Gastrointestinal tuberculosis is not associated with proton pump inhibitors: A retrospective cohort study

Table 1 Clinical information of the patients who were endoscopically diagnosed with suspicious tuberculosis

	Gender/age	Group1	PPI duration before diagnosis (d)	Reason for endoscopy	Endoscopy findings	Pathology findings	Decision for analysis	Note
1	F/65	2	639	Diarrhea	Scar, cecum	No biopsy	Excluded
2	F/73	1	844	Abdominal pain	Scar, cecum	No biopsy	Excluded
3	F/65	2	1177	Routine check	Scar, cecum	No biopsy	Excluded
4	F/60	1	415	Routine check	Scar, terminal ileum	No biopsy	Excluded	Small bowel resection due to tuberculosis 20 years ago
5	F/64	1	616	Anemia	Scar, descending colon	No biopsy	Excluded
6	F/67	2	56	Abdominal pain	Scar, cecum	No biopsy	Excluded
7	F/55	2	87	Routine check	Scar, cecum	No biopsy	Excluded
8	F/82	2	523	Constipation	Scar, cecum	No biopsy	Excluded
9	F/58	1	65	Lower abdominal pain	Scar, cecum	No biopsy	Excluded
10	F/55	1	612	Routine check	Scar, cecum	No biopsy	Excluded
11	M/52	1	894	Blood-tinged stool	Scar, cecum	No biopsy	Excluded
12	F/61	2	29	Bloating	Scar, cecum	No biopsy	Excluded
13	F/72	1	125	Hematochezia	Ulcers, cecum	Chronic active colitis	Included
14	M/44	1	28	Anemia	Ulcers, cecum/ transverse colon	Non-caseating granuloma, negative PCR2	Included
15	F/63	2	55	Epigastric pain	Ulcer, gastric cardia	Non-caseating granuloma, positive PCR2	Included	Palpable right supraclavicular lymph node
16	M/49	1	7	Melena	Ulcers, terminal ileum	Chronic active ileitis	Excluded
17	M/41	1	574	Loose stool	Ulcers, cecum	Non-caseating granuloma, positive PCR2	Included
18	M/20	1	49	Lower abdominal pain	Ulcers, ileocecal valve	Chronic active colitis	Included
19	F/66	1	1	Melena	Ulcers, terminal ileum	Chronic active ileitis	Excluded
20	F/59	1	224	Lower abdominal pain	Ulcers, ileocecal valve	Chronic active colitis,	Included
21	F/46	1	28	Epigastric pain	Ulcers, mid-esophagus	Non-caseating granuloma, positive PCR2	Included

¹Patients with PPI treatment for three months or less as group 1, and patients with more-than-three-month PPI treatment as group 2;

²Polymerase chain reaction (PCR) for Mycobacterium tuberculosis. PPI: Proton pump inhibitor; M: Male; F: Female.

Table 2 Summary of descriptive statistical analysis n (%)

	Group 1	Group 2
Patients (n)	50  534	11  300
Cases	6 (0.012)	1 (0.009)
Esophageal tuberculosis	1	0
Gastric tuberculosis	0	1
Colonic tuberculosis	5	0
Total follow-up (person-mo)	1  102  947	388  345
Average follow-up (mo)	21.8	34.4
Incidence per 1000 person/yr	0.65	0.03

Table 3 Demographic and clinical characteristics of each group (mean ± SD)

	Group 1	Group 2	P-value
No. of patients	50  534	11  300
Age, yr	54.96 ± 14.50	58.18 ± 13.31	< 0.001
Gender, male (%)	52.5	46.7	< 0.001
PPI duration, d	25.17 ± 21.51	285.78 ± 437.02	< 0.001
Co-morbidities, n (%)
AIDS	75 (0.15)	6 (0.05)	0.011
Cerebrovascular disease	3655 (7.23)	1201 (10.63)	< 0.001
Congestive heart failure	196 (0.39)	71 (0.63)	< 0.001
Chronic pulmonary disease	184 (0.36)	64 (0.57)	0.002
Dementia	332 (0.66)	159 (1.41)	< 0.001
DM	4438 (8.78)	1600 (14.16)	< 0.001
DM without chronic complication	4280 (8.47)	1532 (13.56)	< 0.001
DM with chronic complication	158 (0.31)	68 (0.60)	< 0.001
Liver disease, mild	3182 (6.30)	1475 (13.05)	< 0.001
Hemiplegia or paraplegia	57 (0.11)	8 (0.07)	0.213
Liver disease, moderate or severe	488 (0.97)	205 (1.81)	< 0.001
Any malignancy	62 (0.12)	13 (0.12)	0.833
Metastatic solid tumor	310 (0.61)	69 (0.61)	0.972
Myocardial infarction	598 (1.18)	121 (1.07)	0.313
Peripheral vascular disease	368 (0.73)	114 (1.01)	0.002
Peptic ulcer	7011 (13.88)	1569 (13.88)	0.977
Rheumatologic disease	284 (0.56)	421 (3.73)	< 0.001
Renal disease	498 (0.99)	342 (3.03)	< 0.001
Charlson index	0.50 ± 0.93	0.77 ± 1.14	< 0.001
Score = 0 n (%)	33297 (65.89)	6167 (54.58)	< 0.001
Score = 1 n (%)	15536 (30.75)	4363 (38.61)
Score ≥ 3 n (%)	1699 (3.36)	770 (6.81)
History of admission (%)	29138 (57.66)	6692 (59.22)	0.002
History of ICU admission (%)	1668 (3.30)	352 (3.12)	0.315

PPI: Proton pump inhibitor; AIDS: Acquired immune deficiency syndrome; ICU: Intensive care unit; DM: Diabetes mellitus.

Table 4 Demographic and clinical characteristics of the active-tuberculosis and non-tuberculosis groups (mean ± SD)

	Active tuberculosis	Non-tuberculosis1
No. of patients	7	61  790
Age, yr	50.6 ± 17.7	55.6 ± 14.3
Gender, male (%)	3 (43)	31 803 (51)
PPI duration	47.7 ± 97.9	72.8 ± 213.1
Charlson index	1.29 ± 2.36	0.55 ± 0.97
Score = 0 n (%)	5 (71)	39  459 (64)
Score = 1, 2 n (%)	0 (0)	19  899 (32)
Score ≥ 3 n (%)	2 (29)	2467 (4)
History of admission	6 (86)	35  824 (58)

¹Patients without gastrointestinal tuberculosis irrespective of the temporal relationship with proton pump inhibitor treatment or disease activity. PPI: Proton pump inhibitor.

Table 5 Results of the multivariable analysis using logistic regression

Factor	Relative risk (95%CI)	P-value
PPI exposure
Group 1	Reference 1
Group 2	0.697 (0.083-5.891)	0.74
Age, increase by year	0.972 (0.923-1.023)	0.27
Charlson index, increase by score 1	1.518 (1.040-2.216)	0.03
Sex	1.697 (0.374-7.690)	0.49
History of admission	4.317 (0.501-37.220)	0.18

PPI: Proton pump inhibitor.