The global prevalence of Barrett’s esophagus: A systematic review of the published literature

Abstract

Background

Determining the prevalence of Barrett’s esophagus is important for defining screening strategies. We aimed to synthesize the available data, determine Barrett’s esophagus prevalence, and assess variability.

Methods

Three databases were searched. Subgroup, sensitivity, and meta-regression analyses were conducted and pooled prevalence was computed.

Results

Of 3510 studies, 103 were included. In the general population, we estimated a prevalence for endoscopic suspicion of Barrett’s esophagus of (a) any length with histologic confirmation of intestinal metaplasia as 0.96% (95% confidence interval: 0.85–1.07), (b) ≥1 cm of length with histologic confirmation of intestinal metaplasia as 0.96% (95% confidence interval: 0.75–1.18) and (c) for any length with histologic confirmation of columnar metaplasia as 3.89% (95% confidence interval: 2.25–5.54) . By excluding studies with high-risk of bias, the prevalence decreased to: (a) 0.70% (95% confidence interval: 0.61–0.79) and (b) 0.82% (95% confidence interval: 0.63–1.01). In gastroesophageal reflux disease patients, we estimated the prevalence with afore-mentioned criteria to be: (a) 7.21% (95% confidence interval: 5.61–8.81) (b) 6.72% (95% confidence interval: 3.61–9.83) and (c) 7.80% (95% confidence interval: 4.26–11.34). The Barrett’s esophagus prevalence was significantly influenced by time period, region, Barrett’s esophagus definition, Seattle protocol, and study design. There was a significant gradient East-West and North-South. There were minimal to no data available for several countries. Moreover, there was significant heterogeneity between studies.

Conclusion

There is a need to reassess the true prevalence of Barrett’s esophagus using the current guidelines in most regions. Having knowledge about the precise Barrett’s esophagus prevalence, diverse attitudes from educational to screening programs could be taken.

Introduction

The incidence of esophageal adenocarcinoma (EAC) has been increasing.¹ The poor prognosis of EAC has focused interest on Barrett’s esophagus (BE). Identification of BE with treatment of dysplasia is important to prevent invasive cancer. On the other hand, gastroesophageal reflux disease (GERD) has been associated with an increased risk of BE. Despite recommendations against population-based screening, the majority of guidelines recommend considering screening of chronic GERD patients. However, 50% of EAC patients report no previous GERD.^2–5 Therefore, understanding the epidemiology of BE is difficult because the majority remain undiagnosed. Indeed, the prevalence of BE is unknown: some studies estimate a 15% prevalence in chronic GERD patients and 1–2% in the general population.⁶ The BE prevalence (priori probability) is important to define and evaluate screening strategy.

BE has been an area of controversy.^1–3 Its definition and practice have varied along time and across the world.^7,8 The Prague classification, described in 2006, has improved BE diagnosis and increased reliability in reporting.⁹ While the European, American Society for Gastrointestinal Endoscopy and American College of Gastroenterology define BE as intestinal metaplasia (IM) lining in the distal esophagus with a minimum length of 1 cm, the American Gastroenterological Association defines it as any extent of intestinal metaplasia and the British Society as any columnar metaplasia (CM) (fundic type, cardiac type, and intestinal type) lining in the distal esophagus with a minimum length of 1 cm.^2–5

We aimed to synthesize the data of all studies assessing BE prevalence and determine its prevalence. We also aimed to assess the variability of BE prevalence according to the definition, geographical region, time period, and method used in order to identify the best methodology to determine it.

Methods

Search strategy

We conducted a systematic review according to the PRISMA guidelines. The research question was defined using the PICO acronym (P-population, I-intervention, C-comparator, O-outcome): what is the BE prevalence (O) in different settings (P) and which are the methodologies used (I). A sensitive search in PubMed, Scopus and Web of Knowledge was performed using the following query: “(prevalence(Title) OR epidemiolog*(Title) OR incidence(Title) OR risk(Title) OR screen*(Title)) AND (Barrett’s esophagus(Title/Abstract) OR Barrett(Title/Abstract) OR columnar-lined esophagus(Title/Abstract)).”

Selection of manuscripts

Inclusion criteria were original full-text articles published up to September 2018 and addressing BE in general and the GERD population, that met the globally accepted criteria for BE (endoscopic suspicion of BE (ESBE) with or without histologic confirmation of any CM or IM) and with a sample size of ≥100 individuals. The general population was defined as any population with or without gastrointestinal symptoms or with or without indication for esophagogastroduodenoscopy (EGD). Exclusion criteria were reviews, case-reports, case-control studies with BE cases, and non-English, non-French, non-Spanish, and non-Portuguese language. An attempt to contact corresponding authors was made when the full text was not available. When similar data was identified, we included the most recent report.

After all references (n = 3510) were imported and duplicated records were discarded, the records (n = 1531) were screened by title and abstract by two independent investigators (gastroenterology trainees). Concordance between the reviewers was measured by proportion of agreement and k-statistics achieving a good agreement (83% of agreement). Full-text eligibility was done by the same investigators. Conflicts were resolved through discussion.

