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e138 (30.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e32 (31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e425 (77.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e354 ( 79.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e\u0026nbsp;71 ( 69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e123 (22.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e92 ( 20.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e31 ( 30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eHDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e1.15 (0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e1.15 (0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e1.11 (0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.121\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.8088%;\"\u003e\n \u003cp\u003eTG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.7712%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.279%;\"\u003e\n \u003cp\u003e2.09 (2.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.4953%;\"\u003e\n \u003cp\u003e2.00 (2.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9279%;\"\u003e\n \u003cp\u003e2.45 (2.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.71787%;\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eRE,\u003c/em\u003e reflux esophagitis; \u003cem\u003eBMI\u003c/em\u003e, body mass index;\u003cem\u003e\u0026nbsp;WC\u003c/em\u003e, waist circumference; \u003cem\u003eMS,\u003c/em\u003e metabolic syndrome; \u003cem\u003eHp\u003c/em\u003e, helicobacter pylori; \u003cem\u003eDOB\u003c/em\u003e, delta over baseline; \u003cem\u003eFBG,\u003c/em\u003e fasting blood glucose; \u003cem\u003eHDL-C,\u003c/em\u003e high density lipoprotein cholesterol; \u003cem\u003eTG\u003c/em\u003e,\u0026nbsp;triglycerides\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation Between Hp Infection and Reflux Esophagitis\u003c/strong\u003e\u003cbr\u003eAmong obese patients, 34.1% (187/548) were Hp-positive. The proportion of RE was significantly lower in Hp-positive vs. Hp-negative groups (21.6% vs. 78.4%, \u003cem\u003eP\u003c/em\u003e = 0.004) (\u003cstrong\u003eTable 1\u003c/strong\u003e). Stratifying RE into none, mild (Grading A) and moderate/severe (Grading B to D), it revealed that Hp infection prevalence (37.0% vs 27.2%, \u003cem\u003eP\u003c/em\u003e =0.001) and severity (6.3 vs 3.4, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) were only significant between none and mild group, and in the non-RE group compared to mild and moderate/severe RE groups, the trend between non-RE and mild group, \u0026nbsp;(\u003cstrong\u003eFig. 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eSubgroup analyses stratified by sex, FBG, obesity severity and metabolic syndrome, demonstrated that Hp infection conferred stronger protection against RE in female (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) and obese patients with BMI \u0026ge; 32.5 kg/m\u0026sup2; (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05) (\u003cstrong\u003eFig. 2A and C\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk Factors for RE in Obese Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor univariate Analysis, Hp infection reduced RE risk by 53.2% (OR 0.468, 95% CI 0.281\u0026ndash;0.780, \u003cem\u003eP\u003c/em\u003e = 0.004). Female sex was also a protective factor (OR 0.219, 95% CI 0.117\u0026ndash;0.413, \u003cem\u003eP\u003c/em\u003e \u0026lt;0.001), while risk factors included hypertension (OR 1.680, 95% CI 1.039\u0026ndash;2.716, \u003cem\u003eP\u003c/em\u003e = 0.034) and smoking (OR 1.998, 95% CI 1.228\u0026ndash;3.249, \u003cem\u003eP\u003c/em\u003e = 0.005). After adjusting for sex, hypertension and smoking, Hp infection remained independently protective for RE (OR 0.416, 95% CI 0.245 \u0026ndash; 0.709, \u003cem\u003eP\u003c/em\u003e = 0.001). Females exhibited an 81.3% lower risk of suffering from RE compared to males (\u003cem\u003eP\u003c/em\u003e \u0026lt;0.001) (\u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Table 2. Univariate and multivariate logistic regression analysis of the risk of reflux esophagitis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"581\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 201px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eGender \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.219 (0.117-0.413)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e0.187 (0.074-0.472)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.013\u0026nbsp;(0.987-1.041)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eHypertension\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.680 (1.039-2.716)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.034\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e1.297\u0026nbsp;(0.774-2.174)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.323\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eSmoking \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.998\u0026nbsp;(1.228-3.249)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e0.871 (0.421-1.799)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.708\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eDrinking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.539\u0026nbsp;(0.940-2.521)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eBMI category\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.606\u0026nbsp;(0.350-1.050)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.027\u0026nbsp;(0.995-1.061)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.065\u0026nbsp;(0.988-1.148)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eHDL-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.493\u0026nbsp;(0.201-1.207)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eFBG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.020\u0026nbsp;(0.642-1.623)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.932\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 133px;\"\u003e\n \u003cp\u003eHp infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.468\u0026nbsp;(0.281-0.780)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e0.416\u0026nbsp;(0.245-0.709)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eRE,\u003c/em\u003e reflux esophagitis; \u003cem\u003eBMI\u003c/em\u003e, body mass index;\u003cem\u003e\u0026nbsp;TG\u003c/em\u003e,\u0026nbsp;triglycerides;\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eHDL-C,\u003c/em\u003e high density lipoprotein cholesterol; \u003cem\u003eFBG,\u003c/em\u003e fasting blood glucose;\u003cem\u003e\u0026nbsp;Hp\u003c/em\u003e, helicobacter pylori\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study, investigating obese patients scheduled for bariatric surgery from one Chinese tertiary-center, is the first to systematically elucidate the independent protective effect of \u003cem\u003eHelicobacter pylori\u003c/em\u003e (Hp) infection against reflux esophagitis (RE) in obese populations, while exploring the modifying role of metabolic disturbances. Hp infection demonstrated a significant inverse correlation with RE risk, particularly for mild RE (LA-A grade). We observed 58.4% reduction in RE risk among Hp-infected obese patients, aligning with previous meta-analyses in general populations (OR\u0026thinsp;=\u0026thinsp;0.70, 95% CI: 0.58\u0026ndash;0.84) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, the stronger protective effect in obese individuals may reflect their inherently higher baseline RE susceptibility. In contrast, studies from Turkey and Greece failed to replicate this trend[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], likely due to regional variations in Hp strains. East-Asian CagA strains (carrying the EPIYA-D motif) exhibit greater virulence, reducing parietal cell mass and suppressing gastric acid secretion[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Additionally, Hp, especially CagA-positive strains, enhances esophageal mucosal defense by stimulating gastric mucin release[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]and modulates gastric microbiota to mitigate oxidative stress and inflammation in the esophageal mucosa[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. These findings challenge the simplistic notion of Hp as universally harmful, urging re-evaluation of its pathophysiological role in obese populations.\u003c/p\u003e \u003cp\u003eThe gender disparity in Hp\u0026rsquo;s protective effects, with females deriving greater benefit, may stem from hormonal differences, as estrogen may upregulate esophageal tight junction proteins such as occluding and increase the barrier resistance of the esophageal mucosa[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Metabolic dysregulation, such as insulin resistance, appears to amplify Hp\u0026rsquo;s protective role by impairing immune responses, disrupting the gastric mucosal barrier, and facilitating Hp colonization[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Reduced gastric acid secretion creates a more favorable environment for Hp, while insulin resistance-associated hormonal imbalances (e.g., gastrin and leptin dysregulation) and hyperglycemia-induced oxidative damage further compromise mucosal repair [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Notably, the protective effect of Hp was more pronounced in patients with severe obesity (BMI\u0026thinsp;\u0026ge;\u0026thinsp;32.5 kg/m\u0026sup2;), likely due to the counteraction of Hp\u0026rsquo;s acid-suppressive effects against mechanical dysfunction of lower esophageal sphincter caused by extreme visceral adiposity[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur findings have critical implications for Hp management in obese patients. For those with mild RE scheduled for bariatric surgery, indiscriminate Hp eradication may exacerbate reflux symptoms due to post-eradication acid rebound, whereas retaining Hp could aid symptom control [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. It should especially be warranted in females and severely obese patients (BMI\u0026thinsp;\u0026ge;\u0026thinsp;32.5 kg/m\u0026sup2;), where Hp\u0026rsquo;s protective value may be heightened. Current guidelines lack robust evidence to support routine Hp eradication in patients with isolated GERD/RE and no additional Hp-related conditions (e.g., peptic ulcers, gastric cancer family history, or MALT lymphoma) [\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. For Hp-negative patients at high reflux risk, Roux-en-Y gastric bypass (RYGB) should be prioritized over sleeve gastrectomy (SG) to minimize postoperative RE. However, existing Hp guidelines, predominantly based on general population data, lack obesity-specific recommendations [\u003cspan additionalcitationids=\"CR30 CR31 CR32\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Our study underscores the unintended consequences of blind Hp eradication in obese populations and highlights the urgent need for RCTs to establish tailored management of these patients.\u003c/p\u003e \u003cp\u003eWhile this study provides novel insights through large-scale, multidimensional analyses, several limitations should be acknowledged. First, residual confounding bias may persist due to unmeasured factors such as dietary patterns (e.g., frequency of high-fat intake) and socioeconomic status. Second, the depth of Hp strain characterization was limited, and Hp detection relied solely on the 13C-urea breath test without whole-genome sequencing, potentially missing the effects of virulence factors like CagA, BabA and VacA [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Additionally, the cross-sectional design precludes establishing dynamic causal relationships between Hp infection and the development of reflux esophagitis (RE) following metabolic-bariatric surgery.\u003c/p\u003e \u003cp\u003eFuture studies should prioritize multicenter randomized controlled trials to compare long-term outcomes between Hp eradication and retention groups in obese RE patients, with a focus on monitoring Barrett\u0026rsquo;s esophagus and esophageal adenocarcinoma risks. Furthermore, integrating metagenomics and metabolomics to precisely subtype Hp strains could identify subtypes with the strongest RE-protective effects, thereby advancing the development of targeted Hp vaccines.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study confirms that Hp infection is inversely associated with RE risk in obese populations, with amplified protection in females. These findings challenge conventional Hp management paradigms, advocating for stratified screening and treatment strategies in obesity-related RE. Mechanistic and interventional studies are essential to clarify Hp\u0026rsquo;s dual roles and optimize personalized therapeutic approaches.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003eLJC, YZY, HRO, SFH and JGY were responsible for the study concept and design. ZPW, YW, ZWS, YH and LNW contributed to the acquisition of data. LJC, YZY and HRO analyzed the data and wrote the initial draft. SFH and JGY critically reviewed the manuscript. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e Ethical committees of the First Affiliated Hospital of Jinan University. Consent to participate Written consent was obtained from all individual\u003c/p\u003e\n\u003cp\u003eparticipants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDunbar KB. Gastroesophageal Reflux Disease. 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Mol Cell Proteomics. 2022; 21: 100421.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaulrasu K, Caspa Gokulan R, El-Rifai W, et al. Chronic Gastroesophageal Reflux Dysregulates Proteostasis in Esophageal Epithelial Cells. Cell Mol Gastroenterol Hepatol. 2025; 19: 101434.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBains K, Iqbal H, Attri A, et al. Impact of Gender on Gastroesophageal Reflux Disease Complications: Analysis of 27 Million Hospitalizations. J Gastrointestin Liver Dis. 2024; 33: 19\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHonda J, Iijima K, Asanuma K, et al. Estrogen Enhances Esophageal Barrier Function by Potentiating Occludin Expression. Dig Dis Sci. 2016; 61: 1028\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSahoo OS, Mitra R, Bhattacharjee A, et al. Is Diabetes Mellitus a Predisposing Factor for Helicobacter pylori Infections? Curr Diab Rep. 2023; 23: 195\u0026ndash;205.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMou WL, Feng MY, Hu LH. Eradication of Helicobacter Pylori Infections and GERD: A systematic review and meta-analysis. Turk J Gastroenterol. 2020; 31: 853\u0026ndash;59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoon JY, Lim F, Shah SC, et al. Endoscopic Surveillance of Intestinal Metaplasia of the Esophagogastric Junction: A Decision Modeling Analysis. Am J Gastroenterol. 2024; 119: 1289\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChey WD, Howden CW, Moss SF, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2024; 119: 1730\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou L, Lu H, Song Z, et al. 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment. Chin Med J (Engl). 2022; 135: 2899\u0026ndash;910.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJi YH, Shi YM, Hei QW, et al. Evaluation of guidelines for diagnosis and treatment of Helicobacter pylori infection. Helicobacter. 2023; 28: e12937.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatelaris P, Hunt R, Bazzoli F, et al. Helicobacter pylori World Gastroenterology Organization Global Guideline. J Clin Gastroenterol. 2023; 57: 111\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung BW, Kim YJ, Park CH. Nationwide Trends in Helicobacter pylori Eradication Therapies in Korea: Impact of Guideline Updates on Treatment Practices. Helicobacter. 2024; 29: e13152.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAguilar C, Pauzuolis M, Pompaiah M, et al. Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis. Nat Commun. 2022; 13: 5878.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Reflux esophagitis, Helicobacter pylori, Obesity","lastPublishedDoi":"10.21203/rs.3.rs-6456131/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6456131/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eReflux esophagitis (RE) is common in obese individuals and impairs quality of life. We aimed to investigate the association between RE and Helicobacter pylori (Hp) infection in obese patients and provide evidence for Hp management strategies in this population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study was conducted on obese patients (BMI\u0026thinsp;\u0026ge;\u0026thinsp;28 kg/m\u0026sup2;) scheduled for bariatric surgery between July 2019 and June 2023. Patients were categorized into RE and non-RE groups based on endoscopic findings. Demographic, metabolic and Hp infection data were analyzed using t-tests, chi-square tests and logistic regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 548 patients, the RE prevalence was 34.1%. The Hp-positive rate was significantly lower in the RE group (21.6% vs. 37.0%, P\u0026thinsp;=\u0026thinsp;0.004), and Hp infection severity (ΔDOB 3.28 vs. 6.12, P\u0026thinsp;=\u0026thinsp;0.002) was reduced in RE patients. Mild RE (LA-A) was more common in Hp-negative patients (19.1% vs. 9.6%, P\u0026thinsp;=\u0026thinsp;0.023). Subgroup analyses revealed stronger Hp-associated protection in females and in obese patients with BMI over 32.5kg/m\u003csup\u003e2\u003c/sup\u003e. After adjusting confounders, Hp infection remained inversely associated with RE risk (OR\u0026thinsp;=\u0026thinsp;0.416, 95% CI: 0.245\u0026ndash;0.709).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHp infection is inversely correlated with RE in obese populations, particularly among females. These findings challenge the universal eradication of Hp in obese patients and highlight the need for tailored management strategies to avoid exacerbating reflux symptoms.\u003c/p\u003e","manuscriptTitle":"Helicobacter pylori Infection Modulates Reflux Esophagitis Severity in Obesity: Paradoxical Associations from a Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 12:15:50","doi":"10.21203/rs.3.rs-6456131/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"466f1bed-857e-445a-9b98-853d479f03fd","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-12T08:38:39+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 12:15:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6456131","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6456131","identity":"rs-6456131","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}