High prevalence of cholestasis, with increased conjugated bile acids in inflammatory bowel diseases patients

Table 1 Clinical characteristics of patients¹n (%)

	TBA > 8	TBA < 8	P value
	(n = 96)	(n = 1246)
Age (mean ± SD, yr)	44 ± 1.6	41.5 ± 0.4	0.118
Male	60 (63)	639 (51)	0.027
Female	35 (36)	603 (48)
CD	47 (49)	716 (57)	0.267
UC	45 (47)	498 (40)
IC	3 (3)	26 (2)
Disease duration (mean ± SD, yr)	11 ± 1.2	9.8 ± 0.3	0.446
CDAI (mean ± SD)	92.8 ± 8.7	82.1 ± 2.7	0.316
MTWI (mean ± SD)	3.6 ± 0.6	4.1 ± 0.2	0.436
Smokers	16 (17)	339 (27)	0.023
Non smokers	80 (83)	903 (72)
Extra intestinal manifestations
Arthritis	21 (22)	362 (2)	0.133
Uveitis	4 (4)	68 (5)	0.588
Pyoderma gangrenosum	1 (1)	12 (1)	0.938
Erythema nodosum	4 (4)	42 (3)	0.679
Oral soars	5 (5)	70 (6)	0.867
Spondylarthritis	3 (3)	52 (4)	0.617
Primary sclerosing cholangitis	5 (5)	10 (1)	0.000
Colorectal cancer	0 (0)	5 (0)	0.533
Colonic dysplasia	1 (1)	5 (0)	0.364
Lymphoma	0 (0)	0 (0)	Ns
Osteoporosis	17 (18)	184 (15)	0.436
Anemia	11 (11)	229 (18)	0.088
Thrombosis	5 (5)	20 (2)	0.011
Gallstone	5 (5)	33 (3)	0.145
Urinary stones	2 (2)	38 (3)	0.591
Malabsorption	5 (5)	38 (3)	0.247
Lab values
TBA (mean ± SD, μmol/L)	21.9 ± 5.5	3.1 ± 0.1	1.36 × 10-30
CRP (mean ± SD, mg/L)	9.8 ± 1.6	11.7 ± 0.7	0.460
Ferritine (mean ± SD, μg/L)	158.5 ± 39.9	239.2 ± 35.9	0.516
B12 vitamin (mean ± SD, pmol/L)	604.1 ± 155.9	446.8 ± 27.1	0.130
Alkaline phosphatase (mean ± SD, U/L)	108.1 ± 10.8	69.7 ± 1.2	10.00 × 10-13
Albumin (mean ± SD, g/L)	38.0 ± 0.8	39.8 ± 0.2	0.016
Medical therapies
Oral 5-ASA	39 (41)	415 (33)	0.147
Topical 5-ASA	9 (9)	114 (9)	0.855
Sulfasalazine	0 (0)	28 (2)	Ns
Metronidazole	1 (1)	31 (2)	0.723
Ciprofloxacine	4 (4)	28 (2)	0.281
Clarithromycine	0 (0)	1 (0)	Ns
Cyclosporine	0 (0)	12 (1)	Ns
Tacrolimus	3 (3)	8 (1)	0.009
Azathioprine	38 (40)	407 (33)	0.177
6-Mercaptopurine	5 (5)	67 (5)	Ns
Remicade	9 (9)	183 (15)	0.174
Humira	1 (1)	51 (4)	0.172
Cimzia	0 (0)	19 (2)	Ns
Methotrexate	5 (5)	79 (6)	0.827
Budesonide	9 (9)	107 (9)	0.708
Systemic prednisone	20 (21)	170 (14)	0.051
Topical prednisone	2 (2)	28 (2)	0.716
Ursodesoxycholic acid	10 (10)	7 (1)	2.84 × 10-8
Cholestiramine	2 (2)	24 (2)	0.708
Supplements
Iron	12 (13)	188 (15)	0.492
Vitamin B12	13 (14)	191 (15)	0.638
Folate	8 (8)	125 (10)	0.591
Multivitamin	2 (2)	76 (6)	0.105
Magnesium	6 (6)	54 (4)	0.381
Calcium	37 (39)	356 (29)	0.038
Vitamin D	28 (29)	270 (22)	0.088
Vitamin E	3 (3)	9 (1)	0.016
Potassium	1 (1)	16 (1)	Ns
Lactase	0 (0)	3 (0)	Ns
Pancreatic enzymes	0 (0)	6 (0)	Ns
Fishoil	4 (4)	37 (3)	0.511
Enteric nutrition	0 (0)	6 (0)	Ns
Parenteric nutrition	1 (1)	3 (0)	0.165
Probiotics	3 (3)	16 (1)	0.141

¹Results expressed in number with percentage in parenthesis otherwise stated. Clinical characteristics of patients with elevated or normal total bile acid level. SD: Standard deviation; CD: Crohn’s disease; UC: Ulcerative colitis; IC: Indeterminate colitis; CDA: Crohn’s disease activity index; MTWI: Modified Truelove and Witts index; TBA: Total bile acid; CRP: C-reactive protein.