Data extraction and quality assessment

A data extraction sheet was developed. Data were extracted independently by both investigators and then cross-checked by one. Studies were divided into the general and GERD population. The pooled BE prevalence was estimated according to its definition: ESBE with histologic confirmation of IM (any length or ≥1 cm of length), ESBE with histologic confirmation of CM (any length or ≥1 cm of length) and ESBE only (any length or ≥1 cm of length). The group “ESBE any length” included the studies from the group “ESBE≥1 cm of length.” For studies assessing ESBE with histologic confirmation of IM, sources of variability were evaluated.

The appraisal of study quality was done independently by both investigators using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist and the NewCastle-Ottawa Scale. Discrepancies were resolved through discussion.

Statistical analysis

The pooled prevalence was calculated using the random-effect model. Heterogeneity across studies was assessed by I² statistic (<30%, 30–60%, 60–75% and >75% suggestive of low, moderate, substantial, and considerable heterogeneity, respectively). We explored sources of heterogeneity by subgroup analysis, sensitivity analysis, and meta-regression. We used the z-test for the logit of the prevalence to examine the impact of different factors (year of publication, geographical setting, sample size, percentage of male, type of sampling, Seattle protocol, and ESBE length) on estimates. After logit transformation, we analyzed publication bias using funnel plot and Egger’s test. Statistical significance was set at p<0.05. The STATA software was used.

Results

Study characteristics

After screening, 175 records were assessed for eligibility (Figure 1). We did not have access to 3% of these articles, with 66% unrecoverable records dating before 2006. We finally included 80 studies assessing BE prevalence in the general population (ESBE with IM: 49, ESBE with CM: 8 and ESBE only: 23) and 23 in the GERD population (ESBE with IM: 17, ESBE with CM: 1 and ESBE only: 5). Characteristics of studies are depicted in Table 1.^10–112 Of the 80 studies in the general population, 12 studies performed a subgroup analysis in GERD patients: 11 studies were included in the GERD analysis,^{10,15,19,23,27,30,32,42,43,56,79} but one was not included due to the small sample (n = 26). There was considerable heterogeneity among studies. There was no data available regarding BE prevalence in the general and GERD populations for the majority of countries (Figures 1 and 2, Supplementary Material).

Figure 1.

Flowchart of study selection. (*51 articles only published as abstracts). BE: Barrett’s esophagus.

Table 1.

Characteristics of included studies.

