Gastric Atrophy and Intestinal Metaplasia before and after Helicobacter pylori Eradication: A Meta-Analysis

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Original Paper

Digestion 2011;83:253–260 DOI: 10.1159/000280318

Gastric Atrophy and Intestinal Metaplasia before and after Helicobacter pylori Eradication: A Meta-Analysis

Jin Wang a, c Lijuan Xu a Ruihua Shi a Xiayue Huang a Simon Wing Heng Li d Zuhu Huang b Guoxin Zhang a

Departments of a Gastroenterology, and b

Infectious Disease, First Affiliated Hospital of Nanjing Medical University, Nanjing , c

Department of Gastroenterology, Municipal Hospital of Dongtai, Yancheng , and d Department of

Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong , China

pooled WMD was 0.32 (0.09–0.54), p = 0.006. For antral IM, the pooled WMD was 0.02 (–0.12–0.16), p = 0.76, and for cor-pus IM, the pooled WMD was –0.02 (–0.05–0.02), p = 0.42. Conclusion: Our study shows that eradication of H. pylori re-sults in significant improvement in GA in the corpus but not in the antrum; it also does not improve gastric mucous IM. Consequently, all patients with GA in the corpus should be tested for H. pylori infection, and eradication therapy should be prescribed for H. pylori -positive patients in those with GA in corpus. Copyright © 2011 S. Karger AG, Basel

Introduction

Gastric cancer is the second most common fatal ma-lignancy and the fourth most common cancer in terms of new cases in the world [1–4] . The mechanisms by which gastric cancer develops and progresses are not complete-ly understood. The premise that a combination of host genetic factors, bacterial virulence factors, and environ-mental and life style factors determine the severity of gas-

Key Words

Helicobacter pylori � Gastric atrophy � Intestinal metaplasia � Eradication � Meta-analysis

Abstract

Objective: Whether gastric atrophy (GA) and intestinal meta-plasia (IM) are reversible after the eradication of Helicobacter pylori remains controversial. The purpose of this meta-anal-ysis was to systematically review histological alterations in GA and IM by comparing histological scores before and after H. pylori eradi cation. Methods: English-language articles in the medical literature containing information about the as-sociation between infection with H. pylori and gastric prema-lignant lesions (i.e. GA and IM) were identified by searching the Medline, PubMed, and EMBASE databases with suitable key words up to December 2009. Review Manager 4.2.8 was used for the meta-analysis. Results: Twelve studies contain-ing a total of 2,658 patients were included in the first meta-analysis. Before treatment, 2,648 patients had antrum GA, 2,401 patients had corpus GA, 2,582 patients had antrum IM, and 2,460 patients had corpus IM. Comparing the histologi-cal alterations before and after H. pylori eradication, the pooled weighted mean difference (WMD) with 95% CI for antral GA was 0.12 (0.00–0.23), p = 0.06. For corpus GA, the

Received: September 18, 2009 Accepted: January 25, 2010 Published online: February 1, 2011

Guoxin Zhang Department of Gastroenterology First Affiliated Hospital of Nanjing Medical University Nanjing 210029 (China) Tel. +86 25 8371 8836, ext. 6973, Fax +86 25 8367 4636, E-Mail guoxinz @ njmu.edu.cn

© 2011 S. Karger AG, Basel 0012–2823/11/0834–0253$38.00/0

Accessible online at: www.karger.com/dig

J.W. and L.X. contributed equally to this paper.

http://dx.doi.org/10.1159%2F000280318

Wang /Xu /Shi /Huang /Li /Huang /Zhang

Digestion 2011;83:253–260254

tric damage has been well accepted. However, to date no effective strategies to cure gastric cancer exist, so preven-tion seems to be the most effective means to reduce its incidence and mortality rate.

Many studies have identified Helicobacter pylori infec-tion as the main cause of many gastroduodenal diseases, including histological chronic gastritis, peptic ulcer, and mucosal-associated lymphoid tissue lymphoma, and it is believed that H. pylori is one of the important causes of gastric carcinoma [5–9] . H. pylori was classified as a class I carcinogen by the World Health Organization and the International Agency for Research on Cancer Consensus Group in 1994 [10] . Recently, epidemiological data dem-onstrated that H. pylori are responsible for gastric cancer in 60–90% of cases [11, 12] . Meta-analysis showed that the infection confers a 2- to 3-fold increased risk of gastric cancer development [13, 14] .

