. 2020 Jan 9;10(1):e031951. doi: 10.1136/bmjopen-2019-031951

Table 1.

Description of 60 meta-analyses of H. pylori infection and prevalence or incidence of diseases included in umbrella review

Included meta-analyses	Outcomes^¶	HP detection method	Number of studies	Number of participants	Number of cases	Type of metric	Relative risk (95% CI)	P value^*	P value^†	I² (%)	P value^‡	Whether exist publication bias
Cancer outcomes
Xuan et al ¹³	Hepatocellular carcinoma	HP DNA	9 CCS; 1 CSS	522	129	OR	16.52 (6.63 to 41.12)	0.00	0.07	44	0	Yes
Mounika ⁴⁴	Lung cancer	ELISA	5 CCS;1 PNCCS; 1 PCS	17 951	16 244	OR	2.29 (1.34 to 3.91)	0.032	<0.01	83.9	NA	No^§
Xie et al ¹⁸	ESCC in Eastern populations	S; H; R; His ⁺; HpSe ⁺	16 OS	7665	1961	OR	0.66 (0.43 to 0.89)	NA	<0.01	74.5	0.42	No
Xie et al ¹⁸	EAC in the overall population	S; H; U; His ⁺; HpSe ⁺	15 OS	6035	1330	OR	0.59 (0.51 to 0.68)	NA	0.13	29.9	0.37	No
Wang et al ⁵⁸	Colorectal adenomatous polyp	S; H; several	12 CS	2678	1783	OR	1.89 (1.59 to 2.25)	0	0.10	35.9	0.61	No
Xiao et al ¹⁴	Cholangiocarcinoma	PCR; ELISA; WB	10 CCS	489	220	OR	8.88 (3.67 to 21.49)	0	0.02	56	0.01	Yes
Dong and Hao⁷⁵	Colorectal cancer	IgG; UBT; CagA	21 CCS; 2 CSS	182 561	24 295	OR	1.42 (1.38 to 1.46)	0	<0.01	71	0.74	No
Zhou et al ⁷⁴	Laryngeal carcinoma	ELISA; H; PCR	11 CCS	1030	418	OR	2.87 (1.7 to 4.84)	0	0.00	67.1	0.62	No
Liu²⁸	Colon neoplasia	IgG; IgA; UBT; H; CaA	24 CCS; 7 CSS; 2 NCCS	25 897	12 145	OR	1.63 (1.39 to 1.90)	0	<0.01	80	0.14	No
Li et al ¹²	Gastric cancer	WB; Chip; ELISA; neutralisation assay; EIA	10 CCS	1094	664	OR	2.78 (1.98 to 3.89)	0	0.23	22.8	0.1	No
Ma et al ⁴²	Oesophagogastric junction adenocarcinoma	NA	9 CCS; 4 PCS	5547	2893	OR	0.95 (0.06 to 1.36)	0.769	0.00	78	0.61	No
Liu et al ⁴¹	Pancreatic cancer	ELISA	6 NCCS; 2 PCS	44 193	NA	OR	1.09 (0.81 to 1.47)	0.58	<0.01	76	0.59	No
Cardiovascular and cerebrovascular diseases
Pasceri et al ⁴⁷	Ischaemic heart disease	CagA	3 PCS	2140	966	OR	1.26 (1.05 to 1.51)	<0.00001	0.01	53	NA	No^§
Pasceri et al ⁴⁷	Cerebral ischaemia	CagA	4 RCCS	1103	446	OR	2.43 (1.89 to 3.13)	<0.00001	0.43	0	NA	No^§
Wang et al ⁵⁵	Diabetic IHD	S; H	5 CS	1805	469	RR	1.12 (0.95 to 1.32)	0.172	0.14	42.30	0.21	No
Liu et al ¹⁵	Myocardial infarction	NA	19 CSS; 7 PCS	21 960	11 156	OR	1.73 (1.37 to 2.17)	0	0.00	87.9	0.71	No
Chen et al ⁴⁸	Coronary heart disease	NA	12 CSS; 5 PCS; 1 NA	17 514	9165	OR	1.64 (1.22 to 2.23)	0.001	<0.01	90	0.58	No
Saburi et al ⁴³	Atherosclerosis	PCR	4 CCS	222	102	OR	5.98 (0.69 to 51.99)	0.105	0.03	67.6	0.04	Yes
Yan et al ⁶⁵	Arrhythmia	IgG; ¹³C-UBT; UBT	7 CCS	2014	1032	OR	1.80 (1.08 to 2.99)	0.024	<0.001	80	0.28	No
Dong et al ⁷⁶	Carotid intima thickness	NA	9 CCS	1370	694	SMD	0.80 (0.69 to 0.92)	<0.01	0.00	89.7	NA	No^§
Respiratory disorders