General population
Study first author (year)	Country	Sampling	Sample size	Male (%)	Mean age	Caucasian (%)/African-American (%)/Asian (%)	Quality of endoscopy reported ?	How EGJ was defined ?	Seattle protocol used?	Esophagitis present during BE diagnosis?	Prevalence (%)
Endoscopic suspicion of BE (ESBE) with histologic confirmation of intestinal metaplasia
ESBE≥1 cm
Prospective study
Crews (2016)10	USA	Prospective population cohort	205	46	70	98.5/−/−	Yes	Gastric folds	Unknown	No	7.8
Jacobson (2011)11	USA	Women that underwent EGD	20,167	0	30–55 (range)	−/−/−	No	Unknown	Unknown	Unknown	0.73
Jung (2011)12	USA	Prospective population cohort	182,605	–	63	89/−/−	Yes	Gastric folds	Unknown	Yes	0.22
Connor (2004)13	USA	Patients with dyspepsia that underwent EGD	264	95	57	73/22/-	Yes	Gastric folds	Unknown	Yes	6.1
Pascarenco (2014)14	Romania	Patients that underwent EGD	286	52.4	59.9	−/−/−	Yes	Gastric folds	Yes	Yes	6.6
Kuo (2010)15	Taiwan	Patients that underwent EGD	736	51	50.5	−/−/−	Yes	Unknown	Yes	Yes	1.8
Cross-sectional study
Rex (2003)16	USA	Patients that underwent colonoscopy	961	59.5	59	78/20.3/-	Yes	Gastric folds	Yes	No	3.3
Retrospective study
Khoury (2012)17	USA	Patients that underwent EGD	7308	36.4	57.3	83/14/-	Yes	Gastric folds	Yes	Unknown	1.57
Kula (2007)18	Poland	Patients that underwent EGD	6326	–	–	−/−/−	Yes	Unknown	Yes	Unknown	1.1
Elizondo (2017)19	Mexico	Patients that underwent EGD	500	37.6	54	−/−/−	Yes	Gastric folds	Yes	No	1.8
Kim (2007)20	South Korea	Patients that underwent 1st EGD	70,103	–	51	−/−/−	Yes	Gastric folds	Unknown	Yes	0.22
ESBE irrespective of length
Prospective study
Gerson (2002)21	USA	Asymptomatic patients that underwent colonoscopy	110	91,8	61	73/14/4	Yes	Gastric folds	Yes	Unknown	25
Gerson (2009)22	USA	Asymptomatic women that underwent colonoscopy or EGD before bariatric surgery	126	0	58 (colonoscopy)42 (bariatric)	72/2/20 (colonoscopy) 71/19/2 (bariatric)	Yes	Unknown	Yes	Unknown	6
Zagari (2008)23	Italy	Prospective population cohort	1033	–	–	−/−/−	No	Unknown	Unknown	Unknown	1.3
Zaninotto (2001)24	Italy	Patients with dyspepsia that underwent their 1st EGD	240	51.7	56	−/−/−	Yes	Gastric folds	No	Unknown	0.83
GOSPE (1991)25	Italy	Patients that underwent EGD	14,898	57.3	57	−/−/−	Yes	Unknown	No	Yes	0.46
Katsinelos (2013)26	Greece	Patients with dyspepsia that underwent an EGD	1990	52	47.48	−/−/−	Yes	Gastric folds	Yes	Yes	3.8
Dina (2015)27	Romania	Patients that underwent EGD	1261	53	57	−/−/−	No	Unknown	Unknown	Unknown	2.85
Jonaitis (2011)28	Lithuania	Patients n with upper gastrointestinal symptoms that underwent EGD	4032	39.6	45.13	−/−/−	Yes	Gastric folds	Yes	Yes	0.82
Fagundes (2003)29	Brazil	Patients that underwent EGD	1276	–	–	100/−/−	No	Unknown	Unknown	Unknown	0.63
Csendes (2000)30	Chile	Patients with dyspepsia	306	32.7	48	−/−/−	Yes	Gastric folds	No	Yes	0
Amano (2006)31	Japan	Patients that underwent EGD	1668	57.2	63.5	−/−/−	Yes	Gastric folds	No	Yes	6.4
Peng (2009)32	China	Patients that underwent EGD	2580	49.5	45	−/−/−	Yes	Gastric folds	Yes	Yes	1.05
Zhang (2012)33	China	Patients that underwent EGD	139,416	–	–	−/−/−	Yes	Gastric folds	Yes	Yes	0,17
Wong (2002)34	China	Patients that underwent EGD	16,606	–	67.4	−/−/−	No	Unknown	Unknown	Yes	0.06
Yeh (1997)35	Taiwan	Patients that underwent 1st EGD	464	43.3	47	−/−/96	No	Unknown	Unknown	Unknown	1.98
Khamechian (2013)36	Iran	Patients with dyspepsia that underwent their 1st EGD	1144	–	45.2	−/−/−	Yes	Unknown	No	Yes	3.7
Cross-sectional study
Chak (2014)37	USA	Hospital cohort	177	100	58	41/58/-	No	Unknown	Unknown	Unknown	4.5
Ward (2006)38	USA	Patients that underwent colonoscopy	300	54	71.8 (median)	83/14/2	Yes	Unknown	Yes	Unknown	16.7
Spechler (1994)39	USA	Patients that underwent EGD	156	48.7	53	90/7/1	Yes	Gastric folds	No	Yes	10
van Zanten (2006)40	Canada	Patients with dyspepsia that underwent their 1st EGD	1040			95/−/−	No	Unknown	No	Unknown	2.4
Johansson (2005)41	Sweden	Patients that underwent 1st EGD	769	43	53	−/−/−	Yes	Gastric folds	No	Yes	3.8
Ronkainen (2005)42	Sweden	Population sample	1000	49	53.5 (median)	−/−/−	Yes	Gastric folds	No	Yes	1.6
Voutilaine (2000)43	Finland	Patients that underwent EGD	1128	42	47 (median)	−/−/−	No	Unknown	Unknown	Unknown	0.98
de Mas (1999)44	Germany	Patients that underwent EGD	370	48.4	58.7	−/−/−	No	Unknown	Unknown	Unknown	10
Freitas (2008)45	Brazil	Patients that underwent 1st EGD	104	49	65	85.6/−/−	Yes	Unknown	Yes	Unknown	3.8
Cárdenas (2010)46	Peru	Patients that underwent EGD	11,970	–	–	−/−/−	Yes	Unknown	No	Yes	0.25