The development of gastric cancer is generally be-lieved to be a multistep progression from chronic gastritis to gastric atrophy (GA), intestinal metaplasia (IM), dys-plasia, and finally invasive cancer [15] , which is usually triggered by chronic H. pylori infection. Because of the long lead time in gastric cancer development, whether eradication of H. pylori infection could actually prevent cancer is still being debated. Many genomic and cellular changes are present in the inflamed gastric epithelium long before the appearance of the cancer itself. H. pylori infection has been shown to affect the biology, growth, and death of gastric epithelial and cancer cells, both di-rectly and through ongoing gastric inflammation [16] . Many studies have suggested that it is possible to reverse precancerous lesions after H. pylori eradication. The link between infection and gastric cancer provides scientists with hope that curative therapy for H. pylori infection would indirectly reduce the risk of gastric cancer. How-ever, despite the benefits of H. pylori eradication in pre-venting gastric cancer or progression of premalignant gastric lesions, many people with atrophic gastritis and IM were found to progress to gastric cancer after H. py-lori eradication. Thus, there might be a point of no return at which genetic changes have al-ready occurred and are irreversible despite elimination of H. pylori .

Whether GA and IM can be expected to improve after eradication of H. pylori remains controversial, and this study was designed to address this question. We per-formed an updated systematic review with meta-analysis to assess gastric histological alteration before and after H. pylori eradication. We compared histological scores of patients before and after H. pylori eradication according to the Sydney System or Updated Sydney System.

Methods

Literature Search The Medline, PubMed, and EMBASE digital dissertation da-

tabases were searched for clinical trials that were published in English up to December 2009. The search methodology used combinations of the following keywords: H. pylori OR Helico-bacter pylori OR HP; eradication OR treatment OR cure OR ther-apy; gastric atrophy OR atrophic OR GA; intestinal metaplasia OR IM. We also emailed the authors of some studies to ask for more details when it was difficult to calculate the histological scores.

Inclusion Criteria We included articles for the meta-analysis when they met the

following inclusion criteria: (1) adults; (2) tested positive for the presence of H. pylori prior to treatment; (3) H. pylori infection was documented both by histology and 14 C-UBT or 13 C-UBT (sensi-tivity, 100%; specificity, 96%) [17] ; (4) gastric histology was evalu-ated separately for the antrum and corpus; (5) examination of stomach biopsy specimens was done at baseline and at least 12 months later; (6) the Sydney System [18] or updated Sydney Sys-tem [19] was used for histology scoring, and (7) patients enrolled in the studies had no malignant lesions. All full articles were writ-ten in English. To avoid the same or overlapping datasets, only data from the largest or most recent studies were included.

Exclusion Criteria After excluding duplicate publications, we excluded studies

without raw data and in addition studies with patients with other treatments, such as nonsteroidal anti-inflammatory drugs and steroids, which might interfere with H. pylori status were exclud-ed, studies without a clearly defined follow-up duration for erad-ication confirmation were also excluded.

Data Extraction Data from each paper meeting the inclusion criteria were re-

viewed and separately extracted by two independent reviewers. The two investigators recorded details about authors, year of pub-lication, number of patients in the treated group, number of pa-tients with successfully eradicated H. pylori , time of follow-up, treatment regimen of H. pylori , and methodology for histology scoring, and they extracted the histological scores before and af-ter H. pylori eradication. The assessment tool was based on the schema suggested by the National Health Service Centre for Re-views and Dissemination [20] and was used to assess the quality of the methods of the full-text studies. Any differences that could not be resolved through discussion were decided by a third inves-tigator, and consensus was obtained in all cases.

Statistical Analysis We used Review Manager 4.2.8 to perform the meta-analysis.

To compare the histological scores before and after H. pylori eradication, the inverse variance weighted mean differences (WMD) and 95% confidence intervals (CIs) for gastric mucosal histological scores were estimated for each study. We examined heterogeneity using � 2 tests (p ! 0.1 was considered significant). We used a random effects model if the � 2 tests were significant; otherwise we used a fixed effects model. To enhance the confi-dence of the results of the statistics when the number of com-

Effect of H. pylori Eradication on Gastric Precancerous Lesions

Digestion 2011;83:253–260 255

bined studies was lacking, we used the I 2 metric, which describes the proportion of variability across studies that is due to score heterogeneity. If I 2 = 0, there is no heterogeneity. I 2 1 50% is con-sidered to be indicative of heterogeneity. Larger values indicate greater heterogeneity.