Wang et al ⁵⁷	COPD	S; ¹⁴C-UBT	9 CCS	9465	3192	OR	2.25 (1.73 to 2.92)	0	0.00	75.5	0.27	No
Wang et al ⁵⁷	Chronic bronchitis	S; ¹⁴C-UBT	5 CCS	5674	1824	OR	1.57 (1.33 to 1.86)	0	0.04	58.2	0.51	No
Chen et al ¹⁶	Asthma	SA; ELISA; IgG; ¹³C-UBT	8 CCS; 16 CSS	53 947	5648	OR	0.83 (0.74 to 0.94)	0.002	0.00	53.4	0.67	No
Endocrine disease
Upala et al ⁵⁴	Metabolic syndrome	S; R; H; SA; UBT; biopsy	5 CSS; 1 CS	19 771	NA	OR	1.34 (1.17 to 1.53)	NA	<0.01	39	0.92	No
Upala et al ⁵⁴	Fasting blood glucose	S; R; H; SA	11 CSS; 3 CS	7905	NA	MD	2.37 (0.98 to 3.77)	NA	0.04	55	0.92	No
Upala et al ⁵⁴	HDL-C	UBT; biopsy	9 CSS; 3 CS	7701	NA	MD	-2.43 (-3.75 to -1.12)	NA	<0.01	92	0.92	No
Upala et al ⁵⁴	Triglyceride level	S; R; H; SA	8 CSS; 3 CS	7596	NA	MD	8.12 (3.05 to 13.2)	NA	0.04	71	0.92	No
Upala et al ⁵⁴	Systolic blood pressure	UBT; biopsy; culture	5 CSS; 1 CS	7172	NA	MD	2.88 (0.20 to 5.57)	NA	0.01	89	0.92	No
Upala et al ⁵⁴	Body mass index	S; R; H; SA	8 CSS; 2 CS	10 707	NA	MD	0.30 (0.01 to 0.58)	NA	<0.01	57	0.92	No
Upala et al ⁵⁴	HOMA-IR	UBT; biopsy	7 CSS; 3 CS	7935	NA	MD	0.38 (0.03 to 0.73)	NA	0.03	85	0.92	No
Li et al ³⁹	DM	¹³C-UBT; R; ¹⁴C-UBT; SA; biopsy; culture; H	8 CSS; 68 CCS; 3 PCS	57 397	28 542	OR	1.69 (1.47 to 1.95)	0	<0.00001	86	0	Yes
Li et al ³⁹	T2 DM	¹³C-UBT; R; ¹⁴C-UBT; SA; biopsy; culture; H	8 CSS; 57 CCS; 2 PCS	41 684	21 286	OR	2.05 (1.67 to 2.52)	0	<0.00001	89	0	Yes
Li et al ³⁹	T1 DM	¹³C-UBT; R; ¹⁴C-UBT; biopsy; H	1 PCS; 11 CCS	3175	969	OR	1.23 (0.77 to 1.96)	0.499	<0.00001	82	0.46	No
Urological disease
Wang et al ⁵⁶	Diabetic nephropathy	¹³C-UBT; ELISA; H	6 CCS	636	211	OR	1.6 (1.1 to 2.33)	0.018	0.44	0	0.98	No
Wijarnpreecha et al ⁶²	ESRD in adult	A; H; R; UBT; SA; culture	33 CSS	NA	NA	RR	0.71 (0.55 to 0.94)	NA	<0.00001	79	NA	No^§
Digestive disorders
Erőss et al ³²	Barrett’s oesophagus	S; H; UBT; PCR; R; SA	70 CCS	91 656	12 134	OR	0.68 (0.58 to 0.79)	0	0.00	84	<0.001	Yes
Li et al ¹²	Gastric ulcer	WB; Chip; ELISA; neutralisation assay; EIA	8 CCS	517	260	OR	1.64 (1.02 to 2.62)	0.042	0.26	20.8	0.96	No
Li et al ¹²	Duodenal ulcer	WB; Chip; ELISA; neutralisation assay; EIA	17 CCS	2359	1333	OR	2.06 (1.50 to 2.84)	0	0.01	51.3	0.63	No
Cremonini et al ³⁰	GERD in population with HP-negative status	R; S; biopsy; H; UBT; Gram stain; culture; H&E; Giemsa stain	14 CCS	2010	1683	OR	1.34 (1.15 to 1.55)	0	<0.001	NA	NA	No^§
Weck and Brenner¹¹	Chronic atrophic gastritis	NA	34 OS	7726	5048	OR	6.37 (4.01 to 10.11)	0	0.00	91.2	0.01	Yes
Zhou et al ⁷³	Biliary lithiasis	ELISA; PCR; culture	13 CCS	1333	432	OR	2.59 (1.21 to 5.55)	0.014	<0.0001	69.5	0.18	No
Shiota et al ¹⁰	Peptic ulcer disease	PCR	42 CCS	4601	2524	OR	1.25 (1.09 to 1.44)	0.002	0.39	4.6	0.78	No
Jiang et al ³⁷	Ammonia levels in cirrhotic patients	¹⁴C-UBT; R; H; culture; IgG	6 OS	396	632	SMD	0.34 (0.21 to 0.47)	NA	0.12	42.1	0.11	No