Chacaltana (2009)47	Peru	Population cohort	2273	–	–	−/−/−	No	Unknown	Unknown	Unknown	0.48
Toruner (2004)48	Turkey	Patients that underwent EGD	395	43.3	57	−/−/−	Yes	Gastric folds	Yes	Yes	7.4
Lee (2011)49	Malaysia	Patients that underwent 1st EGD	1895	–	–	−/−/−	No	Unknown	Unknown	Yes	0.37
Rosaida (2004)50	Malaysia	Patients with dyspepsia that underwent EGD	1000	44.2	51.1	−/−/68.9	No	Unknown	Unknown	Unknown	2
Xiong (2010)51	China	Patients that underwent EGD	2022	52	46.97	−/−/−	Yes	Gastric folds	Yes	Unknown	1.04
Lee (2003)52	South Korea	Patients n with upper gastrointestinal symptoms that underwent EGD	1553	–	–	−/−/−	Yes	Intramucosal vessels	No	Yes	0.32
Fireman (2001)53	Israel	Patients that underwent EGD	112	51.8	49.8	−/−/−	Yes	Unknown	No	Yes	2.7
Retrospective study
Bersentes (1998)54	USA	Patients that underwent EGD	1541	98	65	75.9/1.7/<0.1	No	Unknown	Unknown	Unknown	12.4
Robles (1995)55	Spain	Patients that underwent EGD	5303	–	–	−/−/−	No	Unknown	Unknown	Unknown	0.53
De Carli (2017)56	Brazil	Patients that underwent EGD	5996	–	–	−/−/−	No	Unknown	Unknown	Unknown	0.78
Peña (2005)57	Mexico	Patients that underwent EGD	4947	–	–	−/−/−	No	Unknown	Unknown	Unknown	0.26
Yilmaz (2006)58	Turkey	Patients that underwent EGD	18,766	–	–	−/−/−	Yes	Unknown	Yes	Yes	0.4
Endoscopic suspicion of BE (ESBE) with histologic confirmation of columnar metaplasia
ESBE≥1 cm
ESBE irrespective of length
Cross-sectional study
Siwiec (2012)59	USA	Volunteers	150	–	–	−/−/−	No	Unknown	Unknown	Unknown	3.3
Connio (2001)60	USA	Database with EGD	Unknown	–	–	−/−/−	No	Unknown	Unknown	Unknown	0.08
Cameron (1990)61	USA	Autopsy with endoscopy performed in 83% of the autopsy esophagus	733	61	–	−/−/−	No	Unknown	Unknown	Unknown	0.95
Cameron (1992)62	USA	Patients that underwent EGD	51,311	–	–	−/−/−	No	Unknown	Unknown	Yes	0.83
Coleman (2011)63	North Ireland	Patients that underwent EGD	197,635	–	–	−/−/−	No	Unknown	Unknown	Unknown	4.7
Ford (2004)64	UK	Patients that underwent EGD	20,417	48	56	69/5/26	No	Unknown	Unknown	Yes	3.6
GOSPE (1991)25	Italy	Patients that underwent EGD	14,898	57.3	57	−/−/−	Yes	Unknown	No	Yes	0.58
Taghipour-Zahir (2012)65	Iran	Patients that underwent EGD	681	62.7	62.04	−/−/−	No	Unknown	Unknown	Unknown	18.86
Retrospective study
Andreollo (1997)66	Brazil	Patients that underwent EGD	2381	–	–	−/−/−	No	Unknown	Unknown	Yes	2.57
Endoscopic suspicion of BE (ESBE)
ESBE≥1 cm
Cross-sectional study
Yamagishi (2008)67	Japan	Patients that underwent EGD	6307	49.2	62.7	−/−/−	No	Intramucosal vessels	NA	Unknown	1.7
Azuma (2000)68	Japan	Hospital cohort	650	79	52.6	−/−/−	No	Intramucosal vessels	NA	Unknown	3.12
ESBE irrespective of length
Prospective study
Zullo (2014)69	Italy	Patients that underwent 1st EGD	1054	37	57.5	−/−/−	No	Unknown	NA	Unknown	1.6
Cross-sectional study
Akiyama (2010)70	Japan	Patients that underwent EGD with intact stomach	160	75.6	68 (median)	−/−/−	Yes	Gastric folds	NA	Unknown	47.5
Alexandropoulou (2012)71	UK	National database	Unknown	–	–	−/−/−	No	Unknown	NA	Unknown	1.29
Blankenstein (2005)72	UK	Patients that underwent 1st EGD	21,899	50	–	−/−/−	No	Unknown	NA	Unknown	2.25
Loffeld (2003)73	Netherlands	Patients that underwent 1st EGD	11,691	–	–	−/−/−	No	Unknown	NA	Unknown	2.4
López-Colombo (2018)74	Mexico	Patients that underwent EGD	239	45.6	53	−/−/−	No	Intramucosal vessels	NA	Unknown	23
Shimoyama (2012)75	Japan	Patients that underwent EGD	832	40.7	67.6	−/−/−	Yes	Intramucosal vessels	NA	Yes	22.1
Okita (2008)76	Japan	Patients that underwent EGD	5338	60	69	−/−/−	Yes	Gastric folds	NA	Unknown	37.6
Fujiwara (2003)77	Japan	Patients that underwent EGD	548	54	57.3	−/−/−	Yes	Intramucosal vessels	NA	Unknown	12.2
Niu (2012)78	China	Population cohort	1995	72	44	0/0/100	No	Unknown	NA	Unknown	2.8
Zou (2011)79	China	Population sample	1029	42.4	–	−/−/−	No	Unknown	NA	Yes	1.8
Tseng (2008)80	China	Patients that underwent EGD	19,812	55.2	51.6	0/0/100	Yes	Gastric folds	NA	Yes	0.28
Park (2009)81	Korea	Patients that underwent EGD	25,536	59.5	46.7	0/0/100	No		NA	Yes	3.4
Choi (2002)82	Korea	Patients that underwent EGD	847	45.1	48.7	−/−/−	Yes	Intramucosal vessels	NA	Yes	17
Masri (2015)83	Lebanon	Patients that underwent EGD	16,787	–	–	−/−/−	No	Unknown	NA	Unknown	1.3
Rezailashkajani (2007)84	Iran	Patients that underwent EGD	501	39	44.7	−/−/−	No	Unknown	NA	Yes	0.2
Retrospective study
Smith (2009)85	USA	Patients that underwent EGD	135	–	–	12.6/1/-	No	Unknown	NA	Unknown	3.6
Masclee (2014)86	Netherlands	National database	1,487,191	–	–	−/−/−	No	Unknown	NA	Unknown	0.15
Alcedo (2009)87	Spain	Patients that underwent EGD	58,190	–	–	−/−/−	No	Unknown	NA	Yes	0.66