Results

Studies and Study Characteristics Figure 1 shows the flowchart of the inclusion criteria

for the studies. Our search strategy initially yielded 2,463 citations. Among these, 295 were excluded because of du-plications, 618 were rejected as reviews, and 1,478 were rejected because the titles suggested that the articles were irrelevant. Of the remaining 72 abstracts, 60 were reject-ed on the basis of not meeting the inclusion criteria. We ultimately included 12 studies with a total of 2,658 pa-tients in the meta-analysis. Before treatment, 2,648 pa-tients had antrum GA, 2,401 patients had corpus GA, 2,582 patients had antrum IM, and 2,460 patients had corpus IM.

Table 1 shows the main characteristics of the papers that met the inclusion criteria. Of these, three were ran-domized control studies [22, 24, 26] and the rest were ob-servational studies [21, 23, 25, 27–32] . They were conduct-ed in different parts of the world. Not all the papers pro-vided data for the two histological parameters evaluated (i.e. GA and IM separately for the gastric antrum and cor-

Database search(n = 2,463)

Excluded (n = 295) Duplicate

Potentially relevant studiesidentified (n = 2,168)

Excluded (n = 618)Review

Potentially relevant studiesidentified (n = 1,550)

Excluded (n = 1,478) Irrelevant studies

Studies with usableinformation included in the

analysis (n = 12)

Potentially relevant studiesidentified (n = 72)

Excluded (n = 60) Not meeting the inclusion criteria

Table 1. Main characteristics of the 12 studies selected for meta-analysis

Refer-enceNo.

Investigator(country)

Numberof patientsin treatedgroup

Number ofpartients whowere success-fully cured

Follow-upyears

Treatmentregimen

Histology assessment Histologic parameters

GA I M

antrum corpus antrum corpus

21 Iacopini F, 2003 (Italy) 10 10 1 OMC updated Sydney System yes no yes no22 Kamada T, 2003 (Japan) 45 37 3 OMC updated Sydney System yes no no no23 Lu B, 2005 (China) 154 92 3 O/LAC updated Sydney System yes no yes no24 Sung JJ, 2000 (China) 295 226 1 OAC updated Sydney System yes yes yes yes25 Tucci A, 1998 (Italy) 20 20 1 BAM Sydney System yes no yes no26 Ruiz B, 2001 (Colombia) 50 29 6 O/LAC updated Sydney System yes no no no27 Ito M, 2002 (Japan) 36 22 5 PPI/A/C updated Sydney System yes yes yes yes28 Kamada T, 2005 (Japan) 2,157 1,767 1 O/L/A/C updated Sydney System yes yes yes yes29 Lahner E, 2005 (Italy) 38 38 6.7 bismuth-based

triple regimensupdated Sydney System yes yes yes yes

30 Oda Y, 2004 (Japan) 59 59 1 O/A/C updated Sydney System yes yes yes yes31 Wambura C, 2004 (Japan) 118 107 1 L/A/C updated Sydney System yes yes yes yes 32 Toyokawa, 2009 (Japan) 260 241 5 PPI/A/C updated Sydney System yes yes yes yes

O = Omeprazole; L = lansoprazole; B = bismuth subcitrate; C = clarithromycin; A = amoxicillin; M = metronidazole; PPI = proton pump inhibitor.

Fig. 1. Meta-analysis profile summarizing trial flow.


Digestion 2011;83:253–260256

pus). Two studies [27, 28] enrolled patients with early gas-tric cancer who underwent endoscopic mucosal resec-tion, and no recurrence was found before enrollment in the study. One paper [25] calculated the histological score twice because people of two different groups underwent H. pylori eradication at a different point in time in this study. Another paper [31] calculated the histological score two times before and after H. pylori eradication separate-ly because in this study, the histological score for the less-er and greater parts of the antrum and corpus were eval-uated before and after eradication of H. pylori . In these 12 studies, bacterial eradication consisted of standard ther-apy of proton pump inhibitor (PPI), bismuth-based triple regimens, or dual regimens for 1–2 weeks. The quality of the studies was assessed using the score proposed by Jadad et al. [33] .

