Helicobacter pylori infection is associated with the risk and phenotypes of cholelithiasis: A multi-center study and meta-analysis

Table 1 The characteristics of participants

	Cholelithiasis group	Control group	P value
H. pylori+ (n)	974	16970	0.001
H. pylori- (n)	2864	56926
Male (n)	2287	45872	0.002
Female (n)	1551	28024
Age (years), mean ± SD	51.01 ± 11.95	43.61 ± 12.06	< 0.001
Total bilirubin (μmol/L), mean ± SD	13.1 ± 5.7	13.2 ± 5.5	0.627
Direct bilirubin (μmol/L), mean ± SD	3.8 ± 1.9	3.8 ± 2.4	0.665
Total bile acid (μmol/L), mean ± SD	4.7 ± 7.0	4.0 ± 5.3	< 0.001
Total cholesterol (mmol/L), mean ± SD	5.06 ± 0.99	5.00 ± 0.97	0.001
Triglyceride (mmol/L), mean ± SD	1.98 ± 1.81	1.85 ± 1.84	< 0.001
HDL-cholesterol (mmol/L), mean ± SD	1.28 ± 0.27	1.32 ± 0.30	< 0.001
LDL-cholesterol (mmol/L), mean ± SD	2.89 ± 0.85	2.85 ± 0.82	0.002

H. pylori: Helicobacter pylori; H. pylori+: Helicobacter pylori-positive; H. pylori-: Helicobacter pylori-negative; LDL: Low-density lipoprotein; HDL: High-density lipoprotein.

Table 2 The results of multivariable logistic regression on factors associated with cholelithiasis

	OR (95%CI)	P value
H. pylori infection	1.103 (1.001-1.216)	0.049
Age > 60 years	2.031 (1.821-2.266)	< 0.001
Total bile acid (μmol/L)	1.017 (1.011-1.023)	< 0.001
HDL-cholesterol (mmol/L)	0.361 (0.296-0.441)	< 0.001
Total bilirubin (μmol/L)	1.027 (1.012-1.043)	0.001
Direct bilirubin (μmol/L)	0.938 (0.897-0.982)	0.006
Total cholesterol (mmol/L)	1.095 (1.038-1.154)	0.001
Triglyceride (mmol/L)	0.969 (0.942-0.997)	0.032
Female gender	1.493 (1.355-1.644)	< 0.001

H. pylori: Helicobacter pylori; HDL: High-density lipoprotein; OR: Odds ratio; CI: Confidence interval.

Table 3 The results of phenotype analysis and parameters comparison

	H. pylori+	H. pylori-	P value
Phenotype
Hepatolithiasis (n)	21	53	0.546
Cholecystolithiasis (n)	942	2782
Parameters
Total bilirubin (μmol/L)	12.5 ± 5.2	13.2± 5.2	< 0.001
Direct bilirubin (μmol/L)	3.6 ± 1.6	3.9 ± 1.6	< 0.001
Total bile acid (μmol/L)	3.8± 5.1	3.6 ± 4.3	0.055
Total cholesterol (mmol/L)	4.84 ± 0.90	4.77 ± 0.86	< 0.001
Triglyceride (mmol/L)	1.26 ± 0.94	1.27 ± 1.00	0.489
HDL-cholesterol (mmol/L)	1.41 ± 0.29	1.41 ± 0.29	0.994
LDL-cholesterol (mmol/L)	2.83 ± 0.76	2.76 ± 0.73	< 0.001

H. pylori: Helicobacter pylori; H. pylori+: Helicobacter pylori-positive; H. pylori-: Helicobacter pylori-negative; LDL: Low-density lipoprotein; HDL: High-density lipoprotein.