Ford et al ⁹	Dyspepsia	NA	13 CSS	25 305	9010	OR	1.18 (1.04 to 1.33)	NA	<0.001	63	0.3	No
Feng et al ³³	Alcoholic cirrhosis in all population	R; UBT; H; ELISA	8 CCS	14 226	10053	OR	0.82 (0.35 to 1.91)	0.648	0.00	84.5	0.67	No
Feng et al ³³	Alcoholic cirrhosis in European	R; H; ELISA	3 CCS	1171	516	OR	2.14 (1.19 to 3.86)	0.011	0.31	15.5	0.74	No
Wu et al ¹⁷	Inflammatory bowel disease	IgG; UBT; H; culture	10 OS	3116	1202	RR	0.48 (0.43 to 0.54)	0	0.25	21	0.2	No
Wang et al ⁶⁰	Chronic hepatitis C	PCR; S	12 CCS	3826	2185	OR	2.93 (2.30 to 3.75)	0	0.05	45	0.31	No
Wang et al ⁵⁹	Chronic hepatitis B	S	15 CCS	5129	2845	OR	3.17 (2.38 to 4.22)	0	0.00	77.9	0.02	Yes
Wijarnpreecha et al ⁶³	NAFLD	EIA; IgG; ¹⁴C-UBT; H; S; SA	5 CSS; 1 CCS	38 594	NA	OR	1.21 (1.07 to 1.37)	0.002	0.08	49	NA	No^§
Cen et al ²⁷	Chronic cholecystitis and cholelithiasis	H; PCR; culture	18 CCS	1544	NA	OR	3.02 (1.90 to 4.82)	NA	0.21	20.1	0.43	No
Shah et al ⁴⁹	Eosinophilic oesophagitis	Biopsy; R; H; IgG; ELISA; EIA; H&E; SA; ¹³C-UBT	5 CCS; 3 CS or CCS	371 274	26 442	OR	0.63 (0.51 to 0.78)	0.00	0.02	57.9	0.77	No
Shah et al ⁴⁹	Oesophageal eosinophilia	Biopsy; R; H; IgG; ELISA; EIA; H&E; SA; ¹³C-UBT	5 CCS; 6 CS or CCS	377 976	28 007	OR	0.64 (0.52 to 0.78)	0.00	0.00	69.4	0.7	No
Neurocognitive disorders
Wang et al ⁵⁵	Diabetic neuropathy	S; H	5 CS	1607	520	RR	1.20 (1.03 to 1.40)	0.018	0.29	19.1	0.99	No
Wang et al ⁶¹	Ischaemic stroke	IgG; CagA; C-UBT	13 CCS	4041	NA	OR	1.60 (1.21 to 2.11)	NA	0.00	65.2	0.01	Yes
Yu et al ⁷⁰	Stroke	S	6 CS; 4 CCS	166 041	1769	OR	0.96 (0.78 to 1.14)	NA	0.03	48	0.68	No
Shindler-Itskovitch et al ⁵¹	Dementia	Biopsy; IgG; IgA; R; H; CagA	1 CS; 6 CCS	86 606	NA	OR	1.71 (1.17 to 2.49)	0.01	<0.001	76.1	0.33	No
Shen et al ⁵⁰	Parkinson’s disease	ELISA; PCR; ¹³C-UBT; H; prescriptions for HP eradication drug	6 CCS; 2 CSS	28 201	1101	OR	1.59 (1.37 to 1.85)	0	0.55	0	0.02	Yes
Pregnancy-related disorders
Ng et al ⁴⁵	Hyperemesis gravidarum	Biopsy; H; ELISA; IgG; CagA; EIA; ¹³C-UBT; SA	33 CCS; 4 CSS; 1 CS	10 289	NA	OR	1.35 (1.16 to 1.54)	<0.01	0.06	28	0.76	No
Zhan et al ⁷²	Pre-eclampsia	ELISA; CLIA; Heli‐Blot assay; SA; UBT; WB	3 CS; 12 CCS; 1 CSS	10 402	1077	OR	2.51 (1.18 to 3.34)	0	0.00	63	0.02	Yes
Zhan et al ⁷²	Fetal growth restriction	Heli‐Blot assay; ELISA; SA	3 CCS; 2 CS	6009	202	OR	2.28 (1.21 to 4.32)	0.011	0.02	66	0.17	No
Zhan et al ⁷²	Gestational DM	ELISA; SA; WB; UBT	2 CCS; 3 CS	3697	270	OR	2.03 (1.56 to 2.64)	0	0.81	0	0.77	No
Zhan et al ⁷²	Spontaneous abortion	ELISA; SA	2 CS; 3 CCS; 1 CSS	5909	226	OR	1.5 (1.05 to 2.14)	0.024	0.23	27	0.76	No
Zhan et al ⁷²	Birth defect	ELISA; CLIA	1 CS; 2 CCS	737	132	OR	1.63 (1.05 to 2.54)	0.031	0.48	0	0.14	No
Zhan et al ⁷²	Stillbirth	SA; ELISA	1 CS; 1 CCS	3008	28	OR	2.53 (0.79 to 8.13)	0.118	0.61	0	0.79	No