Outcomes for the Meta-Analysis Three of 12 articles included in the meta-analysis

showed that GA in the antrum was reversed after H. py-

lori eradication, and three of six articles showed that GA in the corpus was reversed after H. pylori eradication. Figures 2 and 3 show the pooled WMD with 95% CI of GA in the gastric antrum and corpus, respectively, before and after H. pylori eradication. A significant improve-ment in GA in the corpus after H. pylori eradication was observed. For antral GA, the pooled WMD with 95% CI was 0.12 (0.00–0.23), p = 0.06. For corpus GA, the pooled WMD was 0.32 (0.09–0.54), p = 0.006. Only one of nine articles showed that IM in the antrum was reversed after H. pylori eradication, and no articles showed that IM in the corpus was improved markedly after eradication. Fig-ures 4 and 5 display the pooled WMD with 95% CI of IM in the gastric antrum and corpus, respectively, before and after H. pylori eradication. No significant difference was found either in the antrum or the corpus. For antral IM, the pooled WMD was 0.02 (–0.12 to 0.16), p = 0.76. For corpus IM, the pooled WMD was –0.02 (–0.05 to 0.02),p = 0.42.

Review: AtrophyComparison: 01 before eradication vs. after eradicationOutcome: 01 (antrum) before eradication vs. after eradication

Studyor subcategory

n Beforeeradicationmean (SD)

n Aftereradicationmean (SD)

WMD (random)95% CI

Weight%

WMD (random)95% CI

Wambura C-2, 2004 107 1.71 (0.95) 107 2.00 (1.16) 7.78 –0.29 (–0.57, –0.01)Tucci A-1, 1998 10 0.90 (0.90) 10 0.30 (0.50) 2.75 0.60 (–0.04, 1.24)Tucci A-2, 1998 10 0.60 (0.70) 10 0.20 (0.50) 3.64 0.40 (–0.13, 0.93)Sung JJ, 2000 226 0.64 (0.78) 226 0.70 (0.82) 11.60 –0.06 (–0.21, 0.09)Ruiz B, 2001 29 0.28 (0.16) 29 0.31 (0.11) 13.49 –0.03 (–0.10, 0.04)Ito M, 2002 22 2.14 (0.80) 22 1.36 (0.80) 4.33 0.78 (0.31, 1.25)Kamada T, 2003 37 1.40 (134) 37 0.74 (1.34) 2.96 0.66 (0.05, 1.27)Oda Y, 2004 59 0.95 (0.68) 59 0.77 (0.60) 9.17 0.18 (–0.05, 1.27)Wambura C, 2004 107 1.43 (1.13) 107 1.38 (0.92) 7.98 0.05 (–0.23, 0.33)Kamada T, 2005 1,767 1.90 (21.02) 1,767 1.60 (16.81) 0.83 0.30 (–0.95, 1.55)Lahner E, 2005 38 0.41 (0.61) 38 0.34 (0.61) 8.03 0.07 (–0.20, 0.34)Lu B, 2005 92 1.25 (0.44) 92 0.97 (0.83) 10.31 0.28 (0.09, 0.47)Toyokawa T, 2009 241 2.10 (0.70) 241 2.20 (0.66) 12.33 –0.10 (–0.22, 0.02)Iacopini F, 2003 10 1.20 (0.63) 10 0.80 (0.32) 4.80 0.40 (–0.04, 0.84)

Total (95% CI) 2,755 2,755 100.00 0.12 (0.00, 0.23)Test for heterogeneity: � 2 = 42.60, d.f. = 13 (p < 0.0001), I 2 = 69.5%Test for overall effect: Z = 1.91 (p = 0.06)

–10 –5 0 5Favors treatment Favors control

10

Fig. 2. Forest plot of studies comparing antral gastric atrophy before versus after eradication. Gastric atrophy in the antrum did not improve after H. pylori eradication.


