Increased Risk of Pyogenic Liver Abscess after Endoscopic Sphincterotomy for Treatment of Choledocholithiasis

Figures & data

Figure 1 Schematic flowchart of the study design.

Abbreviations: ERCP, endoscopic retrograde cholangio-pancreatography; ES, endoscopic sphincterotomy.

Table 1 Patient’s Characteristics Prior to the Index Hospitalization between the Two Groups

	ES Group (n=7,111)	Other ERCP (n=4,586)	p-value
Age at the index date, years	64.70±16.28	63.87±15.22	0.0051
Sex, n (%)			0.1015
Male	3,658 (51.44)	2,288 (49.89)
Female	3,453 (48.56)	2,298 (50.11)
Covariate, n (%)
Liver cirrhosis	293 (4.12)	285 (6.21)	<0.0001
Chronic kidney disease	1,124 (15.81)	698 (15.22)	0.3933
Diabetes mellitus	1,765 (24.82)	1,060 (23.11)	0.0352
Disorders of lipoid metabolism	1,143 (16.07)	648 (14.13)	0.0044
CAD	611 (8.59)	388 (8.46)	0.8034
HCVD	3,126 (43.96)	1,700 (37.07)	<0.0001
Baseline Medication
NSAID/COX-2 inhibitors	3,302 (46.44)	1,743 (38.01)	<0.0001
Aspirin	773 (10.87)	392 (8.55)	<0.0001
Clopidogrel	262 (3.68)	137 (2.99)	0.0426
Warfarin	51 (0.72)	44 (0.96)	0.1541
Dipyridamole	67 (0.94)	30 (0.65)	0.0935
Cilostazol	68 (0.96)	31 (0.68)	0.1062
Systemic steroids	322 (4.53)	184 (4.01)	0.1805
Anti-hypertensives
Anti-hypertensives	127 (1.79)	70 (1.53)	0.2868
Diuretics	657 (9.24)	415 (9.05)	0.7282
Beta blocking agents	784 (11.03)	440 (9.59)	0.0136
Calcium channel blockers	1,080 (15.19)	587 (12.8)	0.0003
ACEI/ARB	1,119 (15.74)	669 (14.59)	0.0920
Ursodeoxycholic acid	362 (5.09)	324 (7.06)	<0.0001
Statin	681 (9.58)	374 (8.16)	0.0088
Other Lipid lowering drugs	199 (2.8)	105 (2.29)	0.0912
Concomitant covariate (during follow-up)
ERBD	399 (5.61)	324 (7.06)	0.0014
EPBD	385 (5.41)	278 (6.06)	0.1391
Surgery for hepato-pancreato-biliary system	691 (9.72)	612 (13.34)	<0.0001
Cholecystectomy	1,072 (15.08)	545 (11.88)	<0.0001
Hepatobiliary malignancy	403 (5.67)	378 (8.24)	<0.0001

Notes: Continuous data are presented as mean±SD; Number of event are presented as n (%).

Abbreviations: CAD, coronary artery disease; HCVD, hypertensive cardiovascular disease; NSAIDs, nonsteroidal anti-inflammatory drugs; COX-2, cyclooxygenase-2; ACEI, angiotensin- converting enzyme inhibitors; ARB, angiotensin receptor blockers; ERBD, endoscopic retrograde biliary drainage; EPBD, endoscopic papillary balloon dilation.

Table 2 Outcomes

	ES Group (n=7,111)	Other ERCP (n=4,586)	p-value
Primary outcome, n (%)
- Liver abscess	143 (2.01)	77 (1.68)	0.1970
Complications of liver abscess, n (%)
- Endophthalmitis	0 (0)	0 (0)
- Brain abscess	0 (0)	0 (0)
- Intra-spinal abscess	0 (0)	0 (0)
- Bacterial meningitis	2 (0.03)	0 (0)	0.2560
- Lung abscess	1 (0.01)	0 (0)	0.4219
- Osteomyelitis	0 (0)	0 (0)
- Abscess of the prostate	0 (0)	0 (0)
Secondary outcome, n (%)
- Acute pancreatitis	270 (3.80)	255 (5.56)	<0.0001
- Cholangitis	1,290 (18.14)	975 (21.26)	<0.0001
- Recurrent CBD stones <180 days	896 (12.60)	690 (15.05)	0.0002
- Recurrent CBD stones ≧180 days	1,028 (14.46)	699 (15.24)	0.2423
- In-hospital mortality	316 (4.44)	198 (3.80)	0.7448

Notes: Number of event are presented as n (%).

