Bidirectional associations among gallstone disease, non-alcoholic fatty liver disease, kidney stone disease

Table 1 Demographic and clinical characteristics distribution of the included subjects, n (%)/mean ± SD

Characteristics	Beijing	Chongqing-Urban area	Chongqing-Rural area	Tianjin
	n = 81158	n = 170038	n = 372289	n = 10940
Age (year)	43.88 ± 13.97	41.79 ± 13.45	43.97 ± 13.14	43.47 ± 13.63
Sex
Male	48041 (59.2)	93071 (54.7)	198769 (53.4)	4814 (44.0)
Female	33117 (40.8)	76967 (45.3)	173520 (46.6)	6126 (56.0)
BMI (kg/m2)
≤ 18.5	1733 (2.1)	8465 (5.0)	12602 (3.4)
18.5-24.0	27211 (33.5)	81859 (48.1)	168766 (45.3)
24.0-28.0	29881 (36.8)	48026 (28.2)	129141 (34.7)
≥ 28.0	15310 (18.9)	12221 (7.2)	40787 (11.0)
Missing	7023 (8.7)	19467 (11.4)	20993 (5.6)
Non-alcoholic fatty liver disease
Yes	29415 (36.2)	42957 (25.3)	100830 (27.1)	3454 (31.6)
No	51211 (63.1)	127080 (74.7)	271350 (72.9)	7486 (68.4)
Missing	532 (0.7)	1 (0.0)	109 (0.0)	0 (0.0)
Kidney stone disease
Yes	2749 (3.4)	6957 (4.1)	11672 (3.1)	255 (2.3)
No	77935 (96.0)	163081 (95.9)	360508 (96.9)	10685 (97.7)
Missing	474 (0.6)	0 (0.0)	109 (0.0)	0 (0.0)
Gallstone disease
Yes	4333 (5.3)	12518 (7.4)	32367 (8.7)	507 (4.6)
No	76438 (94.1)	157520 (92.6)	339813 (91.3)	10433 (95.4)
Missing	477 (0.6)	0 (0.0)	109 (0.0)	0 (0.0)
Gallstones
Yes	3120 (3.8)	6173 (3.6)	14598 (3.9)	361 (3.3)
No	77817 (95.9)	163865 (96.4)	357582 (96.1)	10579 (96.7)
Missing	221 (0.3)	0 (0.0)	109 (0.0)	0 (0.0)
Cholecystectomy
Yes	1213 (1.5)	6345 (3.7)	17769 (4.8)	146 (1.3)
No	79468 (97.9)	163693 (96.3)	354411 (95.2)	10794 (98.7)
Missing	477 (0.6)	0 (0.0)	109 (0.0)	0 (0.0)
Hypertension
Yes	21194 (26.1)	31608 (18.6)	256137 (68.8)	2838 (25.9)
No	57783 (71.2)	120006 (70.6)	71490 (19.2)	7486 (68.4)
Missing	2181 (2.7)	18424 (10.8)	44662 (12.0)	616 (5.6)
HDL-C (mmol/L)
≤ 0.89	402 (0.5)	6423 (3.8)	11177 (3.0)
0.90-2.00	53344 (65.7)	144041 (84.7)	308084 (82.8)
≥ 2.01	24685 (30.4)	8654 (5.1)	15490 (4.2)
Missing	2727 (3.4)	10920 (6.4)	37538 (10.0)
GLU (mmol/L)
≤ 6.09	66804 (82.3)	142049 (83.5)	307884 (82.7)	9101 (83.2)
6.10-7.09	4551 (5.6)	9344 (5.5)	29550 (7.9)	1022 (9.3)
≥ 7.10	7539 (9.3)	8680 (5.1)	20822 (5.6)	718 (6.6)
Missing	2264 (2.8)	9965 (5.9)	14033 (3.8)	99 (0.9)
TC (mmol/L)1
Lower	402 (0.5)	556 (0.3)	3346 (0.9)	10 (0.1)
Normal	53344 (65.7)	106310 (62.5)	273989 (73.6)	5145 (47.0)
Higher	24685 (30.4)	54298 (31.9)	75048 (20.2)	5686 (52.0)
Missing	2727(3.4)	8874 (5.2)	19906 (5.3)	99 (0.9)
TG (mmol/L)1
Lower	398 (0.5)	172 (0.1)	460 (0.1)	10 (0.1)
Normal	56178 (69.2)	113472 (66.8)	238867 (64.2)	8870 (81.1)
Higher	21854 (26.9)	47520 (27.9)	113047 (30.4)	1961 (17.9)
Missing	2728 (3.4)	8874 (5.2)	19915 (5.3)	99 (0.9)
ALT (u/L)1
Low	69977 (86.2)	137996 (81.2)	31304 (84.1)	9365 (85.6)
High	8965 (11.0)	24353 (14.3)	48992 (13.2)	1475 (13.5)
Missing	2216 (2.7)	7689 (4.5)	10250 (2.8)	100 (0.9)
UA (u/L)1
Low	61613 (75.9)	93931 (55.2)	272306 (73.1)	9500 (86.8)
High	16672 (20.6)	67150 (39.5)	55310 (14.9)	1341 (12.3)
Missing	2873 (3.5)	8957 (5.3)	44673 (12.0)	99 (0.9)