Table 2 Univariate analysis¹n (%)

	TBA > 8	TBA < 8	P value
	(n = 80)	(n = 1190)
TBA (mean ± SD, μmol/L)	14.66 ± 1.24	3.07 ± 0.06	6.15 × 10-144
Alkaline phosphatase (mean ± SD, U/L)	81 ± 5.81	69.3 ± 1.25	0.021
Albumin (mean ± SD, g/L)	38.0 ± 0.92	39.9 ± 0.21	0.017
Vitamin D	25 (31)	254 (21)	0.038
Vitamin E	2 (3)	9 (1)	0.103
Calcium	30 (38)	336 (28)	0.076
Prednisone	16 (20)	160 (13)	0.100
Azathioprine	37 (46)	383 (32)	0.009
Smokers	12 (15)	330 (28)	0.012
Thrombosis	4 (5)	17 (1)	0.015

¹Results expressed in number with percentage in parenthesis otherwise stated. Univariate analysis of factors differentiating patients with or without cholestasis. TBA: Total bile acid; SD: Standard deviation.

Table 3 Multivariate analysis

	OR	CI	P value
Gender	1.48	0.83-2.67	0.188
Alkaline phosphatase	1.00	0.99-1.01	0.282
Albumin	0.96	0.92-1.01	0.108
Current smoking status	0.42	0.17-0.91	0.041
Azathioprine treatment	1.57	0.873-2.79	0.128
Prednisone treatment	1.15	0.53-2.36	0.707
Vitamin D supplement	0.72	0.29-1.79	0.471
Vitamin E supplement	4.36	0.56-24.46	0.110
Calcium supplement	2.36	1.00-5.21	0.040
Thrombosis	1.38	0.19-5.89	0.701

Multivariate analysis of factors associated with a cholestasis comparing 80 patients with cholestasis and 1190 patients without cholestasis. CRP: C-reactive protein; OR: Odd-ratio; CI: Confidence interval.

Table 4 Bile acids subtypes

	TBA > 8 (80)	TBA < 8 (80)	P value
TBA	14.64 (1.24)	3.31 (0.22)	1.07 × 10-15
Primary
CA	1.09 (0.29)	0.29 (0.04)	0.008
Cholic acid
CDC chenodeoxycholate	2.06 (0.41)	0.68 (0.13)	0.002
Secondary
DC	1.35 (0.27)	0.28 (0.04)	0.000
deoxycholate
LCA	0.07 (0.01)	0.07 (0.01)	0.9
lithocholic acid
Tertiary
UDC	0.34 (0.05)	0.14 (0.03)	0.000
ursodeoxycholate
Primary conjugated
TC	0.37 (0.08)	0.04 (0.01)	0.000
taurocholate
GCA	1.78 (0.28)	0.38 (0.05)	1.83 × 10-6
gylcocholate acid
TCDC	0.74 (0.11)	0.18 (0.02)	1.58 × 10-6
taurochenodeoxycholate
GCDC	4.72 (0.33)	1.42 (0.12)	1.54 × 10-16
glycochenodeoxycholate
Secondary conjugated
GDC	1.01 (0.10)	0.30 (0.04)	1.38 × 10-9
glycodeoxycholate
TDC	0.20 (0.03)	0.05 (0.01)	8.78 × 10-7
taurodeoxycholate
TLC	0.04 (0.01)	0.01 (0.00)	8.46 × 10-5
taurolithocholate
GLC	0.09 (0.01)	0.09 (0.01)	0.646
glycolithocholate
Tertiary conjugated
TUDC	0.06 (0.01)	0.001 (0.00)	1.69 × 10-8
tauroursodeoxycholate
GUDC	0.84 (0.12)	0.19 (0.03)	4.58 × 10-7
glycoursodeoxycholate
Hydroxydes
DHCA	0.004 (0.002)	0.001 (0.001)	0.291
dihydroxycholestanoic acid
THCA	0.001 (0.001)	0.000 (0.000)	0.275
trihydroxycholestanoic acid
Ratio
Primary/secondary	3.48 (0.92)	4.42 (1.34)	0.566
Primary/TBA	0.23 (0.05)	0.31 (0.04)	0.211
Conjugated glycine/taurine
Primary	11.64 (1.18)	10.70 (0.89)	0.537
Secondary	6.40 (0.61)	5.15 (0.66)	0.209

Bile acids subtypes expressed in μmol/L with standard deviation under bracket, in 80 patients with a total bile acids level of more than 8 μmol/L compared with 80 patients with a total bile acids level of less than 8 μmol/L. TBA: Total bile acids; CA: Cholic acid; CDC: Chenodeoxycholate; DC: Deoxycholate; LCA: Lithocholic acid; UDC: Ursodeoxycholate; TC: Taurocholate; GCA: Gylcocholate acid; TCDC: Taurochenodeoxycholate; GCDC: Glycochenodeoxycholate; TDC: Taurodeoxycholate; GDC: Glycodeoxycholate; TLC: Taurolithocholate; GLC: Glycolithocholate; TUDC: Tauroursodeoxycholate; GUDC: Glycoursodeoxycholate; DHCA: Dihydroxycholestanoic acid; THCA: Trihydroxycholestanoic acid.