Digestion 2011;83:253–260 257

Review: AtrophyComparison: 01 before eradication vs. after eradicationOutcome: 02 (corpus) before eradication vs. after eradication

Studyor subcategory

n Before eradicationmean (SD)


WMD (random)95% CI

Weight%

WMD (random)95% CI

Wambura C-2, 2004 107 1.86 (1.07) 107 1.13 (1.25) 15.01 0.73 (0.42, 1.04)Sung JJ, 2000 226 0.06 (0.31) 226 0.02 (0.18) 20.98 0.04 (-0.01, 0.09)Ito M, 2002 22 2.09 (0.70) 22 0.90 (0.80) 11.55 1.19 (0.75, 1.63)Wambura C, 2004 107 0.57 (1.13) 107 0.39 (1.49) 13.83 0.18 (–0.17, 0.53)Kamada T, 2005 1,767 1.80 (21.02) 1,767 1.60 (16.81) 2.77 0.20 (–1.05, 1.45)Lahner E, 2005 38 2.16 (0.62) 38 2.22 (0.62) 15.94 –0.06 (–0.34, 0.22)Toyokawa T, 2009 241 0.73 (0.76) 241 0.53 (0.60) 19.92 0.20 (0.08, 0.32)

Total (95% CI) 2,508 2,508 100.00 0.32 (0.09, 0.54)Test for heterogeneity: � 2 = 48.50, d.f. = 6 (p < 0.00001), I 2 = 87.6%Test for overall effect: Z = 2.77 (p = 0.006)


10

Fig. 3. Forest plot of studies comparing corpus gastric atrophy before versus after eradication. Gastric atrophy in the corpus improved after H. pylori eradication.

Review: Intestinal metaplasiaComparison: 01 before eradication vs. after eradicationOutcome: 01 (antrum) before eradication vs. after eradication

Studyor subcategory



WMD (random)95% CI

Weight%

WMD (random)95% CI

Tucci A-1, 1998 10 0.30 (0.50) 10 0.20 (0.40) 7.08 0.10 (–0.30, 0.50)Tucci A-2, 1998 10 0.60 (0.80) 10 0.20 (0.50) 4.15 0.40 (–0.18, 0.98)Sung JJ, 2000 226 0.78 (0.98) 226 0.61 (0.94) 13.69 0.17 (–0.01, 0.35)Ito M, 2002 22 1.41 (0.94) 22 1.00 (0.75) 5.19 0.41 (–0.09, 0.91)Iacopini F, 2003 10 1.60 (0.63) 10 1.40 (0.63) 4.53 0.20 (–0.35, 0.75)Oda Y, 2004 59 0.59 (0.97) 59 0.52 (0.85) 8.72 0.07 (–0.36, 0.40)Wambura C-1, 2004 107 0.57 (1.13) 107 0.50 (0.56) 11.50 0.07 (–0.17, 0.31)Wambura C-2, 2004 107 1.71 (1.60) 107 2.38 (1.19) 7.50 –0.67 (–1.05, –0.29)Kamada T, 2005 1,767 1.50 (21.02) 1,767 1.30 (21.02) 0.91 0.20 (–1.19, 1.59)Lahner E, 2005 38 0.41 (0.61) 38 0.34 (0.61) 10.33 0.07 (–0.20, 0.34)Lu B, 2005 92 0.64 (0.76) 92 0.73 (0.77) 12.12 –0.09 (–0.31, 0.13)Toyokawa T, 2009 241 0.50 (0.88) 241 0.63 (0.92) 14.27 –0.13 (–0.29, 0.03

Total (95% CI) 2,689 2,689 100.00 0.02 (–0.12, 0.16)Test for heterogeneity: � 2 = 24.69, d.f. = 11 (p = 0.01), I 2 = 55.4%Test for overall effect: Z = 0.30 (p = 0.76)


10

Fig. 4. Forest plot of studies comparing antrum gastric intestinal metaplasia before versus after eradication. In-testinal metaplasia in the antrum did not improve after H. pylori eradication.


Digestion 2011;83:253–260258

Discussion

A considerable number of studies have investigated the effects of H. pylori eradication on premalignant le-sions such as GA and IM of the stomach. Some of them reported that eradication halts the progression of pre-neoplastic lesions; however, disease progression was still observed in many studies [34–37] . In this meta-analysis, we confirmed the association between H. pylori infec-tion and premalignant lesions such as GA and IM of the stomach. The main result of the present meta-analysis is that GA in the corpus could regress after eradicating H. pylori ; however, this result was not seen for GA of the antrum or for IM of the corpus and antrum. The devel-opment of IM in the stomach is not reversible by H. py-lori eradication and possibly represents a point of no re-turn.