¹The characteristics with different criterion.

ALT: Alanine aminotransferase; BMI: Body mass index; GLU: Glucose; HDL-C: High-density lipoprotein cholesterol; KSD: Kidney stone disease; TC: Total cholesterol; TG: Triglycerides; UA: Uric acid.

Table 2 Pooled results for meta-analyses assessing the bidirectional associations among gallstone disease, kidney stone disease, non-alcoholic fatty liver disease

Type of groups	Sample size	Pooled OR (95%CI)	I2 (%)	P for Begg’s test	P for Egger’s test	No. of filled data	Trim and fill adjusted pooled OR (95%CI)	Number of studies
KSD-GSD
Overall	363960	1.44 (1.14-1.81)	94.4	1.000	0.741	0	1.44 (1.14-1.81)	5
Subgroups
Geographic background
America	245690	1.32 (1.15-1.52)	82.7	0.296	0.276	0	1.32 (1.15-1.52)	3
Asia	118270	1.71 (0.97-3.02)	37.2	1.000	NA	0	1.71 (0.97-3.02)	2
Type of GSD
KSD-cholecystectomy	97185	1.17 (1.06-1.29)	NA	NA	NA	0	1.17 (1.06-1.29)	1
KSD-gallstones	118270	1.71 (0.97-3.02)	37.2	1.000	NA	0	1.71 (0.97-3.02)	2
Study design						0
Cross-sectional study	195	0.94 (0.30-2.97)	NA	NA	NA	0	0.94 (0.30-2.97)	1
Cohort study	363765	1.46 (1.15-1.85)	95.7	1.000	0.383	0	1.46 (1.15-1.85)	4
Study quality
Moderate	195	0.94 (0.30-2.97)	NA	NA	NA	0	0.94 (0.30-2.97)	1
High	363765	1.46 (1.15-1.85)	95.7	1.000	0.383	0	1.46 (1.15-1.85)	4
GSD-KSD
Overall	496094	1.50 (1.32-1.71)	84.7	1.000	0.210	0	1.50 (1.32-1.71)	7
Subgroups
Geographic background
America	266252	1.34 (1.24-1.45)	0.0	0.462	0.847	0	1.34 (1.24-1.45)	5
Asia	229842	1.79 (1.56-2.05)	82.4	1.000	NA	0	1.79 (1.56-2.05)	2
Type of GSD
Cholecystectomy-KSD	95537	1.26 (1.10-1.45)	NA	NA	NA	0	1.26 (1.10-1.45)	1
Gallstones-KSD	229842	1.79 (1.56-2.05)	82.4	1.000	NA	0	1.79 (1.56-2.05)	2
Study design
Cross-sectional study	12161	1.54 (1.31-1.81)	NA	NA	NA	0	1.54 (1.31-1.81)	1
Cohort study	483933	1.49 (1.28-1.73)	87.1	1.000	0.269	0	1.49 (1.28-1.73)	6
Study quality
Moderate	12161	1.54 (1.31-1.81)	NA	NA	NA	0	1.54 (1.31-1.81)	1
High	483933	1.49 (1.28-1.73)	87.1	1.000	0.269	0	1.49 (1.28-1.73)	6
NAFLD-GSD
Overall	352255	1.38 (1.25-1.54)	56.3	0.005	0.014	3	1.26 (1.12-1.41)	11
Subgroups
