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©The Author(s) 2022.
World J Gastroenterol. Oct 21, 2022; 28(39): 5764-5783
Published online Oct 21, 2022. doi: 10.3748/wjg.v28.i39.5764
Published online Oct 21, 2022. doi: 10.3748/wjg.v28.i39.5764
Table 1 Characteristics of enrolled population in the metabolic profiling study
Clinical parameters | PBC (n = 54) | AIH (n = 26) | Control (n = 30) | P value (PBC vs control) | P value (AIH vs control) | P value (PBC vs AIH) |
Age (mean, range) (yr), n | 56 (38-73) | 54.6 (17-75) | 54.9(34-70) | 0.922 | 0.805 | 0.890 |
Sex (Male/Female), n | 7/47 | 3/23 | 4/26 | - | - | - |
AST (U/L) median, range | 113.3 (14-1300) | 168.8 (23-961) | 23.3 (7-38) | < 0.001 | < 0.001 | 0.423 |
ALT (U/L) median, range | 95.9 (12-734) | 153.3 (10-780) | 19.0 (7-39) | < 0.001 | < 0.001 | 0.125 |
ALP (U/L) median, range | 292.4 (55-953) | 240.1 (46-795) | 73.6 (32-116) | < 0.001 | < 0.001 | 0.123 |
γ-GT (U/L) median, range | 299.4 (32-1631) | 245.2 (26-957) | 21.1 (9-77) | < 0.001 | < 0.001 | 0.377 |
TBA (μmol/L) median, range | 60.0 (2.7-295.7) | 126.0 (1.1-1335) | - | - | - | 0.696 |
TBiL (μmol/L) median, range | 65.5 (5.6-825.8) | 89.1 (6.5-543.9) | 10.9 (6.3-19.5) | < 0.001 | < 0.001 | 0.481 |
DBIL (μmol/L) median range | 35.9 (2.4-407.4) | 52.9 (2.1-300.8) | 3.3 (0.4-6) | < 0.001 | < 0.001 | 0.648 |
Liver cirrhosis (%) | 65 (35/54) | 62 (16/26) | - | - | - | - |
Liver biopsy (%) | 18 (10/54) | 53 (14/26) | - | - | - | - |
Positive of AMA (%) | 81 (44/54) | 0 (0/26) | - | - | - | - |
Positive of ANA (%) | 61 (33/54) | 100 (26/26) | - | - | - | - |
Table 2 Characteristics of classified enrolled population according to Child-Pugh in the metabolic profiling study
Clinical parameters | PBC-A (n = 26) | PBC-B (n = 19) | PBC-C (n = 9) | AIH-A (n = 17) | AIH-B (n = 9) |
Age (mean, range) (yr), n | 54 (38, 68) | 57.11 (40, 73) | 59.33 (51, 67) | 52.35 (17, 75) | 59.11 (36, 73) |
Sex (Male/Female), n | 6/20 | 3/16 | 0/9 | 2/15 | 1/8 |
AST (U/L) median, range | 62.77 (20, 210) | 182.62 (14, 1300) | 113.27 (35, 235) | 122.28 (23, 961) | 256.78 (64, 472) |
ALT (U/L) median, range | 74.18 (15, 293) | 130.32 (12, 734) | 84.51 (17, 236) | 100.54 (10, 780) | 253.11 (103, 598) |
ALP (U/L) median, range | 276.41 (75, 53) | 352.73 (79, 913) | 211.43 (55, 483) | 230.33 (57, 795) | 258.78 (46, 738) |
γ-GT (U/L) median, range | 380.18 (40, 631) | 281.77 (40, 744) | 103.49 (32, 235) | 166.46 (26, 654) | 393.89 (73, 957) |
TBA (μmol/L) median, range | 31.04 (2.9, 09.3) | 75.16 (2.7, 295.7) | 127.37 (23.4, 267.5) | 116.46 (1, 1335) | 144.29 (15, 379) |