Fujimoto (2013)88	Japan	Patients that underwent EGD	18,792	70.8	54.2	−/−/−	No	Unknown	NA	Unknown	7.9
Akiyama (2009)89	Japan	Patients that underwent EGD	846	53	66	−/−/−	Yes	Gastric folds	NA	Yes	43
Endoscopic suspicion of BE (ESBE) with histologic confirmation of intestinal metaplasia
ESBE≥1 cm
Prospective study
Crews (2016)10	USA	Prospective population cohort	68	–	–	−/−/−	Yes	Gastric folds	Unknown	No	8.8
Mathew (2011)90	India	Patients with symptoms	278	53.6	39.97	−/−/−	Yes	Gastric folds	Yes	No	8.99
Kuo (2010)15	Taiwan	Patients that underwent EGD	344	55.5	49.8	−/−/−	Yes	Unknown	Yes	Yes	3.8
Retrospective study
Elizondo (2017)19	Mexico	Patients that underwent EGD	125	–	–	−/−/−	Yes	Gastric folds	Yes	No	7.2
ESBE irrespective of length
Prospective study
Romero (2002)91	USA	Patients with GERD symptoms and no family relatives with BE	100	59	47	−/−/−	Yes	Gastric folds	Yes	Yes	6
Zagari (2015)23	Italy	Prospective population cohort	458	–	–	−/−/−	No	Unknown	Unknown	Unknown	1.5
Dina (2015)27	Romania	Patients that underwent EGD	527	–	–	−/−/−	No	Unknown	Unknown	Unknown	4.93
Fagundes (2003)29	Brazil	Patients that underwent EGD	326	–	–	100/−/−	No	Unknown	Unknown	Unknown	2.5
Csendes (2003)92	Chile	Patients that underwent EGD	1480	–	54.5	−/−/−	Yes	Gastric folds	Yes	Unknown	13.65
Csendes (2000)30	Chile	Patients with symptoms	376	41.5	49	−/−/−	Yes	Gastric folds	No	Yes	11.4
Sharifi (2014)93	Iran	Patients with symptoms	736	55.8	48.9	−/−/−	Yes	Unknown	Yes	Yes	4.6
Fouad (2009)94	Egypt	Patients with symptoms	1000	76.4	38.81	−/−/−	Yes	Unknown	Unknown	No	7.3
Zhang (2012)95	China	Patients that underwent EGD	593	57.1	–	−/−/−	Yes	Unknown	Yes	Unknown	4.6
Peng (2009)32	China	Patients that underwent EGD	310	–	–	−/−/−	Yes	Gastric folds	Yes	Yes	5.2
Cross-sectional study
Ramirez (2008)96	USA	Patients with symptoms	100	86	–	−/−/−	Yes	Gastric folds	Yes	Unknown	27
Ward (2006)38	USA	Patients that underwent colonoscopy	105	–	–	−/−/−	Yes	Unknown	Yes	Unknown	19.8
Jobe (2006)97	USA	Patients with symptoms	121	80	59	95/4/-	Yes	Gastric folds	Yes	Unknown	29.8
Winters (1987)98	USA	Patients with symptoms	97	–	–	−/−/−	No	Unknown	No	Unknown	6.18
Ronkainen (2011)99	Sweden	Population cohort	284	–	–	−/−/−	Yes	Unknown	Unknown	Yes	8.1
Ronkainen (2005)42	Sweden	Population sample	399	–	–	−/−/−	Yes	Gastric folds	No	Yes	2.3
Voutilaine (2000)43	Finland	Patients that underwent EGD	248	52	56	−/−/−	No	Unknown	Unknown	Unknown	4
Conio (1988)100	Italy	Patients that underwent EGD	102	55.9	30–83 (range)	−/−/−	No	Unknown	Unknown	Unknown	4.9
Wani (2014)101	India	Patients with symptoms	378	66.7	48.15	−/−/−	Yes	Gastric folds	Yes	Unknown	2.38
Yin (2012)102	China	Patients with symptoms	528	–	–	−/−/−	Yes	Gastric folds	Yes	Unknown	6.06
Retrospective study
Chavalitdhamrong (2011)103	USA	Patients that underwent esophageal capsule endoscopy	502	54.9	54.2	−/−/−	No	Unknown	Unknown	Unknown	1.19
Banki (2005)104	USA	Patients with symptoms	796	58	52	−/−/−	No	Gastric folds	Yes	Unknown	26
Spechler (2002)105	USA	Patients that underwent EGD	2477	48	58	87.8/10/2	No	Unknown	Unknown	Unknown	8.1
De Carli (2017)56	Brazil	Patients that underwent EGD	1769	–	–	−/−/−	No	Unknown	Unknown	Unknown	2.7
Gado (2015)106	Egypt	Patients that underwent EGD	433	59	45	−/−/−	Yes	Gastric folds	No	Unknown	1.2
Endoscopic suspicion of BE (ESBE) with histologic confirmation of columnar metaplasia
ESBE≥1 cm
ESBE irrespective of length
Cross-sectional study
Siwiec (2012)59	USA	Volunteers	67	–	–	−/−/−	No	Unknown	Unknown	Unknown	4.5
Winters (1987)98	USA	Patients with symptoms	97	–	–	−/−/−	No	Unknown	No	Unknown	12.3
Conio (1988)100	Italy	Patients that underwent EGD	102	55.9	30–83 (range)	−/−/−	No	Unknown	Unknown	Unknown	11.8
Arróspide (2003)107	Peru	Patients that underwent EGD	345	49.6	–	−/−/−	No	Unknown	Unknown	Unknown	5.8
Endoscopic suspicion of BE (ESBE)
ESBE≥1 cm
ESBE irrespective of length
Prospective study
Lin (2018)108	USA	Patients that underwent EGD	73,535	48.2	53.8	80.9/4.2/1.8	No	Unknown	NA	Unknown	5.6
Kulig (2004)109	Germany, Austria, and Switzerland	Hospital based-cohort	6215	53	54	99/−/−	No	Unknown	NA	Unknown	11
Pelechas (2013)110	Greece	Patients with symptoms	406	63.1	48.7	−/−/−	No	Unknown	NA	Unknown	4.9
Cross-sectional study
Abdul-Razzak (2007)111	Jordan	Patients that underwent EGD	100	50	37.62	−/−/−	No	Unknown	NA	Unknown	4
Zou (2011)79	China	Population sample	48	–	–	−/−/−	No	Unknown	NA	Yes	2.1
Retrospective study
Nassif (2012)112	Brazil	Patients that underwent EGD	207	34.78	47.43	−/−/−	No	Unknown	NA	Unknown	6.28