Figure 2 Cumulative incidence between groups: (A) liver abscess; (B) acute pancreatitis; (C) cholangitis; (D) recurrent CBD stones ≥ 180 days.

Table 3 Factors Associated with Liver Abscess

Variable	Adjusted HR	95% CI	p-value
ES group vs Other ERCP	1.49	1.12–1.98	0.0058
Age	1.02	1.00–1.03	0.0048
Sex (female versus male)	0.74	0.57–0.97	0.0298
Covariate
Liver cirrhosis	0.95	0.54–1.68	0.8557
Chronic kidney disease	1.04	0.68–1.59	0.8698
Diabetes mellitus	1.29	0.93–1.78	0.1292
Disorders of lipoid metabolism	0.94	0.58–1.53	0.8155
CAD	0.66	0.37–1.16	0.1467
HCVD	1.02	0.73–1.42	0.9207
Baseline Medication
NSAID/COX-2 inhibitors	0.95	0.72–1.25	0.7079
Aspirin	0.94	0.55–1.61	0.8328
Clopidogrel	1.92	0.97–3.78	0.0603
Warfarin	0.69	0.09–5.08	0.7176
Dipyridamole	0.92	0.22–3.84	0.9052
Cilostazol	2.35	0.83–6.67	0.1071
Systemic steroids	0.75	0.35–1.61	0.4577
Anti-hypertensives
Anti-hypertensives	1.60	0.63–4.05	0.3234
Diuretics	1.09	0.64–1.85	0.7610
Beta blocking agents	0.58	0.33–1.05	0.0706
Calcium channel blockers	0.89	0.55–1.45	0.6442
ACEI/ARB	1.01	0.61–1.65	0.9823
Ursodeoxycholic acid	1.35	0.81–2.22	0.2484
Statin	0.79	0.41–1.50	0.4674
Other Lipid lowering drugs	1.44	0.64–3.25	0.3846
Concomitant covariate
ERBD	1.66	1.08–2.54	0.0196
EPBD	0.61	0.35–1.04	0.0694
Surgery for hepato- pancreato-biliary system	1.60	1.13–2.28	0.0080
Cholecystectomy	0.83	0.56–1.23	0.3483
Hepatobiliary malignancy	2.91	2.07–4.08	<0.0001

Abbreviations: CAD, coronary artery disease; HCVD, hypertensive cardiovascular disease; NSAIDs, nonsteroidal anti-inflammatory drugs; COX-2, cyclooxygenase-2; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; ERBD, endoscopic retrograde biliary drainage; EPBD, endoscopic papillary balloon dilation.

Table 4 Factors Associated with Acute Pancreatitis

Variable	Adjusted HR	95% CI	p-value
ES group vs Other ERCP	0.72	0.60–0.85	0.0002
Age	0.99	0.99–1.00	0.0111
Sex (female vs male)	0.96	0.81–1.14	0.6604
Covariate
Liver cirrhosis	1.08	0.74–1.58	0.6890
Chronic kidney disease	1.28	0.99–1.65	0.0551
Diabetes mellitus	1.02	0.82–1.27	0.8572
Disorders of lipoid metabolism	1.17	0.88–1.56	0.2885
CAD	1.02	0.74–1.40	0.9127
HCVD	0.87	0.69–1.09	0.2287
Baseline Medication
NSAID/COX-2 inhibitors	1.23	1.03–1.46	0.0242
Aspirin	1.25	0.91–1.70	0.1661
Clopidogrel	1.11	0.70–1.75	0.6598
Warfarin	1.24	0.55–2.81	0.6104
Dipyridamole	0.79	0.32–1.94	0.6126
Cilostazol	1.53	0.74–3.17	0.2465
Systemic steroids	0.96	0.63–1.47	0.8668
Anti-hypertensives
Anti-hypertensives	0.75	0.37–1.55	0.4429
Diuretics	1.16	0.85–1.58	0.3434
Beta blocking agents	1.07	0.79–1.46	0.6466
Calcium channel blockers	0.99	0.74–1.33	0.9715
ACEI/ARB	1.16	0.86–1.57	0.3225
Ursodeoxycholic acid	1.18	0.84–1.64	0.3358
Statin	0.70	0.48–1.01	0.0562
Other Lipid lowering drugs	1.02	0.61–1.71	0.9351

Abbreviations: CAD, coronary artery disease; HCVD, hypertensive cardiovascular disease; NSAIDs, nonsteroidal anti-inflammatory drugs; COX-2, cyclooxygenase-2; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers.