TBiL (μmol/L) median, range | 19.7 (5.6, 48.8) | 81.0 (11.3, 306.5) | 181.62 (17.7, 825.8) | 48.33 (6.5, 229.5) | 166.23 (50.0, 543.9) |
DBIL (μmol/L) median, range | 9.18 (2.4, 32.0) | 48.3 (4.1, 207.9) | 99.71 (6.6, 407.4) | 27.40 (2.1, 139.3) | 101.24 (30.6, 300.8) |
Liver cirrhosis (%) | 0.38 (10/26) | 0.84 (16/19) | 1 (9/9) | 0.47 (8/17) | 0.33 (3/9) |
Liver biopsy (%) | 0.35 (9/26) | 0.05 (1/19) | 0 (0/9) | 0.64 (11/17) | 0.33 (3/9) |
Positive of AMA (%) | 80 (21/26) | 80 (15/19) | 89 (8/9) | 0 (0/17) | 0 (0/9) |
Positive of ANA (%) | 73 (19/26) | 52 (10/19) | 44 (4/9) | 100 (17/17) | 100 (9/9) |
Table 3 Potential serum biomarkers for primary biliary cirrhosis compared to healthy control in positive and negative ions model
Name | VIP | MZ | Time | PBC/control | |
t-test | Fold change (P/C) | ||||
ESI+ | |||||
Taurodeoxycholic acid | 1.747 | 500.3033 | 10.598 | 0.001 | 8.146 |
Glycodeoxycholate | 2.175 | 450.3207 | 12.146 | 0.000 | 4.558 |
Tetracosahexaenoic acid | 1.100 | 357.2786 | 9.333 | 0.045 | 3.490 |
Bilirubin | 1.511 | 585.2701 | 10.218 | 0.006 | 3.334 |
Sphinganine | 1.953 | 302.3052 | 12.792 | 0.000 | 3.285 |
Phytosphingosine | 2.482 | 318.2999 | 10.734 | 0.000 | 3.039 |
L-Phenylalanine | 1.690 | 166.0860 | 2.037 | 0.002 | 0.372 |
L-Proline | 1.194 | 116.0706 | 0.725 | 0.030 | 0.180 |
12-Ketodeoxycholic acid | 1.573 | 391.2842 | 15.210 | 0.004 | -0.324 |
ESI- | |||||
Taurocholic acid | 1.493 | 514.2805 | 9.146 | 0.000 | 6.634 |
LysoPC [18:3(6Z, 9Z, 12Z)] | 1.184 | 516.3064 | 13.057 | 0.001 | 5.263 |
Tauroursodeoxycholic acid | 1.843 | 498.2861 | 10.456 | 0.000 | 4.627 |
Glycocholic Acid | 1.866 | 464.2988 | 9.957 | 0.000 | 3.644 |
LysoPE [0:0/18:4 (6Z, 9Z, 12Z, 15Z)] | 1.316 | 472.2430 | 9.798 | 0.000 | 3.274 |
LysoPE [20:3 (11Z, 14Z, 17Z)/0:0] | 1.882 | 500.2947 | 10.456 | 0.000 | 3.225 |
L-Urobilinogen | 1.027 | 595.3478 | 11.784 | 0.003 | 3.202 |
L-Urobilin | 1.032 | 593.3315 | 11.665 | 0.003 | 2.411 |
Deoxycholic acid | 1.032 | 391.2833 | 11.641 | 0.003 | 2.121 |
α-ketoisovaleric acid | 1.040 | 115.0399 | 1.831 | 0.003 | -0.348 |
Pyroglutamic acid | 1.252 | 128.0350 | 0.931 | 0.000 | -0.392 |
Lactic acid | 1.548 | 89.0242 | 0.938 | 0.000 | -0.402 |
Hypoxanthine | 1.384 | 135.0308 | 0.886 | 0.000 | -0.431 |
LysoPE [0:0/20:2 (11Z, 14Z)] | 1.335 | 504.3072 | 14.333 | 0.000 | -0.453 |
Ketoleucine | 1.392 | 129.0555 | 4.110 | 0.000 | -0.486 |
LysoPE [0:0/22:4 (7Z, 10Z, 13Z, 16Z)] | 1.333 | 528.2850 | 13.617 | 0.000 | -0.544 |
MG [0:0/18:4 (6Z, 9Z, 12Z, 15Z)/0:0] | 2.060 | 349.2373 | 8.969 | 0.000 | -2.181 |
Table 4 Potential serum biomarkers for autoimmune hepatitis compared to healthy control
Name | VIP | MZ | Time | AIH/control | |
t-test | Fold change (A/C) | ||||
ESI+ | |||||
Taurodeoxycholic acid | 1.900 | 500.3033 | 10.598 | 0.000 | 8.791 |
Glycodeoxycholate | 1.912 | 450.3207 | 12.146 | 0.000 | 5.217 |
L-Urobilin | 1.442 | 595.3484 | 7.835 | 0.007 | 5.164 |
Sphinganine | 2.308 | 302.3052 | 12.792 | 0.000 | 4.509 |
Phytosphingosine | 2.344 | 318.2999 | 10.734 | 0.000 | 4.118 |
I-Urobilin | 1.454 | 591.3169 | 7.628 | 0.006 | 3.661 |
Bilirubin | 1.876 | 585.2701 | 10.218 | 0.000 | 3.578 |
Kynurenine | 2.279 | 209.0919 | 1.944 | 0.000 | 0.592 |
L-Threonine | 1.446 | 120.0655 | 0.708 | 0.007 | 0.386 |
L-Phenylalanine | 1.551 | 166.0860 | 2.037 | 0.004 | 0.262 |
Urea | 1.160 | 61.0395 | 0.730 | 0.032 | 0.113 |
12-Ketodeoxycholic acid | 1.125 | 391.2842 | 15.210 | 0.037 | -0.270 |
Uric acid | 1.208 | 169.0354 | 1.035 | 0.025 | -0.265 |
Pyroglutamic acid | 2.489 | 130.0499 | 1.029 | 0.000 | -0.517 |
ESI- | |||||
Taurocholic acid | 1.605 | 514.281 | 9.146 | 0.000 | 7.368 |
LysoPC [18:3 (6Z, 9Z, 12Z)] | 1.454 | 516.306 | 13.057 | 0.000 | 6.614 |
Tauroursodeoxycholic acid | 1.807 | 498.286 | 10.456 | 0.000 | 5.151 |
Glycocholic Acid | 1.961 | 464.299 | 9.957 | 0.000 | 3.946 |
LysoPE [20:3 (11Z, 14Z, 17Z)/0:0] | 1.807 | 500.295 | 10.456 | 0.000 | 3.670 |
LysoPE [0:0/20:2 (11Z, 14Z)] | 1.234 | 504.307 | 14.333 | 0.001 | -0.471 |
Lactic acid | 1.489 | 89.024 | 0.938 | 0.000 | -0.489 |
Hypoxanthine | 1.380 | 135.031 | 0.886 | 0.000 | -0.562 |
CPA (16:0/0:0) | 1.629 | 391.224 | 26.118 | 0.000 | -2.159 |
MG [0:0/18:4 (6Z, 9Z, 12Z, 15Z)/0:0] | 1.771 | 349.237 | 8.969 | 0.000 | -2.464 |
Table 5 Changes of the serum bile acid profile between primary biliary cirrhosis, autoimmune hepatitis and controls
AIH (mean ± SD) | PBC (mean ± SD) | Control (mean ± SD) | PBC/AIH | AIH/control | PBC/control | |
P value | P value | P value | ||||
CA | 2.38 ± 0.69 | 2.26 ± 0.85 | 1.60 ± 0.51 | 0.53 | < 0.001b | < 0.001a |
GCA | 3.00 ± 1.02 | 2.91 ± 0.91 | 1.33 ± 0.50 | 0.69 | < 0.001b | < 0.001a |
TCA | 2.12 ± 1.23 | 2.12 ± 0.93 | 0.03 ± 0.46 | 0.99 | < 0.001b | < 0.001a |
UDCA | 2.41 ± 1.03 | 2.60 ± 1.05 | 2.05 ± 0.36 | 0.62 | 0.2 | 0.01a |
GUDCA | 2.59 ± 1.17 | 3.04 ± 1.14 | 1.64 ± 0.50 | 0.09 | < 0.001b | < 0.001a |
TUDCA | 1.48 ± 1.07 | 1.84 ± 1.09 | 0.13 ± 0.25 | 0.15 | < 0.001b | < 0.001a |
CDCA | 2.88 ± 0.39 | 3.07 ± 0.48 | 2.63 ± 0.38 | 0.046c | 0.01b | < 0.001a |