BE: Barrett’s esophagus; EGD: esophagogastroduodenoscopy; EGJ: means esophagogastric junction; ESBE: endoscopic suspicion of Barrett’s esophagus; GERD: gastroesophageal reflux disease; GOSPE: Gruppo Operativo per lo Studio delle Precancerosi dell’Esofago; NA: not applicable.

Figure 2.

Forest plot of all studies assessing the prevalence of endoscopic suspicion of Barrett’s esophagus (ESBE) any length with histologic confirmation of intestinal metaplasia (IM) (a), of ESBE ≥1 cm of length with histologic confirmation of IM (b), and of ESBE any length with histologic confirmation of columnar metaplasia (CM) (c) in general population.

BE prevalence according to various definitions

General population

The BE prevalence varied according to definition: 0.96% (95% confidence interval (CI_95%): 0.85–1.07) for ESBE any length with IM, 0.96% (CI_95%: 0.75–1.18) for ESBE ≥1 cm with IM, 3.89% (CI_95%: 2.25–5.54) for ESBE any length with CM, 7.04% (CI_95%: 6.35–7.74) for ESBE any length and 2.26% (CI_95%: 0.90–3.61) for ESBE with ≥1 cm (Figure 2).

Regarding ESBE with IM, we analyzed the statistical outliers (Figure 2). Ward et al. (16.7% of BE prevalence) and Spechler et al. (10%) conducted studies in a population with a high prevalence of GERD. In the study of Spechler et al. and Pascarenco el al. (6.6%) esophagitis was present. Bersentes et al. (12.4%), Gerson et al. (2002) (20%) and Connor et al. (6.1%) conducted studies with a high percentage of males. In the study of Gerson et al. (2009) (6%), 50% of the population was obese/overweight. Bersentes et al., De Mas et al. (10%), Amano et al. (6.4%) and Toruner et al. (7.4%) did not consider ESBE≥1 cm. Crews et al. (7.8%) estimated BE prevalence by EGD and transnasal endoscopy in an older population. By excluding these outliers, the prevalence was: BE any length with IM – 0.70% (CI_95%: 0.61–0.79); BE ≥1 cm with IM – 0.82% (CI_95%: 0.63–1.01).^{10,13,14,21,22,31,38,39,44,48,54}

GERD population

The BE prevalence varied based on the definition: 7.21% (CI_95%: 5.61–8.81) for ESBE any length with IM, 6.72% (CI_95%: 3.61–9.83) for ESBE ≥1 cm with IM, 7.80% (CI_95%: 4.26–11.34) for ESBE any length with CM and 6.51% (CI_95%: 3.34–9.68) for ESBE any length.