Table 5 Factors Associated with Cholangitis

Variable	Adjusted HR	95% CI	p-value
ES group vs Other ERCP	0.91	0.84–0.99	0.0259
Age	1.01	1.00–1.01	0.0001
Sex (female vs male)	0.82	0.75–0.89	<0.0001
Covariate
Liver cirrhosis	1.34	1.13–1.58	0.0007
Chronic kidney disease	0.92	0.81–1.05	0.2411
Diabetes mellitus	1.14	1.02–1.26	0.0172
Disorders of lipoid metabolism	0.86	0.74–1.00	0.0476
CAD	0.90	0.76–1.06	0.1882
HCVD	0.89	0.80–0.99	0.0385
Baseline Medication
NSAID/COX-2 inhibitors	0.89	0.82–0.97	0.0077
Aspirin	1.01	0.86–1.19	0.8724
Clopidogrel	1.05	0.83–1.35	0.6703
Warfarin	0.90	0.55–1.48	0.6828
Dipyridamole	1.30	0.88–1.92	0.1850
Cilostazol	1.11	0.71–1.75	0.6405
Systemic steroids	1.36	1.12–1.64	0.0016
Anti-hypertensives
Anti-hypertensives	1.07	0.77–1.49	0.6695
Diuretics	1.07	0.91–1.25	0.4370
Beta blocking agents	0.87	0.74–1.02	0.0920
Calcium channel blockers	0.99	0.86–1.15	0.9192
ACEI/ARB	1.07	0.91–1.24	0.4142
Ursodeoxycholic acid	1.27	1.08–1.49	0.0036
Statin	0.95	0.78–1.15	0.5723
Other Lipid lowering drugs	0.85	0.63–1.15	0.2987

Abbreviations: CAD, coronary artery disease; HCVD, hypertensive cardiovascular disease; NSAIDs, nonsteroidal anti-inflammatory drugs; COX-2, cyclooxygenase-2; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers.

Table 6 Factors Associated with Recurrent Bile Duct Stones ≥180 Days

Variable	Adjusted HR	95% CI	p-value
ES group vs Other ERCP	1.09	0.99–1.20	0.0781
Age	1.02	1.01–1.02	<0.0001
Sex (female vs male)	1.01	0.92–1.12	0.7781
Covariate
Liver cirrhosis	1.33	1.10–1.62	0.0033
Chronic kidney disease	1.18	1.02–1.37	0.0256
Diabetes mellitus	0.97	0.86–1.10	0.6366
Disorders of lipoid metabolism	0.82	0.69–0.98	0.0275
CAD	0.85	0.71–1.02	0.0794
HCVD	0.97	0.86–1.10	0.6550
Baseline Medication
NSAID/COX-2 inhibitors	0.92	0.84–1.02	0.1113
Aspirin	1.03	0.86–1.23	0.7663
Clopidogrel	1.00	0.76–1.32	0.9739
Warfarin	0.84	0.46–1.53	0.5735
Dipyridamole	0.99	0.61–1.58	0.9517
Cilostazol	0.73	0.40–1.34	0.3159
Systemic steroids	1.18	0.94–1.48	0.1626
Anti-hypertensives
Anti-hypertensives	0.92	0.62–1.36	0.6691
Diuretics	0.99	0.83–1.19	0.9405
Beta blocking agents	0.95	0.79–1.13	0.5612
Calcium channel blockers	1.04	0.88–1.22	0.6522
ACEI/ARB	1.00	0.84–1.18	0.9577
Ursodeoxycholic acid	1.32	1.09–1.58	0.0037
Statin	1.07	0.86–1.32	0.5529
Other Lipid lowering drugs	1.06	0.77–1.45	0.7153

Abbreviations: CAD, coronary artery disease; HCVD, hypertensive cardiovascular disease; NSAIDs, nonsteroidal anti-inflammatory drugs; COX-2, cyclooxygenase-2; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers.