Inverse time trends of peptic ulcer and reflux esophagitis show significant association with reduced prevalence of Helicobacter pylori infection

Figures & data

Figure 1. Rapidly changed prevalence of H. pylori infection from 1996 to 2010 in Japan. Seropositivity rates of anti-H. pylori IgG at ages <35 (20–34), 35–39, 40–44, 45–49, 50–54, 55–59, and ≥60 (60–88) years among the generally healthy persons are shown, based on the data of 6,452 subjects in 1996 and 13,263 subjects in 2010. Total numbers tested in each age group/year are in parentheses.

Figure 2. The prevalence of gastric ulcer, duodenal ulcer, and reflux esophagitis from 1991 to 2015 in Japan. Total 211,347 general population subjects who underwent upper gastrointestinal endoscopy from 1991 to 2015 were investigated.

Table 1. Univariate analyses of three acid-related diseases with age, sex, and H. pylori infection, based on the data of 6,452 generally healthy subjects in 1996 and 13,263 generally healthy subjects in 2010.

		1996			2010
	Factors	Presence of the disease	Absence of the disease	p value	Presence of the disease	Absence of the disease	p value
Gastric ulcer	Age 20–34	2.6%	97.4%	.0047*	0.0%	100.0%	.0292*
	Age 35–39	4.6%	95.4%		0.1%	99.9%
	Age 40–44	6.0%	94.0%		0.4%	99.6%
	Age 45–49	7.6%	92.4%		0.5%	99.5%
	Age 50–54	6.9%	93.1%		0.6%	99.4%
	Age 55–59	8.6%	91.4%		1.0%	99.0%
	Age 60–88	6.4%	93.6%		0.7%	99.3%
	Male	8.3%	91.7%	<.0001*	0.70%	99.30%	.0117*
	Female	3.2%	96.8%		0.40%	96.80%
	H. pylori (+)	9.4%	90.6%	<.0001*	1.60%	98.40%	<.0001*
	H. pylori (–)	3.8%	96.2%		0.20%	99.80%
Duodenal ulcer	Age 20–34	6.2%	93.8%	.1273	0.0%	100.0%	.0158*
	Age 35–39	7.3%	92.7%		0.3%	99.7%
	Age 40–44	6.6%	93.4%		0.3%	99.7%
	Age 45–49	6.6%	93.4%		0.9%	99.1%
	Age 50–54	5.8%	94.2%		0.4%	99.6%
	Age 55–59	5.1%	94.9%		0.4%	99.6%
	Age 60–88	4.0%	96.0%		0.2%	99.8%
	Male	6.6%	93.4%	.0092*	0.50%	99.50%	.0181*
	Female	5.0%	95.0%		0.30%	99.70%
	H. pylori (+)	8.8%	91.2%	<.0001*	1.20%	98.80%	<.0001*
	H. pylori (–)	3.3%	96.7%		0.10%	99.90%
Reflux Esophagitis	Age 20–34	0.5%	99.5%	.1301	8.2%	92.8%	.0010*
	Age 35–39	1.1%	98.9%		11.0%	89.0%
	Age 40–44	1.9%	98.1%		12.4%	87.6%
	Age 45–49	2.5%	97.5%		14.1%	85.9%
	Age 50–54	1.5%	98.5%		13.6%	86.4%
	Age 55–59	2.2%	97.8%		12.5%	87.5%
	Age 60–88	1.5%	98.5%		10.8%	89.2%
	Male	2.4%	97.6%	<.0001*	17.00%	83.00%	<.0001*
	Female	0.8%	99.2%		5.60%	94.40%
	H. pylori (+)	1.5%	98.5%	.046*	5.90%	94.10%	<.0001*
	H. pylori (–)	2.2%	97.8%		15.40%	84.60%

*The levels of significance were set at p < .05.

Table 2. Multivariable logistic regression analyses to evaluate associations of age, sex, and H. pylori infection with three major benign acid-related diseases using the data of 6,452 generally healthy subjects in 1996 and 13,263 generally healthy subjects in 2010.