A recent meta-analysis by Rokkas et al. [38] found sig-nificant improvement of GA in both the antrum and the corpus. However, that study included different articles than those used in our study, and Rokkas et al. [38] used different selection criteria and extracted different data from each article. That study also did not include a recent trial with negative results: the addition of this small trial, which did not show that GA in the antrum was improved

after H. pylori eradication, was sufficient to make the re-sults of our updated meta-analysis significant.

Some limitations of this meta-analysis should be men-tioned. First, our conclusions can only be as accurate as the trials upon which they are based. Of note, in the pres-ent study, we included only three randomized studies and nine observational cohort studies. Although observa-tional studies may lack the experimental element of a ran-dom allocation to an intervention, they can be regarded as a useful tool in assessing the effectiveness of an inter-vention in a community as opposed to the special setting of controlled trials [39] . There are many instances in which available clinical evidence relies on observational studies rather than on randomized trials. Second, biases also existed in the present study because unpublished data were not included, nor were conference abstracts or articles published in a language other than English. Fur-thermore, not all articles included in the meta-analysis assessed mucosal changes in the corpus, and that reduces the reliability of the data included in the analysis. Third, the number of subjects included in our study also affect-ed the quality of the meta-analysis. Although we used Medical Subject Heading terms and keywords to search as many publications as possible in English, we cannot rule out the possibility that some studies were missed,

Review: Intestinal metaplasiaComparison: 01 before eradication vs. after eradicationOutcome: 02 (corpus) before eradication vs. after eradication

Studyor subcategory



WMD (random)95% CI

Weight%

WMD (random)95% CI

Sung JJ, 2000 226 0.04 (0.32) 226 0.06 (0.30) 41.80 –0.02 (–0.08, 0.04)Ito M, 2002 22 0.91 (1.13) 22 0.50 (0.75) 0.43 0.41 (–0.16, 0.98)Oda Y, 2004 59 0.07 (0.37) 59 0.02 (0.13) 13.65 0.05 (–0.05, 0.15)Wambura C-1, 2004 107 1.14 (1.46) 107 1.13 (1.36) 0.96 0.01 (–0.37, 0.39)Wambura C-2, 2004 107 1.00 (1.41) 107 1.25 (1.49) 0.90 –0.25 (–0.64, –0.14)Kamada T, 2005 1,767 0.90 (21.02) 1,767 0.80 (16.81) 0.09 0.10 (–1.15, 1.35)Lahner E, 2005 38 1.22 (1.22) 38 1.38 (1.22) 0.45 –0.16 (–0.71, 0.39)Toyokawa T, 2009 241 0.05 (0.34) 241 0.08 (0.30) 41.72 –0.03 (–0.09, 0.03)

Total (95% CI) 2,567 2,567 100.00 –0.02 (–0.05, 0.02)Test for heterogeneity: � 2 = 5.80, d.f. = 7 (p = 0.56), I 2 = 0%Test for overall effect: Z = 0.80 (p = 0.42)


10

Fig. 5. Forest plot of studies comparing corpus gastric intestinal metaplasia before versus after eradication. In-testinal metaplasia in the corpus did not improve after H. pylori eradication.


Digestion 2011;83:253–260 259

especially studies in which the association of H. pylori infection with GA and IM was not the primary research question. Fourth, we did not compare the malignant risk of corpus dominant or H. pylori pangastritis compared to antrum predominant H. pylori gastritis because so few trials reported results about this topic. Lastly, heterogene-ity existed when comparing GA before and after H. py-lori eradication. Therefore, we used a random effects model, which results in wider confidence intervals and, thus, a more conservative estimate of treatment effects.

In conclusion, our study illustrates a very strong cor-relation between H. pylori infection and GA in the corpus but not in the antrum, and no correlation at all between

H. pylori infection and IM in either the antrum or the corpus. Further evidence from randomized clinical trials with a longer follow-up period will be necessary to con-firm the long-term effect of eradication treatment on gas-tric premalignant conditions.

Acknowledgements

This work was supported by Natural Science Funds of China (No. 30770992 and 30672397) and Social Development Funds of Jiangsu Province, China (No. B52007070).

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Gastric Atrophy and Intestinal Metaplasia before and after Helicobacter pylori Eradication: A Meta-Analysis