Geographic background
Asia	351249	1.35 (1.21-1.51)	57.8	0.009	0.057	2	1.26 (1.11-1.43)	9
Europe	1006	1.60 (1.24-2.06)	1.9	1.000	NA	0	1.60 (1.24-2.06)	2
Type of GSD
NAFLD-cholecystectomy	283446	1.10 (0.96-1.26)	NA	NA	NA	0	1.10 (0.96-1.26)	1
NAFLD-gallstones	326887	1.43 (1.22-1.67)	67.3	0.060	0.083	0	1.43 (1.22-1.67)	6
Study design
Cross-sectional study	56313	1.49 (1.26-1.76)	62.0	0.035	0.017	2	1.27 (1.06-1.52)	8
Cohort study	295942	1.25 (1.18-1.34)	0.0	0.296	0.517	0	1.25 (1.18-1.34)	3
Study quality
Moderate	57609	1.47 (1.27-1.69)	56.9	0.029	0.012	2	1.32 (1.12-1.55)	9
High	294646	1.24 (1.16-1.32)	0.0	1.000	NA	0	1.24 (1.16-1.32)	2
GSD-NAFLD
Overall	474151	1.29 (1.14-1.47)	66.7	0.230	0.060	0	1.29 (1.14-1.47)	7
Subgroups
Geographic background
America	12232	1.56 (1.27-1.91)	NA	NA	NA	0	1.56 (1.27-1.91)	1
Asia	457130	1.19 (1.07-1.33)	54.5	0.089	0.060	0	1.19 (1.07-1.33)	4
Europe	4789	1.39 (0.82-2.35)	58.7	1.000	NA	0	1.39 (0.82-2.35)	2
Type of GSD
Cholecystectomy-NAFLD	252772	1.37 (1.00-1.87)	86.0	0.308	0.590	0	1.37 (1.00-1.87)	4
Gallstones-NAFLD	248690	1.15 (1.08-1.22)	0.0	0.296	0.681	0	1.15 (1.08-1.22)	3
Study design
Cross-sectional study	34869	1.46 (1.17-1.83)	0.589	0.462	0.392	0	1.46 (1.17-1.83)	5
Cohort study	439282	1.15 (1.08-1.22)	0.0	1.000	NA	0	1.15 (1.08-1.22)	2
Study quality
Moderate	34869	1.46 (1.17-1.83)	0.589	0.462	0.392	0	1.46 (1.17-1.83)	5
High	439282	1.29 (1.14-1.47)	0.0	1.000	NA	0	1.29 (1.14-1.47)	2
NAFLD-KSD
Overall	439933	1.37 (1.04-1.81)	86.1	0.099	0.354	0	1.37 (1.04-1.81)	7
Subgroups
Geographic background
America	11859	1.29 (1.02-1.63)	NA	NA	NA	0	1.29 (1.02-1.63)	1
Asia	428074	1.41 (1.00-1.99)	88.3	0.133	0.429	0	1.41 (1.00-1.99)	6
Study type
Cross-sectional study	22777	1.64 (0.94-2.88)	88.2	0.221	0.548	0	1.64 (0.94-2.88)	5
Cohort study	417156	1.08 (0.90-1.30)	68.4	1.000	NA	0	1.08 (0.90-1.30)	2
Study quality
Moderate	22777	1.64 (0.94-2.88)	88.2	0.221	0.548	0	1.64 (0.94-2.88)	5
High	417156	1.08 (0.90-1.30)	68.4	1.000	NA	0	1.08 (0.90-1.30)	2

GSD: Gallstone disease; KSD: Kidney stone disease; NAFLD: Non-alcoholic fatty liver disease; OR: Odds ratio.