GCDCA | 3.78 ± 0.80 | 3.79 ± 0.67 | 2.93 ± 0.33 | 0.96 | < 0.001b | < 0.001a |
TCDCA | 2.73 ± 0.40 | 2.84 ± 0.44 | 2.49 ± 0.57 | 0.27 | 0.09 | 0.004a |
GCDCS | 2.39 ± 0.82 | 2.42 ± 0.70 | 1.08 ± 0.39 | 0.95 | < 0.001b | < 0.001a |
DCA | 2.76 ± 0.35 | 2.75 ± 0.40 | 2.76 ± 0.18 | 0.87 | 0.7 | 0.59 |
GDCA | 3.18 ± 0.58 | 3.14 ± 0.53 | 2.64 ± 0.32 | 0.8 | < 0.001b | < 0.001a |
TDCA | 3.32 ± 0.64 | 3.16 ± 0.50 | 2.57 ± 0.19 | 0.33 | < 0.001b | < 0.001a |
LCA | 0.94 ± 0.68 | 1.28 ± 0.66 | 0.72 ± 0.43 | 0.04c | 0.14 | < 0.001a |
TLCA | 0.30 ± 0.41 | 0.48 ± 0.47 | 0.02 ± 0.06 | 0.07 | < 0.001b | < 0.001a |
LCA + TLCA | 1.25 ± 0.18 | 1.75 ± 0.14 | 0.74 ± 0.07 | 0.034c | 0.031b | < 0.001a |
CDCA/CA | 1.30 ± 0.35 | 1.56 ± 0.65 | 1.74 ± 0.42 | 0.26 | < 0.001b | < 0.001a |
pBA | 3.11 ± 0.45 | 3.17 ± 0.51 | 2.67 ± 0.38 | 0.98 | < 0.001b | < 0.001a |
sBA | 3.14 ± 0.52 | 3.19 ± 0.61 | 2.87 ± 0.17 | 0.75 | 0.003b | 0.002a |
pBA/sBA | 1.02 ± 0.18 | 1.01 ± 0.17 | 1.08 ± 0.13 | 0.85 | 0.087 | < 0.001 |
sBA | 2.77 ± 0.35 | 2.79 ± 0.40 | 2.77 ± 0.18 | 0.81 | 0.02b | 0.003a |
G-BA | 4.14 ± 0.70 | 4.12 ± 0.64 | 3.16 ± 0.31 | 0.97 | < 0.001b | < 0.001a |
T-BA | 3.58 ± 0.54 | 3.47 ± 0.46 | 2.89 ± 0.27 | 0.34 | < 0.001b | < 0.001a |
G-BA/T-BA | 0.55 ± 0.34 | 0.65 ± 0.34 | 0.27 ± 0.30 | 0.25 | < 0.001b | < 0.001a |
total BA | 36.31 ± 6.00 | 37.69 ± 7.40 | 24.80 ± 3.12 | 0.41 | < 0.001b | 0.026a |
Table 6 Area under the curve, sensitivity and specificity of difference bile acids, conventional biochemical indicators in primary biliary cirrhosis, autoimmune hepatitis and control group
AUC | Sensitivity | Specificity | |
LCA | 0.68 | 0.82 | 0.50 |
LCA + TLCA | 0.73 | 0.74 | 0.46 |
CDCA | 0.74 | 0.74 | 0.54 |
AST | 0.54 | 0.67 | 0.58 |
ALT | 0.61 | 0.64 | 0.61 |
ALP | 0.41 | 0.56 | 0.35 |
GGT | 0.43 | 0.50 | 0.46 |
TBiL | 0.53 | 0.59 | 0.42 |
DBiL | 0.47 | 0.44 | 0.62 |
TBA | 0.52 | 0.52 | 0.42 |
Table 7 Changes of the serum bile acid profile between primary biliary cirrhosis and autoimmune hepatitis in different grade of Child-Pugh
AIH-A/PBC/A | AIH-B/PBC-B | AIH-A/AIH-B | PBC-A/PBC-B | PBC-B/PBC-C | PBC-A/PBC-C | AIH-A/control | AIH-B/control | PBC-A/control | PBC-B/control | PBC-C/control | |
P value | P value | P value | P value | P value | P value | P value | P value | P value | P value | P value | |
CA | 0.75 | 0.34 | 0.24 | 0.67 | 0.82 | 0.50 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | 0.03 |
GCA | 0.79 | 0.03 | < 0.001 | 0.07 | 0.43 | 0.02 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