Regarding ESBE with IM, we analyzed the statistical outliers (Figure 3). Ward et al. (19.8% of BE prevalence) conducted a study in an older population. In the study of Jobe et al. (29.8%) and Ramirez et al. (27%) >80% were men. Banki et al. (26%) assessed patients that warrant evaluation for antireflux surgery. By excluding these studies, the pooled prevalence of ESBE any length with IM was 4.53% (CI_95%: 3.46–5.60).^38,96,97,104

Figure 3.

Forest plot of all studies assessing the prevalence of endoscopic suspicion of Barrett’s esophagus (ESBE) any length with histologic confirmation of intestinal metaplasia (IM) (a), of ESBE ≥1 cm of length with histologic confirmation of IM (b), and of ESBE any length with histologic confirmation of columnar metaplasia (CM) (c) in the gastroesophageal reflux disease (GERD) population.

Variability in the prevalence of BE

Geographical setting

General population

The pooled prevalence of BE in Western, Eastern and Latin American countries was 2.30% (CI_95%: 1.94–2.65), 0.59% (CI_95%: 0.45–0.73), and 0.51% (CI_95%: 0.28–1.07) respectively (Figure 4). There was a North-South gradient in the West: in North was 2.97% (CI_95%:2.44–3.50) and in South was 1.72% (CI_95%:1.09–2.36).

Figure 4.

Subgroup analysis of the pooled prevalence of Barrett’s esophagus (BE) in general population (a), and in gastroesophageal reflux disease (GERD) patients (b) for geographical setting, date of publication, length of endoscopic suspicion of Barrett’s esophagus (ESBE) considered, use of Seattle protocol, study design, and type of sampling.

GERD population

The pooled prevalence of BE in Western, Eastern, and Latin American countries was 9.30% (CI_95%: 6.35–12.25), 4.73% (CI_95%: 3.11–6.35) and 7.43% (CI_95%: 2,50–8.81) respectively (Figure 4).

Time trends

General population

There was a temporal trend with the most recent studies reporting lower estimates especially in the West. Indeed, the BE prevalence was 0.80% (CI_95%: 0.69–0.92) when considering only the studies published after 2006 (date of publications of Prague classification) while it was 1.96% (CI_95%: 1.62–2.30) when considering only the studies published before 2006. This difference was also found in a subgroup analysis for Western (before: 4.05% (CI_95%: 3.16–4.95) vs after: 1.71% (CI_95%: 1.25–2.17)) and Eastern countries (before: 1.28% (CI_95%: 0.81–1.74) vs after: 0.54% (CI_95%: 0.45–0.73)) (Figure 4).

GERD population

Likewise, there was a temporal trend: 5.27% (CI_95%: 3.79–6.76) when considering only the studies published after 2006 vs 8.80% (CI_95%: 5.91–11.69) when considering only the studies published before 2006 (Figure 4).

Length of BE

General population

When comparing studies that considered ESBE with ≥1 cm with those that did not, the prevalence of BE was significantly different (0.96% (CI_95%: 0.75–1.18) vs 2.31% (CI_95%: 1.56–3.05)) (Figure 4).

GERD population

The prevalence of BE was similar between studies that considered ESBE ≥1 cm and studies that did not (6.72% (CI_95%: 3.61–9.83) vs 7.27% (CI_95%: 5.53–8.81)) (Figure 4).

Use of the Seattle protocol

General population

When comparing studies that used Seattle protocol with those that did not, the prevalence was significantly different (1.76% (CI_95%: 0.85–1.07) vs 0.88% (CI_95%: 0.74–1.02)) (Figure 4).

GERD population

When comparing studies that used Seattle protocol with those that did not, the prevalence was significantly different (10.67% (CI_95%: 7.31–14.02) vs 4.62% (CI_95%: 3.13–6.12))(Figure 4).

Study characteristics

General population

The studies with larger sample size, lower male percentage, and lower mean/median age had the lowest BE prevalence. Prospective studies estimated a higher BE prevalence than retrospective studies (1.34% (CI_95%: 1.16–1.53) vs 0.74% (CI_95%: 0.56–0.91)). When comparing studies that estimated BE prevalence in patients undergoing EGD and studies that estimated BE prevalence in population cohorts/sample (these studies proposed endoscopy to individuals from a cohort conducted for unrelated reasons to BE or GERD or from a population sample) there was no difference (0.96 (CI_95%: 0.85–1.07) vs 0.87 (CI_95%: 0.74–1.01)) (Figure 4).

GERD population

The studies with the larger sample size, lower percentage of males, and with lower mean/median age had a lower prevalence. The prevalence was similar between prospective and retrospective studies. There was no difference between studies that estimated BE prevalence in patients undergoing EGD and studies that estimated BE prevalence in population cohorts/sample. However, the BE prevalence significantly increased to 11.23% (CI_95%: 7.04–15.41) if studies assessed patients with GERD (Figure 4).

Meta-regression

General population

The univariate analysis showed a significant relationship between the BE prevalence and the geographical setting, sample size, and percentage of males. Considering the univariate and the subgroup analysis, we included publication date, geographical setting, sample size, percentage of male, and ESBE≥1 cm as independent variables in a multivariate analysis. Although only sample size had a significant impact on BE prevalence (p<0.0001), 55.63% of cross-study variance could be explained by this model (R² = 55.63%).