Zhan et al ⁷²	Low birth weight	NA	7 CS or CCS	10 121	NA	OR	1.35 (0.88 to 2.08)	NA	0.16	72	NA	Unclear
Zhan et al ⁷²	Premature delivery	NA	8 CS or CCS	12 356	NA	OR	1.35 (0.86 to 2.12)	NA	0.18	70	NA	Unclear
Ophthalmic diseases
Wang et al ⁵⁵	Diabetic retinopathy	S; H	7 CS	1815	406	RR	1.32 (0.97 to 1.80)	0.058	0.04	55	0.27	No
Zeng et al ⁷¹	Open-angle glaucoma	H; IgG; ¹³C-UBT	18 CCS	1580	695	OR	2.08 (1.42 to 3.04)	NA	<0.001	63.6	0.36	No
Thyroid disease
Hou et al ⁶⁷	Autoimmune thyroid diseases	ELISA; WB; UBT; SA	15 CCS	3046	2408	OR	2.25 (1.72 to 2.93)	0	0.00	61.6	0.68	No
Hou et al ⁶⁷	Grave’s disease	ELISA; SA; UBT	5 CCS	917	498	OR	2.78 (1.68 to 4.61)	0	0.07	53.4	1.51	No
Hou et al ⁶⁷	Hashimoto’s thyroiditis	ELISA; SA; UBT; NR	8 CCS	1594	872	OR	2.16 (1.44 to 3.23)	0	0.00	68.2	0.51	No
Haematological disorders
Hudak et al ³⁵	Iron deficiency anaemia	R; H; ¹³C-UBT; ¹⁴C-UBT; IgG; SA; IgA; gastroscopy	11 CSS; 3 CCS	15 905	NA	OR	1.72 (1.23 to 2.42)	NA	0.00	61.5	0.38	No
Hudak et al ³⁵	Iron deficiency		30 CSS	23 521	NA	OR	1.33 (1.15 to 1.54)	NA	0.01	41.1	0.49	No
Hudak et al ³⁵	Anaemia		23 CSS	11 622	NA	OR	1.15 (1.00 to 1.32)	NA	0.01	NA	0.81	No
Other outcomes
Nweneka and Prentice⁴⁶	Circulating ghrelin levels	UBT; ELISA; S; H; culture; R; PCR	7 CS; 11 CSS; 6 CCS	956	1288	SMD	−0.42 (−0.57 to −0.27)	<0.00001	0.00	59	0.12	No
Xiong et al ⁶⁴	Henoch-Schonlein purpura	R; UBT; IgG; H. pylori antigen	10 CCS	1309	500	OR	3.46 (2.68 to 4.47)	0	0.06	46	0.03	Yes
Su et al ⁵²	Migraine	¹³C-UBT; ELISA; biopsy	5 CCS or CSS	903	355	OR	1.92 (1.05 to 3.51)	0.033	0.00	77.4	0.08	yes
Li et al ⁴⁰	Recurrent aphthous stomatitis	PCR; UBT	7 CCS	510	154	OR	1.85 (1.24 to 2.74)	0.002	0.21	28.5	0.49	No
Taye et al ⁵³	Atopy	H; IgG; ELISA; UBT; SA; IgA	2 CS; 3 CCS; 11 CSS	10 968	NA	OR	0.82 (0.73 to 0.91)	<0.01	0.66	0	0.85	No
Hwang et al ³⁶	Chronic tonsillitis	R; PCR; culture; CLO	6 OS	436	NA	OR	1.99 (0.91 to 4.37)	0.09	0.06	53.6	0.42	No
Gu et al ³⁴	Chronic urticaria	ELISA; UBT; S; H; IgG	16 CCS	2200	984	OR	1.66 (1.12 to 2.45)	0.022	<0.0001	66	0.01	Yes
Yao et al ⁶⁶	Multiple sclerosis	ELISA; WB; CIA IF	9 CCS	2806	782	OR	0.73 (0.56 to 0.96)	0	0.05	48	0.07	yes
Dou et al ³¹	Halitosis	R; H; BUT; culture; PCR; Gram stain; ELISA; SA; endoscopy; CLO	6 CCS;1 CSS	2312	467	OR	4.03 (1.41 to 11.5)	0.009	<0.0001	89	0.05	Yes
Jørgensen et al ³⁸	Rosacea	NA	14 OS	2455	1268	OR	1.74 (1.03 to 2.93)	0.039	0.00	85.6	0.09	yes
Chen et al ²⁹	Sjogren’s syndrome	Biopsy; ELISA; IgG	9 CCS	2018	1054	OR	1.19 (1.01 to 1.41)	0.033	0.86	0	0.77	No
Yong et al ⁶⁸	Psoriasis	IgG; ELISA; UBT; SA	4 CSS; 3 PCS; 2 CCS	1546	728	OR	1.58 (1.02 to 2.46)	0.041	0.00	64	0.03	Yes
Yong et al ⁶⁹	Systemic sclerosis	IgG; ELISA; IgM; ¹³C-UBT; R	7 CSS; 1 PCS	1446	749	OR	2.11 (1.62 to 2.76)	0.00	0.33	13	0.84	No