TCA | 0.79 | 0.03 | < 0.001 | 0.0522 | 0.71 | 0.0567 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
UDCA | 0.77 | 0.26 | 0.07 | 0.70 | 0.30 | 0.38 | < 0.001 | 0.52 | <0.001 | 0.05 | < 0.001 |
GUDCA | 0.60 | 0.33 | 0.40 | 0.58 | 0.21 | 0.06 | < 0.001 | 0.13 | < 0.001 | < 0.001 | < 0.001 |
TUDCA | 0.97 | 0.22 | 1.00 | 0.10 | 0.29 | 0.02 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
CDCA | 0.26 | 0.09 | 0.07 | 0.30 | 0.44 | 0.78 | < 0.001 | 0.47 | < 0.001 | < 0.001 | < 0.001 |
GCDCA | 0.89 | 0.19 | 0.01 | 0.06 | 0.17 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
TCDCA | 0.82 | 0.20 | 0.31 | 0.34 | 0.92 | 0.26 | 0.05 | 0.48 | 0.02 | 0.01 | 0.04 |
GCDCS | 0.33 | 0.04 | < 0.001 | 0.15 | 0.24 | 0.01 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
DCA | 0.71 | 0.26 | 0.02 | 0.13 | 0.66 | 0.38 | 0.24 | 0.01 | 0.64 | 0.21 | 0.45 |
GDCA | 0.50 | 0.08 | 0.09 | 0.37 | 0.09 | 0.11 | < 0.001 | < 0.001 | < 0.001 | 0.01 | < 0.001 |
TDCA | 0.69 | 0.03 | < 0.001 | 0.01 | 0.33 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
LCA | 0.29 | 0.13 | 0.57 | 0.82 | 0.24 | 0.33 | 0.08 | 0.51 | < 0.001 | < 0.001 | < 0.001 |
TLCA | 0.07 | 0.88 | 0.05 | 0.13 | 0.74 | 0.29 | 0.01 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
CDCA/CA | 0.46 | 0.04 | 0.04 | 0.66 | 0.50 | 0.27 | < 0.001 | < 0.001 | < 0.001 | 0.06 | 0.26 |
Primary bile acid | 0.75 | 0.81 | 0.96 | 0.42 | 0.70 | 0.96 | < 0.001 | 0.02 | < 0.001 | < 0.001 | < 0.001 |
Secondary bile acid | 0.92 | 0.80 | 0.20 | 0.33 | 0.20 | 0.45 | < 0.001 | 0.45 | < 0.001 | 0.15 | < 0.001 |
Secondary/primary | 0.61 | 0.99 | 0.32 | 0.27 | 0.23 | 0.44 | 0.30 | 0.05 | 0.06 | 0.01 | 0.78 |
Secondary bile acid | 0.89 | 0.91 | 0.08 | 0.05 | 0.24 | 0.79 | 0.13 | 0.08 | 0.09 | 0.12 | 0.35 |
Glycoconjugates | 0.53 | 0.16 | < 0.001 | 0.21 | 0.16 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Tauroconjugted | 0.48 | 0.08 | < 0.001 | 0.02 | 0.42 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Glyco/tauro | 0.21 | 0.56 | 0.23 | 0.63 | 0.07 | 0.18 | 0.01 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Total BA | 0.62 | 0.72 | 0.05 | 0.26 | 0.19 | 0.01 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
- Citation: Ma ZH, Wang XM, Wu RH, Hao DL, Sun LC, Li P, Niu JQ. Serum metabolic profiling of targeted bile acids reveals potentially novel biomarkers for primary biliary cholangitis and autoimmune hepatitis. World J Gastroenterol 2022; 28(39): 5764-5783
- URL: https://www.wjgnet.com/1007-9327/full/v28/i39/5764.htm
- DOI: https://dx.doi.org/10.3748/wjg.v28.i39.5764