Table 4 The characteristics of included studies

Ref.	Region	Cholelithiasis type	Sample source for H. pylori	Method for H. pylori	No. of cholelithiasis	No. of non-cholelithiasis
Loosen et al[54], 2024	Germany	Cholelithiasis	Medical records	Medical records	2394	34669
Sermet[55], 2024	Turkey	Cholelithiasis	Gastric biopsy	Histology	8753	5565
Azimirad et al[12], 2023	Iran	Common bile duct stones	Bile	16S rDNA sequencing	9	6
Cen et al[15], 2023	China	Gallstones	Breath	13C/14C-UBT	60	1132
Hashimoto et al[56], 2022	Japan	Gallstones	Serum	Antibody test	14	47
Higashizono et al[57], 2022	Japan	Gallstones	Medical records	Medical records	23843	588087
Jahantab et al[58], 2021	Iran	Cholelithiasis	Bile	Antigen test	132	/
Kucuk and Küçük[13], 2021	Turkey	Gallstones	Gallbladder	Giemsa	131	82
Zhang et al[16], 2020	China	Gallstones	Breath	13C/14C-UBT	935	935
Ari et al[59], 2019	Turkey	Gallstones	Gallbladder	Giemsa	27	33
Cherif et al[60], 2019	Morocco	Bile duct stones	Gallbladder	IHC	48	41
Kerawala et al[61], 2019	Pakistan	Gallstones	Serum	Antibody test	45	45
Fatemi et al[62], 2018	Iran	Gallstones	Serum	ELISA	52	25
Xu et al[63], 2018	China	Gallstones	Serum	ELISA	995	16976
Seyyedmajidi[64], 2017	Iran	Common bile duct stones	Bile	PCR	150	/
Choi et al[65], 2016	Korea	Gallstones	Gastric biopsy	CLO test	39	607
Dar et al[66], 2016	India	Hepatobiliary lithiasis	Bile	PCR	50	25
Patnayak et al[67], 2016	India	Gallstones	Gallbladder	IHC	40	5
Tajeddin et al[68], 2016	Iran	Gallstones	Bile	PCR	74	28
Guraya et al[69], 2015	Saudi Arabia	Gallstones	Serum	ELISA	95	30
Zhang et al[70], 2015	China	Gallstones	Breath	13C-UBT	882	9134
Murphy et al[71], 2014	Finland	Gallstones	Serum	Serology	10	214
Takahashi et al[50], 2014	Japan	Gallstones	Serum	ELISA	694	14857
Zhou et al[36], 2013	China	Gallstones	Gallbladder	PCR	267	59
Boonyanugomol et al[72], 2012	Thailand	Cholelithiasis	Bile	PCR	53	103
Jahani Sherafat et al[73], 2012	Iran	Gallstones	Bile	PCR	74	28
Yakoob et al[74], 2011	Pakistan	Cholelithiasis	Gallbladder/bile	IHC/PCR	89	49
Bostanoğlu et al[75], 2010	Turkey	Calculous cholecystitis	Gallbladder/bile/stone	PCR	47	3
Lee et al[14], 2010	Korea	Gallstones	Gallstone	PCR	22	/
Popović et al[76], 2010	Serbia	Cholelithiasis	Blood	Serology	3	204
Griniatsos et al[77], 2009	Greece	Cholesterol gallstones	Gallbladder	Histology	89	42
Yucebilgili et al[78], 2009	Turkey	Cholelithiasis	Gallbladder	PCR	41	27
Misra et al[79], 2007	India	Gallstones	Gallbladder	Histology	116	45
Abayli et al[80], 2005	Turkey	Mixed cholesterol gallstones	Gallbladder	HE	77	20
Kobayashi et al[81], 2005	Japan	Cholelithiasis	Bile	PCR	30	27
Farshad et al[82], 2004	Iran	Gallstones	Gallstone/bile	PCR	33	40
Chen et al[83], 2003	New Zealand	Gallstones	Gallbladder	PCR	70	52
Silva et al[84], 2003	Brazil	Cholelithiasis	Gallbladder	PCR	46	18
Bulajic et al[43], 2002	Yugoslavia	Gallstones	Bile	PCR	63	26
Bulajic et al[85], 2002	Yugoslavia	Biliary lithiasis	Bile	PCR	65	7
Fukuda et al[86], 2002	Japan	Cholecystolithiasis	Gallbladder/bile	PCR	15	23
Harada et al[87], 2001	Japan	Cholelithiasis	Bile/biliary epithelium	PCR	53	16
Myung et al[88], 2000	Korea	Hepatolithiasis	Serum	ELISA	30	13
Roe et al[89], 1999	Korea	Intrahepatic duct stones	Bile	PCR	11	21
Figura et al[90], 1998	Italy	Gallstones	Serum	ELISA	112	112
Kochhar et al[91], 1993	India	Common bile duct stone	Gastric biopsy	Giemsa	3	15
Kellosalo et al[92], 1991	Finland	Gallstones	Gastric biopsy	WS	47	41

H. pylori: Helicobacter pylori; WS: Warthin-Starry silver stain; ELISA: Enzyme-Linked Immunosorbent Assay; PCR: Polymerase chain reaction; HE: Hematoxylin and eosin staining; 13C/14C-UBT: 13C or 14C urease breath test; IHC: Immunohistochemistry; CLO: Campylobacter-like organism.