*p value of significance level.

†p value of Q test.

‡p value for Egger’s test.

§The publication bias was assessed using funnel plot.

¶ prevalence or incidence unless otherwise specified.

A, antibody; CagA, cytotoxin-associated gene A; CCS, case–control study; CI, confidence intervals; CLIA, chemiluminescent immunoassay; CLO, Campylobacter-like organism test; COPD, chronic obstructive pulmonary disease; CS, cohort study; CSS, cross-sectional study; DM, diabetes mellitus; EAC, oesophageal adenocarcinoma; EIA, enzyme immunoassay; ESCC, oesophageal squamous cell carcinoma; ESRD, end-stage renal disease; GERD, gastro-oesophageal reflux disease; H, histology; HDL-C, high-density lipoprotein cholesterol; H&E, Hematoxylin and eosin stain; His +, positive histological examination of tissue samples; HOMA-IR, homeostatic model assessment of insulin resistance; HP, H. pylori; HpSe ⁺, seropositivity for antibodies to whole cell; IF, immunofluorescence; IHD, ischaemic heart disease; MD, mean difference; NA, not applicable; NAFLD, non-alcoholic fatty liver disease; NCCS, nested case-control study; NR, not reported; OS, observational study; PCR, polymerase chain reaction; PCS, prospective cohort study; PNCS, prospective nested cohort study; R, rapid urease test; RCCS, retrospective case–control study; RCSS, retrospective cross-sectional study; RR, relative rate; S, serology; SA, stool antigen; several, several methods; SMD, standard mean difference; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; U, rapid urease test; UBT, urea breath test; WB, western blot.