		1996			2010
Acid-related diseases	Variables	Standardised coefficients	Odds ratio (95% C.I.)	p value	Standardised coefficients	Odds ratio (95% C.I.)	p value
Gastric ulcer	Age 35–39	0.19	1.21 (0.88–1.66)	.2385	–0.047	0.95 (0.43–3.75)	1
	Age 40–44	0.358	1.43 (0.97–2.10)	.0677	0.328	1.39 (0.67–7.47)	.267
	Age 45–49	0.421	1.52 (1.04–2.23)	.0296*	0.343	1.41 (0.66–8.42)	.2601
	Age 50–54	0.351	1.42 (1.00–2.02)	.0497*	0.371	1.45 (0.65–9.91)	.247
	Age 55–59	0.363	1.44 (1.06–1.95)	.0191*	0.463	1.59 (0.71–11.18)	.1629
	Age 60–88	0.226	1.25 (0.94–1.68)	.1264	0.274	1.32 (0.59–8.97)	.3542
	Male	0.491	1.63 (1.44–1.85)	<.0001*	0.262	1.30 (1.03–1.68)	.0274*
	H. pylori	0.471	1.60 (1.44–1.79)	<.0001*	1.033	2.81 (2.18–3.74)	<.0001*
Duodenal ulcer	Age 35–39	0.019	1.02 (0.83–1.28)	.8644	0.183	1.20 (0.63–4.61)	.503
	Age 40–44	–0.039	0.96 (0.75–1.28)	.7735	0.222	1.25 (0.59–6.74)	.4359
	Age 45–49	–0.067	0.94 (0.73–1.24)	.6139	0.519	1.68 (0.80–10.0)	.0999
	Age 50–54	–0.122	0.89 (0.70–1.15)	.3295	0.156	1.17 (0.52–8.02)	.5636
	Age 55–59	–0.167	0.85 (0.69–1.07)	.1383	0.111	1.12 (0.49–7.90)	.6513
	Age 60–88	–0.246	0.78 (0.63–0.98)	.0263*	0.168	0.85 (0.36–5.82)	1
	Male	0.147	1.16 (1.04–1.29)	.0081*	0.307	1.36 (1.03–1.86)	.0296*
	H. pylori	0.552	1.74 (1.55–1.95)	<.0001*	1.247	3.48 (2.53–5.06)	<.0001*
Reflux esophagitis	Age 35–39	0.308	1.36 (0.68–2.70)	.3793	0.103	1.11 (0.99–1.26)	.0778
	Age 40–44	0.632	1.88 (0.81–4.34)	.138	0.1671	1.18 (1.03–1.38)	.0158*
	Age 45–49	0.746	2.11 (0.92–4.82)	.0767	0.2394	1.27 (1.10–1.49)	.0009*
	Age 50–54	0.492	1.63 (0.76–3.53)	.2101	0.282	1.33 (1.13–1.57)	.0002*
	Age 55–59	0.555	1.74 (0.90–3.37)	.1001	0.2625	1.30 (1.11–1.55)	.0008*
	Age 60–88	0.401	1.49 (0.79–2.81)	.2138	0.191	1.21 (1.03–1.44)	.0147*
	Male	0.531	1.70 (1.33–2.17)	<.0001*	0.6302	1.88 (1.76–2.01)	<.0001*
	H. pylori	–0.207	0.82 (0.68–0.99)	.0305*	–0.5365	0.59 (0.55–0.63)	<.0001*

Age 20–34, female, and non-infection of H. pylori were respectively references for age, sex, and H. pylori infection in the analyses. *The levels of significance were set at p < .05.

Table 3. Panel data analyses to evaluate variables using the data of 6,452 generally healthy subjects in 1996 and 13,263 generally healthy subjects in 2010.

Acid–related diseases	Variables	Coefficients	Standardised Error	p value
Gastric ulcer	Year 1996	2.237	0.126	<.0001*
	Age 20–39	0.495	0.171	.0022*
	Age 40–49	0.590	0.175	.0003*
	Age 50–59	0.384	0.211	.0675
	Age 60–88	–0.174	0.465	.6181
	Male	0.951	0.119	<.0001*
	H. pylori	1.169	0.104	<.0001*
Duodenal ulcer	Year 1996	2.354	0.146	<.0001*
	Age 20–39	–0.102	0.141	.4912
	Age 40–49	–0.426	0.153	.0068*
	Age 50–59	–0.773	0.219	.0002*
	Age 60–88	–2.065	0.833	.0002*
	Male	0.365	0.109	.0006*
	H. pylori	1.305	0.112	<.0001*
Reflux esophagitis	Year 1996	–1.965	0.098	<.0001*
	Age 20–39	0.342	0.096	.0003*
	Age 40–49	0.417	0.095	<.0001*
	Age 50–59	0.205	0.111	.0611
	Age 60–88	0.309	0.185	.1100
	Male	1.270	0.065	<.0001*
	H. pylori	–1.066	0.068	<.0001*

*The levels of significance were set at p < .05.

Figure 3. Age-period-cohort analysis to evaluate the time trend of reflux esophagitis from 1996 to 2010 (A: age affect, B: period effect, C: cohort effect).