GERD population

The univariate analysis showed a significant relationship between pooled prevalence and the use of Seattle protocol. Considering the univariate and the subgroup analysis, we included year of publication, geographical setting, sample size, percentage of male, type of sampling, and Seattle protocol in a multivariate analysis. Although 64.96% of the variance inter-studies was explained by this model, only year of publication (p = 0.011) and type of sampling (p = 0.016) had a significant impact on BE prevalence.

Quality assessment

Among the 103 studies, 65% were at a high risk of bias due to sample characterization and 87% due to endoscopic practice (Supplementary Material Figure 3).

Publication bias

For the general population, the funnel plot and the Egger test (p = 0.1177) indicated low risk of bias. For the GERD population, although the funnel plot indicated low risk of bias, the p-value was 0.0016 with a z-statistic of -2.06 in the Egger test (Supplementary Material Figure 4).

Discussion

The poor prognosis of EAC has been focus attention to BE. Despite BE surveillance, EAC incidence has been rising, bringing into question whether the population at risk is being correctly identified. Indeed, the precise prevalence of BE is unknown.

This study is an important review assessing global BE prevalence according to the most recent guidelines and the first study assessing variability of BE prevalence due to BE definition, geographical region, time period, and methodology. We have found that there are no data available from the majority of the countries. In some countries, the estimations are higher than expected because of BE definition and methodology used (Supplementary Material Figures 1 and 2). We also found heterogeneity among the studies.

In the general population, we estimated a pooled prevalence of 0.96% (CI_95%: 0.85–1.07) for ESBE any length with histologic confirmation of IM, 0.96% (CI_95%: 0.75–1.18) for ESBE ≥1 cm of length with histologic confirmation of IM and 3.89% (CI_95%: 2.25–5.54) for ESBE any length with histologic confirmation of CM. By excluding studies with high risk of bias, the prevalence of ESBE any length with histologic confirmation of IM was 0.70% (CI_95%: 0.61–0.79) and of ESBE ≥1 cm of length with histologic confirmation of IM was 0.82% (CI_95%: 0.63–1.01). Therefore, it would be necessary to perform endoscopy in 122 individuals of the general population for the diagnosis of one patient with BE. There is no difference in the prevalence between BE any length with IM and BE ≥1 cm with IM, because the first included the studies from the last group. Indeed, when comparing studies that considered ESBE with ≥1 cm with those that did not, the prevalence was significantly different (Figure 4). In GERD, we estimated a pooled prevalence of 7.21% (CI_95%: 5.61–8.81) for ESBE any length with histologic confirmation of IM, 6.72% (CI_95%: 3.61–9.83) for ESBE ≥1 cm of length with histologic confirmation of IM and, 7.80% (CI_95%: 4.26–11.34) for ESBE any length with histologic confirmation of CM. The prevalence was significantly influenced by the date of publication, geographical setting, BE length, the use of Seattle protocol, and the study design. There was a significant gradient East-West and North-South of BE prevalence. By including studies prior to 2006, we found a temporal trend with the most recent studies reporting lower prevalence, particularly after Prague classification.⁹ Moreover, the presence of esophagitis was a source of bias, probably by making BE diagnosis difficult. The impact of ethnicity was not assessed since the studies did not estimate BE prevalence by ethnic group.

Shiota et al.¹¹³ conducted a systematic review of BE prevalence in Asia, estimating a BE prevalence of 1.3% (0.7–2.2) in the general population with high heterogeneity. This higher value might result from studies in high-risk patients and studies that diagnosed BE without IM confirmation. They also included studies that excluded patients with known BE (that estimated incidence). No study from this review was excluded in ours.¹¹³ Qumseya et al.¹¹⁴ have conducted a systematic review of 47 studies assessing BE prevalence in different risk populations. They included studies with less than 100 patients and studies that excluded patients with known BE. Moreover, the authors differentiate the prevalence of population without any risk factor (0.8%) from the prevalence of population with ≥50 years (6.7%). However, the majority of the studies included in the first group had a mean/median age higher than 50 years and the last group included studies with mean age of 45 years.¹¹⁴

The limitations of our analysis extend from the various biases within each study and the heterogeneity among studies impacting our meta-analysis. Although the BE prevalence varied based on the definition, we have attempted to provide precise estimates based on the population being evaluated (general vs GERD), BE length (any vs ≥1 cm), using Seattle protocol and geographical location.

Our findings confirm the need for well-conducted studies in order to accurately estimate BE prevalence and decrease heterogeneity. In the future, prospective population-based or EGD-based studies with a minimum sample size of 100 individuals and according to the most recent guidelines, namely using the definition of BE with ≥1 cm and histologic confirmation of IM, the Prague classification, the Seattle protocol, and in the absence of esophagitis, should be conducted.

Having knowledge about precise BE prevalence, we could draw more tailored screening strategies and ultimately assess their impact.